ORCID Profile
0000-0002-4506-5233
Current Organisations
Victorian Department of Health
,
Monash University
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Medical Biotechnology | Regenerative Medicine (incl. Stem Cells and Tissue Engineering) |
Disability and Functional Capacity | Expanding Knowledge in the Medical and Health Sciences
Publisher: Elsevier BV
Date: 05-2012
DOI: 10.1016/J.AJOG.2012.02.038
Abstract: The objective of the study was to explore whether human amnion epithelial cells (hAECs) can mitigate ventilation-induced lung injury. An established in utero ovine model of ventilation-induced lung injury was used. At day 110 of gestation, singleton fetal lambs either had sham in utero ventilation (IUV) (n = 4), 12 hours of IUV alone (n = 4), or 12 hours of IUV and hAEC administration (n = 5). The primary outcome, structural lung injury, was assessed 1 week later. Compared with sham controls, IUV alone was associated with significant lung injury: increased collagen (P = .03), elastin (P = .02), fibrosis (P = .02), and reduced secondary-septal crests (P = .009). This effect of IUV was significantly mitigated by the administration of hAECs: less collagen (P = .03), elastin (P = .04), fibrosis (P = .02), normalized secondary-septal crests (P = .02). The hAECs were immunolocalized within the fetal lung and had differentiated into type I and II alveolar cells. The hAECs mitigate ventilation-induced lung injury and differentiated into alveolar cells in vivo.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2006
Publisher: Springer Science and Business Media LLC
Date: 19-08-2010
Publisher: CSIRO Publishing
Date: 2019
DOI: 10.1071/AH17266
Abstract: Learning from medical errors to prevent their recurrence is an important component of any healthcare system’s quality and safety improvement functions. Traditionally, this been achieved principally from review of adverse clinical outcomes. The opportunity to learn systematically and in a system manner from patient complaints and litigation has been less well harnessed. Herein we describe the pathways and processes for both patient complaints and medicolegal claims in Victoria, and Australia more broadly, and assess the potential for these to be used for system improvement. We conclude that both patient complaints and medicolegal claims could afford the potential to additionally inform and direct safety and quality improvement. At present neither patient complaints nor medicolegal claims are used systematically to improve patient safety. We identify how this may be done, particularly through sharing findings across agencies. What is known about the topic? Patient complaints and medicolegal claims are accepted parts of the healthcare industry. However, using these in a shared and collated manner as part of an improvement agenda has not been widely considered or proposed. What does the paper add? This paper provides a summary of the patient complaint and medicolegal landscape in public hospital system in Australia broadly, and Victoria more specifically, identifying the agencies involved and the opportunities for sharing learnings. The paper draws on existing literature and experiences from both Australia and elsewhere to propose a framework whereby complaints and claims data could be shared systematically and strategically to reduce future harm and improve patient care. What are the implications for practitioners? We offer an approach for practitioners, healthcare managers and policy makers in all Australian jurisdictions to design and implement a statewide capacity to share patient complaints and medicolegal claims as an additional component of system quality and safety.
Publisher: The Endocrine Society
Date: 03-2007
DOI: 10.1210/EN.2006-1058
Abstract: Intrauterine growth restriction (IUGR) is associated with altered fetal cardiovascular function to ensure adequate perfusion of essential organs. IUGR fetuses are at risk of preterm delivery and so are likely to receive antenatal glucocorticoids to promote lung maturation. Because glucocorticoids alter vascular tone, we questioned whether such treatment may induce fetal cardiovascular alterations. Using pregnant sheep carrying twins, we induced IUGR at approximately 0.7 gestation by single umbilical artery ligation in one twin, using the other twin as a control. In each fetus, we monitored carotid blood flow and arterial blood gases. We administered 11.4 mg betamethasone (n = 5) or vehicle (n = 4) to the ewe on d 5 (BM1) and 6 (BM2) postsurgery. On d 7, fetal brains were collected for immunohistochemistry. In control fetuses, carotid blood flow decreased 3.5 h post-BM1 by 24% (P < 0.001), returning to baseline at 5.5 h. In IUGR fetuses, carotid flow decreased 2.5 h post-BM1 by 27% and then increased by 25% over baseline, peaking at 11 h (P IUGR + saline = control + BM). There was a significant correlation between carotid blood flow reperfusion after betamethasone and the number of 4-hydroxynonenal-positive cells in the cortex and hippoc us. These data suggest that antenatal betamethasone may induce brain injury in the IUGR fetus but not in the normally grown fetus.
Publisher: Wiley
Date: 09-2011
DOI: 10.1111/J.1440-1754.2011.02172.X
Abstract: The term 'stem cell' most commonly refers to embryonic stem cells, particularly in the lay media however, it also describes other cell types. A stem cell represents a cell of multi-lineage potential with the ability for self-renewal. It is now clear that the plasticity and immortality of a given stem cell will depend on what type of stem cell it is, whether an embryonic stem cell, a fetal-placental stem cell or an adult stem cell. Stem cells offer great promise as cell-based therapies for the future. With evolving technology, much of the socio-political debate regarding stem cells can now be avoided.
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.PLACENTA.2017.02.013
Abstract: Tryptophan is a substrate for kynurenine pathway metabolism in the placenta. We investigated if kynurenine metabolites change over gestation, if they are different between pregnancies with normal and fetal growth restriction (FGR), and if the oxygen environment modulated kynurenine pathway activity in the human placenta. Tryptophan, kynurenine, and downstream kynurenine metabolites were determined in maternal venous blood, umbilical cord blood, and placental s les obtained in 1st and 3rd trimester pregnancies including FGR, and in the media of placental explants incubated with 20% or 5-8% O All the major kynurenine metabolites were present in cord blood, and in general were higher than in maternal blood. IDO and TDO mRNA and protein expression, responsible for kynurenine production from tryptophan, were significantly lower in placentas from FGR pregnancies compared with control. Explants prepared from 1st and 3rd trimester placentas actively produced all the major kynurenine pathway metabolites which, together with expression of IDO, TDO, KYN-OHase and 3HAO mRNAs, were significantly lower after 24 h exposure to 5-8% O
Publisher: Wiley
Date: 16-06-2016
DOI: 10.1002/SONO.12065
Publisher: Wiley
Date: 22-02-2014
DOI: 10.1111/JPI.12121
Abstract: Fetal intrauterine growth restriction (IUGR) is a serious pregnancy complication associated with increased rates of perinatal morbidity and mortality, and ultimately with long-term neurodevelopmental impairments. No intervention currently exists that can improve the structure and function of the IUGR brain before birth. Here, we investigated whether maternal antenatal melatonin administration reduced brain injury in ovine IUGR. IUGR was induced in pregnant sheep at 0.7 gestation and a subset of ewes received melatonin via intravenous infusion until term. IUGR, IUGR + melatonin (IUGR + MLT) and control lambs were born naturally, neonatal behavioral assessment was used to examine neurological function and at 24 hr after birth the brain was collected for the examination of neuropathology. Compared to control lambs, IUGR lambs took significantly longer to achieve normal neonatal lamb behaviors, such as standing and suckling. IUGR brains showed widespread cellular and axonal lipid peroxidation, and white matter hypomyelination and axonal damage. Maternal melatonin administration ameliorated oxidative stress, normalized myelination and rescued axonopathy within IUGR lamb brains, and IUGR + MLT lambs demonstrated significant functional improvements including a reduced time taken to attach to and suckle at the udder after birth. Based on these observations, we began a pilot clinical trial of oral melatonin administration to women with an IUGR fetus. Maternal melatonin was not associated with adverse maternal or fetal effects and it significantly reduced oxidative stress, as evidenced by reduced malondialdehyde levels, in the IUGR + MLT placenta compared to IUGR alone. Melatonin should be considered for antenatal neuroprotective therapy in human IUGR.
Publisher: Wiley
Date: 22-10-2010
Publisher: Springer New York
Date: 2014
Publisher: Wiley
Date: 2003
DOI: 10.1002/PD.577
Abstract: To assess the effect of altering image size on the absolute nuchal translucency (NT) measurement. NT was measured at three image magnifications (60%, 100% and 200%) in 120 singleton pregnancies. The mean +/- SD NT measurements were 1.52 +/- 0.57 mm, 1.35 +/- 0.53 mm and 1.18 +/- 0.48 mm at 60%, 100% and 200% magnification, respectively (p = 0.00001). The measurement of NT decreases significantly with increasing image size. Optimisation of NT as a method of screening will require agreed standardisation of image magnification.
Publisher: Wiley
Date: 09-2002
DOI: 10.1046/J.1469-0705.2002.00782.X
Abstract: To determine the timing of the onset of the umbilical artery flow velocity waveform changes following maternal administration of betamethasone in pregnancies complicated by umbilical artery absent end-diastolic flow, and to explore whether these changes are associated with flow velocity waveform changes in other fetoplacental vessels. This was a prospective study of 12 women with pregnancies complicated by umbilical artery absent end-diastolic flow. Flow velocity waveforms were recorded from the umbilical artery, fetal middle cerebral artery, renal artery, aorta and ductus venosus, before and after maternal betamethasone administration, using real-time pulsed wave Doppler. In all 12 pregnancies, the administration of maternal betamethasone was followed by the return of end-diastolic flow within 24 h. End-diastolic flow was first observed at 4 h and was present in all women studied at 8 h. In addition, there was a statistically significant decrease in the pulsatility index in the fetal aorta at 8 h and the middle cerebral artery at 24 h. No change was observed in the ductus venosus or the renal artery flow velocity waveforms. The findings suggest that, in pregnancies complicated by absent end-diastolic flow in the umbilical artery, maternally administered betamethasone induces a return in umbilical artery end-diastolic flow as early as 4 h, along with widespread vasodilatation throughout the fetoplacental vasculature.
Publisher: AMPCo
Date: 08-2016
DOI: 10.5694/MJA16.00443
Abstract: To compare contemporary pregnancy outcomes in women with and without type 1 diabetes, and to examine the effects of obesity and glycaemic control on these outcomes. Historical cohort study in a specialist diabetes and maternity network in Victoria. All singleton births (at least 20 weeks' gestation), 2010-2013, were analysed: 107 pregnancies to women with type 1 diabetes and 27 075 pregnancies to women without diabetes. Women with type 2 diabetes or gestational diabetes were excluded. Data were extracted from the Birthing Outcomes System database associations between type 1 diabetes and pregnancy outcomes were analysed by multivariable regression. Mode of birth maternal and neonatal outcomes. The mean body mass index was higher for women with type 1 diabetes than for women without diabetes (mean, 27.3 kg/m(2) [SD, 5.0] v 25.7 kg/m(2) [SD, 5.9] P = 0.01) the median gestation period for their babies was shorter (median, 37.3 weeks [IQR, 34.6-38.1] v 39.4 weeks [IQR, 38.4-40.4] P < 0.001) and they were more likely to be large for gestational age (LGA) (adjusted odds ratio [aOR], 7.9 95% CI, 5.3-11.8). Women with type 1 diabetes were more likely to have had labour induced (aOR, 3.0 95% CI, 2.0-4.5), a caesarean delivery (aOR, 4.6 95% CI, 3.1-7.0), or a pre-term birth (aOR, 6.7 95% CI, 4.5-10.0) their babies were more likely to have shoulder dystocia (aOR, 8.2 95% CI, 3.6-18.7), hypoglycaemia (aOR, 10.3 95% CI, 6.8-15.6), jaundice (aOR, 5.1 95% CI, 3.3-7.7), respiratory distress (aOR, 2.5 95% CI, 1.4-4.4) or to suffer perinatal death (aOR, 4.3 95% CI, 1.9-9.9). In women with type 1 diabetes, greater obesity was associated with increased odds for an LGA baby or congenital malformation, and increased HbA1c levels were associated with pre-term birth and perinatal death. Women with type 1 diabetes, even when managed in a specialist setting, still experience adverse obstetric and neonatal outcomes. Poor glycaemic control is not wholly responsible for adverse outcomes, reinforcing the importance of other risk factors, such as obesity and weight gain.
Publisher: The Endocrine Society
Date: 1997
DOI: 10.1210/JC.82.1.218
Publisher: Springer Science and Business Media LLC
Date: 29-09-2016
DOI: 10.1186/S12884-016-1087-5
Abstract: We aimed to determine whether the association between obesity and a range of adverse maternal and perinatal outcomes differed in South Asian and Australian and New Zealand born women. A retrospective cohort study of singleton births in South Asian (SA) and Australian/New Zealand (AUS/NZ) born women at an Australian hospital between 2009 and 2013. The interaction between maternal region of birth and obesity on a range of maternal and perinatal outcomes was assessed using multivariate logistic regression. Obesity was more strongly associated with gestational hypertension/Preecl sia/HELLP and Gestational Diabetes Mellitus in AUS/NZ born women (p = 0.001 and p < 0.001, respectively for interaction) and was only associated with shoulder dystocia in SA born women (p = 0.006 for interaction). There was some evidence that obesity was more strongly related with admission to NICU/Special care nursery (SCN) (p = 0.06 for interaction) and any perinatal morbidity (p = 0.05 for interaction) in SA born women. Interventions targeted at reducing maternal obesity will have different impacts in SA compared to AUS/NZ born women.
Publisher: Wiley
Date: 10-1994
DOI: 10.1111/J.1365-2265.1994.TB02579.X
Abstract: Maternal serum immunoreactive inhibin has been shown to be significantly elevated in Down's affected pregnancies in the second trimester, suggesting that it may be useful in prenatal diagnosis. We have investigated whether it is similarly elevated in the first trimester. Stored maternal sera from women with Down's affected pregnancies and chromosomally normal control pregnancies were retrieved for analysis. These sera had been collected prospectively at either 11 or 12 weeks gestation as a routine antenatal booking procedure. From records, 11 women were identified as having had a Down's pregnancy. For each of these, 4 controls matched for gestation and duration-of-storage were also identified. Two different inhibin immunoassays were evaluated, one using an antibody raised against 31 kDa bovine inhibin and the other, a commercial two-site assay, using two antibodies directed against two distinct alpha-subunit epitopes. Neither assay detected a significant effect of gestation on serum inhibin levels. After combining the data from both gestations, no significant difference between the Down's s les and controls for either assay was detected. However, analysis of the data for each gestation separately revealed that one assay detected a significant difference in inhibin levels between Down's affected and unaffected pregnancies at 11 weeks gestation (mean +/- SEM 3186 +/- 195 vs 2020 +/- 172 ng/l, P < 0.01) but not at 12 weeks. The other, commercial, assay did not detect a significant difference at either gestation. In addition, there was poor association between the results of the two assays. These data suggest that immunoreactive inhibin, as detected by these assays, will not be useful as a late first trimester marker for Down's syndrome and also that these two assays detect different inhibin species in pregnancy serum.
Publisher: Elsevier BV
Date: 2004
Publisher: Springer Science and Business Media LLC
Date: 30-10-2018
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.PREGHY.2019.02.002
Abstract: The maternal endothelial dysfunction characteristic of preecl sia arises, in part, from excessive placental production of anti-angiogenic factors, including soluble Flt-1, soluble endoglin and activin A, inducing oxidative stress. We assessed whether the antioxidant and NRF2-activator sulforaphane could mitigate endothelial and trophoblast dysfunction in vitro. We induced dysfunction in human umbilical vein endothelial cells (HUVECs) with TNF-α, assessing endothelial activation and dysfunction (endothelin-1, vascular cell adhesion molecule VCAM1, intracellular adhesion molecule ICAM1, e-selectin and endothelial permeability) in the presence or absence of sulforaphane. We also assessed the effects of sulforaphane in mitigating hypoxic and hyperoxic injury in term placental explants by measuring secretion of anti-angiogenic factors. To assess the role of NRF2 we silenced NRF2 in HUVECs and primary trophoblast cells. Sulforaphane reduced TNF-α mediated HUVEC secretion of endothelin-1, VCAM1, ICAM1 and E-selectin, and prevented increased endothelial permeability. In placental explants, sulforaphane reduced the secretion of soluble Flt-1, soluble endoglin and activin A. Sulforaphane induced activation and nuclear translocation of NRF2 in HUVECs, inducing heme oxygenase 1. NRF2 silencing blocked some but not all of sulforaphane's effects in HUVECs. NRF2 silencing did not prevent sulforaphane's inhibition of trophobast secretion of soluble Flt-1 or activin A. In reducing placental and endothelial oxidative stress, sulforaphane may offer a new adjuvant therapeutic approach for the treatment of preecl sia.
Publisher: Wiley
Date: 05-2000
DOI: 10.1111/J.1479-828X.2000.TB01138.X
Abstract: It has been previously shown that the uptake of prenatal diagnosis by Victorian women of a non-English speaking background is significantly lower than that of comparable English speaking women. To explore this further we have examined the uptake of Down syndrome screening and diagnosis by Vietnamese women attending a community-based antenatal clinic in metropolitan Melbourne over a two year period. Of the 207 women studied, 161 (78%) were offered screening or diagnosis and of these women 139 (86%, 95%CI 81-92%) accepted the offer, representing 67% (95%CI 61-74%) of the entire population. Of the 127 women who had screening, rather than diagnosis, 12 (9%) had an 'increased risk' result. Eleven of these women accepted diagnosis. We also explored the reasons why 45 (22%) of women were not offered screening. Almost half (44%) of these women first attended the clinic at a too advanced stage of gestation but in 25 women there were no obvious reasons. These results are discussed in the context of current prenatal screening and diagnostic practice in Victoria and simple recommendations made.
Publisher: Wiley
Date: 25-03-2018
DOI: 10.1111/JPI.12479
Publisher: Oxford University Press (OUP)
Date: 31-05-2016
Abstract: Stem cells are emerging as a scientifically plausible treatment and possible cure for cerebral palsy, but are not yet proven. The lack of valid animal models has significantly h ered the scope of clinical trials. Despite the state of current treatment evidence, parents remain optimistic about the potential improvements from stem cell intervention and feel compelled to exhaust all therapeutic options, including stem cell tourism. Receiving unproven therapies from unvalidated sources is potentially dangerous. Thus it is essential that researchers and clinicians stay up to date. A systematic review and meta-analysis summarizing and aggregating current research data may provide more conclusive evidence to inform treatment decision making and help direct future research.
Publisher: Frontiers Media SA
Date: 2013
Publisher: Elsevier BV
Date: 06-2018
Publisher: Oxford University Press (OUP)
Date: 03-01-2018
DOI: 10.1002/SCTM.17-0185
Abstract: Idiopathic pulmonary fibrosis (IPF) is characterized by chronic inflammation, severe scarring, and stem cell senescence. Stem cell-based therapies modulate inflammatory and fibrogenic pathways by release of soluble factors. Stem cell-derived extracellular vesicles should be explored as a potential therapy for IPF. Human amnion epithelial cell-derived exosomes (hAEC Exo) were isolated and compared against human lung fibroblasts exosomes. hAEC Exo were assessed as a potential therapy for lung fibrosis. Exosomes were isolated and evaluated for their protein and miRNA cargo. Direct effects of hAEC Exo on immune cell function, including macrophage polarization, phagocytosis, neutrophil myeloperoxidase activity and T cell proliferation and uptake, were measured. Their impact on immune response, histological outcomes, and bronchioalveolar stem cell (BASC) response was assessed in vivo following bleomycin challenge in young and aged mice. hAEC Exo carry protein cargo enriched for MAPK signaling pathways, apoptotic and developmental biology pathways and miRNA enriched for PI3K-Akt, Ras, Hippo, TGFβ, and focal adhesion pathways. hAEC Exo polarized and increased macrophage phagocytosis, reduced neutrophil myeloperoxidases, and suppressed T cell proliferation directly. Intranasal instillation of 10 μg hAEC Exo 1 day following bleomycin challenge reduced lung inflammation, while treatment at day 7 improved tissue-to-airspace ratio and reduced fibrosis. Administration of hAEC Exo coincided with the proliferation of BASC. These effects were reproducible in bleomycin-challenged aged mice. The paracrine effects of hAECs can be largely attributed to their exosomes and exploitation of hAEC Exo as a therapy for IPF should be explored further.
Publisher: Wiley
Date: 03-2003
Publisher: Wiley
Date: 04-2015
DOI: 10.1111/AJO.12278
Abstract: Vitamin D deficiency is common. What the optimum level of vitamin D in pregnancy and whether vitamin D supplementation in pregnancy confers improved health benefits remain controversial. To assess vitamin D status in pregnant women in a maternity service that recommends routine antenatal screening and advises supplementation where necessary, and to assess relationships between early pregnancy vitamin D levels and changes in vitamin D across pregnancy with pregnancy outcomes. Vitamin D serum concentrations were measured in early and late pregnancy. The relationships between initial vitamin D status, maternal factors and pregnancy outcomes were estimated. Change in vitamin D over pregnancy was quantified. The relationship between change in vitamin D over pregnancy and pregnancy outcomes was also estimated. Of 1550 women, 849 (55%) were vitamin D deficient (<50 nmol/L), 571 (37%) were insufficient (50-74 nmol/L), and 130 (8%) were replete (≥75 nmol/L) in early pregnancy. Factors associated with deficiency were increased body mass index, pregnancy in either winter or spring months, and maternal country of birth (South-East, South and East Asia, and Africa). Vitamin D deficiency or insufficiency in early pregnancy was significantly associated with developing gestation diabetes mellitus. Levels of vitamin D significantly increased over pregnancy among nonreplete women. Increasing vitamin D over pregnancy was not related to pregnancy outcomes. Vitamin D 'deficiency' is common but may not be associated with most adverse pregnancy outcomes. Routine vitamin D testing of all pregnant women does not appear warranted.
Publisher: Hindawi Limited
Date: 2016
DOI: 10.1155/2016/4565612
Abstract: The effects of human amnion epithelial cells (hAECs) on angiogenesis remain controversial. It is yet unknown if the presence of inflammation and/or gestational age of hAEC donors have an impact on angiogenesis. In this study, we examined the differences between term and preterm hAECs on angiogenesis in vitro and in vivo . Conditioned media from term hAECs induced the formation of longer huVEC tubules on Matrigel. Both term and preterm hAECs expressed VEGFA , PDGFB, ANGPT1, and FOXC1 , which significantly increased after TNF α and IFN γ stimulation. In the presence of TNF α and IFN γ , coculture with term hAECs reduced gene transcription of Tie-2 and Foxc1 in huVECs, while coculture with preterm hAECs increased gene transcription of PDGFR α and PDGFR β and reduced gene transcription of FOXC1 in huVECs. In vivo assessment of angiogenesis using vWF immunostaining revealed that hAEC treatment decreased angiogenesis in a bleomycin model of lung fibrosis but increased angiogenesis in a neonatal model of hyperoxia-induced lung injury. In summary, our findings suggested that the impact of hAECs on angiogenesis may be influenced by the presence of inflammation and underlying pathology.
Publisher: Informa UK Limited
Date: 12-2011
DOI: 10.2147/NRR.S26543
Publisher: JMIR Publications Inc.
Date: 26-01-2020
Abstract: irtual reality is increasingly being utilized by clinicians to facilitate analgesia and anxiolysis within an inpatient setting. There is however, a lack of a clinically relevant review to guide its use for this purpose. o systematically review the current evidence for the efficacy of virtual reality as an analgesic in the management of acute pain and anxiolysis in an inpatient setting. comprehensive search was conducted up to and including January 2019 on PubMed, Ovid Medline, EMBASE, and Cochrane Database of Systematic reviews according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Search terms included virtual reality, vr, and pain. Primary articles with a focus on acute pain in the clinical setting were considered for the review. Primary outcome measures included degree of analgesia afforded by virtual reality therapy, degree of anxiolysis afforded by virtual reality therapy, effect of virtual reality on physiological parameters, side effects precipitated by virtual reality, virtual reality content type, and type of equipment utilized. ighteen studies were deemed eligible for inclusion in this systematic review 67% (12/18) of studies demonstrated significant reductions in pain with the utilization of virtual reality 44% (8/18) of studies assessed the effects of virtual reality on procedural anxiety, with 50% (4/8) of these demonstrating significant reductions 28% (5/18) of studies screened for side effects with incidence rates of 0.5% to 8% 39% (7/18) of studies evaluated the effects of virtual reality on autonomic arousal as a biomarker of pain, with 29% (2/7) demonstrating significant changes 100% (18/18) of studies utilized a head mounted display to deliver virtual reality therapy, with 50% being in active form (participants interacting with the environment) and 50% being in passive form (participants observing the content only). vailable evidence suggests that virtual reality therapy can be applied to facilitate analgesia for acute pain in a variety of inpatient settings. Its effects, however, are likely to vary by patient population and indication. This highlights the need for in idualized pilot testing of virtual reality therapy’s effects for each specific clinical use case rather than generalizing its use for the broad indication of facilitating analgesia. In addition, virtual reality therapy has the added potential of concurrently providing procedural anxiolysis, thereby improving patient experience and cooperation, while being associated with a low incidence of side effects (nausea, vomiting, eye strain, and dizziness). Furthermore, findings indicated a head mounted display should be utilized to deliver virtual reality therapy in a clinical setting with a slight preference for active over passive virtual reality for analgesia. There, however, appears to be insufficient evidence to substantiate the effect of virtual reality on autonomic arousal, and this should be considered at best to be for investigational uses, at present.
Publisher: Elsevier BV
Date: 05-2002
Publisher: Informa UK Limited
Date: 07-01-2018
Publisher: Wiley
Date: 12-2005
Publisher: CSIRO Publishing
Date: 2012
DOI: 10.1071/RD11143
Abstract: Antenatal glucocorticoids are administered to mature the fetal lungs before preterm birth. Glucocorticoids also have non-pulmonary effects, including reducing fetal body and brain growth. The present study examined whether glucocorticoid administration has a sex-specific effect on growth in appropriately grown (control) and intrauterine growth-restricted (IUGR) fetal sheep. IUGR was induced at 0.7 gestation in fetal sheep by single umbilical artery ligation. On Days 5 and 6 after surgery, IUGR or control fetuses were exposed to the synthetic glucocorticoid betamethasone (BM 11.4 mg) or saline via intramuscular maternal administration. On Day 7, a postmortem was conducted to determine fetal sex and weight. Compared with control fetuses, the birthweight of male and female IUGR fetuses was significantly reduced (by 18.5 ± 4.4% (P = 0.002) and 21.7 ± 6.0% (P = 0.001), respectively). Maternal administration of BM significantly reduced bodyweight in both control and IUGR fetuses (by 11.3 ± 2.8% and 20.5 ± 3.6% in control male and female fetuses, respectively and by 22.9 ± 3.1% and 38.3 ± 3.4% in IUGR male and female fetuses, respectively P 0.001 for all, versus control + saline) fetuses. In control and IUGR animals the degree of growth restriction was greater in females than males (P 0.05) following administration of BM. These data suggest that antenatal glucocorticoids reduce fetal growth in a sex-specific manner, with females more growth restricted than males.
Publisher: Wiley
Date: 14-12-2016
DOI: 10.1113/JP271104
Publisher: SAGE Publications
Date: 08-1995
DOI: 10.1177/003693309504000405
Abstract: Intracranial neoplasms presenting during pregnancy are uncommon. We report the case of a woman with a giant acoustic neuroma, presenting with hyperemesis gravidarum, and detail the surgical excision of the tumour during the third trimester. The case illustrates the unusual presentation and that such surgery can be performed safely without detriment to mother or fetus.
Publisher: Elsevier BV
Date: 09-2021
Publisher: Wiley
Date: 10-01-2015
DOI: 10.1111/AOGS.12557
Abstract: To examine associations between maternal Asian ethnicity (South Asian and South East/East Asian) and anal sphincter injury. Retrospective cross-sectional study, comparing outcomes for Asian women with those of Australian and New Zealand women. A large metropolitan maternity service in Victoria, Australia. Australian/New Zealand, South Asian and South East/East Asian women who had a singleton vaginal birth from 2006 to 2012. The relation between maternal ethnicity and anal sphincter injury was assessed by logistic regression, adjusting for potential confounders. Anal sphincter injury was defined as a third or fourth degree tear (with or without episiotomy). Among 32,653 vaginal births there was a significant difference in the rate of anal sphincter injury by maternal region of birth (p < 0.001). After adjustment for confounders, nulliparous women born in South Asian and South East/East Asia were 2.6 (95% confidence interval 2.2-3.3 p < 0.001) and 2.1 (95% confidence interval 1.7-2.5 p < 0.001) times more likely to sustain an anal sphincter injury than Australian/New Zealand women, respectively. Parous women born in South Asian and South East/East Asia were 2.4 (95% confidence interval 1.8-3.2 p < 0.001) and 2.0 (95% confidence interval 1.5-2.7 p < 0.001) times more likely to sustain an anal sphincter injury than Australian/New Zealand women, respectively. There are ethnic differences in the rates of anal sphincter injury not fully explained by known risk factors for such trauma. This may have implications for care provision.
Publisher: Wiley
Date: 11-03-2016
Publisher: MDPI AG
Date: 03-03-2021
Abstract: Preecl sia is a disease specific to pregnancy characterised by new-onset hypertension with maternal organ dysfunction and/or fetal growth restriction. It remains a major cause of maternal and perinatal morbidity and mortality. For sixty years, antihypertensives have been the mainstay of treating preecl sia and only recently have insights into the pathogenesis of the disease opened new avenues for novel therapies. Melatonin is one such option, an endogenous and safe antioxidant, that may improve the maternal condition in preecl sia while protecting the fetus from a hostile intrauterine environment. Here we review the evidence for melatonin as a possible adjuvant therapy for preecl sia, including in vitro evidence supporting a role for melatonin in protecting the human placenta, preclinical models, vascular studies, and clinical studies in hypertension and pregnancy.
Publisher: Wiley
Date: 13-11-2014
DOI: 10.1111/AJO.12147
Abstract: The effects of place of birth on birth outcomes have been examined in several studies both locally and internationally. However, none has examined the impact on caesarean section rates of different level maternity hospitals operating within the one health service. This study aimed to examine the impact of place of (Hospital level 6 4-5 or 4) on birth outcomes in a large metropolitan health service in Victoria. A cross-sectional study utilising data on births to low-risk first-time mothers during 2010-2011. Data were obtained from the Birthing Outcome System (BOS) database of Monash Health. Unadjusted and adjusted analyses were undertaken using logistic regression to examine the association between place of birth and caesarean section. In this group of low-risk nulliparae, there was evidence of a significant association between place of birth and caesarean section. The lower the acuity of the hospital, the higher the odds for the caesarean section. Compared with the level 6 hospital, the AdjOR for caesarean section at the level 4 hospital was 1.81 (95% CI: 1.37-2.41) and at the level 4-5 hospital, 1.30 (95% CI: 1.0-1.7). Low-risk nulliparae in spontaneous labour giving birth at the level 4 hospital in this health service are at significantly increased risk of caesarean section. This may have implications for the organisation and resource management of other level 4 public maternity units. Care in a tertiary (level 6) service may not necessarily equate to the higher rates of intervention reported by others.
Publisher: Elsevier BV
Date: 04-2003
Abstract: Previous studies have identified the presence of unidentified small molecular weight (mol wt) forms of inhibin and the pro-alphaC region of the inhibin alpha subunit in serum from women during late pregnancy. The aim of this study was to investigate if these gestational-related changes in mol wt forms arose from changing placental production. Pooled placental extracts, derived from normal healthy singleton pregnancies in the 1st, 2nd and 3rd trimesters of pregnancy, were fractionated by a combined immunoaffinity chromatography, preparative PAGE and electroelution procedure. Inhibin A, inhibin B and the pro-alphaC region of the inhibin alpha subunit were determined in the eluted fractions by specific ELISAs, with the profiles of immunoactivity characterized in terms of molecular size and percentage recovery. Inhibin B was undetectable in all s les. Mol wt peaks of 36k, 75K and 97K for inhibin A and 29k, 55K and 97K for pro-alphaC were detected in placental extracts across all three trimesters. The relative abundancy of small mol wt inhibin A forms (<30K) present in the placenta increased significantly in the third trimester placenta, increasing from 0.3 per cent in the first trimesters to 6 per cent in the third trimester (P=0.01, chi-squared test). The relative abundances of various mol wt forms of pro-alphaC was similar at all three gestations (P=0.67). In serum, small mol wt inhibin A and pro-alphaC forms accounted for 23.4 per cent and 37.4 per cent of inhibins, respectively, in the third trimester. These data suggest that the presence of small mol wt forms of both inhibin A and pro-alphaC in maternal serum is only partially attributed to placental production and/or secretion. We conclude that inhibin A and pro-alphaC inhibins in maternal serum are processed in late pregnancy by more than one mechanism to form low mol wt circulating forms of, as yet, undetermined structure.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2017
DOI: 10.1097/AOG.0000000000002097
Abstract: To compare the rates of attempted and successful instrumental births, intrapartum cesarean delivery, and subsequent perinatal and maternal morbidity before and after implementing a training intervention to arrest the decline in forceps competency among resident obstetricians. This retrospective cohort study examined all attempted instrumental births at Monash Health from 2005 to 2014. We performed an interrupted time-series analysis to compare outcomes of attempted instrumental births in 2005–2009 with those in 2010–2014. There were 72,490 births from 2005 to 2014 at Monash Health, of which 8,789 (12%) were attempted instrumental vaginal births. After the intervention, rates of forceps births increased [autoregressive integrated moving average coefficient (β) 1.5, 95% confidence interval (CI) 1.03–1.96 P .001], and vacuum births decreased (β −1.43, 95% CI −2.5 to −0.37 P .01). Rates of postpartum hemorrhage decreased (β −1.3, 95% CI −2.07 to −0.49 P =.002) and epidural use increased (β 0.03, 95% CI 0.02–0.05 P .001). There was no change in rates of unsuccessful instrumental births (β −0.39, 95% CI −3.03 to 2.43 P =.83), intrapartum cesarean delivery (β −0.29, 95% CI −0.55 to 0.14 P =.24), third- and fourth-degree tears (β −1.04, 95% CI −3.1 to 1.00 P =.32), or composite neonatal morbidity (β −0.18, 95% CI −0.38 to 0.02, P =.08). Unsuccessful instrumental births were more likely to be in nulliparous women ( P .001), less likely to have a senior obstetrician present ( P .001), be at later gestation ( P .001), and involved larger birth weight neonates ( P .001). A policy of ensuring obstetric forceps competency before beginning vacuum training results in more forceps births, fewer postpartum hemorrhages, and no increase in third- and fourth-degree perineal injuries or episiotomies.
Publisher: Oxford University Press (OUP)
Date: 04-1997
Abstract: Inhibin has been postulated to be secreted by Sertoli cells in response to follicle stimulating hormone (FSH) and in turn to exert an inhibitory effect on FSH production. We have investigated this relationship using an assay specific for dimeric inhibin B. A total of 56 normal men received 200 mg testosterone enanthate (TE) i.m. weekly, for 65 +/- 1 weeks in a trial of hormonal male contraception. Before treatment a significant negative correlation between inhibin B and FSH concentration (r = 0.49, P < 0.001) was observed. During TE treatment, luteinizing hormone (LH) and FSH were rapidly suppressed. This was followed by a parallel decline in inhibin B and sperm concentration. During the early recovery phase, inhibin B concentrations remained suppressed in men who showed a delay in resumption of spermatogenesis, despite higher FSH concentrations. Inhibin B returned to pretreatment concentrations after 24 weeks recovery, when the inverse relationship with FSH was restored. Our results showed the expected inverse physiological relationship between inhibin B and FSH in normal men, with a decline during TE treatment and alpha subsequent resumption of the inverse relationship during recovery. These data clearly support the hypothesis that inhibin B plays a physiological role in the feedback control of FSH secretion, and reflects FSH-stimulated Sertoli cell function.
Publisher: Elsevier BV
Date: 1990
DOI: 10.1016/0010-7824(90)90127-H
Abstract: Ten normal men were given three monthly intramuscular injections of 200mg of depot medroxyprogesterone acetate (DMPA) and 250mg of testosterone oenanthate (TE) as part of a male contraceptive trial. During the three months of treatment, serum high density lipoprotein cholesterol (HDL-C) and the HDL-C:LDL-C (low density lipoprotein cholesterol) ratio were significantly depressed compared to baseline. Although the long-term effect of this alteration in lipoprotein cholesterol metabolism in normolipidaemic men is currently uncertain, these results suggest that the potential cardiovascular risks of progestagen-containing regimens for male contraception will have to be seriously considered.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2018
DOI: 10.1161/STROKEAHA.117.019136
Abstract: Human amnion epithelial cells (hAECs) are nonimmunogenic, nontumorigenic, anti-inflammatory cells normally discarded with placental tissue. We reasoned that their profile of biological features, wide availability, and the lack of ethical barriers to their use could make these cells useful as a therapy in ischemic stroke. We tested the efficacy of acute (1.5 hours) or delayed (1–3 days) poststroke intravenous injection of hAECs in 4 established animal models of cerebral ischemia. Animals included young (7–14 weeks) and aged mice (20–22 months) of both sexes, as well as adult marmosets of either sex. We found that hAECs administered 1.5 hours after stroke in mice migrated to the ischemic brain via a CXC chemokine receptor type 4-dependent mechanism and reduced brain inflammation, infarct development, and functional deficits. Furthermore, if hAECs administration was delayed until 1 or 3 days poststroke, long-term functional recovery was still augmented in young and aged mice of both sexes. We also showed proof-of-principle evidence in marmosets that acute intravenous injection of hAECs prevented infarct development from day 1 to day 10 after stroke. Systemic poststroke administration of hAECs elicits marked neuroprotection and facilitates mechanisms of repair and recovery.
Publisher: Springer New York
Date: 2014
Publisher: Informa UK Limited
Date: 02-2019
DOI: 10.1080/14656566.2019.1570134
Abstract: Preecl sia is a disease specific to pregnancy characterised by new onset hypertension with maternal organ dysfunction and/or fetal growth restriction. It remains a major cause of maternal and perinatal morbidity and mortality. For fifty years, antihypertensives have been the mainstay of treating preecl sia, reducing maternal morbidity and mortality. With increased knowledge of the mechanisms underlying the disease has come opportunities for novel therapies that complement antihypertensives by protecting the maternal vasculature. Areas covered: In this review, the authors consider, in detail, the antihypertensives commonly used today in the emergency care of women with severe preecl sia. They also review less common anti-hypertensive agents and discuss the role of magnesium sulphate in the management of preecl sia and the prevention of ecl sia. Finally, they explore novel therapeutics for the acute management of preecl sia. Expert opinion: The rapid control of maternal hypertension will, and must, remain the mainstay of emergency treatment for women with severe preecl sia. The role of magnesium sulphate as a primary prevention for ecl sia is context dependant and should not displace a focus on correcting blood pressure safely. The exploration of novel adjuvant therapies will likely allow us to prolong pregnancy longer and improve perinatal outcomes safely for the mother.
Publisher: Elsevier BV
Date: 08-2001
Publisher: Wiley
Date: 05-2000
Publisher: Elsevier BV
Date: 2000
Publisher: Wiley
Date: 03-2004
DOI: 10.1002/PD.791
Abstract: To measure maternal serum and amniotic fluid levels of macrophage inhibitory cytokine‐1 (MIC‐1) in Down syndrome and normal pregnancies, assessing the utility of MIC‐1 as a prenatal marker of Down syndrome. Stored serum from 64 Down syndrome and 399 control pregnancies, collected at 8 to 17 weeks of pregnancy, and stored amniotic fluid from 17 Down syndrome and 53 controls, collected at 15 to 19 weeks of pregnancy, were retrieved for analysis. MIC‐1 was measured using an established in‐house ELISA, blinded to s le type. In maternal serum, MIC‐1 levels are not altered in Down syndrome in either the first or second trimester. Levels, expressed as median (95% CI) multiples of the median (MoM), in the Down syndrome cases and controls were 1.07 (0.9–1.1) MoM and 1.0 (0.95–1.03) MoM respectively. In amniotic fluid, MIC‐1 levels were significantly decreased compared to controls, 0.52 (0.44–0.64) MoM versus 1.0 (0.85–1.08) MoM ( p 0.0001). MIC‐1 is decreased in amniotic fluid but not in maternal serum in Down syndrome pregnancies. MIC‐1 will not be useful as a prenatal marker of Down syndrome. Copyright © 2004 John Wiley & Sons, Ltd.
Publisher: Elsevier BV
Date: 09-2020
DOI: 10.1016/J.WOMBI.2019.09.007
Abstract: Home births provide women a birth choice where they may feel more comfortable and confident in their ability to give birth. Most women in Victoria do not have publicly funded access to appropriately trained health professionals if they choose to give birth at home. This paper describes the process of setting up a publicly funded home birth service and provide details of description of the set up and governance. We also report outcomes over 9 years with respect to parity, transfer to hospital, adverse maternal and neonatal outcomes. Of the 191 women who were still booked into the home birth program at 36 weeks gestation, 148 (77.5%) women gave birth at home and 43 (22.5%) women were transferred into the hospital. The overall rate of vaginal birth was also high among the women in the home birth program, 185 (96.9%) with no added complications ascribed to home births. Such as severe perineal trauma [n=1] 0.6% PPH [n=4] 2.7%, Apgar score less than 7 at 5min [n=0] admissions post home birth to special care nursery [n=2] 1.35%. This unique study provides a detailed road map of setting up a home birth practice to facilitate other institutions keen to build a publicly funded home birth service. The birth outcome data was found to be consistent with other Australian studies on low risk home births. Well-designed home birth programs following best clinical practices and procedures can provide a safe birthing option for low risk women.
Publisher: F1000 Research Ltd
Date: 11-2018
DOI: 10.12688/F1000RESEARCH.15475.1
Abstract: The vaccination of pregnant women has enormous potential to protect not only mothers from vaccine-preventable diseases but also their infants through the passive acquisition of protective antibodies before they are able to themselves acquire protection through active childhood immunisations. Maternal tetanus programmes have been in place since 1989, and as of March 2018, only 14 countries in the world were still to reach maternal neonatal tetanus elimination status. This has saved hundreds of thousands of lives. Building on this success, influenza- and pertussis-containing vaccines have been recommended for pregnant women and introduced into immunisation programmes, albeit predominantly in resource-rich settings. These have highlighted some important challenges when additional immunisations are introduced into the antenatal context. With new vaccine candidates, such as respiratory syncytial virus (RSV) and group B streptococcus (GBS), on the horizon, it is important that we learn from these experiences, identify the information gaps, and close these to ensure safe and successful implementation of maternal vaccines in the future, particularly in low- and middle-income countries with a high burden of disease.
Publisher: Mary Ann Liebert Inc
Date: 05-2017
Abstract: We aimed to compare glycemic control, insulin requirements, and outcomes in women with type 1 diabetes in pregnancy treated with continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI). A retrospective cohort study was conducted of singleton pregnancies (>20 weeks gestation) in women with type 1 diabetes (2010-2015) at a specialist multidisciplinary maternity network in Australia. Antenatal characteristics, diabetes history and treatment details, and maternal and neonatal outcomes were compared for women with type 1 diabetes using CSII and MDI. Bolus calculator settings were reviewed for CSII. Data were obtained from in idual medical records, linkage to pathology, and the Birthing Outcomes System database. There were no differences in maternal characteristics or diabetes history between women managed with CSII (n = 40) and MDI (n = 127). Women treated with CSII required less insulin and less increase in total daily insulin dose/kg than MDI (40% vs. 52%). Both groups achieved similar glycemic control and no differences in pregnancy outcome. In the CSII group, carbohydrate:insulin ratios were intensified across gestation (30% breakfast, 27% lunch, 22% dinner), and insulin sensitivity factors (ISFs) changed little (7% breakfast, 0% lunch, -10% dinner). There was no difference in glycemic control or pregnancy outcomes in women using CSII or MDI managed in a multidisciplinary setting. Greater adjustments are needed to ISFs with CSII therapy. Overall, these data do not support recommending CSII in pregnancy with potentially higher patient and staff demands and costs and lack of improvement in HbA1c and pregnancy outcomes.
Publisher: Wiley
Date: 06-1996
DOI: 10.1111/J.1365-2044.1996.TB12570.X
Abstract: We report the case of a 30-year-old pregnant woman with an Arnold-Chiari malformation, who presented with severe pregnancy-induced hypertension at 30 weeks gestation. She was known to have had a difficult tracheal intubation during a previous general anaesthetic. Caesarean section was performed under an incremental epidural anaesthetic block.
Publisher: Springer Science and Business Media LLC
Date: 21-02-2020
DOI: 10.1038/S41598-020-60040-3
Abstract: External cephalic version ( ECV ) is associated with a moderate degree of pain. Virtual reality ( VR ) is a technology that has shown promise in offering procedural analgesia. We undertook a clinical pilot to assess the viability of VR to reduce pain during ECV. In an open randomised controlled trial ( RCT ) , we randomised 50 women to either VR or standard care each ( 25 per group ) . Women receiving VR were administered VR content ( Skylights ) via a headset. Pre- and post-procedural measures of pain, anxiety, device experience and vital signs were measured. There were no significant differences between groups ( VR/no VR ) in pain scores ( 60.68 vs 49.76 p = 0.2 ) , ECV success rates ( 80% vs 76% p = 0.7 ) or anxiety levels. The women receiving VR had a significantly higher anticipation of pain pre-procedurally ( 70.0 vs 50.0 p = 0.03 ) . 20 ( 80% ) of the VR women indicated that they would use VR again and 22 ( 88% ) indicated they would recommend it to a friend having ECV. There were no significant differences between groups for side effects encountered or changes in vital signs. We have shown that using VR during ECV is feasible and appears safe. Our results inform the design of future RCTs.
Publisher: Wiley
Date: 26-03-2021
DOI: 10.1111/AJO.13340
Abstract: Increasing the detection of fetal growth restriction (FGR), while reducing stillbirth, also leads to unnecessary early intervention, and associated morbidity, for normally grown babies who are incorrectly suspected of FGR. We sought to design a balance measure that addresses the specificity of FGR detection. A retrospective cohort study on all singleton births ≥32 weeks gestation in 2016 and 2017 in Victoria. We compared two balance measures for the detection of FGR, defined as the proportion of all babies iatrogenically delivered before 39 weeks gestation for suspected FGR that had a birthweight ≥10th centile (balance measure 1) or ≥25th centile (balance measure 2). Hospital level performance on each balance measure was derived and compared to an existing performance measure for severe FGR detection in Victoria. Of the 38 hospitals analysed, 12 (32%) had a favourable performance on an existing indicator of FGR detection, seven (18%) hospitals had a favourable performance on balance measure 1, and 15 (39%) had a favourable performance on balance measure 2. There was a moderate correlation between hospital performance on the existing indicator and on balance measure 1 ( r = 0.447, P = 0.005) but not balance measure 2 ( r = −0.063, P = 0.71). There was no difference in perinatal mortality between high performing hospitals and low performing hospitals. Introducing a balance measure into routine reporting may bring greater awareness to the unintended harm associated with increased detection of FGR.
Publisher: Springer Science and Business Media LLC
Date: 08-12-2017
DOI: 10.1038/JP.2016.190
Abstract: To determine if apparently healthy post-term South Asian-born (SA) women were more likely to have abnormal post-term fetal surveillance than Australian- and New Zealand-born (AUS/NZ) women, whether those abnormalities were associated with increased rates of obstetric intervention and adverse perinatal outcomes, and whether SA women and their babies were at higher risk of adverse outcomes in the post-term period irrespective of their post-term surveillance outcomes. Post-term surveillance and perinatal outcomes of 145 SA and 272 AUS/NZ nulliparous women with a singleton post-term pregnancy were compared in a retrospective multicentre cohort analysis. Post-term SA women were not significantly more likely to have a low amniotic fluid index (AFI) than AUS/NZ women. However, they were nearly four times more likely (odds ratio 3.75 95% CI 1.49-9.44) to have an abnormal CTG (P=0.005). Irrespective of maternal region of birth having an abnormal cardiotocography (CTG) or AFI was not associated with adverse intrapartum or perinatal outcomes. However, post-term SA women were significantly more likely than AUS/NZ women to have intrapartum fetal compromise (P=0.03) and an intrapartum cesarean section (P=0.002). Babies of SA women were more also significantly likely to be admitted to the Special Care Nursery or Neonatal Intensive Care Unit (P=0.02). Post-term SA women experience higher rates of fetal compromise (antenatal and intrapartum) and obstetric intervention than AUS/NZ women. Irrespective of maternal region of birth an abnormal CTG or AFI was not predictive of adverse outcomes.
Publisher: Wiley
Date: 11-10-2014
DOI: 10.1111/AJO.12252
Abstract: Core clinical skills acquisition is an essential component of undergraduate medical and midwifery education. Although interprofessional education is an increasingly common format for learning efficient teamwork in clinical medicine, its value in undergraduate education is less clear. We present a collaborative effort from the medical and midwifery schools of Monash University, Melbourne, towards the development of an educational package centred around a core skills-based workshop using low fidelity simulation models in an interprofessional setting. Detailed feedback on the package was positive with respect to the relevance of the teaching content, whether the topic was well taught by task trainers and simulation models used, pitch of level of teaching and perception of confidence gained in performing the skill on a real patient after attending the workshop. Overall, interprofessional core skills training using low fidelity simulation models introduced at an undergraduate level in medicine and midwifery had a good acceptance.
Publisher: Wiley
Date: 03-2021
Abstract: To quantify how the changing stillbirth risk profile of women is affecting the interpretation of the stillbirth rate. A retrospective, population‐based cohort study from 1983 to 2018. Victoria, Australia. A total of 2 419 923 births at ≥28 weeks of gestation. Changes in maternal characteristics over time were assessed. A multivariable logistic regression model was developed for stillbirth, based on maternal characteristics in 1983–1987, and used to calculate in idual predictive probabilities of stillbirth from the regression equation. The number of expected stillbirths per year as a result of the change in maternal demographics was then calculated, assuming no changes in care and in the associations between maternal characteristics and stillbirth over time. Stillbirth. Compared with 1983–1987, there were more women in older age groups giving birth, more nulliparous women, more indigenous women and women born in Oceania, Asia and Africa, more multiple pregnancies and more women with pre‐existing diabetes in 2014–2018. Despite this, the rate of stillbirth fell from 5.42 per 1000 births in 1983 to 1.72 per 1000 births in 2018 ( P 0.001). Applying the multivariable logistic regression equation, derived from the 1983–87 data, to each year, had there been no changes in care or in the associations between maternal characteristics and stillbirth, the rate of stillbirth would have increased by 12%, from 4.94 per 1000 in 1983 to 5.54 per 1000 in 2018, as a result of the change in maternal characteristics. Population rates of stillbirth are falling faster than is generally appreciated. Population reductions in stillbirth have been underestimated as a result of changing maternal characteristics.
Publisher: Wiley
Date: 10-2014
DOI: 10.1111/AJO.12134
Abstract: Pre-ecl sia remains a major burden of disease, accounting for approximately 50,000-70,000 maternal deaths each year worldwide. Frustratingly, the management of pre-ecl sia has remained essentially unchanged for much of the last century and focussed primarily on maternal blood pressure control to allow fetal maturation. Recent advances in the understanding of the pathogenesis of pre-ecl sia and the elucidation of distinct underlying mechanisms offer the genuine prospect of new and effective therapies that may transform outcomes for millions of women and their babies.
Publisher: Wiley
Date: 20-08-2020
DOI: 10.1111/AJO.13227
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.PLACENTA.2015.06.004
Abstract: Pre-ecl sia remains a major cause of maternal and fetal morbidity and mortality. Despite intensive research over the last 50 years, significant therapeutic advances have yet to be realised. We recently reported on the role of activin A in the pathophysiology of pre-ecl sia, whereby a pre-ecl sia-like disease state was induced in pregnant mice through activin A infusion. Using the same animal model, the effects of inhibiting activin A signalling on this pre-ecl sia-like disease state have now been assessed with low molecular weight compounds structurally related to activin-receptor-like kinase (ALK) inhibitors. 23 synthetic compounds were screened for ability to reduce activin A-induced free radical production in HUVECs. Further, following administration of activin A (50 μg) via a subcutaneous mini-osmotic pump from day 10 of pregnancy, the most active inhibitor, MKP-1-140A, (1 mg/kg) was also concomitantly administered via subcutaneous injections. Significant reductions in activin A-induced systolic blood pressure and urine albumin:creatinine ratio were observed with inhibitor-treated animals. However, these findings were accompanied by sustained elevation of liver enzymes and albumin extravasation in the brains of pregnant mice that received MKP-1-140A. Furthermore, inhibition of activin A signalling with MKP-1-140A failed to rescue fetal growth restriction, and treatment with MKP-1-140A alone resulted in craniofacial and karyotypic abnormalities. These data indicate that whilst inhibition of activin A signalling by the low molecular weight ALK kinase inhibitor, MKP-1-140A, reduced some of the physiological manifestations of pre-ecl sia, the potential for serious maternal and fetal side effects may preclude it from clinical applications.
Publisher: BMJ
Date: 06-2019
DOI: 10.1136/BMJOPEN-2018-028243
Abstract: Fetal growth restriction (FGR) is a serious pregnancy complication, associated with increased rates of perinatal death and morbidity among survivors. Most commonly FGR results from placental insufficiency, where the placenta fails to deliver the oxygen and nutrients required for normal fetal growth. This leads to fetal oxidative stress, resulting in organ damage through lipid peroxidation. The early developing brain is particularly susceptible, such that FGR is associated with poorer neurodevelopment, witnessed as cognitive and behavioural dysfunction, and cerebral palsy. Promisingly, melatonin, a lipid soluble antioxidant is neuroprotective in animal models of FGR. We present a protocol outlining a randomised, placebo-controlled trial to explore whether antenatal maternal melatonin supplementation in pregnancies with severe, early-onset FGR can improve neurodevelopment among survivors at 2 years of age. We will recruit 336 women with a singleton pregnancy complicated by FGR between 23+0 and 31+6 weeks gestation. Participants will be randomised, stratified by gestational age, to either 30 mg melatonin per day or a visually identical placebo, continued until birth. Measures of maternal and fetal health will be collected until birth. Timing of birth will be determined by the treating clinical team in discussion with the woman. Neonatal and infant neurodevelopmental assessments will be undertaken, consisting of brain MRI at term corrected age, general movements assessment at term and 3 months’ corrected age, and Bayley Scales of Infant & Toddler Development-III and Infant Toddler Social Emotional Assessment at 2.5 years corrected age. Analyses will be on intention to treat. The primary outcome is a difference of 5 points in the cognitive domain of the Bayley-III. Secondary outcomes address maternal and fetal safety. This trial has Monash Health Human Research and Ethics committee approval (17-0000-583A). Findings will be disseminated through peer-reviewed publications, conference presentations and to participants. ACTRN12617001515381 Pre-results
Publisher: Cambridge University Press (CUP)
Date: 22-11-2012
DOI: 10.1017/THG.2012.114
Abstract: The Peri ostnatal Epigenetic Twins Study (PETS) is a longitudinal cohort of 250 pairs of Australian twins and their mothers, who were recruited mid-way through pregnancy from January 2007 to September 2009. The study is centered on the developmental origins of health and disease paradigm (DOHaD) in which an adverse intrauterine environment predisposes the in idual to complex disease in later life by reducing growth in utero and adversely altering developmental plasticity. Data concerning diet and lifestyle were collected from mothers during pregnancy, and s les of plasma and serum taken at 28 weeks’ gestation. We attended 75% of all births, at which time we collected multiple biological s les including placenta, cord blood, and neonatal cheek cells, the latter from 91% of pairs. Chorionicity was recorded and zygosity was determined by DNA testing where necessary. Approximately 40% of the twins are monozygotic, two-thirds of which are dichorionic. Twins were seen again at 18 months of age and repeat blood and cheek swabs taken where possible. Studies of gene expression and the epigenetic marks of DNA methylation have so far revealed that twins exhibit a wide range of epigenetic discordance at birth, that one-third of the epigenome changes significantly between birth and 18 months shared (maternal) environment, genetic factors, and non-shared intrauterine environment contribute to an increasing proportion of epigenetic variation at birth, respectively, and affect tissues differently, and that within-pair birth weight discordance correlates with epigenetic discordance in genes associated with lipid metabolism, supporting an epigenetic mechanism for DOHaD.
Publisher: Wiley
Date: 04-2006
Publisher: Wiley
Date: 23-08-2016
Abstract: To estimate creatine concentrations in maternal plasma and urine, and establish relationships with maternal characteristics, diet and fetal growth. Retrospective cohort study. Lyell McEwin Hospital, Adelaide, Australia. A biobank of plasma and urine s les collected at 13, 18, 30 and 36 weeks' gestation from 287 pregnant women from a prospective cohort of asthmatic and non-asthmatic women. Creatine was measured by enzymatic analysis. Change in creatine over pregnancy was assessed using the Friedman test. Linear mixed models regression was used to determine associations between maternal factors and diet with creatine across pregnancy and between creatine with indices of fetal growth at birth. Maternal creatine concentrations, associations between maternal factors and creatine and between creatine and fetal growth parameters. Maternal smoking, body mass index, asthma and socio-economic status were positively and parity negatively associated with maternal plasma and/or urine creatine. Maternal urine creatine concentration was positively associated with birthweight centile and birth length. After adjustment, each μmol/l increase in maternal urinary creatine was associated with a 1.23 (95% CI 0.44-2.02) unit increase in birthweight centile and a 0.11-cm (95% CI 0.03-0.2) increase in birth length. Maternal factors and fetal growth measures are associated with maternal plasma and urine creatine concentrations. Maternal creatine is altered by pregnancy fetal growth measures are associated with maternal creatine concentrations.
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/709763
Abstract: Acute and chronic lung injury represents a major and growing global burden of disease. For many of these lung diseases, the damage is irreparable, exhausting the host’s ability to regenerate new lung, and current therapies are simply supportive rather than restorative. Cell-based therapies offer the promise of tissue regeneration for many organs. In this paper, we examine the potential application of amnion epithelial cells, derived from the term placenta, to lung regeneration. We discuss their unique properties of plasticity and immunomodulation, reviewing the experimental evidence that amnion epithelial cells can prevent and repair lung injury, offering the potential to be applied to both neonatal, childhood, and adult lung disease. It is amazing to suggest that the placenta may offer renewed life after birth as well as securing new life before.
Publisher: MyJove Corporation
Date: 21-12-2014
DOI: 10.3791/52085
Publisher: Springer Science and Business Media LLC
Date: 04-03-2013
Abstract: Despite the widespread use of multiple-choice assessments in medical education assessment, current practice and published advice concerning the number of response options remains equivocal. This article describes an empirical study contrasting the quality of three 60 item multiple-choice test forms within the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) Fetal Surveillance Education Program (FSEP). The three forms are described below. The first form featured four response options per item. The second form featured three response options, having removed the least functioning option from each item in the four-option counterpart. The third test form was constructed by retaining the best performing version of each item from the first two test forms. It contained both three and four option items. Psychometric and educational factors were taken into account in formulating an approach to test construction for the FSEP. The four-option test performed better than the three-option test overall, but some items were improved by the removal of options. The mixed-option test demonstrated better measurement properties than the fixed-option tests, and has become the preferred test format in the FSEP program. The criteria used were reliability, errors of measurement and fit to the item response model. The position taken is that decisions about the number of response options be made at the item level, with plausible options being added to complete each item on both psychometric and educational grounds rather than complying with a uniform policy. The point is to construct the better performing item in providing the best psychometric and educational information.
Publisher: Frontiers Media SA
Date: 23-08-2017
Publisher: Elsevier BV
Date: 2005
DOI: 10.1016/J.AJOG.2004.06.090
Abstract: The purpose of this study was to determine whether placental-derived kynurenines (neuroactive metabolites that are derived from tryptophan) contributes to infection-mediated fetal cerebral injury. Placentae and cord blood were obtained from term deliveries (n = 16) and preterm deliveries with or without intrauterine bacterial infection (n = 8 per group). We investigated whether the placenta expressed messenger RNAs of kynurenine metabolite-forming enzymes, the effects of infection in vivo on the expression of these enzymes by the placenta, the in vitro effects of bacterial endotoxin lipopolysaccharide on expression and kynurenine metabolite output by the placenta, and the kynurenine metabolite levels in umbilical cord blood. Placentae expressed messenger RNA of tryptophan-degrading enzymes and synthesized several compounds. The expression of several enzymes increased significantly in placentae that were exposed to infection and/or lipopolysaccharide. Lipopolysaccharide also induced significant increases in placental kynurenine and quinolinic acid output. Kynurenine and quinolinic acid in cord blood of fetuses who were exposed to infection were elevated significantly. Inflammatory mediated release of kynurenines from placentae exposes the fetus to significant amounts of potentially neurotoxic substances.
Publisher: Springer New York
Date: 2014
Publisher: Springer Science and Business Media LLC
Date: 29-01-2015
DOI: 10.1186/SCRT542
Publisher: Oxford University Press (OUP)
Date: 09-2017
Publisher: Bioscientifica
Date: 10-2001
Abstract: Maternal serum activin A levels are elevated in women with preecl sia. To explore whether this could be due, at least in part, to increased production by the gestational tissues, we have measured activin A in the serum of women with (n=23) or without preecl sia (n=62) at 29-40 weeks of gestation and in placenta and fetal membranes from preterm preecl tic (PT-PE, n=8), term preecl tic (T-PE, n=10) and healthy term controls (T-C, n=10). We have also explored if there are associated changes in activin receptor Alk2, ActRII and ActRIIB in these tissues. The relative amounts of receptor proteins were measured by densitometry on Western blots and receptors and activin beta(A) subunit localised by immunohistochemistry in PT-PE, T-PE and T-C gestational tissues (n=8-10/group). Maternal serum activin A levels were significantly elevated in women with preecl sia (multiples of the normal median (MoM)=3.5, P .0001, Mann-Whitney U test) compared with healthy women (median MoM=1.0). Compared with control tissues, the activin A content was significantly higher in preecl tic placentae (P=0.001 and P=0.0005 for PT-PE and T-PE respectively, Mann-Whitney U test), but significantly lower in the amnion (P=0.005 and P=0.014 for PT-PE and T-PE respectively) and choriodecidua (P=0.009 for T-PE). The maternal serum activin A level in women with preecl sia was significantly correlated with elevated placental production (P=0.01, Pearson's correlation). Receptor Alk2 protein levels were significantly elevated in T-PE placentae (P=0.0006, Mann-Whitney U test), ActRIIB levels were significantly lower in PT-PE placentae (P=0.01) and ActRII levels were significantly lower in PT-PE choriodecidua (P=0.0002) compared with controls. There were no apparent differences in the distribution of the beta(A) subunit and receptors Alk2, ActRII and ActRIIB between control and preecl tic tissues. These findings suggest that elevated levels of activin A in the maternal circulation in association with preecl sia are due, at least in part, to increased placental production, and that the regulation of activin synthesis in placenta and fetal membranes is differentially regulated. Further, the differences in activin receptor protein levels between preecl tic and control placenta and choriodecidua suggest that activin A-induced regulation may be altered in preecl sia.
Publisher: Wiley
Date: 06-2004
Publisher: Wiley
Date: 10-2003
DOI: 10.1046/J.0004-8666.2003.00104.X
Abstract: Objectives: It has been previously shown that glucocorticoids alter umbilical artery flow velocity waveforms in singleton pregnancies complicated by umbilical artery absent end diastolic flow. Whether similar effects are evident in multiple pregnancies where one fetus has umbilical artery absent end diastolic flow is not known. Methods: Women with a twin or triplet pregnancy complicated by umbilical artery absent end diastolic flow in one fetus were admitted to hospital for intensive fetal surveillance including daily umbilical artery flow velocity waveform studies, as per hospital protocol. All women received prophylactic betamethasone (11.4 mg × 2, 24 h apart) in anticipation of preterm delivery. Results: Between October 1996 and February 2002, 24 women with a multiple pregnancy complicated by umbilical artery absent end diastolic flow were cared for. Of these, six had a pregnancy with feto‐fetal transfusion and excluded from further analysis. Of the remaining 18 women, eight had monochorionic diamniotic twins, eight had dichorionic twins, and two had trichorionic, triamniotic triplets. The median (range) gestation at diagnosis of umbilical artery absent end diastolic flow was 210.5 days (173–241). In nine (50%) of the 18 pregnancies the administration of betamethasone was associated with return of umbilical artery end diastolic flow for a median of 5 days. There was no association between this effect and chorionicity. The median (range) interval from diagnosis of umbilical artery absent end diastolic flow to delivery was 11 days (1–46). Conclusions: As previously reported in singleton pregnancies, the maternal administration of betamethasone in multiple pregnancies with umbilical artery absent end diastolic flow is associated with a transient return of end diastolic flow.
Publisher: Wiley
Date: 22-11-2018
DOI: 10.1111/APA.14144
Abstract: To investigate the effects of foetal growth restriction (FGR) and prematurity on cardiac morphology and function in infancy. We hypothesised that FGR and prematurity would both alter cardiac development. Cardiac morphology and function were evaluated in 24 preterm FGR infants (p-FGR) and 23 preterm and 19 term appropriately grown for gestational age infants (p-AGA and t-AGA, respectively) by conventional echocardiography and Tissue Doppler Imaging. p-FGR and p-AGA infants were studied on postnatal day 1 and all groups were studied at one-and six-months post-term age. p-FGR infants demonstrated increased cardiac sphericity compared to AGA peers on postnatal day 1 (p = 0.004) and at one-month post-term age (p = 0.004). Posterior and relative wall thickness increased overtime in the p-FGR group only (p < 0.05). Systolic function was not different between groups. E/e' ratio was higher in both preterm groups compared to the term group at one-month post-term age (p = 0.01). No statistically significant group differences were found at six-months post-term age. Foetal growth restriction was associated with subtle cardiac morphological changes, whereas both prematurity and FGR were associated with subclinical alterations in diastolic function.
Publisher: Springer Science and Business Media LLC
Date: 15-02-2012
DOI: 10.1038/PR.2012.19
Abstract: Intrauterine growth restriction (IUGR) is associated with high rates of neonatal morbidity. IUGR babies are often born preterm and are, therefore, exposed to antenatal glucocorticoids. Antenatal glucocorticoids significantly improve overall survival rates of preterm infants, but there is a paucity of information about their effects on IUGR Infants. We induced IUGR in sheep by single umbilical artery ligation (SUAL), or sham in control fetuses. To half the ewes, we administered betamethasone (BM) on d 5 (BM1) and 6 (BM2) following surgery, and collected fetal lung tissue on d 7. SUAL alone was associated with higher circulating fetal cortisol levels (2.8 ± 0.4 vs. 1.0 ± 0.4, P = 0.001) as compared with controls but not with changes in lung morphology or surfactant protein (SP) gene expression. BM was associated with a significant reduction in lung tissue density (P = 0.048). There were no significant differences between groups in lung DNA concentration or septal crest density. SP-A, SP-B, and SP-C gene expressions were significantly increased in control and SUAL fetuses that were administered BM. These results show that in SUAL fetuses, maternal BM is associated with acceleration of fetal lung structure, as occurs in normally grown fetuses, and that BM induces SP production, an effect not observed in SUAL-induced IUGR fetuses alone.
Publisher: Bentham Science Publishers Ltd.
Date: 02-2013
Publisher: Wiley
Date: 10-2012
DOI: 10.1111/AJO.12001
Abstract: To quantify late-pregnancy weight gain in women with and without gestational diabetes mellitus (GDM) and to determine factors associated with gestational weight gain. A prospective clinical audit of 212 women (115 GDM and 97 non-GDM) who were weighed at each antenatal visit from 24-32 weeks gestation until delivery. Women received routine antenatal clinical care. For women with GDM, this included a 2-h lifestyle counselling session, capillary blood glucose testing and frequent clinical review. Women with GDM gained less weight than nondiabetic women (GDM: 1.18 kg (1.6%) [range, 3.8-7.1 kg] non-GDM: 4.0 kg (4.8%) [range, 0.7-18.5 kg] P < 0.0001). Weight gain was influenced by body mass index and country of birth. Women with GDM showed reduced weight gain at weeks 1-4 postrecruitment, relative to weeks 4-8 (0.04 kg/week vs 0.45 kg/week P < 0.0001). Nondiabetic women gained weight at a constant rate. GDM status was the only independent predictor of postrecruitment weight gain. Application of a model of care for GDM (lifestyle advice and regular clinical review, in addition to home glucose monitoring) may reduce weight gain in women with GDM. The potential for applying a modified version of this model to all women in pregnancy warrants further study.
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.PREGHY.2016.03.001
Abstract: Circulating markers for endothelial activation such as endothelin-1 (ET-1), ICAM-1 and VCAM-1 are elevated in women with preecl sia. Using human umbilical vein endothelial cells (HUVECs) as an in vitro model of the maternal vasculature, we show that activin A and preecl tic serum upregulate ET-1, ICAM-1, and VCAM-1 in HUVECs. Further, we show that follistatin, a specific binding protein for activin, mitigates the upregulation of ET-1, ICAM-1 and VCAM-1 in HUVECs exposed to either activin A or preecl tic serum. These data are consistent with activin A contributing to the pathophysiology of preecl sia and suggest that therapies targeting activin signalling are worth exploring.
Publisher: Wiley
Date: 05-2001
DOI: 10.1111/J.1479-828X.2001.TB01202.X
Abstract: At their first hospital antenatal visit, 209 women were interviewed to explore their level of knowledge of Down syndrome and the available prenatal tests. Overall, the women had limited knowledge. Non-Caucasian women had less knowledge of Down syndrome, available prenatal tests and the association of Down syndrome with advanced maternal age than Caucasian women. Women with a history of a previous pregnancy and women over 35 years of age were not more aware of Down syndrome or the available tests than other women. These findings have significant implications for antenatal education and the implementation of screening programs for Down syndrome.
Publisher: BMJ
Date: 03-2020
DOI: 10.1136/BMJOPEN-2019-034974
Abstract: Cerebral palsy (CP) is the most common physical disability of childhood but has no cure. Stem cells have the potential to improve brain injury and are proposed as a therapy for CP. However, many questions remain unanswered about the most appropriate cell type, timing of infusions, dose required and associated risks. Therefore, human safety and efficacy trials are necessary to progress knowledge in the field. This is a single group study with s le size n=12 to investigate safety of single-dose intravenous 12/12 human leucocyte antigen-matched sibling cord blood cell infusion to children with CP aged 1–16 years without immune suppression. The study is similar to a 3+3 design, where the first two groups of participants have severe CP, and the final six participants include children with all motor severities. Children will be monitored for adverse events and the duration that donor cells are detected. Assessments at baseline, 3 and 12 months will investigate safety and preliminary evidence of change in gross motor, fine motor, cognitive and quality of life outcomes. Full approval was obtained from The Royal Children’s Hospital Human Research Ethics Committee, and a clinical trial notification was accepted by Australia’s Therapeutic Goods Administration. Participant guardian informed consent will be obtained before any study procedures. The main results of this study will be submitted for publication in a peer-reviewed journal. ACTRN12616000403437, NCT03087110 .
Publisher: Informa UK Limited
Date: 30-08-2018
DOI: 10.1080/13561820.2018.1511525
Abstract: Collaboration between teams is an essential component of patient safety in the complex ever-changing environment of healthcare. Collaborative practice requires training, which needs to start prior to registration for it to be established in the clinical workforce by graduation. Despite the perceived value and motivation of course coordinators, interprofessional training programs often struggle to sustain, due to various reasons related to logistics of timetabling, staff availability and/or absence of institutional support. We present a guide, outlining the lessons learned from implementing a sustainable change from our 6-year experience of the Women's Health Interprofessional Learning through Simulation (WHIPLS) program. The WHIPLS program was initially piloted to teach clinical skills in an interprofessional environment for pre-registration medical and midwifery students and has become a core component of the clinical curriculum. We describe the steps that were required to attain this outcome using the Kotter's 8-step plan for management change. The key lessons learned were
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.EXPNEUROL.2014.07.009
Abstract: Moderate to severe neonatal hypoxic ischemic encephalopathy remains an important cause of infant death and childhood disability. Early and accurate diagnosis of encephalopathy is difficult but critical for timely intervention. Thus, we have utilized a clinically relevant large animal model of asphyxia in-utero, followed by immediate lamb delivery, resuscitation and clinical care over the next 72h for assessment of potential biomarkers of brain injury. In-utero asphyxia was induced in twelve near-term lambs and outcomes compared with seven controls. Asphyxia resulted in bradycardia (97±12beats/min), hypotension (12.1±1mm Hg) and metabolic acidosis (pH6.9±0.02 base-excess -13.8±0.8mmol/l). 72h following asphyxia, cerebrospinal concentrations of malondialdehyde and S100B were elevated 2-fold and 5-fold, respectively, in asphyxic lambs compared to control lambs. Magnetic resonance spectroscopy (MRS) at 72h showed a significant decrease in n-acetyl aspartate: choline ratio in asphyxia lambs compared to that observed at 12h (0.56±0.23 vs. 0.82±0.15, respectively) lactate:choline ratio was not changed over this time. Marked neuropathology was observed in asphyxia lambs with neuronal degeneration in the hippoc us, thalamus, striatum and cortex. Astrogliosis was observed in the hippoc us and thalamus. Early blood markers of metabolic state showed limited predictive value of histological damage at 72h. MRS outcomes at 72h showed a modest but significant correlation with histological evidence of neuronal brain injury (lactate:N-acetyl aspartate ratio in the thalamus r(2)=0.2, p<0.01). MRS at 72h was best able to detect established brain injury, but a combination of biomarkers over multiple phases of injury may be able to assess the evolution of neonatal brain injury.
Publisher: Oxford University Press (OUP)
Date: 20-12-2017
Abstract: What is the association between placental formyl peptide receptor 2 (FPR2) and trophoblast and endothelial functions in pregnancies affected by foetal growth restriction (FGR)? Reduced FPR2 placental expression in idiopathic FGR results in significantly altered trophoblast differentiation and endothelial function in vitro. FGR is associated with placental insufficiency, where defective trophoblast and endothelial functions contribute to reduced feto-placental growth. The expression of FPR2 in placental tissues from human pregnancies complicated with FGR was compared to that in gestation-matched uncomplicated control pregnancies (n = 25 from each group). Fpr2 expression was also determined in placental tissues obtained from a murine model of FGR (n = 4). The functional role of FPR2 in primary trophoblasts and endothelial cells in vitro was assessed in erse assays in a time-dependent manner. Placentae from third-trimester pregnancies complicated by idiopathic FGR (n = 25) and those from gestation-matched pregnancies with appropriately grown infants as controls (n = 25) were collected at gestation 27-40 weeks. Placental tissues were also collected from a spontaneous CBA/CaH × DBA/2 J murine model of FGR. Placental FPR2/Fpr2 mRNA expression was determined by real-time PCR, while protein expression was examined by immunoblotting and immunohistochemistry. siRNA transfection was used to silence FPR2 expression in primary trophoblasts and in human umbilical vein endothelial cells (HUVEC), and the quantitation of cytokines, chemokines and apoptosis was performed following a cDNA array analyses. Functional effects of trophoblast differentiation were measured using HCGB/β-hCG and syncytin-2 expression as well as markers of apoptosis, tumour protein 53 (TP53), caspase 8, B cell lymphoma 2 (BCL2) and BCL associated X (BAX). Endothelial function was assessed by proliferation, network formation and permeability assays. Placental FPR2/Fpr2 expression was significantly decreased in FGR placentae (n = 25, P < 0.05) as well as in murine FGR placentae compared to controls (n = 4, P < 0.05). FPR2 siRNA (siFPR2) in term trophoblasts significantly increased differentiation markers, HCGB and syncytin-2 cytokines, interleukin (IL)-6, CXCL8 and apoptotic markers, TP53, caspase 8 and BAX, but significantly reduced the expression of the chemokines CXCL12 and its receptors CXCR4 and CXCR7 CXCL16 and its receptor, CXCR6 and cytokine, IL-10, compared with control siRNA (siCONT). Treatment of HUVECs with siFPR2 significantly reduced proliferation and endothelial tube formation, but significantly increased permeability of HUVECs. N/A. Reduced expression of placental FPR2/Fpr2 was observed in the third trimester at delivery after development of FGR, suggesting that FPR2 is associated with FGR pregnancies. However, there is a possibility that the decreased placental FPR2 observed in FGR may be a consequence rather than a cause of FGR, although our in vitro functional analyses using primary trophoblasts and endothelial cells suggest that FPR2 may have a direct or indirect regulatory role on trophoblast differentiation and endothelial function in FGR. This is the first study linking placental FPR2 expression with changes in the trophoblast and endothelial functions that may explain the placental insufficiency observed in FGR. P.M. and P.R.E. received funding from the Australian Institute of Musculoskeletal Science, Western Health, St. Albans, Victoria 3021, Australia. M.L. is supported by a Career Development Fellowship from the National Health and Medical Research Council (NHMRC Grant no. 1047025). Monash Health is supported by the Victorian Government's Operational Infrastructure Support Programme. The authors declare that there is no conflict of interest in publishing this work.
Publisher: AMPCo
Date: 09-2012
DOI: 10.5694/MJA12.10125
Abstract: To determine if maternal country of birth is associated with the risk of antepartum stillbirth in late pregnancy. Retrospective cross-sectional study of all singleton births at 37-42 weeks' gestation, excluding those with congenital abnormalities and intrapartum stillbirths, between 1 June 2001 and 31 May 2011 at Southern Health, a large metropolitan maternity service in Melbourne, Australia. Rate of late-pregnancy antepartum stillbirth, analysed by maternal country of birth. Among 44 326 births, there was a significant difference in the stillbirth rate by maternal country of birth (P < 0.001). The rate of stillbirth per 1000 births was 1.48 among Australian-born women, 3.55 among South Asian-born women and 1.06 among South-East-East Asian-born women. Women born in South Asia were 2.4 (95% CI, 1.4-4.0) times more likely to have a late-pregnancy stillbirth than women born in Australia (P < 0.001). There was no significant difference between women born in Australia and women born in South-East-East Asia (P = 0.34). Adjusting for potential confounding factors, South Asian maternal birth remained an independent risk factor for stillbirth (adjusted odds ratio, 2.5 95% CI, 1.3-5.1 P = 0.009). Women born in South Asia have an increased risk of antepartum stillbirth in late pregnancy, compared with other women. This observation may have implications for the delivery of pregnancy care in Australia.
Publisher: Springer Science and Business Media LLC
Date: 17-05-2017
DOI: 10.1038/PR.2017.37
Abstract: Fetal growth restriction (FGR) is a common complication of pregnancy and, in severe cases, is associated with elevated rates of perinatal mortality, neonatal morbidity, and poor neurodevelopmental outcomes. The leading cause of FGR is placental insufficiency, with the placenta failing to adequately meet the increasing oxygen and nutritional needs of the growing fetus with advancing gestation. The resultant chronic fetal hypoxia induces a decrease in fetal growth, and a redistribution of blood flow preferentially to the brain. However, this adaptation does not ensure normal brain development. Early detection of brain injury in FGR, allowing for the prediction of short- and long-term neurodevelopmental consequences, remains a significant challenge. Furthermore, in FGR infants the detection and diagnosis of neuropathology is complicated by preterm birth, the etiological heterogeneity of FGR, timing of onset of growth restriction, its severity, and coexisting complications. In this review, we examine existing and emerging diagnostic tools from human and preclinical studies for the detection and assessment of brain injury in FGR fetuses and neonates. Increased detection rates, and early detection of brain injury associated with FGR, will offer opportunities for developing and assessing interventions to improve long-term outcomes.
Publisher: Springer Science and Business Media LLC
Date: 30-04-2015
Publisher: The Endocrine Society
Date: 12-2001
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.EJOGRB.2017.07.031
Abstract: While antenatal vaccination is the most effective strategy to reduce newborn pertussis infection and its associated morbidity and mortality, uptake has consistently been reported to be suboptimal. "Cocooning" or vaccination of the close contacts of newborns therefore remains an important strategy for protecting newborns when maternal vaccination has not occurred or with insufficient time for antibody transfer. This study assesses the uptake of pertussis vaccination by parents and close contacts of newborns providing insight into the vulnerability of newborns to pertussis upon discharge from hospital to their primary carers. The study was conducted at three public and two private hospitals in Melbourne, Australia. A survey was administered to 689 women and/or their partners admitted on maternity wards of participating hospitals after delivery of a healthy newborn between August and December 2016. The main outcomes measured were reported vaccination rates and factors associated with uptake of pertussis vaccination. Kappa statistic and logistic regression were used to determine factors associated with vaccination. 70% of women and 66% of partners reported pertussis vaccination according to national recommendations. Significantly 22% of newborns were discharged to a household where neither parent reported vaccination. Compared to when maternal vaccination did occur, in families where it didn't there were low rates of vaccination of partners (83% vs 26%) and other carers, particularly carers usually resident overseas (76% vs 18.5%). While the majority of mothers and partners reported pertussis vaccination in accordance with recommended guidelines, concerningly nearly a quarter of newborns were discharged to a home where neither parent was vaccinated. When maternal vaccination did not occur, rates of vaccination of the other close contacts was poor. Educating women to encourage vaccination of partners and carers particularly those coming from overseas, prior to their arrival is an important consideration when maternal immunization does not occur. Cocooning remains an important approach to protect newborns of mothers vaccinated late or not vaccinated in pregnancy.
Publisher: Elsevier BV
Date: 06-1998
DOI: 10.1016/S0950-3552(98)80060-6
Abstract: It is often accepted that fibroids cause a variety of female reproductive problems, such as menorrhagia, pain, infertility, pregnancy loss and pregnancy complications. Understandably, therefore, many 'successful' medical or surgical interventions have been proposed. However, while fibroids are certainly commonly associated with these conditions, it remains unclear whether this is coincidental, because of the high prevalence of fibroids, or causal. In particular, this chapter explores the roles of fibroids in menorrhagia, discussing possible pathophysiological mechanisms and the utility of medical and surgical management. Similarly, the relationship between fibroids and infertility is examined, concluding that fibroids are not causative in the vast majority of cases and thereby questioning the effectiveness of myomectomy as a treatment for infertility. The use of hormone replacement therapy in post-menopausal women with existing fibroids is also discussed, concluding that this is generally safe and appropriate. In pregnancy, it is a commonly held tenet that uterine fibroids enlarge and that they are associated with various adverse outcomes such as miscarriage, placental abruption, fetal growth retardation and Caesarean section. This chapter evaluates the available evidence for this and concludes that, as with infertility, the role of fibroids has been exaggerated. Nonetheless, pregnancy management options are discussed.
Publisher: Elsevier BV
Date: 07-2001
DOI: 10.1016/S0303-7207(01)00504-4
Abstract: Unexplained fetal death in utero in late pregnancy represents an increasing proportion of perinatal deaths. It has been assumed that critical hypoxia is the likely mechanism underlying these losses, but the lack of a physiological marker has h ered both confirmation and prediction which could lead to timely intervention. In this paper, we report studies on hypoxia that we have performed in chronically cannulated late pregnant sheep, complemented by parallel investigations undertaken in human pregnancies. Our initial studies were directed towards determining activin secretion in the fetus and mother during late gestation, and immediately after fetal surgery using a sheep model. This led us to propose that there may be a relationship between hypoxia and activin A, follistatin and prostaglandin (PG) release from the feto-placental unit. Subsequent studies have been directed towards examining this potential relationship in sheep and in humans with compromised pregnancies. As a result of these studies, we have identified a potential mechanism by which activin A may be involved in regulating the response of the fetus to hypoxic insult. Activin A and follistatin concentrations increased in late gestation in ovine maternal plasma and in fetal fluids. Feto-placental hypoxemia or maternal isocapnic hypoxemia, leading to fetal hypoxia, were specific triggers for an acute increase in fetal activin A and follistatin concentrations during late gestation. The source and secretion of activin A, follistatin, and the associated release of PGE(2,) from within the feto-placental unit varied according to the site of the insult. The concomitant secretion of activin A and PGE(2) into the fetal circulation and amniotic fluid during reduced uterine blood flow provides an insight into the physiological regulatory mechanisms that might be involved. Changes observed in maternal activin A concentrations in mid and late gestation in the human may also be associated with fetal compromise. In human pregnancies, elevated activin A concentrations were observed in maternal plasma in mid and late gestation, in association with severe pre-ecl sia and with severe fetal growth restriction, compared to those observed in pregnancies with constitutionally small, healthy fetuses. Activin A was also elevated in maternal and arterial cord plasma in women at term during labour and immediately prior to undergoing emergency Caesarean section for failure to progress. These findings offer exciting new possibilities to gain insights into the mechanisms that underlie the maintenance of fetal wellbeing and provide a rationale for the potential that activin A may prove to be a useful clinical marker of fetal distress.
Publisher: Elsevier BV
Date: 02-2016
Publisher: Massachusetts Medical Society
Date: 09-05-1996
DOI: 10.1056/NEJM199605093341904
Abstract: The Chronic Disease Self-Management Program (CDSMP) improves self-efficacy and health outcomes in people with chronic diseases. In the context of the EFFICHRONIC project, we evaluated the efficacy of CDSMP in relieving frailty, as assessed by the self-administered version of Multidimensional Prognostic Index (SELFY-MPI), identifying also potential predictors of better response over 6-month follow-up. The SELFY-MPI explores mobility, basal and instrumental activities of daily living (Barthel mobility, ADL, IADL), cognition (Test Your Memory-TYM Test), nutrition (Mini Nutritional Assessment-Short Form-MNA-SF), comorbidities, medications, and socio-economic conditions (social-familiar evaluation scale-SFES). Participants were stratified in three groups according to the 6-month change of SELFY-MPI: those who improved after CDSMP (Δ SELFY-MPI 0). Multivariable logistic regression was modeled to identify predictors of SELFY-MPI improvement. Among 270 participants (mean age = 61.45 years, range = 26-93 years females = 78.1%) a benefit from CDSMP intervention, in terms of decrease in the SELFY-MPI score, was observed in 32.6% of subjects. SELFY-MPI improvement was found in participants with higher number of comorbidities (1-2 chronic diseases: adjusted odd ratio (aOR)=2.38, 95% confidence interval (CI) =1.01, 5.58 ⩾ 3 chronic diseases: aOR = 3.34, 95% CI = 1.25, 8.90 vs no chronic disease), poorer cognitive performance (TYM ⩽ 42: aOR = 2.41, 95% CI = 1.12, 5.19 vs TYM > 42) or higher risk of malnutrition (MNA-SF ⩽ 11: aOR = 6.11, 95% CI = 3.15, 11.83 vs MNA-SF > 11). These findings suggest that the CDSMP intervention contributes to decreasing the self-perceived severity of frailty (SELFY-MPI score) in more vulnerable participants with several chronic diseases and lower cognitive performance and nutritional status.
Publisher: Wiley
Date: 27-05-2003
DOI: 10.1046/J.0004-8666.2003.00070.X
Abstract: To assess the level of knowledge about Down syndrome screening among a s le of health professionals providing antenatal care. A structured questionnaire-based survey. Health professionals allied to a tertiary level maternity hospital in metropolitan Melbourne. A self-administered questionnaire was given or posted to 166 health care providers to assess their knowledge of prenatal Down syndrome screening. A total of 140 completed surveys were returned (83% response rate), including 70 from general practitioners, 34 from midwives, 33 from obstetricians and three from geneticists. Of these, 130 confirmed that they regularly counsel women about prenatal screening for Down syndrome. Sixteen per cent of those indicated that they only offered testing to selected 'high risk' women rather than all women. Overall, there was a high level of awareness regarding the gestations at which the commonly used screening tests are offered but a poor appreciation of the relative performances of those tests. Seventy-eight (60%) of those counselling indicated that they discussed detection and screen positive rates specific for the age of the woman. However, less than 10% were able to provide those rates. Knowledge of Down syndrome screening was variable among those who regularly counsel women about these tests. The results of the present survey highlight the need for professional education about prenatal screening.
Publisher: Springer Science and Business Media LLC
Date: 06-01-2021
DOI: 10.1007/S43032-020-00439-5
Abstract: Sulforaphane, an isothiocyanate found in cruciferous vegetables such as broccoli, shows promise as an adjuvant therapy for preecl sia. To inform future clinical trials, we set out to determine the bioavailability of sulforaphane in non-pregnant and preecl tic women. In six healthy female volunteers, we performed a crossover trial to compare the bioavailability of sulforaphane and metabolites afforded by an activated and non-activated broccoli extract preparation. We then undertook a dose escalation study of the activated broccoli extract in 12 women with pregnancy hypertension. In non-pregnant women, an equivalent dose of activated broccoli extract gave higher levels of sulforaphane and metabolites than a non-activated extract (p < 0.0001) and greater area under the curve (AUC) (3559 nM vs. 2172 nM, p = 0.03). Compared to non-pregnant women, in women with preecl sia, the same dose of activated extract gave lower levels of total metabolites (p < 0.000) and AUC (3559 nM vs. 1653 nM, p = 0.007). Doubling the dose of the activated extract in women with preecl sia doubled levels of sulforaphane and metabolites (p = 0.02) and AUC (1653 nM vs. 3333 nM, p = 0.02). In women with preecl sia, activated broccoli extract was associated with modest decreases in diastolic blood pressure (p = 0.05) and circulating levels of sFlt-1 (p = 0.0002). A myrosinase-activated sulforaphane formulation affords better sulforaphane bioavailability than a non-activated formulation. Higher doses of sulforaphane are required to achieve likely effective doses in pregnant women than in non-pregnant women. Sulforaphane may improve endothelial function and blood pressure in women with pregnancy hypertension.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2013
Publisher: Wiley
Date: 09-11-2009
DOI: 10.1111/J.1365-2265.2009.03569.X
Abstract: Recent studies report an association between maternal thyroid auto-antibodies and preterm birth. None have made the important distinction between spontaneous and iatrogenic preterm birth. We investigated the association between spontaneous preterm birth before 35-week gestation and both thyroid function and auto-antibody status. Retrospective nested case-control study, s les retrieved from a biobank of around 8000 s les. Forty-six cases of spontaneous preterm birth /= 0.18 for both comparisons, compared using three statistical models). In the preterm group, the median TSH level was 0.70 mIU/l (range 0.04-3.84), similar to controls (0.88 (0.01-2.87), P = 0.1). Free T3 and T4 levels were also similar in both groups. Thyroid function and thyroid autoantibody status among women who have a spontaneous preterm delivery before 35 weeks gestation are not different from women delivering at term.
Publisher: Wiley
Date: 30-08-2006
Publisher: Springer Science and Business Media LLC
Date: 30-09-2017
DOI: 10.1007/S11657-017-0380-X
Abstract: This study assessed all fractures occurring in pregnancy at a tertiary referral centre over a 17-year period. Most fractures were due to minimal trauma, and those involving the ankle were the most common. Women tended to fracture during their second and third trimesters and most required surgical intervention during pregnancy. To characterise fractures in pregnancy over a 17-year period at a tertiary referral health service. Medical records at the Monash Health in Australia were examined from 2000-2016 for fractures in pregnancy using the birthing outcome system database and the tenth revision of the International Statistical Classification of Diseases and Related Health Problems coding. Site, mechanism, investigations, management and outcomes were documented. Of the 114,673 live births during this period, 33 women (mean age 30.3 ± 1.9 years) were identified with fracture in pregnancy (~ 2.9 maternal fractures/10,000 live births). Minimal-trauma fractures (MTFs) occurred in 28 women whilst 5 were due to motor vehicle accidents. Of the MTF, 2/28 (7.1%), 13/28 (46.4%) and 13/28 (46.4%) occurred in the first, second and third trimesters, respectively. MTF involved the lower limb (60.7%), upper limb (25.0%), ribs (10.7%) and clavicle (3.6%). The ankle was involved in 39.3% of MTFs. Diabetes (14.3%), asthma (10.7%) and thyroid dysfunction (7.1%) affected these women with MTF vitamin D levels were not routinely measured. Surgical interventions requiring anaesthesia were required in 57.1% with MTF: 50.0% during their second, 31.3% in their third and 12.5% in their first trimesters 6.3% had surgery post partum. Pre-term birth and emergency caesarean section complicated 6/28 (21.4%) of MTF pregnancies. One patient received post-partum bisphosphonate therapy only two 2/32 (6.25%) received medical follow-up. Fractures in pregnancy are uncommon. Lower limb fractures are frequently due to minimal trauma, and surgical intervention is often required. The low rate of medical follow-up in MTF is of concern and reinforces the need for greater recognition of potential osteoporosis in this population.
Publisher: Wiley
Date: 09-1999
Publisher: Wiley
Date: 2002
DOI: 10.1002/PD.406
Abstract: It appears from current evidence that the most effective screening strategy for Down syndrome will involve a combination of first trimester nuchal translucency and serum biochemistry, whether performed in the first or second trimester. The aim of this study was to determine the optimum gestation based upon menstrual dates at which to schedule nuchal translucency (NT) measurement for the evaluation of fetal Down syndrome risk. Five thousand eight hundred and thirty-five pregnancies had an ultrasound scan scheduled between 11 and 14 completed weeks of gestation based upon either the last menstrual period (n = 3199) or a prior ultrasound scan (n = 2636). For last menstrual period-based ultrasound scans, with advancing gestation the frequency of missed miscarriage significantly decreased (p = 0.009, chi squared test), as did the need to reschedule a further scan because the gestation of the scheduled scan was too early to measure NT (p < 0.0001, Chi-squared test). In contrast, with advancing gestation the rate of unsuccessful NT measurement because the crown-rump length (CRL) was greater than 84 mm significantly increased (p < 0.0001, Chi-squared test). Of the women who had had an earlier ultrasound, 42 (1.6%) had a missed miscarriage and 9 (0.3%) were over gestation at the time of the NT scan. These data suggest that when only the last menstrual period is known the optimum time to schedule a nuchal translucency measurement is at 12 to 13 weeks' gestation.
Publisher: Oxford University Press (OUP)
Date: 07-11-2016
Abstract: Human amnion epithelial cells (hAECs) have been shown to possess potent immunomodulatory properties across a number of disease models. Recently, we reported that hAECs influence macrophage polarization and activity, and that this step was dependent on regulatory T cells. In this study, we aimed to assess the effects of hAEC-derived proresolution lipoxin-A4 (LXA4) on T-cell, macrophage, and neutrophil phenotype and function during the acute phase of bleomycin-induced lung injury. Using C57Bl6 mice, we administered 4 million hAECs intraperitoneally 24 hours after bleomycin challenge. Outcomes were measured at days 3, 5, and 7. hAEC administration resulted in significant changes to T-cell, macrophage, dendritic cell, and monocyte/macrophage infiltration and phenotypes. Endogenous levels of lipoxygenases, LXA4, and the lipoxin receptor FPR2 were elevated in hAEC-treated animals. Furthermore, we showed that the effects of hAECs on macrophage phagocytic activity and T-cell suppression are LXA4 dependent, whereas the inhibition of neutrophil-derived myleoperoxidase by hAECs is independent of LXA4. This study provides the first evidence that lipid-based mediators contribute to the immunomodulatory effects of hAECs and further supports the growing body of evidence that LXA4 is proresolutionary in lung injury. This discovery of LXA4-dependent communication between hAECs, macrophages, T cells, and neutrophils is important to the understanding of hAEC biodynamics and would be expected to inform future clinical applications.
Publisher: Wiley
Date: 19-12-2017
DOI: 10.1111/CEN.13281
Publisher: MDPI AG
Date: 03-04-2020
DOI: 10.3390/IJMS21072504
Abstract: In preecl sia, widespread maternal endothelial dysfunction is often secondary to excessive generation of placental-derived anti-angiogenic factors, including soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), along with proinflammatory cytokines such as tumour necrosis factor-α (TNF-α) and activin A, understanding of which offers potential opportunities for the development of novel therapies. The antimalarial hydroxychloroquine is an anti-inflammatory drug improving endothelial homeostasis in lupus. It has not been explored as to whether it can improve placental and endothelial function in preecl sia. In this in vitro study, term placental explants were used to assess the effects of hydroxychloroquine on placental production of sFlt-1, sEng, TNF-α, activin A, and 8-isoprostane after exposure to hypoxic injury or oxidative stress. Similarly, human umbilical vein endothelial cells (HUVECs) were used to assess the effects of hydroxychloroquine on in vitro markers of endothelial dysfunction. Hydroxychloroquine had no effect on the release of sFlt-1, sEng, TNF-α, activin A, or 8-isoprostane from placental explants exposed to hypoxic injury or oxidative stress. However, hydroxychloroquine mitigated TNF-α-induced HUVEC production of 8-isoprostane and Nicotinanamide adenine dinucleotide phosphate (NADPH) oxidase expression. Hydroxychloroquine also mitigated TNF-α and preecl tic serum-induced HUVEC monolayer permeability and rescued the loss of zona occludens protein zona occludens 1 (ZO-1). Although hydroxychloroquine had no apparent effects on trophoblast function, it may be a useful endothelial protectant in women presenting with preecl sia.
Publisher: Wiley
Date: 20-06-2021
DOI: 10.1111/JPI.12744
Abstract: Therapeutic hypothermia (TH) is standard care in high‐resource birth settings for infants with neonatal encephalopathy. TH is partially effective and adjuvant therapies are needed. Here, we examined whether the antioxidant melatonin (MLT) provides additive benefit with TH, compared to TH alone or MLT alone, to improve recovery from acute encephalopathy in newborn lambs. Immediately before cesarean section delivery, we induced asphyxia in fetal sheep via umbilical cord occlusion until mean arterial blood pressure fell from 55 ± 3 mm Hg in sham controls to 18‐20 mm Hg (10.1 ± 1.5 minutes). Lambs were delivered and randomized to control, control + MLT (60 mg iv, from 30 minutes to 24 hours), asphyxia, asphyxia + TH (whole‐body cooling to 35.1 ± 0.8°C vs. 38.3 ± 0.17°C in sham controls, from 4‐28 hours), asphyxia + MLT, and asphyxia + TH + MLT. At 72 hours, magnetic resonance spectroscopy (MRS) was undertaken, and then brains were collected for neuropathology assessment. Asphyxia induced abnormal brain metabolism on MRS with increased Lactate:NAA ( P = .003) and reduced NAA:Choline ( P = .005), induced apoptotic and necrotic cell death across gray and white matter brain regions ( P .05), and increased neuroinflammation and oxidative stress ( P .05). TH and MLT were independently associated with region‐specific reductions in oxidative stress, inflammation, and cell death, compared to asphyxia alone. There was an interaction between TH and MLT such that the NAA:Choline ratio was not significantly different after asphyxia + TH + MLT compared to sham controls but had a greater overall reduction in neuropathology than either treatment alone. This study demonstrates that, in newborn lambs, combined TH + MLT for neonatal encephalopathy provides significantly greater neuroprotection than either alone. These results will guide the development of further trials for neonatal encephalopathy.
Publisher: Wiley
Date: 02-2007
Publisher: Wiley
Date: 07-08-2015
DOI: 10.1111/BIRT.12182
Abstract: Across Australia there are substantial disparities in uptake of antenatal testing for fetal anomalies, with very low uptake observed among Aboriginal women. The reasons behind these disparities are unclear, although poorer access to testing has been reported in some communities. We interviewed health care practitioners to explore the perceived barriers to providing fetal anomaly screening to Aboriginal women. In 2009 and 2010, in-depth interviews were undertaken with 59 practitioners in five urban and remote sites across the Northern Territory (NT) of Australia. Data were analyzed thematically. Maximum variation s ling, independent review of findings by multiple analysts, and participant feedback were undertaken to strengthen the validity of findings. Participants included midwives (47%), Aboriginal health practitioners (AHP) (32%), general practitioners (12%), and obstetricians (9%) almost all (95%) were female. Participants consistently reported difficulties counseling women. Explaining the concept of "risk" (of abnormalities and the screening test result) was identified as particularly challenging, because of a perceived lack of an equivalent concept in Aboriginal languages. While AHPs could assist with overcoming language barriers, they are underutilized. Participants also identified impediments to organizing testing including difficulties establishing gestational age, late presentation for care, and a lack of standardized information and training. The availability of fetal anomaly testing is challenged by communication difficulties, including a focus on culturally specific biomedical concepts, and organizational barriers to arranging testing. Developing educational activities that address the technical aspects of screening and communication skills will assist in improving access. These activities must include AHPs.
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.JCYT.2014.06.004
Abstract: The severely preterm infant receives a multitude of life-saving interventions, many of which carry risks of serious side effects. Cell therapy is an important and promising arm of regenerative medicine that may address a number of these problems. Most forms of cellular therapy use stem rogenitor cells or stem-like cells, which have the capacity to migrate, engraft and exert anti-inflammatory effects. Although some of these cell-based therapies have made their way to clinical trials in adults, little headway has been made in the neonatal patient group. This review discusses the efficacy of cell therapy in preclinical studies to date and their potential applications to diseases that afflict many prematurely born infants. Specifically, we identify the major hurdles that must be overcome before cell therapies can be safely used in the neonatal intensive care unit.
Publisher: Informa UK Limited
Date: 06-01-2018
Publisher: MDPI AG
Date: 26-01-2020
DOI: 10.3390/IJMS21030806
Abstract: Creatine is a metabolite important for cellular energy homeostasis as it provides spatio-temporal adenosine triphosphate (ATP) buffering for cells with fluctuating energy demands. Here, we examined whether placental creatine metabolism was altered in cases of early-onset pre-ecl sia (PE), a condition known to cause placental metabolic dysfunction. We studied third trimester human placentae collected between 27–40 weeks’ gestation from women with early-onset PE (n = 20) and gestation-matched normotensive control pregnancies (n = 20). Placental total creatine and creatine precursor guanidinoacetate (GAA) content were measured. mRNA expression of the creatine synthesizing enzymes arginine:glycine aminotransferase (GATM) and guanidinoacetate methyltransferase (GAMT), the creatine transporter (SLC6A8), and the creatine kinases (mitochondrial CKMT1A & cytosolic BBCK) was assessed. Placental protein levels of arginine:glycine aminotransferase (AGAT), GAMT, CKMT1A and BBCK were also determined. Key findings total creatine content of PE placentae was 38% higher than controls (p 0.01). mRNA expression of GATM (p 0.001), GAMT (p 0.001), SLC6A8 (p = 0.021) and BBCK (p 0.001) was also elevated in PE placentae. No differences in GAA content, nor protein levels of AGAT, GAMT, BBCK or CKMT1A were observed between cohorts. Advancing gestation and birth weight were associated with a down-regulation in placental GATM mRNA expression, and a reduction in GAA content, in control placentae. These relationships were absent in PE cases. Our results suggest PE placentae may have an ongoing reliance on the creatine kinase circuit for maintenance of cellular energetics with increased total creatine content and transcriptional changes to creatine synthesizing enzymes and the creatine transporter. Understanding the functional consequences of these changes warrants further investigation.
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.PLACENTA.2022.01.007
Abstract: Nuclear factor erythroid 2-related factor-2 (Nrf2), and the less well characterised proteins Nrf1 and Nrf3, are member of the cap 'n' collar family of transcription factors. Nrf proteins regulate the expression of endogenous antioxidant enzymes and have recently become the targets for various therapeutic treatments. Recently, Nrf proteins have been of particular interest as a target in placental-derived oxidative stress induced pregnancy disorders. Here, we report the presence of Nrf1, Nrf2 and Nrf3 proteins in both human primary trophoblast and human trophoblast choriocarcinoma cell line (BeWo). We also detail the steps taken to successfully silence all Nrf proteins in both human primary trophoblast cells and BeWo via detection of mRNA and protein using quantitative PCR, and SDS-PAGE and Western Blotting respectively.
Publisher: Wiley
Date: 02-2021
DOI: 10.1111/AJO.13317
Publisher: Bioscientifica
Date: 04-2000
Abstract: Activin A levels are elevated in maternal serum of pregnant women with hypertensive disturbances. Because follistatin is a circulating binding protein for activin A, the present study was designed to evaluate whether serum follistatin and activin A levels also change in patients with hypertensive disorders in the last gestational trimester. The study design was a controlled survey performed in the setting of an academic prenatal care unit. Healthy pregnant women (controls, n=38) were compared with patients suffering from pregnancy-induced hypertension (PIH, n=18) or pre-ecl sia (n=16). In addition, the study included a subset of patients with pre-ecl sia associated with intrauterine growth restriction (IUGR, n=5). Maternal blood s les were withdrawn at the time of diagnosis (patients) or in a random prenatal visit (controls), and serum was assayed for follistatin and activin A levels using specific enzyme immunoassays. Hormone concentrations were corrected for gestational age by conversion to multiples of median (MoM) of the healthy controls of the same gestational age. Follistatin levels were not different between controls and patients, while activin A levels were significantly increased in patients with PIH (1.8 MoM), pre-ecl sia (4.6 MoM), and pre-ecl sia+IUGR (3.2 MoM, P .01, ANOVA). The ratio between activin A and follistatin was significantly increased in patients with PIH (1.5 MoM) and was further increased in patients with pre-ecl sia (4.5 MoM) and in the group with pre-ecl sia+IUGR (2.6 MoM). Follistatin levels were positively correlated with gestational age in control subjects (r=0. 36, P .05) and in patients with PIH (r=0.46, P .05) or pre-ecl sia (r=0.61, P .01), while activin A correlated with gestational age only in the healthy control group (r=0.69, P .0001). The finding of apparently normal follistatin and high activin A levels in patients with PIH and pre-ecl sia suggests that unbound, biologically active, activin A is increased in women with these gestational diseases.
Publisher: Informa UK Limited
Date: 26-03-2018
Publisher: Wiley
Date: 05-2000
Publisher: Elsevier BV
Date: 05-2020
DOI: 10.1016/J.WOMBI.2019.06.001
Abstract: 'Bundles of care' are being implemented to improve key practice gaps in perinatal care. As part of our development of a stillbirth prevention bundle, we consulted with Australian maternity care providers. To gain the insights of Australian maternity care providers to inform the development and implementation of a bundle of care for stillbirth prevention. A 2018 on-line survey of hospitals providing maternity services included 55 questions incorporating multiple choice, Likert items and open text. A senior clinician at each site completed the survey. The survey asked questions about practices related to fetal growth restriction, decreased fetal movements, smoking cessation, intrapartum fetal monitoring, maternal sleep position and perinatal mortality audit. The objectives were to assess which elements of care were most valued best practice frequency and, barriers and enablers to implementation. 227 hospitals were invited with 83 (37%) responding. All proposed elements were perceived as important. Hospitals were least likely to follow best practice recommendations "all the time" for smoking cessation support (<50%), risk assessment for fetal growth restriction (<40%) and advice on sleep position (<20%). Time constraints, absence of clear guidelines and lack of continuity of carer were recognised as barriers to implementation across care practices. Areas for practice improvement were evident. All elements of care were valued, with increasing awareness of safe sleeping position perceived as less important. There is strong support from maternity care providers across Australia for a bundle of care to reduce stillbirth.
Publisher: MyJove Corporation
Date: 29-06-2013
DOI: 10.3791/50392
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.VACCINE.2017.12.080
Abstract: Maternal vaccination is a safe and effective strategy to reduce maternal and neonatal morbidity and mortality from pertussis and influenza. However, despite recommendations for maternal vaccination since 2010, uptake remains suboptimal. Barriers to uptake have been studied widely and include lack of integration of vaccination into routine pregnancy care and access to vaccination services. Standing orders for administration of vaccines without the need for a physician review or prescription have been demonstrated to improve uptake as part of multi-model interventions to increase antenatal influenza and post-partum pertussis vaccination. Monash Health is a university-affiliated, public healthcare network in Melbourne, Australia providing maternity services across three hospitals. In this study we compared three different immunisation models - an immunisation nurse-led immunisation service, standing orders for midwife-administered pertussis vaccination within pregnancy care clinics, and delivery by general practitioners in primary care. Uptake of maternal pertussis vaccine was measured as recorded in the state-wide perinatal data collection tool. Uptake improved significantly at all three hospitals over the study period with the most significant change (39% to 91%, p < .001) noted at the hospital where standing orders were introduced. Our study highlights the ersity of immunisation service models available in maternity care settings. We demonstrated significant improvement in uptake of maternal pertussis vaccination with introduction of midwife-administered vaccination but each maternity service should consider the model best suited to their needs.
Publisher: Wiley
Date: 08-2018
DOI: 10.1111/JPI.12508
Abstract: Preecl sia remains a leading cause of maternal and perinatal morbidity and mortality. There have been no material advances in the treatment of preecl sia for nearly 50 years. Combining in vitro studies and a clinical trial, we aimed to determine whether melatonin could be a useful adjuvant therapy. In a xanthine/xanthine oxidase (X/XO) placental explant model, melatonin reduced oxidative stress (8-isoprostane) and enhanced antioxidant markers (Nrf2 translocation, HO-1), but did not affect explant production of anti-angiogenic factors (sFlt, sEng, activin A). In cultured HUVECs, melatonin mitigated TNFα-induced vascular cell adhesion molecule expression and rescued the subsequent disruption to endothelial monolayer integrity but did not affect other markers for endothelial activation and dysfunction. In a phase I trial of melatonin in 20 women with preecl sia, we assessed the safety and efficacy of melatonin on (i) preecl sia progression, (ii) clinical outcomes, and (iii) oxidative stress, matching outcomes with recent historical controls receiving similar care. Melatonin therapy was safe for mothers and their fetuses. Compared to controls, melatonin administration extended the mean ± SEM diagnosis to delivery interval by 6 ± 2.3 days reduced the need for increasing antihypertensive medication on days 3-4 (13% vs 71%), days 6-7 (8% vs 51%), and at delivery (26% vs 75%). All other clinical and biochemical measures of disease severity were unaffected by melatonin. We have shown that melatonin has the potential to mitigate maternal endothelial pro-oxidant injury and could therefore provide effective adjuvant therapy to extend pregnancy duration to deliver improved clinical outcomes for women with severe preecl sia.
Publisher: Wiley
Date: 05-12-2006
DOI: 10.1111/J.1471-0528.2005.00791.X
Abstract: To determine whether activin A concentrations are altered in chronic fetal hypoxemia and intrauterine fetal growth restriction (IUGR). In vivo animal experimental model. Department of Physiology, Monash University. Chronically catherised fetal sheep in late pregnancy. Chronic fetal hypoxia and IUGR were experimentally induced by single umbilical artery ligation (SUAL) in catheterised fetal sheep. Maternal and fetal blood s les and amniotic fluid (AF) s les were collected during surgery and thereafter on alternate days, until the time of delivery for analyte measurement. Fetal blood gas parameters were measured daily. Plasma and AF was used to analyse activin A, prostaglandin E2 (PGE2) and cortisol and fetal blood gas analysis was undertaken in whole blood. SUAL produced asymmetric IUGR and non-acidaemic chronic fetal hypoxia and resulted in preterm labour (129 [3] days). AF activin A concentrations were 10-fold higher in the SUAL group than in controls whereas levels in the fetal and maternal circulations were similar between groups. SUAL-induced IUGR and fetal hypoxaemia increases AF activin A. This may be an important adaptive or protective response to IUGR.
Publisher: BMJ
Date: 09-2014
Publisher: Elsevier BV
Date: 06-2012
DOI: 10.1016/J.VACCINE.2012.04.012
Abstract: To assess the uptake of influenza vaccination by pregnant women and maternity care providers and explore their attitudes towards influenza vaccination. Cross-sectional survey administered in a Victorian tertiary level public hospital to 337 pregnant women and 96 maternity care providers. 31.3% of patients planned to or had received influenza vaccination this year, but only a quarter had received education about influenza. Women were more likely to receive influenza vaccination if they had been vaccinated in the last two years (RR 4.5, 95% CI: 3.1-6.4, p<0.001), received education about influenza (RR 2.3, 95% CI: 1.6-3.2, p<0.001) or believed that they were at high risk of influenza-related complications while pregnant (RR 2.0, 95% CI: 1.4-2.7, p<0.001). While only 56.8% of maternity care providers believed pregnant women were at high risk of influenza-related complications, 72.9% would recommend influenza vaccination to all pregnant women. Of the maternity care providers studied, 69% planned to or had been vaccinated in 2011, with this group more likely to recommend vaccination to their patients (RR 2.0, 95% CI: 1.3-3.0, p<0.001). Significantly more maternity care providers indicated that they would routinely recommend influenza vaccination than the proportion of patients who reported receiving education. Influenza vaccination rates in pregnant women are low, reflecting inadequate patient education despite most maternity care providers indicating that they would routinely recommend influenza vaccination. Increasing influenza vaccination uptake by women in pregnancy will require better education of both women and maternity care providers.
Publisher: The Endocrine Society
Date: 12-2000
Publisher: Elsevier BV
Date: 08-1995
DOI: 10.1016/S0010-7824(95)00136-0
Abstract: Sixty-three normal Caucasian men were administered intramuscular testosterone enanthate (TE) 200 mg i.m. weekly for 12 months as part of a male contraceptive trial. This dose of TE caused a 2.5-fold increase in trough serum testosterone concentrations. High density lipoprotein cholesterol (HDL-C) was significantly depressed from pretreatment concentration of 1.19 +/- 0.04 nmol/l to 1.03 +/- 0.04 mmol/l after 12 weeks of treatment, and remained suppressed for the duration of treatment (p < 0.001). There were no changes in serum concentration of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) or triglycerides (TG) during treatment, but the concentrations of TC and LDL-C were depressed at three months post-treatment. There was a sustained elevation in LDL-C:HDL-C ratio during TE treatment (p < 0.005), from 3.41 +/- 0.15 pretreatment to 3.88 +/- 0.19 after 12 weeks of TE treatment. Sex hormone binding globulin (SHBG), but not testosterone (T) or estradiol (E2), was significantly associated with HDL-C (r = 0.83, p = 0.001). Lipoprotein (a) (Lp(a)) was measured in a subgroup of 33 men: serum concentration fell from 187 +/- 45 mg/l pretreatment to 140 +/- 35 mg/l after 16 weeks of TE treatment (p < 0.01).
Publisher: Wiley
Date: 06-2014
DOI: 10.1111/AJO.12215
Publisher: Springer New York
Date: 2016
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.PREGHY.2015.01.005
Abstract: Hypertensive disorders of pregnancy continue to be amongst the leading causes of maternal morbidity and mortality. There is debate about the optimal monitoring and treatment for these women, particularly in regard to circulatory and fluid management. A restrictive fluid strategy is advocated, which conflicts with the prevailing view that the circulating volume is contracted in pre-ecl sia. This belief has been erroneously reinforced by use of the central venous pressure (CVP) as a measure of the volume state. We used a Guytonian model of the circulation involving the mean systemic filling pressure (Pms) to review published data using a cohort of normal pregnant ost partum women and a pre-ecl tic cohort. The Pms is the pressure left in the circulation when the heart is stopped, arguably the true volume state measure. An analogue of the Pms (Pmsa) can be calculated using commonly measured haemodynamic variables. Our results show the Pmsa to be elevated in normal pregnancy versus post partum (10.79 vs. 9.58, a 12.6% difference) and elevated further in pre-ecl tic pregnancy (13.86, 29% higher than the normal pregnant group). There is scope to challenge the long held belief that the volume state is contracted in pre-ecl sia. This approach indicates that the maternal volume state in pre-ecl sia is often elevated. When viewed in combination with recent echocardiographic insights this model helps to explain some of the haemodynamic management paradoxes that these women present. Most importantly, it provides a sound physiological basis for the restrictive fluid strategy that is currently recommended.
Publisher: Elsevier BV
Date: 12-2009
DOI: 10.1016/J.AJOG.2009.07.028
Abstract: The objective was to characterize the effect of glucocorticoid treatment on fetal organ blood flow and regional cerebral blood flow in normally grown fetuses and fetuses with intrauterine fetal growth restriction (IUGR). Studies were undertaken in both control and IUGR fetal sheep growth restriction was induced by ligation of 1 umbilical artery. Fetuses received colored microspheres for organ blood flow calculations before and after 2 maternal betamethasone injections (BM1 and BM2). Following BM1, cardiac output was significantly decreased in the control fetuses and blood flow to the heart and placenta was unchanged, whereas total cerebral blood flow was significantly decreased (P<.001), consistent with cerebral vasoconstriction. In the fetuses with IUGR, the cardiac output was significantly increased at +33 hours relative to BM1, and blood flow was increased in all organs notably, there was a 2-fold increase in cerebral blood flow (P=.03). The cardiovascular response of the fetus with IUGR to glucocorticoids is profoundly different from the control fetuses, which may induce both short- and long-term injury.
Publisher: Springer Science and Business Media LLC
Date: 03-06-2015
Publisher: AMPCo
Date: 21-06-2020
DOI: 10.5694/MJA2.50658
Publisher: Frontiers Media SA
Date: 18-02-2016
Publisher: Wiley
Date: 02-2003
Publisher: CSIRO Publishing
Date: 2011
DOI: 10.1071/RD10110
Abstract: Perinatal morbidity and mortality are significantly higher in pregnancies complicated by chronic hypoxia and intrauterine growth restriction (IUGR). Clinically, placental insufficiency and IUGR are strongly associated with a fetoplacental inflammatory response. To explore this further, hypoxia was induced in one fetus in twin-bearing pregnant sheep (n = 9) by performing single umbilical artery ligation (SUAL) at 110 days gestation. Five ewes were administered the anti-inflammatory drug sulfasalazine (SSZ) daily, beginning 24 h before surgery. Fetal blood gases and inflammatory markers were examined. In both SSZ- and placebo-treated ewes, SUAL fetuses were hypoxic and growth-restricted at 1 week (P 0.05). A fetoplacental inflammatory response was observed in SUAL pregnancies, with elevated pro-inflammatory cytokines, activin A and prostaglandin E2. SSZ did not mitigate this inflammatory response. It is concluded that SUAL induces fetal hypoxia and a fetoplacental inflammatory response and that SSZ does not improve oxygenation or reduce inflammation. Further studies to explore whether alternative anti-inflammatory treatments may improve IUGR outcomes are warranted.
Publisher: Elsevier BV
Date: 05-2017
Publisher: Wiley
Date: 04-2010
DOI: 10.1002/9780470151808.SC01E06S13
Abstract: Human amnion epithelial cells (hAECs) are a heterologous population positive for stem cell markers they display multilineage differentiation potential, differentiating into cells of the endoderm (liver, lung epithelium), mesoderm (bone, fat), and ectoderm (neural cells). They have a low immunogenic profile and possess potent immunosuppressive properties. Hence, hAECs may be a valuable source of cells for cell therapy. This unit describes an efficient and effective method of hAEC isolation, culture, and cryopreservation that is animal product-free and in accordance with current guidelines on preparation of cells for clinical use. Cells isolated using this method were characterized after 5 passages by analysis of karyotype, cell cycle distribution, and changes in telomere length. The differentiation potential of hAECs isolated using this animal product-free method was demonstrated by differentiation into lineages of the three primary germ layers and expression of lineage-specific markers analyzed by PCR, immunocytochemistry, and histology.
Publisher: Wiley
Date: 09-01-2018
DOI: 10.1111/MICC.12522
Abstract: Preecl sia is a pregnancy-specific disorder, primarily characterized by new-onset hypertension in combination with a variety of other maternal or fetal signs. The pathophysiological mechanisms underlying the disease are still not entirely clear. Systemic maternal vascular dysfunction underlies the clinical features of preecl sia. It is a result of oxidative stress and the actions of excessive anti-angiogenic factors, such as soluble fms-like tyrosine kinase, soluble endoglin, and activin A, released by a dysfunctional placenta. The vascular dysfunction then leads to impaired regulation and secretion of relaxation factors and an increase in sensitivity roduction of constrictors. This results in a more constricted vasculature rather than the relaxed vasodilated state associated with normal pregnancy. Currently, the only effective "treatment" for preecl sia is delivery of the placenta and therefore the baby. Often, this means a preterm delivery to save the life of the mother, with all the attendant risks and burdens associated with fetal prematurity. To lessen this burden, there is a pressing need for more effective treatments that target the maternal vascular dysfunction that underlies the hypertension. This review details the vascular effects of key drugs undergoing clinical assessment as potential treatments for women with preecl sia.
Publisher: MDPI AG
Date: 13-02-2020
DOI: 10.3390/MOLECULES25040829
Abstract: (1) Background: There is increasing understanding of the potential health benefits of cruciferous vegetables. In particular sulforaphane (SFN), found in broccoli, and its metabolites sulforaphane-glutathione (SFN-GSH), sulforaphane-cysteine (SFN-Cys), sulforaphane cysteine-glycine (SFN-CG) and sulforaphane-N-acetyl-cysteine (SFN-NAC) have potent antioxidant effects that may offer therapeutic value. Clinical investigation of sulforaphane as a therapeutic antioxidant requires a sensitive and high throughput process for quantification of sulforaphane and metabolites (2) Methods: We collected plasma s les from healthy human volunteers before and for eight hours after consumption of a commercial broccoli extract supplement rich in sulforaphane. A rapid and sensitive method for quantification of sulforaphane and its metabolites in human plasma using Liquid Chromatography–Mass Spectrometry (LC–MS) has been developed (3) Results: The LC–MS analytical method was validated at concentrations ranging between 3.9 nM and 1000 nM for SFN-GSH, SFN-CG, SFN-Cys and SFN-NAC and between 7.8 nM and 1000 nM in human plasma for SFN. The method displayed good accuracy (1.85%–14.8% bias) and reproducibility (below 9.53 %RSD) including low concentrations 3.9 nM and 7.8 nM. Four SFN metabolites quantitation was achieved using external standard calibration and in SFN quantitation, SFN-d8 internal standardization was used. The reported method can accurately quantify sulforaphane and its metabolites at low concentrations in plasma (4) Conclusions: We have established a time- and cost-efficient method of measuring sulforaphane and its metabolites in human plasma suitable for high throughput application to clinical trials.
Publisher: Public Library of Science (PLoS)
Date: 28-09-2012
Publisher: Springer Science and Business Media LLC
Date: 28-11-2014
Publisher: Elsevier BV
Date: 04-1999
Publisher: Wiley
Date: 04-03-2004
DOI: 10.1111/J.1471-0528.2004.00098.X
Abstract: To define the ontogeny of umbilical artery activin A at term and to evaluate activin A as a potential marker of perinatal hypoxia. A cohort study. A university teaching hospital delivery suite. A convenience s le of 141 term pregnancies. At delivery, umbilical artery and vein bloods were collected for blood gas measurements and subsequent measurement of activin A. Activin A levels were correlated with blood gas measurements and with labour and neonatal outcomes. Umbilical arterial activin A and pH. The median (95% CI) umbilical arterial activin A level at delivery was 1.38 (1.34-1.70) ng/mL. Levels varied significantly across gestation (P= 0.03), increasing from 36 to 38 weeks, thereafter decreasing to a nadir at 41 weeks. In 60 matched s les, the median (95% CI) venous and arterial activin A levels were 0.89 (0.81-1.06) ng/mL and 1.38 (1.21-1.61) ng/mL, respectively (P < 0.0001). Mean umbilical arterial pH was 7.20 (7.06-7.38 5-95th centiles) and was not significantly correlated with log10 activin A (r=- 0.01 P= 0.68). Compared with healthy controls, there was no difference in arterial activin A in neonates identified as having suffered significant intrapartum asphyxia (P= 0.96). Fetal activin A levels were significantly lower in cases delivered by emergency caesarean section for complications during the first stage of labour compared with cases delivered vaginally (P= 0.003). Umbilical artery activin A does not appear to be a sensitive marker of fetal oxygenation or of risk of hypoxic-ischaemic encephalopathy.
Publisher: Wiley
Date: 24-01-2013
DOI: 10.1111/AOGS.12075
Abstract: To examine maternal morbidity in primary surgical management of placenta accreta. Retrospective case series. Quaternary perinatal referral center in Melbourne, Australia. Clinically suspected and histologically confirmed cases of placenta accreta, increta and percreta. Women were identified from our hospital database coded for placenta accreta, increta, percreta and peripartum hysterectomy. Relevant details were sought from medical records. Predefined maternal morbidities: blood loss, transfusion requirements, surgical complications, reoperation rate, duration in hospital. Predefined neonatal outcomes: gestational age at birth, birth-weight, admission to intensive (NICU) or special care nurseries (SCN), respiratory distress syndrome. Between 1999 and 2009, 33 women were diagnosised with invasive placentation. A total of 27 were confirmed histologically after hysterectomy: 12 accreta, one increta, and 14 percreta. Median blood loss was 2 L. There was a 1.8-L reduction in mean blood loss with elective vs. emergency hysterectomy (p = 0.04). Nearly two-thirds of women required four or more units of packed red-blood-cells. Half of the women suffered from surgical complications, mostly from bladder injury. The risk of returning to theater for further surgery was 20%. Women with placenta percreta were more likely to require additional blood products (p = 0.03), sustain renal tract injury (p = 0.003) and require intensive care admission (p = 0.002). A primary surgical approach to management of placenta accreta is associated with significant maternal morbidity, even when managed in a dedicated quaternary perinatal referral center.
Publisher: Springer Science and Business Media LLC
Date: 05-2004
Publisher: Wiley
Date: 16-05-2014
Publisher: Elsevier BV
Date: 04-2002
Publisher: Springer New York
Date: 21-09-2018
DOI: 10.1007/978-1-4939-7498-6_4
Abstract: This chapter describes the methodologies which may be used in evaluating in vitro endothelial cell dysfunction in preecl sia.
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.AJOG.2016.03.002
Abstract: There is an increasing incidence of pertussis infection in infants too young to be adequately protected via vaccination. Maternal pertussis vaccination during the third trimester of pregnancy is a new strategy to provide protection to newborn infants. This study sought to determine the optimal gestational window for vaccination in the third trimester. This prospective study recruited 3 groups of women: an early vaccination group, vaccinated between 28-32 weeks' gestation a late vaccination group, vaccinated between 33-36 weeks' gestation and an unvaccinated control group. Maternal venous blood was taken prior to pertussis vaccination. At birth, infant cord blood was collected to determine antibody levels to pertussis toxin (PT), pertactin (PRN), and filamentous hemagglutinin (FHA). In all, 154 women were recruited from April through September 2014. There was no significant difference between maternal PRN and FHA antibody levels among the 3 groups, however, PT was higher in the early compared to late vaccination group (P = .05). Cord blood antibody levels to PT, PRN, and FHA were significantly higher in those born to vaccinated women compared with unvaccinated controls (P < .001, P = .001, and P < .001, respectively). Vaccination between 28-32 weeks' gestation resulted in significantly higher cord blood PT (4.18.0 vs 3.50 IU/mL, P = .009), PRN (5.83 vs 5.31 IU/mL, P = .03), and FHA (5.56 vs 5.03 IU/mL, P = .03) antibody levels than vaccination between 33-36 weeks' gestation. When adjusted for maternal prevaccination antibody levels, PT levels in early vs late vaccination approached significance (P = .06). PRN levels were significantly higher in the early vaccination group (P = .003). There was no significant difference for FHA antibody levels between the 2 groups (P = .16). Maternal vaccination during the third trimester is effective in affording higher levels of pertussis antibody protection to the newborn infant. Vaccination early in the third trimester appears more effective than later in pregnancy.
Publisher: Wiley
Date: 17-05-2012
Publisher: SAGE Publications
Date: 09-1998
DOI: 10.1177/000456329803500510
Abstract: The development of a sensitive and specific enzyme-linked immunoassay (ELISA) for inhibin A stimulated the observation that inhibin A was a useful prenatal marker of Down's syndrome. Modifications of that ELISA, in terms of preassay s le treatment, detection methods and standard preparation, were subsequently introduced to improve assay performance and reduce costs. These modified formats have been validated and reported. We describe the modifications in detail, explaining the rationale for each, and report the results of a study directly comparing the various ELISA formats in terms of assay performance when applied to clinical s les and ability to differentiate between normal and Down's syndrome pregnancies. A format involving s le pretreatment with sodium dodecylsulphate at 100°C was found to give better assay performance and a modest improvement in discrimination between Down's syndrome s les and controls, and we recommend this format for use by other investigators.
Publisher: The Endocrine Society
Date: 07-1993
DOI: 10.1210/JCEM.77.1.8325955
Abstract: Sex-steroid based male contraceptive regimes induce azoospermia in only 40-70% of Caucasian men. The reason(s) why the remainder maintains a low level of spermatogenesis (oligozoospermia) despite gonadotrophin suppression is unclear. In order to improve our understanding of this phenomenon, we examined the changes in sperm density and plasma LH, FSH, testosterone (T), oestradiol (E2), and inhibin (IN) in 28 normal men who received 200 mg testosterone enanthate (TE) im weekly during a male contraceptive efficacy trial. Gonadotrophins were measured by an ultrasensitive time-resolved immunofluorometric assay (DELFIA) with a sensitivity of 0.04 U/L, to determine the adequacy of suppression. Seventeen of the 28 men achieved azoospermia the other 11 remained oligozoospermic (sperm density 3.3-4.7 x 10(6)/mL) after 6 months of TE exposure. Azoospermic subjects displayed a more rapid decline in sperm density, a significant difference being apparent by 5 weeks after starting TE. During TE treatment, both LH and FSH were consistently suppressed to below the limits of detection, whereas there was a 2.5-fold rise in T and E2 with a similar decrease in IN. There were no consistent differences in any of these hormone concentrations between the azoospermic and oligozoospermic groups. Recovery of sperm density to baseline levels or above 20 x 10(6)/mL was significantly slower in the azoospermic group. During the recovery phase, the azoospermic men exhibited significantly higher LH and FSH levels compared to baseline and to the oligozoospermic subjects even though no differences in circulating T, E2, or IN were observed. We conclude that incomplete gonadotrophin suppression or differences in sex steroid or inhibin levels are unlikely to be responsible for the maintenance of minor degrees of spermatogenesis in some men during TE administration. The rebound rise in gonadotrophins in azoospermic but not oligozoospermic responders during recovery may reflect a more profound degree of spermatogenic suppression in the former group.
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.NEUROPHARM.2014.05.031
Abstract: The risk of preterm delivery often means that the fetus will be exposed to exogenous synthetic glucocorticoids to accelerate fetal lung maturation, but effects on other organs, particularly the brain, are not understood. The neurosteroid allopregnanolone (AP) is a GABAA receptor agonist that influences fetal brain development and has neuroprotective properties. In this study we determined the impact of maternal glucocorticoid (betamethasone) administration on brain development and AP synthesis in preterm fetal sheep. Pregnant ewes underwent surgery at 105 days gestation for implantation of fetal catheters. Ewes received either betamethasone (BM 11.4 mg n=10) or vehicle (saline n=5) by i.m injection on days five (BM1) and six (BM2) following surgery. Five fetuses of the BM treated ewes received an infusion of alfaxalone (20 mg) over 48 h commencing 30 min prior to BM1. All animals were euthanased on day 7, and the fetal brains collected to determine AP concentrations and histopathology. BM significantly reduced AP levels in the fetal brain and placental cotyledons, and also in fetal plasma without altering progesterone concentrations. There was a significant decrease in the number of myelinating cells in subcortical white matter, but no change to total oligodendrocyte number. Co-administration of the AP analogue analog alfaxalone with BM prevented this change in MBP expression. BM, given at a dose clinically prescribed to accelerate lung maturation, adversely affects neurosteroid levels in the preterm fetal brain, and affects the maturational profile of white matter development these effects were mitigated by the co-administration of alfaxolone.
Publisher: SAGE Publications
Date: 04-2014
Abstract: Human amnion epithelial cells (hAECs) have been shown to modulate inflammation and restore normal lung structure and respiratory function following bleomycin challenge in immune-competent mice. These effects are exerted despite a lack of significant engraftment of hAECs, suggesting that immunomodulatory effect mechanisms are at play. In this study, using the bleomycin model of injury, we explored the interactions between hAECs and macrophages. We administered 4 million hAECs intraperitoneally to C57Bl6 mice 24 h following a bleomycin challenge. Using FACS analysis and qPCR, we showed that hAEC administration significantly reduced macrophage infiltration into the lungs and that the majority of the pulmonary macrophages were of the M2 phenotype. Using bone marrow-derived macrophages, we then showed that hAEC-conditioned media could alter macrophage polarization, migration, and phagocytosis, without affecting macrophage survival or proliferation in vitro. This study provides the first evidence that hAECs directly influence macrophage behavior in a proreparative manner and suggests that hAECs are able to mediate these effects independently of other immune cell types.
Publisher: S. Karger AG
Date: 2017
DOI: 10.1159/000471797
Abstract: Chronic moderate hypoxia, such as occurs in fetal growth restriction (FGR) during gestation, compromises the blood-brain barrier (BBB) and results in structural abnormalities of the cerebral vasculature. We have previously determined the neuroprotective and antioxidant effects of maternal administration of melatonin (MLT) on growth-restricted newborn lambs. The potential of maternal MLT therapy for the treatment of cerebrovascular dysfunction-associated developmental hypoxia has also been demonstrated in newborn lambs. We assessed whether MLT had an effect on the previously reported structural and cerebral vascular abnormalities in chronically hypoxic FGR lambs. Single umbilical-artery ligation surgery was performed in fetuses at approximately 105 days of gestation (term: 147 days) to induce placental insufficiency and FGR, and treatment with either saline or an MLT infusion (0.1 mg/kg) was started 4 h after surgery. Ewes delivered naturally at term and lambs were euthanased 24 h later. We found a significant reduction in the number of laminin-positive blood vessels within the subcortical and periventricular white matter (SCWM and PVWM) and the subventricular zone (SVZ) in FGR ( i /i 0.0005) and FGR + MLT brains ( i /i 0.0005 vs. controls), with no difference found between FGR and FGR + MLT animals. This was associated with a significant decrease in VEGF immunoreactivity in FGR and FGR + MLT brains versus controls ( i /i 0.0005 SCWM and PVWM) and in the SVZ in FGR brains versus controls ( i /i 0.005) and also with significantly lower levels of proliferating blood vessels versus controls ( i /i 0.0005). Glucose transporter-1 immunoreactivity (vascular endothelium) was decreased in FGR versus control lambs ( i /i 0.0005) in SCWM, PVWM, and the SVZ it was significantly increased in FGR + MLT lambs compared with FGR lambs in SCWM and PVWM ( i /i 0.005) and even more markedly in the SVZ ( i /i 0.0005). FGR brains showed a 72% reduction in pericyte coverage versus control lambs and 68% versus FGR + MLT in PVWM. In SCWM, we found a 77 and 73% reduction compared with control and FGR + MLT lambs, respectively, while in the SVZ, we observed a 68% reduction versus controls and a 70% reduction in FGR versus FGR + MLT lambs. Astrocyte end-feet coverage in the SCWM showed a significant 24% reduction in FGR versus control levels, a 42% decrease within the PVWM, and a 35% decrease within the SVZ versus controls. MLT normalized astrocyte attachment to blood vessels, with no difference seen between controls and FGR + MLT animals in any of the brain regions examined. We also observed a decrease in albumin extravasation and microhemorrhage in controls and FGR + MLT brains versus FGR lambs. Our results demonstrate that umbilicoplacental insufficiency is associated with FGR-produced vascular changes in the white matter and SVZ of FGR newborn brains and that maternal MLT prevented disruption of the BBB by protecting perivascular cells essential for the maintenance of vascular homeostasis and stability.
Publisher: Wiley
Date: 22-12-2020
Abstract: To assess the impact of publicly reporting a statewide fetal growth restriction (FGR) performance indicator. Retrospective cohort study from 2000 to 2017. All maternity services in Victoria, Australia. A total of 1 231 415 singleton births at ≥32 weeks of gestation. We performed an interrupted time-series analysis to assess the impact of publicly reporting an FGR performance indicator on the rate of detection for severe cases of small for gestational age (SGA). Rates of perinatal mortality and morbidity and obstetric intervention were assessed for severe SGA pregnancies and pregnancies delivered for suspected SGA. Gestation at delivery, obstetric management and perinatal outcome. The public reporting of a statewide FGR performance indicator was associated with a steeper reduction per quarter in the percentage of severe SGA undelivered by 40 weeks of gestation, from 0.13 to 0.51% (P = 0.001), and a decrease in the stillbirth rate by 3.3 per 1000 births among those babies (P = 0.01). Of babies delivered for suspected SGA, the percentage with birthweights ≥ 10th centile increased from 41.4% (n = 307) in 2000 to 53.3% (n = 1597) in 2017 (P < 0.001). Admissions to a neonatal intensive care unit for babies delivered for suspected SGA but with a birthweight ≥ 10th centile increased from 0.8 to 2.0% (P < 0.001). The public reporting of an FGR performance indicator has been associated with the improved detection of severe SGA and a decrease in the rate of stillbirth among those babies, but with an increase in the rate of iatrogenic birth for babies with normal growth. The public reporting of hospital performance is associated with a reduction in stillbirth, but also with unintended interventions.
Publisher: Wiley
Date: 03-02-2016
DOI: 10.1111/AJO.12441
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-11-2019
Abstract: Women with a history of preecl sia are at increased risk of cardiovascular morbidity and mortality. However, the underlying mechanisms of disease association, and the ideal method of monitoring this high‐risk group, remains unclear. This review aims to determine whether women with a history of preecl sia show clinical or subclinical cardiac changes when evaluated with an echocardiogram. A systematic search of MEDLINE , EMBASE, and CINAHL databases was performed to identify studies that examined cardiac function in women with a history of preecl sia, in comparison with those with normotensive pregnancies. In the 27 included studies, we found no significant differences between preecl sia and nonpreecl sia women with regard to left ventricular ejection fraction, isovolumetric relaxation time, or deceleration time. Women with a history of preecl sia demonstrated a higher left ventricular mass index and relative wall thickness with a mean difference of 4.25 g/m 2 (95% CI , 2.08, 6.42) and 0.03 (95% CI , 0.01, 0.05), respectively. In comparison with the nonpreecl sia population, they also demonstrated a lower E/A and a higher E/e′ ratio with a mean difference of −0.08 (95% CI , −0.15, −0.01) and 0.84 (95% CI , 0.41, 1.27), respectively. In comparison with women who had a normotensive pregnancy, women with a history of preecl sia demonstrated a trend toward altered cardiac structure and function. Further studies with larger s le sizes and consistent echocardiogram reporting with the use of sensitive preclinical markers are required to assess the role of echocardiography in monitoring this high‐risk population group.
Publisher: S. Karger AG
Date: 25-08-2016
DOI: 10.1159/000448094
Abstract: b i Introduction: /i /b Monochorionic-diamniotic (MCDA) twin pregnancies are high risk, due to twin-to-twin transfusion syndrome (TTTS), twin anaemia polycythaemia sequence (TAPS) and intrauterine growth restriction (IUGR). There is limited evidence to guide ultrasound surveillance protocols. Using a retrospective cohort, we aimed to provide insight into the optimal interval of ultrasound surveillance. b i Methods: /i /b Retrospective cohort of women with MCDA pregnancies who received antenatal care at Monash Medical Centre (January 2011-October 2014). We reviewed all ultrasounds from ≥15 weeks' gestation and collected perinatal outcomes. b i Results: /i /b A total of 162 women with MCDA pregnancies attended our care. Six women were excluded due to late referral. Of the remaining 156, 55% were uncomplicated. TTTS, TAPS, IUGR and fetal demise in utero occurred in 9%, 1%, 31% and 2%, respectively. Median interval between the last ultrasound and TTTS diagnosis was 3.1 weeks (IQR 0.8-5.8). There was a trend towards a longer interval for cases with advanced TTTS compared to early TTTS. Interval between ultrasound scans was longer in cases with unexplained fetal demise in utero and advanced TTTS than early TTTS [3.4 weeks (IQR 2.0-6.9) vs. 0.9 weeks (IQR 0.4-3.7) p 0.05]. b i Discussion: /i /b Our observations support current recommendations for fortnightly ultrasound surveillance in MCDA pregnancies from 16 weeks' gestation and suggest that longer intervals may be associated with poorer outcomes.
Publisher: Springer Science and Business Media LLC
Date: 27-11-2014
Publisher: Wiley
Date: 16-11-2021
DOI: 10.1111/EXD.14223
Abstract: Keloids are benign tumours caused by abnormal wound healing driven by increased expression of cytokines, including activin A. This study compared effects of activins on normal and keloid-derived human dermal fibroblasts and investigated a novel treatment for keloids using follistatin. Normal skin and keloid tissue s les from 11 patients were used to develop primary fibroblast cultures, which were compared in terms of their histology and relevant gene (qRT-PCR and RNAseq) and protein (ELISA) expression. Activin A (INHBA) and connective tissue growth factor (CTGF) gene expression were significantly upregulated in keloid fibroblasts, as was activin A protein expression in cell lysates and culture medium. Activator protein 1 inhibitor (SR11302) significantly decreased INHBA and CTGF expression in keloid fibroblasts and a single treatment of follistatin over 5 days significantly inhibited activin and various matrix-related genes in keloid fibroblasts when compared to controls. Follistatin, by binding activin A, suppressed CTGF expression suggesting a novel therapeutic role in managing keloids and perhaps other fibrotic diseases.
Publisher: Wiley
Date: 29-01-2015
DOI: 10.1016/J.IJDEVNEU.2015.01.004
Abstract: Chronic moderate hypoxia induces angiogenic adaptation in the brain, reflecting a modulatory role for oxygen in determining cerebrovascular development. Chronic intrauterine fetal hypoxia, such as occurs in intrauterine growth restriction (IUGR) is likely to lead to a reduction in oxygen delivery to the brain and long-term neurological abnormalities. Thus we investigated whether vascular remodeling and vascular abnormalities were evident in the brain of IUGR newborn lambs that were chronically hypoxic in utero. Single uterine artery ligation (SUAL) surgery was performed in fetuses at ∼ 105 days gestation (term ∼ 145 days) to induce placental insufficiency and IUGR. Ewes delivered naturally at term and lambs were euthanased 24h later. IUGR brains (n = 9) demonstrated a significant reduction in positive staining for the number of blood vessels (laminin immunohistochemistry) compared with control (n = 8): from 1650 ± 284 to 416 ± 47 cells/mm(2) in subcortical white matter (SCWM) 1793 ± 298 to 385 ± 20 cells/mm(2) in periventricular white matter (PVWM), and 1717 ± 161 to 405 ± 84 cells/mm(2) in the subventricular zone (SVZ). The decrease in vascular density was associated with a significant decrease in VEGF immunoreactivity. The percentage of blood vessels exhibiting endothelial cell proliferation (Ki67 positive) varied regionally between 14 to 22% in white matter of control lambs, while only 1-3% of blood vessels in IUGR brains showed proliferation. A 66% reduction in pericyte coverage (α-SMA and desmin) of blood vessels was observed in SCWM, 71% in PVWM, and 73% in SVZ of IUGR lambs, compared to controls. A reduction in peri-vascular astrocytes (GFAP and laminin) was also observed throughout the white matter of IUGR lambs, and extravasation of albumin into the brain parenchyma was present, indicative of increased permeability of the blood brain barrier. Chronic hypoxia associated with IUGR results in a reduction in vascular density in the white matter of IUGR newborn brains. Vascular pericyte coverage and peri-vascular astrocytes, both of which are essential for stabilisation of blood vessels and the maintenance of vascular permeability, were also decreased in the white matter of IUGR lambs. In turn, these vascular changes could lead to inadequate oxygen supply and contribute to under-perfusion and increased vulnerability of white matter in IUGR infants.
Publisher: Public Library of Science (PLoS)
Date: 17-02-2015
Publisher: Wiley
Date: 06-2009
Publisher: Oxford University Press (OUP)
Date: 02-2006
DOI: 10.1095/BIOLREPROD.105.047324
Abstract: HTRA3 is a newly identified serine peptidase of the mammalian HTRA (high-temperature requirement factor A) family, that is upregulated dramatically during mouse placental development. The current study determined whether HTRA3 was involved in human placentation. During the menstrual cycle, HTRA3 was expressed primarily in the endometrial glands, being significantly upregulated toward the mid- to late secretory phases prominent expression in the stroma detected only in the decidual cells in the late secretory phase. Thus, overall endometrial HTRA3 expression was highest in the late secretory phase, when the endometrium is prepared for maternal-trophoblast interaction. During the first trimester of pregnancy, both glandular and decidual HTRA3 expression increased further with the decidual upregulation being highly significant. The strong link between HTRA3 expression and endometrial stromal cell decidualization was further established in an in vitro model using primary endometrial stromal cells. HTRA3 was also expressed by certain trophoblast subtypes in the first-trimester placenta: strongly in the villous syncytiotrophoblast, trophoblast shell, and endovascular trophoblast and weakly in the distal portion of the trophoblast cell columns but not in villous cytotrophoblast, the proximal region of the cell columns, or interstitial trophoblast. Upregulation of HTRA3 expression in association with placental development was revealed by a significant elevation of this protein in the maternal serum during the first trimester. We thus propose that HTRA3 is a previously unrecognized factor closely associated with and potentially important for human placentation. This study established crucial groundwork for future investigations toward establishing the physiological roles of HTRA3 in human placentation.
Publisher: Wiley
Date: 16-05-2006
Publisher: Wiley
Date: 02-1993
DOI: 10.1111/J.1365-2605.1993.TB01150.X
Abstract: Steroid regimens containing androgens are being evaluated currently as hormonal contraceptives for men. The possible non-reproductive effects of such treatment were assessed during an efficacy trial using a prototype regime of 200 mg testosterone enanthate i.m. weekly. Prostatic function and size were monitored by regular rectal examination, blood levels of prostate-specific androgen (PSA) were measured in 30 men and prostatic size was measured by trans-rectal ultrasound imaging in a representative subgroup of five subjects for 12 months and for a further 6 months after discontinuation. Despite the sustained rise in serum levels of testosterone, oestradiol and dihydrotestosterone during treatment, there was no detectable increase in prostatic size on rectal examination or any significant change in blood concentrations of PSA. A small but significant increase (14.3 +/- 2.0%) in maximal prostate transverse area was observed in four men while the remaining one showed no change. Our preliminary data demonstrate the feasibility and importance of monitoring prostatic function in the development of androgen-containing male hormonal contraceptives.
Publisher: Wiley
Date: 10-02-2012
Publisher: Informa UK Limited
Date: 02-03-2015
Publisher: Wiley
Date: 08-2000
DOI: 10.1111/J.1471-0528.2000.TB10402.X
Abstract: To examine changes in maternal serum levels of activin A and follistatin during pregnancy and labour. In three cross sectional and three longitudinal studies venous blood was collected from women during pregnancy, spontaneous labour, labour induction and prior to elective caesarean section for the measurement of activin A and follistatin. Monash Medical Centre, Clayton, Victoria, Australia. One hundred and twenty-three women participated in a cross sectional study in pregnancy, 18 women in two longitudinal pregnancy studies, 36 women in a cross sectional labour study, nine women in a longitudinal study of labour induction. Ten women undergoing elective caesarean section were also studied. Activin A and follistatin were measured using two sensitive and specific enzyme-linked immunosorbent assays. In the cross sectional study of pregnancy, mean (SEM) maternal serum activin A and follistatin levels increased towards term (2.4 ng/mL (0.3) and 1.8 ng/mL (0.3) in first trimester to 18.9 ng/mL (3.8) and 5.3 ng/mL (0.9) at term, respectively), but the longitudinal study revealed that levels plateau in the last three weeks of pregnancy (16.0 ng/mL (2.6) and 6.2 ng/mL (1.4) at 37 weeks and 16.6 ng/mL (3.5) and 6.2 ng/mL (0.5) before labour for activin A and follistatin, respectively). There was no difference in levels of activin A and follistatin between women delivered by caesarean section and labouring women at term (14.9 ng/mL (2.8) vs 11.0 ng/mL (0.93) and 5.95 ng/mL (0.67) vs 5.71 ng/mL (0.63), respectively) and levels of both proteins did not alter throughout spontaneous or induced labour. We believe that these data argue against activin A playing an acute role in the initiation or regulation of human parturition.
Publisher: Humana Press
Date: 2011
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.WOMBI.2021.01.004
Abstract: Currently <1% of Australian women give birth at home. In Australia there are very few options for women to access public funded homebirth. We aimed to use geo-mapping to identify the number of women eligible for homebirth in Victoria, based on the criteria of uncomplicated pregnancies and residing within 15-25kms of suitable maternity services, to plan future maternity care options. Retrospective study of births between 2015 and 2017 in Victoria, Australia. All women who were identified as having a low risk pregnancy at the beginning of pregnancy were included. The number of women within 15 and 25km of a suitable Victorian public maternity hospital and catchment boundaries around each hospital were determined. Between 2015 and 2017, 126,830 low risk women gave birth in Victoria, of whom half live within 25km of seven Victorian hospitals. Currently, 2% of suitable women who live close to the current public homebirth models accessed them. We present a method to inform the expansion of maternity service options using Victoria as an ex le. On the basis of the maximum number of low risk women living close by, we have also identified the Victorian maternity services that would be most suitable for creation of public homebirth or low risk continuity of midwifery models. This approach could can be used to plan other maternity care services.
Publisher: Wiley
Date: 10-2000
DOI: 10.1111/J.1471-0528.2000.TB11624.X
Abstract: One hundred women were interviewed at their first hospital antenatal visit to assess their knowledge of, and attitudes to, first versus second trimester screening for Down's syndrome. Overall, the women had limited knowledge of Down's syndrome, and the prenatal screening and diagnostic tests that are available. However, when informed, the majority of women expressed a clear preference for first trimester screening tests for Down's syndrome, regardless of the rate of miscarriage of Down's syndrome pregnancies between 10 and 15 weeks of gestation. These findings have implications for the planning of prenatal Down's syndrome screening programmes.
Publisher: Public Library of Science (PLoS)
Date: 27-03-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2017
Publisher: Wiley
Date: 19-03-2013
Publisher: Elsevier BV
Date: 12-2011
DOI: 10.1016/J.MIDW.2010.11.001
Abstract: This literature review summarises the history of patient safety initiatives in health-care systems around the world. The need to improve patient safety is commonly called for following interrogation of data captured as a measure of patient safety including audit, clinical indicator reporting and evaluation methods. Many such reports exist for maternity services. Recommendations for improvement identified after review may be taken up, but there is little in the literature that demonstrates how clinicians consider such recommendations, implement improvement strategies and assess their impact. The authors of this paper concur with other authors who call for more research in this regard.
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1016/J.PEP.2008.10.020
Abstract: The transforming growth factor-beta (TGF-beta) superfamily member, activin A, plays a central role in the regulation of multiple physiological processes including cell differentiation, mitogenesis, embryogenesis, apoptosis and inflammation. In normal cells, activin A signalling is regulated to maintain cellular and tissue health and suppress tumour growth. Disruption of activin A signalling has been implicated in tumour formation and progression. Hence, the availability of activin A is an important target for the development of diagnostics and drugs for therapeutic intervention. To this end, we have expressed human activin A in Pichia pastoris, permitting its secretion into culture medium and purification as the mature homodimer. A construct was engineered encoding the monomeric precursor protein with a N-terminal FLAG affinity tag (DYKDDDDK) and a cleavage site (EKR) for Kex2p protease. Procedures for the two-step purification of human activin A by ion-exchange and anti-FLAG antibody affinity chromatography, and for the removal of the FLAG affinity tag from purified recombinant human activin A by enteropeptidase, are described. The molecular weights of the FLAG-tagged and de-tagged human activin A were confirmed by MALDI-TOF mass spectroscopy. The biological activity of these recombinant activins was assessed for their effects on modulating the secretion of Endothelin-1 (ET-1) by human umbilical vein endothelial cells (HUVECs). The recombinant human activin A containing the intact FLAG tag resulted in a reduced ET-1 secretion from HUVECs, whereas upon removal of this affinity purification tag the purified recombinant human activin A restored ET-1 secretion to levels comparable to the positive control. These results document an approach of considerable potential for the simple, large-scale expression and purification of this important human growth factor for use in diagnostic and therapeutic purposes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2009
Publisher: Wiley
Date: 11-04-2015
DOI: 10.1111/BIRT.12159
Abstract: The relationship between migration and pregnancy outcomes is complex, with little insight into whether women of refugee background have greater risks of adverse pregnancy outcomes than other migrant women. This study aimed to describe maternal health, pregnancy care, and pregnancy outcomes among migrant women from humanitarian and nonhumanitarian source countries. Retrospective, observational study of singleton births, at a single maternity service in Australia 2002-2011, to migrant women born in humanitarian source countries (HSCs, n = 2,713) and non-HSCs (n = 10,606). Multivariable regression analysis assessed associations between maternal HSC-birth and pregnancy outcomes. Compared with women from non-HSCs, the following were more common in women from HSCs: age < 20 years (0.6 vs 2.9% p < 0.001), multiparity (51 vs 76% p < 0.001), body mass index (BMI) ≥ 25 (38 vs 50% p < 0.001), anemia (3.2 vs 5.9% p < 0.001), tuberculosis (0.1 vs 0.4% p = 0.001), and syphilis (0.4 vs 2.5% p 41 weeks gestation) (OR 2.5 [95% CI 1.9-3.4]). Stillbirth (0.8 vs 1.2% p = 0.04, OR 1.5 [95% CI 1.0-2.4]) and unplanned birth before arrival at the hospital (0.6 vs 1.2% p < 0.001, OR 1.3 [95% CI 0.8-2.1]) were more common in HSC-born women but not independently associated with maternal HSC-birth after adjusting for age, parity, BMI and relative socioeconomic disadvantage. These findings suggest areas where women from HSCs may have additional needs in pregnancy compared with women from non-HSCs. Refugee-focused strategies to support engagement in pregnancy care and address maternal health needs would be expected to improve health outcomes in resettlement countries.
Publisher: Wiley
Date: 05-10-2016
DOI: 10.1111/AJO.12554
Abstract: Maternal immunisation is the most effective strategy to reduce infant morbidity and mortality from pertussis infection, and is now standard of care in many countries, including Australia. However, uptake cannot be guaranteed unless the barriers to implementing programs locally are understood. Education and resources for antenatal care providers, embedding vaccination within antenatal care, and provision of culturally appropriate information for pregnant women are integral to a successful antenatal vaccination program.
Publisher: AMPCo
Date: 12-11-2019
DOI: 10.5694/MJA2.50402
Abstract: To examine changes in the modes of delivery of twins in Victoria over 33 years. Retrospective population-based study. All twin births in Victoria, 1 January 1983 - 31 December 2015. Mode of birth (vaginal, planned or unplanned caesarean delivery) indications for caesarean delivery. During 1983-2015, 32 187 twin pregnancies ended in live or stillbirths in Victoria. The proportion of twins born by caesarean delivery increased from 24% (156 twin deliveries) in 1983 to 71% (782 deliveries) in 2015. The proportion of twin births by planned caesarean delivery with twin pregnancy as the sole indication for caesarean delivery increased across this period from 1.8% (12 twin deliveries) to 21% (231 deliveries). The proportion of twin births by caesarean delivery and the proportion of caesarean twin deliveries with twin pregnancy as the principal indication each differed between Victorian regions. During 1983-2015, the proportion of twins born in Victoria by caesarean delivery increased almost threefold, mostly because caesarean delivery has become the preferred mode of birth for twin pregnancies. Regional differences in the delivery of twins suggest that the number of caesarean deliveries can be reduced with appropriate system and training support.
Publisher: Wiley
Date: 15-07-2021
DOI: 10.1111/AJO.13405
Abstract: Preterm birth is the greatest cause of death up to five years of age and an important contributor to lifelong disability. There is increasing evidence that a meaningful proportion of early births may be prevented, but widespread introduction of effective preventive strategies will require financial support. This study estimated the economic cost to the Australian government of preterm birth, up to 18 years of age. A decision‐analytic model was developed to estimate the costs of preterm birth in Australia for a hypothetical cohort of 314 814 children, the number of live births in 2016. Costs to Australia’s eight jurisdictions included medical expenditures and additional costs to educational services. The total cost of preterm birth to the Australian government associated with the annual cohort was estimated at $1.413 billion (95% CI 1047‒1781). Two‐thirds of the costs were borne by healthcare services during the newborn period and one‐quarter of the costs by educational services providing special assistance. For each child, the costs were highest for those born at the earliest survivable gestational age, but the larger numbers of children born at later gestational ages contributed heavily to the overall economic burden. Preterm birth leaves many people with lifelong disabilities and generates a significant economic burden to society. The costs extend beyond those to the healthcare system and include additional educational needs. Assessments of economic costs should inform economic evaluations of interventions aimed at the prevention or treatment of preterm birth.
Publisher: Elsevier BV
Date: 07-2005
DOI: 10.1016/J.PLACENTA.2004.08.009
Abstract: Indoleamine 2,3-dioxygenase (IDO) has been implicated in contributing to immunotolerance in early pregnancy, but the presence in the term placenta of mRNAs for enzymes that produce other biologically active kynurenine end-products suggests other functions for kynurenine pathway metabolites. The aim of this study was to investigate the localisation of two key enzymes - IDO and kynurenine hydroxylase (KYN-OHase) - in first trimester decidua and in the human placenta across pregnancy. Using immunocytochemistry, it was shown that there was strong expression of IDO and KYN-OHase in stromal and glandular epithelial cells of first trimester decidua. In first and second trimester placenta, IDO and KYN-OHase were localised to the syncytiotrophoblast, stroma and macrophages. IDO and KYN-OHase mRNAs were also identified, and the enzymes appear to be functional because kynurenine and 3-hydroxy-anthranilic acid (respective products of the activity of these enzyme) were released into the medium when first trimester placental explants were maintained in culture for 48h. In term placenta, both IDO and KYN-OHase immunoreactivities were confined mainly to vascular endothelial cells of villous blood vessels, and to macrophages within the fetal villus, whereas syncytial staining was very weak or absent. The shift of expression of these enzymes away from the syncytiotrophoblast to fetal endothelial cells in terminal villi suggests that the function of the enzymes may change from a role in immunosuppression at the maternal-fetal interface in early pregnancy, to one associated with regulation of fetoplacental blood flow or placental metabolism in late gestation.
Publisher: Wiley
Date: 27-10-2006
DOI: 10.1002/DVDY.20999
Abstract: Mammalian embryos cannot survive without the placenta. Development of the human placenta requires trophoblast proliferation, differentiation, and invasion as well as highly coordinated modulation of the maternal uterus. HtrA1 is a member of the recently identified mammalian HtrA (high temperature requirement factor A) serine protease family with a high level of expression in the placenta. In this study, we examined whether HtrA1 expression (mRNA and protein) is associated with placental development in the human. HtrA1 is up-regulated in both endometrial glands and decidual cells during endometrial preparation for embryo implantation and during first-trimester pregnancy at placentation. HtrA1 expression was also detected in certain trophoblast subtypes during early pregnancy. The villous syncytiotrophoblast and cytotrophoblast showed the strongest expression while the interstitial extravillous trophoblast showed the lowest or no expression of HtrA1. The distinct distribution of HtrA1 at the maternal-trophoblast interface suggests that HtrA1 may play a role in placental development.
Publisher: Wiley
Date: 22-11-2004
DOI: 10.1111/J.1471-0528.2004.00269.X
Abstract: To determine whether activin A levels reflect oxygen availability in basal and hypoxic conditions in the late pregnant fetus and newborn lamb. In vivo animal experimental study. Department of Physiology, Monash University. Chronically catheterised fetal sheep in late gestation. Fetal hypoxia was induced at 125 (n = 4), 135 (n = 4) or 145 days ('term' n = 3) gestational age by maternal nitrogen exposure, for 4 hours, during which maternal and fetal arterial, and amniotic fluid s les were collected. Lambs (age one, five and eight days n = 3) were exposed to 1 hour of hypoxia via nitrogen exposure. Activin A, prostaglandin E2 (PGE2) and cortisol were analysed in plasma and amniotic fluid, and whole blood was used to determine Pao2, Paco2, %O2, lactate and pH. Basal activin A concentrations in the fetal arterial circulation remained unchanged between 125 days (0.230 [0.10] ng/mL) and term (0.28 [0.10] ng/mL), as did fetal oxygen saturation (59.11% [4.74%] to 52.25% [4.84%]) and pH (7.35 [0.02] to 7.37 [0.02]). Moderate fetal hypoxia (50% fall in fetal arterial %O2) produced a significant increase in circulating activin A (2.05 [0.67] ng/mL) and a significant decrease in pH (7.27 [0.03]) at 125 days of gestation, however, at 135 and 145 days, activin A and pH remained unchanged. Fetal activin A concentration was significantly correlated with pH (P = 0.036) but not %O2 (P = 0.072). Hypoxia in the lambs did not alter circulating activin A. In response to hypoxia, activin A is increased in the circulation of 125-day-old fetuses, but not in older fetuses. Fetal arterial activin A levels sensitively reflect pH but not oxygen saturation, with increasing activin A in conditions of metabolic acidosis.
Publisher: CSIRO Publishing
Date: 1998
DOI: 10.1071/PY98053
Abstract: Down syndrome is the single most common cause of severe mental handicap in Australia. Prenatal screening for Down syndrome is therefore an important component of modern antenatal care. However, while effective second trimester serum screening for Down syndrome has been available in Australia for almost a decade it appears that the majority of Australian women, particularly those outside South Australia and New South Wales, are still not offered it. Newer methods of screening have been recently described and are already being offered in routine clinical practice. These methods, including nuchal translucency, will afford results earlier in pregnancy than second trimester serum screening and so are attractive to women. However, available evidence suggests that nuchal translucency may not perform as well as second trimester serum screening and further evaluation of the newer screening strategies in an Australian population is urgently required. Alteration of practice prior to such an evaluation is simply not warranted at this time.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.PREGHY.2016.09.001
Abstract: Hydroxychloroquine is an anti-malarial drug which, due to its anti-inflammatory and immunomodulatory effects, is widely used for the treatment of autoimmune diseases. In a model of systemic lupus erythematosus hydroxychloroquine has been shown to exert protective endothelial effects. In this study, we aimed to investigate whether hydroxychloroquine was endothelial protective in an in vitro model of TNF-α and preecl tic serum induced dysfunction. We showed that hydroxychloroquine significantly reduced the production of TNF-α and preecl tic serum induced endothelin-1 (ET-1). Hydroxychloroquine also significantly mitigated TNF-α induced impairment of angiogenesis. These findings support the further assessment of hydroxychloroquine as an adjuvant therapy in preecl sia.
Publisher: Elsevier BV
Date: 2011
Publisher: S. Karger AG
Date: 2012
DOI: 10.1159/000336378
Abstract: Pregnancies complicated by impaired placentation, acute severe reductions in oxygen supply to the fetus, or intrauterine infection are associated with oxidative stress to the mother and developing baby. Such oxidative stress is characterized as an upregulation in the production of oxidative or nitrative free radicals and a concomitant decrease in the availability of antioxidant species, thereby creating a state of fetoplacental oxidative imbalance. Recently, there has been a good deal of interest in the potential for the use of antioxidant therapies in the perinatal period to protect the fetus, particularly the developing brain, against oxidative stress in complications of pregnancy and birth. This review will examine why the immature brain is particularly susceptible to oxidative imbalance and will provide discussion on antioxidant treatments currently receiving attention in the adult and perinatal literature – allopurinol, melatonin, α-lipoic acid, and vitamins C and E. In addition, we aim to address the interaction between oxidative stress and the fetal inflammatory response, an interaction that may be vital when proposing antioxidant or other neuroprotective strategies.
Publisher: Oxford University Press (OUP)
Date: 2018
Publisher: Oxford University Press (OUP)
Date: 03-10-2011
DOI: 10.1093/IJE/DYR140
Publisher: Wiley
Date: 03-10-2019
DOI: 10.1111/AJO.13074
Abstract: Melatonin is a potent oxygen scavenger and is capable of altering blood flow in various vascular beds. We aimed to determine the effect of melatonin on ovarian vascular indices during ovarian stimulation for in vitro fertilisation (IVF). This is a pilot double-blind placebo-controlled randomised trial. Sixty-nine women (mean age 35.8 ± 4.3 years) undergoing their first cycle of IVF were randomised to receive either placebo, 2, 4 or 8 mg of melatonin, twice a day. Each participant underwent a transvaginal ultrasound at days 6-10 assessing follicular number and size. The vascularisation index (VI), flow index (FI) and vascularisation-flow index (VFI) were measured. These indices were then correlated with embryological outcomes. Informed consent was obtained from participants. This trial was registered with the Australia New Zealand Clinical Trials Registry (ACTRN12613001317785). The number of follicles did not differ between groups (P = 0.4). There were no differences in the VI (P = 0.4), FI (P = 0.1) or VFI (P = 0.3) in the right ovary or the FI (P = 0.3) or VFI (P = 0.3) in the left ovary between groups. When comparing placebo to any dose of melatonin, there were no differences in any measured parameter. While there was correlation between the number of follicles on ultrasound and all measured embryological outcomes, there was no correlation between ovarian vascular indices and these important clinical outcomes. Melatonin does not appear to change ovarian vascular indices during ovarian stimulation. In addition, such vascular indices cannot predict the number or quality of oocytes or embryos obtained in an IVF cycle. These findings require confirmation in future larger studies.
Publisher: Wiley
Date: 04-2006
DOI: 10.1111/J.1471-0528.2006.00869.X
Abstract: It has been shown previously that the absolute measurement of nuchal translucency (NT) thickness, one of the most effective screening tests for fetal Down syndrome, significantly decreases with increasing image size. We undertook a prospective study to assess whether this effect materially alters the NT-derived risk estimation for fetal Down syndrome. In 350 women, NT was measured at both 100 and 200% image sizes. The median NT measurement at 200% was 8% smaller than at 100%. The screen-positive rates at 100 and 200% image sizes were 5.1% (18/350) and 2.3% (8/350), respectively (P= 0.048). Altering the image magnification settings is likely to decrease the sensitivity of NT-derived Down syndrome risk estimation. Further study is required to test the effect of our finding on the sensitivity of NT screening and to assess whether adjustments in gain settings mitigate the effect.
Publisher: Wiley
Date: 05-2015
Publisher: Elsevier BV
Date: 2003
Abstract: Macrophage inhibitory cytokine-1 (MIC-1), a ergent member of transforming growth factor-beta superfamily, has been recently shown to be produced by the human placenta with detectable levels in maternal serum. In this study, using immunohistochemistry, we have localized MIC-1 in placenta, decidua and foetal membranes across pregnancy and, using an enzyme-linked immunoassay, measured MIC-1 in maternal serum in normal pregnancy, in association with labour and pre-ecl sia. In the placenta MIC-1 was principally localized to the syncytiotrophoblast while in the foetal membranes MIC-1 was present in the amniotic epithelium, chorionic trophoblasts and adherent decidual cells. There were no differences in MIC-1 staining distribution or intensity in the placentae between women in labour and not in labour, or between healthy and pre-ecl tic pregnancies. MIC-1 staining in the foetal membranes was slightly stronger after a labour and delivery compared to those delivered by elective Caesarean section. MIC-1 levels in the maternal serum increased with advancing gestation but there were no significant differences in maternal serum levels associated with either labour or pre-ecl sia.These observations would be consistent with MIC-1 having roles at the maternal-foetal interface, perhaps in the establishment and/or maintenance of pregnancy. Our data argue against MIC-1 having a significant role in the regulation of labour or in the pathophysiology of pre-ecl sia.
Publisher: Oxford University Press (OUP)
Date: 09-2007
DOI: 10.1095/BIOLREPROD.106.055244
Abstract: The amnion is the inner of two membranes surrounding the fetus. That it arises from embryonic epiblast cells prior to gastrulation suggests that it may retain a reservoir of stem cells throughout pregnancy. We found that human amniotic epithelial cells (hAECs) harvested from term-delivered fetal membranes express mRNA and proteins present in human embryonic stem cells (hESCs), including POU domain, class 5, transcription factor 1 Nanog homeobox SRY-box 2 and stage-specific embryonic antigen-4. In keeping with possible stem cell-like activity, hAECs were also clonogenic, and primary hAEC cultures could be induced to differentiate into cardiomyocytic, myocytic, osteocytic, adipocytic (mesodermal), pancreatic, hepatic (endodermal), neural, and astrocytic (neuroectodermal) cells in vitro, as defined by phenotypic, mRNA expression, immunocytochemical, and/or ultrastructural characteristics. However, unlike hESCs, hAECs did not form teratomas upon transplantation into severe combined immunodeficiency mice testes. Last, using flow cytometry we have shown that only a very small proportion of primary hAECs contain class IA and class II human leukocyte antigens (HLAs), consistent with a low risk of tissue rejection. However, following differentiation into hepatic and pancreatic lineages, significant proportions of cells contained class IA, but not class II, HLAs. These observations suggest that the term amnion, an abundant and easily accessible tissue, may be a useful source of multipotent stem cells that possess a degree of immune privilege.
Publisher: Wiley
Date: 28-06-2017
DOI: 10.1111/AJO.12660
Abstract: There is limited published information regarding intensive care unit (ICU) led rapid response team (RRT) calls to obstetric patients. We examined the characteristics of RRT calls to obstetric patients at a tertiary teaching hospital. Details of calls to pregnant and postpartum patients between October 2010 and June 2014 were obtained from the hospital RRT database. Each was retrospectively examined for data on patient demographics, call trigger, interventions and outcomes. Local obstetric-specific escalation practices (Code Pink/Green) for obstetrical concerns (not mandating maternal instability/involvement of the ICU team), were excluded. There were 106 RRT calls logged during 43 months, and 97 had data available for analysis. Women currently pregnant accounted for 33% of calls and postpartum women 67%, with nearly half of these occurring more than 24 h post-delivery. The most common reason (29% of calls) for calling the RRT was hypotension, followed by 'concern about patient' (21%) and decreased Glasgow Coma Score (GCS) (17%). An escalation in the environment of care occurred after 32% of calls, with approximately 11% of calls necessitating direct ICU admission. Twenty-three percent of all calls were to women who had an ICU admission during their hospital stay. Among the cohort who received an RRT call, there was one maternal and three neonatal deaths. At our institution generic RRT calls are called to both pregnant and postpartum women, and frequently result in an escalation in the care environment. Further study is required to understand better the specific needs of this important population.
Publisher: Frontiers Media SA
Date: 20-10-2014
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.SMRV.2015.04.001
Abstract: Intrauterine growth restriction (IUGR) complicates 5-10% of pregnancies and is associated with increased risk of preterm birth, mortality and neurodevelopmental delay. The development of sleep and cardiovascular control are closely coupled and IUGR is known to alter this development. In the long-term, IUGR is associated with altered sleep and an increased risk of hypertension in adulthood. Melatonin plays an important role in the sleep-wake cycle. Experimental animal studies have shown that melatonin therapy has neuroprotective and cardioprotective effects in the IUGR fetus. Consequently, clinical trials are currently underway to assess the short and long term effects of antenatal melatonin therapy in IUGR pregnancies. Given melatonin's role in sleep regulation, this hormone could affect the developing infants' sleep-wake cycle and cardiovascular function after birth. In this review, we will 1) examine the role of melatonin as a therapy for IUGR pregnancies and the potential implications on sleep and the cardiovascular system 2) examine the development of sleep-wake cycle in fetal and neonatal life 3) discuss the development of cardiovascular control during sleep 4) discuss the effect of IUGR on sleep and the cardiovascular system and 5) discuss the future implications of melatonin therapy in IUGR pregnancies.
Publisher: Elsevier BV
Date: 04-2004
Publisher: Elsevier BV
Date: 07-2004
Publisher: BMJ
Date: 12-2013
Publisher: Oxford University Press (OUP)
Date: 20-11-2018
DOI: 10.1093/SLEEP/ZSX193
Abstract: Fetal growth restriction (FGR) occurs in up to 10% of pregnancies and is associated with increased risk of prematurity and neurodevelopmental impairment. FGR also alters sleep-state distribution in utero and maturation in infancy. Currently, limited data on the long-term associations of FGR and childhood sleep exist. Accordingly, we assessed the associations between preterm birth and FGR and sleep in children aged 5-12 years. Seventeen children born preterm and FGR, 15 children born preterm but appropriately grown (appropriate birth weight for gestational age [AGA]), and 20 term AGA children (controls) were studied using overnight polysomnography. Sleep macroarchitecture was assessed using standard criteria, and sleep microarchitecture was assessed using spectral analysis of the electroencephalogram (C4-M1) with total, δ (0.5-3.9 Hz), θ (4.0-7.9Hz), α (8.0-11.9 Hz), σ (12.0-13.9 Hz), and β power (14.0-30 Hz) calculated. For sleep macroarchitecture, preterm FGR children had higher N2% compared with term AGA children (p < .05). Preterm AGA children had reduced total sleep time, NREM%, and sleep efficiency compared with term AGA children (p < .05 for all). For sleep microarchitecture, preterm FGR children had a higher amount of total, δ and α power compared with both groups (p < .05). Sigma and β power was lowest in the preterm AGA group compared with both groups (p < .05 for both). Prematurity and FGR were associated with altered sleep macro- and microarchitecture measures indicative of reduced sleep quantity and quality in childhood. As sleep disturbance can affect both behavior and neurodevelopment in children, sleep in FGR and preterm children warrants further investigation.
Publisher: Massachusetts Medical Society
Date: 21-12-2017
Publisher: Springer Science and Business Media LLC
Date: 07-04-2017
DOI: 10.1038/PR.2017.105
Abstract: BackgroundFetal growth restriction (FGR) is associated with increased perinatal mortality and long-term cardiovascular and neurodevelopmental sequelae. We hypothesized that FGR impacts on the development of autonomic heart rate and blood pressure control, contributing to unfavorable short- and long-term outcomes following FGR.MethodsWe studied 25 preterm FGR and 22 preterm and 19 term appropriate for gestational age (AGA) infants. Preterm neonates were studied on postnatal day 1, and all infants were studied at 1 and 6 months post-term age. To investigate autonomic cardiovascular control, we examined heart rate variability (HRV) and baroreflex sensitivity using spectral power and transfer-function analyses.ResultsPreterm FGR neonates exhibited higher heart rates and reduced HRV compared with preterm AGA controls on postnatal day 1. No significant differences were found between the three groups at 1 or 6 months post-term age.ConclusionPreterm FGR neonates display compromised HRV on postnatal day 1, which may suggest increased vulnerability to circulatory instability. This may predispose these neonates to systemic and cerebral hypoperfusion and increase the risk of long-term neurodevelopmental sequelae. Differences were no longer found at 1 and 6 months post-term age, suggesting that the maturation of autonomic cardiovascular control may be preserved following FGR.
Publisher: Bioscientifica
Date: 03-2007
DOI: 10.1677/JOE-06-0061
Abstract: Circulating levels of activin A are significantly increased in women with preecl sia when compared with those with a normal pregnancy. The mechanisms underlying these increased levels are unknown. We undertook these studies to explore whether oxidative stress might be the mechanism. We exposed trophoblast explants, human umbilical vein endothelial cells (HUVECs) and peripheral blood monocytes to oxidative stress in vitro using xanthine/xanthine oxidase (X/XO), measuring activin A and isoprostane in conditioned media and mRNA for activin β A in explants and HUVECs. We also measured isoprostane and activin A in serum from 21 women with preecl sia and from 20 women with a normal pregnancy. Treatment with X/XO significantly increased 8-isoprostane production from placental explants, HUVECs and monocytes, indicative of oxidative stress, and significantly increased activin A output from placental explants (139.1 ± 27.4 per mg wet weight vs 322.9 ± 89.7 pg/ml per mg wet weight, P = 0.02) and from HUVECs (1.2 ± 0.2 vs 3.2 ± 1.8 ng/ml, P = 0.04). There was no effect on activin A output from monocytes. X/XO significantly increased β A mRNA in placental explants but not in HUVECs. Maternal plasma levels of 8-isoprostane and activin A were significantly higher in women with preecl sia when compared with controls (333.8 ± 70 vs 176.3 ± 26.2 pg/ml, P = 0.04 and 49.5 ± 7 vs 13.1 ± 1.2 ng/ml, P 0.001 respectively). In the women with preecl sia, but not in those with a normal pregnancy, circulating levels of 8-isoprostane and activin A were significantly and positively correlated ( r 2 = 0.72 P 0.001). These data suggest that oxidative stress may be one of the mechanisms underlying increased circulating activin A in preecl sia.
Publisher: Wiley
Date: 11-1997
DOI: 10.1111/J.1471-0528.1997.TB10972.X
Abstract: Despite widespread recognition that prenatal administration of corticosteroids dramatically reduces perinatal mortality and morbidity, clinical practice in this area remains less than ideal. We therefore reviewed our practice to identify reasons for this and to determine attainable standards of care. Retrospective case record review. Level three maternity unit in Edinburgh, UK. All women admitted at gestations of 24 to 34 weeks and 6 days inclusive, and all women receiving corticosteroids in one institution, over a 10-month period. The number and clinical features of women delivering before and after 35 weeks of pregnancy who had received corticosteroids. Seven hundred and two women were admitted during the study period case records were available for 688 of these. One hundred and ninety-two women (28%) delivered before 35 weeks of gestation, of whom 123 (64%) had received dexamethasone. Of 69 women who received no steroids 30 (43%) were in hospital for more than 24 hours before delivery. Overall, 29% of women receiving dexamethasone delivered after 35 weeks of gestation and 42 (24%) women treated with dexamethasone received more than one course. While the grade of admitting doctor did not affect prescribing, there were other significant differences that may help guide future practice. This study provides some guidance for optimising corticosteroid prescribing and for the development of clinical practice guidelines. Approximately 80% of women should be able to receive at least some corticosteroids prior to delivery before 35 completed weeks of pregnancy.
Publisher: Wiley
Date: 04-1995
Publisher: Wiley
Date: 03-1996
DOI: 10.3109/00016349609047089
Abstract: To compare the pharmacokinetics of orally administered dexamethasone with intramuscular administration in antenatal patients at risk of preterm delivery. Ten antenatal patients at risk for preterm delivery were given two intramuscular and then one oral dose of dexamethasone. Plasma which was collected at set intervals following the first intramuscular dose and the oral dose was assayed for dexamenthasone. The results were analyzed using pharmacokinetic data-fitting software and pharMacokinetic parameters calculated. After oral adminIstration of dexamethasone the mean maximum plasma concentration obtained was 65% that of the intramuscular dose and the bioavailability of the oral route was calculated as 72% of the intramuscular route. The terminal half-lives of dexamethasone were similar for both routes. These limited data would suggest that if dexamethasone is to be administered orally, which would be both preferable to patients and more economic, then a proportionately increased dose of oral dexamethasone would be required to provide similar maternal plasma pharmacokinetics to the intramuscular dose in current use. Further, larger studies are now required to confirm this.
Publisher: BMJ
Date: 11-11-2015
DOI: 10.1136/ARCHDISCHILD-2014-307144
Abstract: Delayed umbilical cord cl ing (DCC) affects the cardiopulmonary transition and blood volume in neonates immediately after birth. However, little is known of blood flow in the umbilical vessels immediately after birth during DCC. The objective is to describe the duration and patterns of blood flow through the umbilical vessels during DCC. Arterial and venous umbilical blood flow was measured during DCC using Doppler ultrasound in uncomplicated term vaginal deliveries. Immediately after birth, the probe was placed in the middle of the umbilical cord, pattern and duration of flow in vein and arteries were evaluated until cord cl ing. Thirty infants were studied. Venous flow: In 10% no flow was present, in 57% flow stopped at 4:34 (3:03-7:31) (median (IQR) min:sec) after birth, before the cord was cl ed. In 33%, flow continued until cord cl ing at 5:13 (2:56-9:15) min:sec. Initially, venous flow was intermittent, increasing markedly during large breaths or stopping and reversing during crying, but then became continuous. Arterial flow: In 17% no flow was present, in 40% flow stopped at 4:22 (2:29-7:17) min:sec, while cord pulsations were still palpable. In 43% flow continued until the cord was cl ed at 5:16 (3:32-10:10) min:sec. Arterial flow was pulsatile, unidirectional towards placenta or bidirectional to/from placenta. In 40% flow became continuous towards placenta later on. During delayed umbilical cord cl ing, venous and arterial umbilical flow occurs for longer than previously described. Net placental transfusion is probably the result of several factors of which breathing could play a major role. Umbilical flow is unrelated to cessation of pulsations.
Publisher: Elsevier BV
Date: 07-2001
Publisher: Elsevier BV
Date: 08-2011
DOI: 10.1016/J.AJOG.2011.03.054
Abstract: The purpose of this study was to determine whether human amnion epithelial cells (hAECs) can modulate the pulmonary developmental consequences of intrauterine inflammation in fetal sheep that are exposed to intraamniotic lipopolysaccharide (LPS) injection. At 117 days' gestation, fetal sheep (n=16) received intraamniotic LPS (20 mg). hAECs were delivered at 0, 6, and 12 hours into the fetal jugular vein (n=4), trachea (n=4), or both (n=4). Controls (n=6) received equivalent administration of saline solution. Lungs were collected at 124 days. Intraamniotic LPS caused pulmonary inflammation and altered lung structure and function. hAECs attenuated changes in lung function and structure that had been induced by LPS: lung volume, 40 cm H2O (P<.05, intravenous+intratracheal hAECs vs LPS), tissue-to-airspace ratio (P<.05, intravenous+intratracheal hAECs vs LPS), and septal crest density (P<.001, all hAEC groups vs LPS). Leukocyte infiltration of the lungs was not reduced by hAECs however, inflammatory cytokines were reduced (tumor necrosis factor-α, P<.01, vs LPS interleukin-1b, P<.01, vs LPS interleukin-6, P .05 vs control) there were significant increases in all hAEC-treated animals (surfactant protein-A, P<.05 vs LPS surfactant protein-C, P<.01 vs LPS). Human amnion epithelial cells attenuate the fetal pulmonary inflammatory response to experimental intrauterine inflammation and reduce, but (as administered in our study) do not prevent, consequent alterations in lung development.
Publisher: BMJ
Date: 08-11-2016
Publisher: Wiley
Date: 03-1997
DOI: 10.1111/J.1471-0528.1997.TB11470.X
Abstract: To determine the relation between maternal serum inhibin-A and free beta-hCG concentrations in chromosomally normal pregnancies and to compare the two biochemical markers for their sensitivity in identifying trisomy 21 pregnancies. Inhibin-A and free beta-hCG were measured in maternal serum s les from 800 chromosomally normal singleton pregnancies at 10 to 14 weeks of gestation and 76 singleton pregnancies with fetal trisomy 21. In the normal group maternal serum inhibin-A was significantly associated with both maternal weight and gestational age (F = 11.2, P < 0.0001). In pregnancies with trisomy 21 the maternal serum inhibin-A and free beta-hCG concentrations were significantly increased (mean difference inhibin = 0.51 SD, F = 18, P < 0.0001 and mean difference free beta-hCG = 1.13 SD, F = 80, P < 0.0001). For a 5% false positive rate, the sensitivity of maternal serum free beta-hCG in identifying pregnancies with trisomy 21 was 28.9% compared with 12.8% for maternal serum inhibin-A. Delta inhibin-A was significantly associated with delta-free beta-hCG (r = 0.345, P < 0.01) and the deviation from the normal mean for free beta-hCG was significantly greater than the deviation for inhibin-A (t = 4.0, P < 0.0001). For a 5% false positive rate, the sensitivity achieved by combining information from delta inhibin-A and delta free beta-hCG was similar to the sensitivity of free beta-hCG alone (30.3% compared with 28.9%). At 10 to 14 weeks of gestation fetal trisomy 21 is associated with increased maternal serum inhibin-A and free beta-hCG levels. However, the degree of elevation of inhibin-A is less than that of free beta-hCG, and there is a significant association between levels of the two proteins. The sensitivity for trisomy 21 achieved with the combination of maternal serum inhibin-A and free beta-hCG is not significantly different from that achieved with maternal serum free beta-hCG alone.
Publisher: Wiley
Date: 04-1995
Abstract: While second-trimester prenatal screening programmes for Down's syndrome have become established in prenatal care, it would be advantageous to be able to offer screening in earlier pregnancy. To this end, we have evaluated a new potential maternal serum marker, dimeric inhibin A, as a possible first-trimester marker. Dimeric inhibin A was measured in prospectively collected maternal serum from 23 cases of Down's syndrome and matched chromosomally normal controls, at 11-13 weeks' gestation. Levels of this protein were significantly elevated in the Down's pregnancies compared with the control pregnancies. The median multiple of the normal median (MOM) for the Down's s les was 2.46 (95 per cent confidence interval: 2.11-3.26, P < 0.0001 vs. controls). These results suggest that dimeric inhibin A is a useful discriminator of Down's-affected pregnancies from normal pregnancies in the first trimester and that sensitive screening in combination with maternal age and other possible markers may be practicable in the first trimester.
Publisher: Elsevier BV
Date: 09-2006
DOI: 10.1016/J.PLACENTA.2005.10.011
Abstract: Copper is an essential trace element necessary for normal growth and development. During pregnancy, copper is transported from the maternal circulation to the fetus by mechanisms which have not been clearly elucidated. The copper uptake protein, hCTR1 is predicted to play a role in copper transport in human placental cells. This study has examined the expression and localisation of hCTR1 in human placental tissue and Jeg-3 cells. In term placental tissue the hCTR1 protein was detected as a 105 kDa protein, consistent with the size of a trimer which may represent the functional protein. A 95 kDa band, possibly representing the glycosylated protein, was also detected. hCTR1 was localised within the syncytiotrophoblast layer and the fetal vascular endothelial cells in the placental villi and interestingly was found to be localised toward the basal plasma membrane. It did not co-localise with either the Menkes or the Wilson copper transporting ATPases. Using the placental cell line Jeg-3, it was shown that the 35 kDa monomer was absent in the extracts of cells exposed to insulin, estrogen or progesterone and in cells treated with estrogen an additional 65 kDa band was detected which may correspond to a dimeric form of the protein. The 95 kDa band was not detected in the cultured cells. These results provide novel insights indicating that hormones have a role in the formation of the active hCTR1 protein. Furthermore, insulin altered the intracellular localisation of hCTR1, suggesting a previously undescribed role of this hormone in regulating copper uptake through the endocytic pathway.
Publisher: BMJ
Date: 02-2018
DOI: 10.1136/BMJOPEN-2017-017451
Abstract: The aim of this study was to evaluate the implementation of the Practical Obstetric Multi-Professional Training (PROMPT) simulation using the Kirkpatrick’s framework. We explored participants’ acquisition of knowledge and skills, its impact on clinical outcomes and organisational change to integrate the PROMPT programme as a credentialing tool. We also aimed to assess participants’ perception of usefulness of PROMPT in their clinical practice. Mixed methods approach with a pre-test ost-test design. Healthcare network providing obstetric care in Victoria, Australia. Medical and midwifery staff attending PROMPT between 2013 and 2015 (n=508) clinical outcomes were evaluated in two cohorts: 2011–2012 (n=15 361 births) and 2014–2015 (n=12 388 births). Attendance of the PROMPT programme, a simulation programme taught in multidisciplinary teams to facilitate teaching emergency obstetric skills. Clinical outcomes compared before and after embedding PROMPT in educational practice. Assessment of knowledge gained by participants through a qualitative analysis and description of process of embedding PROMPT in educational practice. There was a change in the management of postpartum haemorrhage by early recognition and intervention. The key learning themes described by participants were being prepared with a prior understanding of procedures and equipment, communication, leadership and learning in a safe, supportive environment. Participants reported a positive learning experience and increase in confidence in managing emergency obstetric situations through the PROMPT programme, which was perceived as a realistic demonstration of the emergencies. Participants reported an improvement of both clinical and non-technical skills highlighting principles of teamwork, communication, leadership and prioritisation in an emergency situation. An improvement was observed in management of postpartum haemorrhage, but no significant change was noted in clinical outcomes over a 2-year period after PROMPT. However, the skills acquired by medical and midwifery staff justify embedding PROMPT in educational programmes.
Publisher: Elsevier BV
Date: 12-2015
Publisher: Elsevier BV
Date: 2003
Abstract: In a retrospective cohort study we have previously shown that administration of betamethasone to women with a pregnancy complicated by absent end-diastolic flow in the umbilical artery (UA) is associated with altered UA flow velocity waveforms. To examine this phenomenon further we undertook a prospective study of 30 similar singleton pregnancies. Umbilical artery FVWs were recorded before and after betamethasone administration using real-time pulsed wave colour flow Doppler. The results of this prospective cohort were similar to those of the retrospective study allowing pooling of the data. Of the 55 total pregnancies with umbilical artery AEDF studied betamethasone administration was associated with the return of end-diastolic flow in 39 (71 per cent 95 per centCI: 59-83 per cent). The median (range) duration of this change was 3 (1-10) days. There is no evidence that this change has either a beneficial or detrimental effect on foetal health. Administration of betamethasone to women with a pregnancy complicated by umbilical artery AEDF is associated with the transient return of end-diastolic flow in most cases. While the mechanisms underlying this effect are yet to be fully elucidated it has implications for foetal surveillance in these high-risk pregnancies.
Publisher: BMJ
Date: 08-2015
Publisher: Springer Science and Business Media LLC
Date: 05-01-2017
Publisher: Elsevier BV
Date: 2003
Abstract: Placental activin A and inhibin A output is increased in pre-ecl sia, a condition characterized by placental hypoxaemia, whereas follistatin secretion is unaltered. We investigated whether hypoxia was the basis for elevated placental activin A and inhibin A output. First trimester and term placental explants were grown in 5-6% dissolved O(2) (n=10/trimester) and 200 microM cobalt chloride (CoCl(2),n =6/trimester) to simulate environmental and cellular hypoxia respectively, for up to 72 h. Activin A, inhibin A and follistatin production were compared with control cultures grown in standard media at 20% O(2). In first trimester and term placenta, activin A output declined significantly under 5-6% O(2) (P=0.006 and 0.001 after 48 h respectively). Inhibin A declined significantly under 5-6% O(2), mainly in first trimester placenta (P=0.03, 24h). CoCl(2) significantly elevated activin A production in term placenta (P=0.003, 48 h), whereas inhibin A output was unaffected. Neither low O(2) or CoCl(2) altered follistatin output from first trimester or term placenta. These findings suggest that there may be novel O(2) sensing mechanism/s that down regulate activin A and inhibin A in the placenta and that low O(2) is not the mechanism behind increased placental inhibin A or activin A output in pre-ecl sia.
Publisher: Springer Science and Business Media LLC
Date: 10-11-2017
Publisher: CSIRO Publishing
Date: 2004
DOI: 10.1071/RD03110
Abstract: The aim of the present study was to determine whether activin A concentrations are dependent on feto–placental oxygen availability and to investigate the temporal relationship of activin A with prostaglandin (PG) E2 and cortisol. Nine fetal sheep (six hypoxic and three control) were instrumented and catheterised at 0.8 gestation. Reduced uterine blood flow was used to achieve three levels of hypoxia (mild = fetal SaO2 40–50% moderate = fetal SaO2 30–40% severe = fetal SaO2 20–30%), for 4 h on 3 consecutive days. Activin A, PGE2 and cortisol levels were determined in maternal and fetal blood and amniotic fluid. Moderate and severe hypoxia produced a significant (P 0.05) increase in fetal plasma activin A concentrations. The amniotic fluid activin A concentrations were 15-fold higher than those in the fetal circulation, but were unchanged by hypoxia. The fetal PGE2 response reflected the degree of hypoxia over the 3 days, with moderate and severe hypoxia producing a significant (P 0.05) increase in PGE2 concentrations. Fetal plasma cortisol concentrations were increased (P 0.05) during all levels of hypoxia. Fetal arterial activin A was increased in response to moderate and severe hypoxia, but levels were not maintained over the hypoxic period. The increases in activin A and cortisol concentrations preceded the increase in PGE2.
Publisher: Bioscientifica
Date: 1997
Abstract: Recently, inhibin-A has been shown to be a useful new prenatal marker of Down's syndrome, significantly increasing detection rates. While the placenta is believed to be the major source of inhibin in pregnancy, there are actually very limited data available on specific inhibin dimers in pregnancy. Using a sensitive and specific ELISA we have measured the inhibin-A content of amniotic fluid (AF) to investigate further the biology of inhibin-A in chromosomally normal and abnormal pregnancies. AF from 51 Down's syndrome and 161 chromosomally normal pregnancies between 16 and 19 weeks of gestation were analysed, blinded as to whether the s le was from a Down's syndrome or normal pregnancy. There were no sex differences in inhibin-A content in either the control or Down's syndrome pregnancies. The median (10th–90th percentiles) inhibin-A level in the control pregnancies increased from 339·6 (175·2–649·1) pg/ml at 16 weeks to 592·9 (256·4–1027·3) pg/ml at 19 weeks of gestation. The median (95% confidence interval) inhibin-A in the Down's syndrome pregnancies, expressed as multiples of the median (MoM) to correct for gestation, was 0·77 (0·68–0·89) MoM, significantly lower than the controls ( P ·001, Mann–Whitney U test). We believe that these data are compatible with more than one source of inhibin-A in pregnancy and suggest that the fetal membranes may be contributing significantly to AF inhibin-A content. Further, our data would suggest that the endocrine function of the placenta and the other inhibin source(s) are differentially regulated. Journal of Endocrinology (1997) 152, 109–112
Publisher: Frontiers Media SA
Date: 06-11-2017
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.JCYT.2013.03.004
Abstract: Human amnion epithelial cells (hAECs) prevent pulmonary inflammation and injury in fetal sheep exposed to intrauterine lipopolysaccharide. We hypothesized that hAECs would similarly mitigate hyperoxia-induced neonatal lung injury. Newborn mouse pups were randomized to either normoxia (inspired O2 content (FiO2) = 0.21, n = 60) or hyperoxia (FiO2 = 0.85, n = 57). On postnatal days (PND) 5, 6 and 7, hAECs or sterile saline (control) was administered intraperitoneally. All animals were assessed at PND 14. Hyperoxia was associated with lung inflammation, alveolar simplification and reduced postnatal growth. Administration of hAECs to hyperoxia-exposed mice normalized body weight and significantly attenuated some aspects of hyperoxia-induced lung injury (mean linear intercept and septal crest density) and inflammation (interleukin-1α, interleukin-6, transforming growth factor-β and platelet-derived growth factor-β). However, hAECs did not significantly alter changes to alveolar airspace volume, septal tissue volume, tissue-to-airspace ratio, collagen content or leukocyte infiltration induced by hyperoxia. Intraperitoneal administration of hAECs to neonatal mice partially reduced hyperoxia-induced lung inflammation and structural lung damage. These observations suggest that hAECs may be a potential therapy for neonatal lung disease.
Publisher: Wiley
Date: 08-03-2007
Publisher: Wiley
Date: 28-06-2018
DOI: 10.1111/AJO.12659
Abstract: Simulation-based programs are increasingly being used to teach obstetrics and gynaecology examinations, but it is difficult to establish student learning acquired through them. Assessment may test student learning but its role in learning itself is rarely recognised. We undertook this study to assess medical and midwifery student learning through a simulation program using a pre-test and post-test design and also to evaluate use of assessment as a method of learning. The interprofessional simulation education program consisted of a brief pre-reading document, a lecture, a video demonstration and a hands-on workshop. Over a 24-month period, 405 medical and 104 midwifery students participated in the study and were assessed before and after the program. Numerical data were analysed using paired t-test and one-way analysis of variance. Students' perceptions of the role of assessment in learning were qualitatively analysed. The post-test scores were significantly higher than the pre-test (P < 0.001) with improvements in scores in both medical and midwifery groups. Students described the benefit of assessment on learning in preparation of the assessment, reinforcement of learning occurring during assessment and reflection on performance cementing previous learning as a post-assessment effect. Both medical and midwifery students demonstrated a significant improvement in their test scores and for most students the examination process itself was a positive learning experience.
Publisher: Wiley
Date: 2003
DOI: 10.1002/PD.701
Abstract: To assess whether women have a preference for Down syndrome screening test performance. A structured questionnaire exploring women's preferences for screening test performance was administered to women attending their first prenatal visit who wished to have Down syndrome screening performed. One hundred and twenty women were interviewed. The majority of women (n=80) chose a screening test with a low screen-positive rate rather than the highest detection rate. The reasons given for this preference were a desire to minimise the risk of miscarriage of a normal baby and a belief that a detection rate of 80 to 90% was acceptable. However, older women (>37 years) chose a test with the highest detection rate possible, regardless of the higher screen-positive rate, preferring to miscarry a normal baby as a result of a diagnostic test rather than miss the detection of a baby with Down syndrome. Preferences were not influenced by previous screening experience. Women express different preferences for screening test performance. Maternal age rather than previous screening experiences appears to be the major influence in these choices.
Publisher: Wiley
Date: 02-2010
Publisher: American Physiological Society
Date: 11-2017
DOI: 10.1152/JAPPLPHYSIOL.00783.2016
Abstract: Oxidative stress arising from suboptimal placental function contributes to a multitude of pathologies in infants compromised by fetal growth restriction (FGR). FGR infants are at high risk for respiratory dysfunction after birth and poor long-term lung function. Our objective was to investigate the contribution of oxidative stress to adverse lung development and the effects of melatonin administration, a powerful antioxidant, on lung structure in FGR lambs. Placental insufficiency and FGR was surgically induced in 13 fetal sheep at ∼105 days of gestation by ligation of a single umbilical artery. Maternal intravenous melatonin infusion was commenced in seven of the ewes 4 h after surgery and continued until birth. Lambs delivered normally at term and lungs were collected 24 h after birth for histological assessment of lung structure and injury and compared with appropriately grown control lambs ( n = 8). FGR fetuses were hypoxic and had lower glucose during gestation compared with controls. Melatonin administration prevented chronic hypoxia. Within the lung, FGR caused reduced secondary septal crest density and altered elastin deposition compared with controls. Melatonin administration had no effect on the changes to lung structure induced by FGR. We conclude that chronic FGR disrupts septation of the developing alveoli, which is not altered by melatonin administration. These findings suggest that oxidative stress is not the mechanism driving altered lung structure in FGR neonates. Melatonin administration did not prevent disrupted airway development but also had no apparent adverse effects on fetal lung development. NEW & NOTEWORTHY Fetal growth restriction (FGR) results in poor respiratory outcomes, which may be caused by oxidation in utero. We investigated the contribution of oxidative stress to adverse lung development and the effects of melatonin administration, a powerful antioxidant, on lung structure in FGR lambs. FGR disrupted septation of the developing alveoli, which is not altered by melatonin administration. Oxidative stress may not be the mechanism driving altered lung structure in FGR neonates.
Publisher: Springer Science and Business Media LLC
Date: 28-02-2017
Publisher: Wiley
Date: 11-2000
DOI: 10.1111/J.1479-828X.2000.TB01173.X
Abstract: A s le of 6,038 obstetric ultrasound referrals and reports between January 1993 and June 1999 in a single Melbourne private ultrasound practice was reviewed to determine whether the referral and reporting pattern for nuchal translucency (NT) measurement has changed. The proportion of both 10-14 week ultrasound scans and mid trimester fetal anatomy scan referrals increased significantly over the study period (p < 0.001 and p < 0.001, respectively). There was also a significant increase in NT reporting and the number of specific referrals for an NT measurement over the study period (p = 0.01 and p < 0.001, respectively). If current trends continue it is likely that the 10-14 week scan for NT measurement will become a routine component of antenatal care. Therefore, as a matter of urgency, it is imperative that the best and most cost-effective screening strategy for Down syndrome in an Australian population is defined.
Publisher: Wiley
Date: 1996
DOI: 10.1046/J.1365-2265.1996.544368.X
Abstract: Prenatal maternal serum screening for Down's syndrome has become an important and established part of modern antenatal care. Previously it has been reported that non-specific immunoreactive inhibin may be useful in this context. Using a novel assay we have evaluated dimeric inhibin A as a possible second trimester marker of Down's syndrome. From 1992-1993 records, stored sera from women with Down's affected pregnancies and chromosomally normal control pregnancies were identified and retrieved for analysis. These sera had been prospectively collected at 15, 16 and 17 weeks gestation. Records revealed 21 women who had had a Down's syndrome pregnancy and who also had serum available for analysis. Sera from 150 chromosomally normal controls, matched for gestation and duration of storage, were also retrieved. Dimeric inhibin A was measured using a recently developed two-site enzyme-linked immunoassay. This employs a capture anti inhibin beta A-subunit monoclonal antibody, covalently bound to a microtitre plate and a second anti inhibin alpha-subunit antibody conjugated to alkaline phosphatase, allowing detection. The mean (95% CI) maternal serum dimeric inhibin A in the s les from control pregnancies was 237 (201.5-273.4) ng/l, 266.9 (235.4-298.5) ng/l and 207.2 (178.5-235.9) ng/l at 15, 16 and 17 weeks gestation respectively. Expressing the results from the Down's s les as multiples of the normal median (MoM), the median (95% CI) MoM was 2.6 (2.25-3.57), significantly higher than the controls (P < 0.0001, Mann-Whitney U-test). In the s le set tested, for a given false positive rate of 5.3% inhibin A alone afforded a detection rate of 62%, detecting cases previously undetected by routine screening. Dimeric inhibin A appears to be a promising new marker for the prenatal detection of Down's syndrome. Further prospective evaluation and assessment with other established markers would now be merited.
Publisher: Elsevier BV
Date: 11-2010
DOI: 10.1016/J.PLACENTA.2010.09.002
Abstract: Catabolism of tryptophan via the kynurenine pathway is up-regulated in the human placenta by infection, resulting in the release of pro-inflammatory and neuroactive metabolites into the fetal circulation. In this study we determined if activation of NFκB is involved in the inflammation-induced increase of kynurenine pathway activity in the human placenta. Placentae obtained after elective caesarian section at 37-40 weeks gestation (n=8), and explants (35-40 mg) prepared from terminal villi were incubated under standard conditions in the presence of 10 μg/ml LPS for 24 or 48 h duplicates of each explant were incubated either with or without 5mM sulfasalazine added to the medium. Expression of mRNAs for key kynurenine-forming enzymes, indoleamine 2,3-dioxygrenase (IDO) and tryptophan 2,3-doalxygenase (TDO) and the inflammatory cytokines TNFα and IL6 was studied by RT-PCR. Kynurenine output by explants was measured in s les in the incubation medium by absorbance at 363nm after separation from other metabolites using an HPLC technique. Expression of IDO, TDO, TNFα and IL6 mRNAs was increased with LPS treatment, a response mitigated by the presence of sulfasalazine (P<0.01, P<0.01, P=0.03 &P=0.04). Kynurenine output into the culture medium increased with LPS treatment but this was also prevented by sulfasalazine at 24h (mean ± SEM 412.1 ± 40 vs. 147.7 ± 48.9 nM/mg, P=0.01) and 48 h (636 ± 39.1 vs. 135.5 ± 29.8 nM/mg, P=0.001, respectively). Sulfasalazine inhibited the LPS induction of both the kynurenine pathway and pro-inflammatory cytokines in the placenta, implicating NFκB in the LPS effect. Direct measurement of NFκB activity showed that sulfasalazine decreased NFκB activation under both control and LPS-treated conditions. These observations show that kynurenine pathway activity in the human placenta is increased by a NFκB dependent pathway, and suggests a new therapeutic strategy for the management of pregnancies with in utero infection.
Publisher: Springer New York
Date: 02-12-2017
DOI: 10.1007/978-1-4939-7498-6_26
Abstract: Radiotelemetry is increasingly being recognized not just as the gold standard but a necessity for validation of gestational hypertension seen in preecl sia. Here we describe radiotelemetry probe implantation into the descending aorta of Sprague-Dawley rats to allow real-time blood pressure recording over the entire gestational period. This is a valuable tool to be able to track changes in maternal blood pressure throughout gestation and the efficacy of novel therapeutic agents in controlling hypertension.
Publisher: Wiley
Date: 16-12-2011
DOI: 10.1111/J.1600-0412.2011.01300.X
Abstract: Subgaleal hemorrhage in the newborn is a serious adverse event that is often unrecognized and under-appreciated. This retrospective case series aimed to determine perinatal factors associated with subgaleal hemorrhage and subsequent neonatal outcomes. Obstetric and neonatal details of 21 infants with subgaleal hemorrhage over a 10-year period were collected. The mother was primiparous in 95% cases, 48% had a prolonged second stage (>120 minutes) and 43% had prolonged rupture of membranes (>12 hours). Thirteen infants (62%) were born by instrumental vaginal delivery. Ten infants (48%) required resuscitation at delivery. The severity of subgaleal hemorrhage was mild in four infants (19%), moderate in 10 (48%) and severe in seven (33%). Hypovolemic shock developed in 10 infants (48%), encephalopathy in 13 (62%) and coagulopathy was present in five infants (24%). There were three (14%) deaths. Long-term outcomes were good in the surviving infants.
Publisher: Springer New York
Date: 02-12-2018
DOI: 10.1007/978-1-4939-7498-6_27
Abstract: This chapter describes the methodologies which may be used in the development of a phase I clinical trial investigating a therapy of choice in treating preecl sia.
Publisher: Elsevier BV
Date: 06-2013
DOI: 10.1016/J.PLACENTA.2013.03.010
Abstract: The collection and use of stem cells from the fetal membranes as cell therapy for a variety of lung diseases, including preterm lung disease, have been previously proposed. To date, only cells from term amnion have been assessed. In the setting of a future therapy for the preterm neonate, it would be ideal if autologous cells could be given. However, the reparative and anti-inflammatory actions of stem cells isolated from preterm amnions have not been evaluated. In this study, with a view to developing an autologous cell therapy for preterm lung injury, we compared the differentiation potential and efficacy of term versus preterm human amnion epithelial cells (hAECs) to protect against inflammation and fibrosis in a bleomycin mouse model of lung injury. We found that, unlike term hAECs, preterm hAECs did not differentiate into a lung lineage following culture in small airway growth media. Preterm hAECs also exerted significantly less protective effects than term hAEC following acute lung injury. Specifically, preterm hAEC did not improve Ashcroft scoring or collagen deposition in the lung despite a reduction in activated myofibroblasts. Term hAECs expressed double the levels of HLA-G compared to preterm hAECs. These findings indicate that while hAECs can be isolated from term and preterm amnions in similar numbers, they bear distinctive characteristics, which may impact upon their clinical use.
Publisher: Springer New York
Date: 21-09-2018
DOI: 10.1007/978-1-4939-7498-6_28
Abstract: This chapter describes the methodologies which may be used in the development of a randomized controlled trial investigating a therapy of choice in preventing preecl sia.
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.AJOG.2014.07.021
Abstract: Clinical management of preecl sia has remained unchanged for almost 5 decades. We now understand that maternal endothelial dysfunction likely arises because of placenta-derived vasoactive factors. Activin A is one such antiangiogenic factor that is released by the placenta and that is elevated in maternal serum in women with preecl sia. Whether activin has a role in the pathogenesis of preecl sia is not known. To assess the effects of activin on endothelial cell function, we cultured human umbilical vein endothelial cells in the presence of activin or serum from normal pregnant women or pregnant women with preecl sia, with or without follistatin, a functional activin antagonist or apocynin, a NADPH oxidase (Nox2) inhibitor. We also administered activin to pregnant C57Bl6 mice, with or without apocynin, and studied maternal and fetal outcomes. Last, we assessed endothelial cell Nox2 and nitric oxide synthase expression in normal pregnant women and pregnant women with preecl sia. Activin and preecl tic serum induced endothelial cell oxidative stress by Nox2 up-regulation and endothelial cell dysfunction, which are effects that are mitigated by either follistatin or apocynin. The administration of activin to pregnant mice induced endothelial oxidative stress, hypertension, proteinuria, fetal growth restriction, and preterm littering. Apocynin prevented all of these effects. Compared with normal pregnant women, women with preecl sia had increased endothelial Nox2 expression. An activin-Nox2 pathway is a likely link between an injured placenta, endothelial dysfunction, and preecl sia. This offers opportunities that are not novel therapeutic approaches to preecl sia.
Publisher: Informa UK Limited
Date: 02-10-2021
Publisher: Wiley
Date: 02-2011
Publisher: Oxford University Press (OUP)
Date: 12-1996
DOI: 10.1093/OXFORDJOURNALS.HUMREP.A019208
Abstract: Inhibins are present in maternal serum during pregnancy. However, the presence of inhibins in the compartments surrounding the fetus in early pregnancy is not well defined. Using novel specific enzyme-linked immunosorbent assays we have demonstrated that the bioactive dimeric inhibin forms, inhibin-A and inhibin-B, and the immunoreactive inhibin forms containing pro- and alpha C sequences are present in different amounts in the extra-embryonic coelomic and amniotic fluids and maternal serum between 8-11 weeks gestation. Of the bioactive dimeric inhibins, both inhibin. A (mean +/- SEM 236.0 +/- 24.8 pg/ml) and inhibin-B (62.0 +/- 8.6 pg/ml) are present in extra-embryonic coelom whereas no dimeric inhibin is present in the amniotic fluid and only inhibin-A (360.2 +/- 32.9 pg/ml) is present in maternal serum. Furthermore, pro-alpha C-related immunoreactivity is present at high concentrations in the extra-embryonic coelom (591.7 +/- 60.5 pg/ml), amniotic fluid (452.4 +/- 76.8 pg/ml) and maternal serum (539.4 +/- 39.5 pg/ml). These findings would indicate that at this stage of gestation inhibin-A, inhibin-B and immunoreactive pro- alpha C-containing inhibin production are likely to arise from different sources including the fetus, placenta and fetal membranes and maternal sources including the ovary. Inhibins may be important regulators of fetal and placental development and involved in the establishment of pregnancy.
Publisher: Wiley
Date: 13-07-2005
DOI: 10.1111/J.0001-6349.2005.00798.X
Abstract: The aim of this study is to review the clinical usefulness of Doppler velocimetry of the uterine artery for the detection of adverse obstetric outcome in a population of women with elevated mid-trimester serum beta-human chorionic gonadotrophin (betahCG). Women with an unexplained elevated mid-trimester betahCG level (> or = 4.0 multiples of the median) are offered uterine artery Doppler assessment at 22-24 weeks of gestation. We have audited the clinical usefulness of this practice by reviewing the prevalence of the adverse outcomes of gestational hypertension, intrauterine growth restriction (IUGR) and preterm birth and the predictive capacity of the test when applied to this subgroup of high-risk patients. Sixty-two women had an elevated serum betahCG and underwent Doppler study of uterine artery flow velocity waveform. Notching afforded better predictive utility for any outcome than the resistance index alone or in combination with notching. For a composite adverse outcome of any or all of gestational hypertension, birthweight < or = 10th centile, and preterm delivery, the presence of a uterine notch alone had sensitivity of 30.7% and specificity of 93.8%. For the identification of severe fetal growth restriction (< 5th centile) and/or preecl sia, the presence of a notch offered a sensitivity of 50%, specificity of 96.3%, a positive likelihood ratio of 13.5, and a negative likelihood ratio of 0.5. The identification of uterine artery notching by means of Doppler ultrasound as a component of the surveillance of women with unexplained elevated betahCG levels significantly improves the prediction of preecl sia and/or severe IUGR, although the low prevalence of 13% of these adverse outcomes limits the usefulness of the test in routine clinical practice.
Publisher: BMJ
Date: 08-01-2021
DOI: 10.1136/BMJQS-2019-010141
Abstract: To determine whether sharing of routinely collected health service performance data could have predicted a critical safety failure at an Australian maternity service. Observational quantitative descriptive study. A public hospital maternity service in Victoria, Australia. A public health service the Victorian state health quality and safety office-Safer Care Victoria the Health Complaints Commission Victorian Managed Insurance Authority Consultative Council on Obstetric and Paediatric Mortality and Morbidity Paediatric Infant Perinatal Emergency Retrieval Australian Health Practitioner Regulation Agency. Numbers and rates for events (activity, deaths, complaints, litigation, practitioner notifications). Correlation coefficients. Between 2000 and 2014 annual birth numbers at the index hospital more than doubled with no change in bed capacity, to be significantly busier than similar services as determined using an independent s les t-test (p<0.001). There were 36 newborn deaths, 11 of which were considered avoidable. Pearson correlations revealed a weak but significant relationship between number of births per birth suite room birth and perinatal mortality ( While clinical activity data and direct-to-service patient complaints appear to offer promise as potential predictors of health service stress, complaints to regulators and medicolegal activity are less promising as predictors of system failure. Significant changes to how all data are handled would be required to progress such an approach to predicting health service failure.
Publisher: Wiley
Date: 05-09-2016
DOI: 10.1111/AJO.12521
Abstract: There are no contemporary cohorts examining pregnancy outcomes in women with type 2 diabetes (T2D) in Australia. To compare pregnancy outcomes in women with and without T2D, and assess effects of body mass index (BMI) and glycaemic control on outcomes. An historical cohort study was conducted of all singleton births > 20 weeks gestation at a specialist maternity network in Australia from 2010 to 2013. Data were extracted from the Birthing Outcomes System database. Multivariable logistic regression analysis was used to examine associations between presence of T2D and pregnancy outcomes. Outcomes for 138 pregnancies with T2D and 27 075 pregnancies in women without diabetes were compared (type 1 diabetes and gestational diabetes excluded). Women with T2D were older and more overweight compared to women without diabetes (P < 0.01). Their babies were born earlier (P < 0.01) with increased risk of large for gestational age (adjusted odds ratio 2.13 (95% CI 1.37-3.32)), hypoglycaemia (4.90 (2.79-8.61)), jaundice (2.58 (1.61-4.13)) and shoulder dystocia (2.72 (1.09-6.78)), but not congenital malformations or perinatal death. Women with T2D had a higher risk of induction (4.03 (2.71-5.99)), caesarean section (2.10 (1.44-3.04)), preterm birth (2.74 (1.78-4.24)) and pre-ecl sia (2.75 (1.49-5.10)). An HbA1c ≥ 6.0% (42 mmol/mol) was associated with increased preterm birth, special care nursery admission, hypoglycaemia and jaundice. Despite availability of preconception care, good glycaemic control and specialist management, T2D remains associated with increased adverse obstetric and neonatal outcomes. Further research to examine predictors of adverse outcomes may assist in targeted antenatal surveillance and management.
Publisher: SAGE Publications
Date: 07-2012
Abstract: Since current treatments for both acute and chronic lung diseases are less than ideal, there has been recent interest in the use of cell-based therapies for inflammatory lung disease. Specifically, human amnion epithelial cells (hAECs) have been shown to reduce bleomycin-induced lung injury and prevent subsequent loss of respiratory function, primarily through modulation of the host immune response. The precise mechanisms of this effect remain unclear. We aimed to investigate the potential of hAECs to mitigate bleomycin-induced lung injury in surfactant protein C deficient ( Sftpc -/- ) mice, which are highly susceptible to pulmonary injury as a result of impairment of macrophage function. Primary hAECs were administered to wild-type ( Sftpc +/+ ) and Sftpc -/- mice 24 h after exposure to bleomycin. Compared to Sftpc +/+ mice receiving bleomycin alone, Sftpc +/+ mice administered hAECs 24 h after bleomycin exposure had decreased expression of proinflammatory genes, decreased macrophage and neutrophil infiltration, fibrosis, collagen content, and α-smooth muscle actin as well as a significant improvement in lung function. Compared to Sftpc -/- mice given bleomycin alone, Sftpc -/- mice administered hAECs 24 h after bleomycin did not have a decrease in inflammatory gene expression or a reduction in macrophage pulmonary infiltration. Subsequently, Sftpc -/- mice did not show any decrease in pulmonary fibrosis or improvement of lung function after hAEC administration. The ability of hAECs to mitigate bleomycin-induced lung injury is abolished in Sftpc -/- mice, suggesting that hAECs require normal host macrophage function to exert their reparative effects.
Publisher: BMJ
Date: 07-2013
Publisher: Frontiers Media SA
Date: 07-06-2018
Publisher: Elsevier BV
Date: 11-2004
DOI: 10.1016/J.FERTNSTERT.2004.05.078
Abstract: In an asymptomatic cohort, serum pregnancy-associated protein-A (PAPP-A) levels among women destined to miscarry were 14% of those seen with ongoing pregnancies. Levels were as low 3 weeks before diagnosis as on the day of diagnosis, suggesting that PAPP-A levels might predict future miscarriage.
Publisher: Wiley
Date: 16-03-2004
Publisher: Wiley
Date: 10-1992
DOI: 10.1111/J.1365-2605.1992.TB01356.X
Abstract: To investigate the fertility of men who remain oligozoospermic despite sex steroid suppression, the in-vitro fertilizing capacity of residual spermatozoa was assessed in 30 men receiving intramuscular testosterone enanthate (TE). Spermatozoa were prepared by either Percoll or repetitive centrifugation/washing. Although the mean (+/- SEM) pretreatment zona-free hamster oocyte penetration (HOP) rates were similar (59.4 +/- 10.1 and 63.8 +/- 10.8%), following the induction of oligozoospermia the Percoll-prepared spermatozoa exhibited a penetration rate (26.9 +/- 10.2%) which was markedly greater than that obtained for sperm prepared by repetitive washing (0 +/- 0%). In addition, the partners of two men exhibiting a HOP test with Percoll-prepared spermatozoa, conceived despite a sperm concentration of 3 x 10(6) ml-1 and a negative HOP test with spermatozoa prepared by repetitive washing. These results suggest that Percoll preparation optimizes the assessment of in-vitro sperm function and that the fertility of men with TE-induced severe oligozoospermia is suppressed but not abolished.
Publisher: Wiley
Date: 10-1996
Publisher: Elsevier BV
Date: 11-2020
Publisher: Springer Science and Business Media LLC
Date: 29-04-2009
Abstract: It is widely recognised that deficiencies in fetal surveillance practice continue to contribute significantly to the burden of adverse outcomes. This has prompted the development of evidence-based clinical practice guidelines by the Royal Australian and New Zealand College of Obstetricians and Gynaecologists and an associated Fetal Surveillance Education Program to deliver the associated learning. This article describes initial steps in the validation of a corresponding multiple-choice assessment of the relevant educational outcomes through a combination of item response modelling and expert judgement. The Rasch item response model was employed for item and test analysis and to empirically derive the substantive interpretation of the assessment variable. This interpretation was then compared to the hierarchy of competencies specified a priori by a team of eight subject-matter experts. Classical Test Theory analyses were also conducted. A high level of agreement between the hypothesised and derived variable provided evidence of construct validity. Item and test indices from Rasch analysis and Classical Test Theory analysis suggested that the current test form was of moderate quality. However, the analyses made clear the required steps for establishing a valid assessment of sufficient psychometric quality. These steps included: increasing the number of items from 40 to 50 in the first instance, reviewing ineffective items, targeting new items to specific content and difficulty gaps, and formalising the assessment blueprint in light of empirical information relating item structure to item difficulty. The application of the Rasch model for criterion-referenced assessment validation with an expert stakeholder group is herein described. Recommendations for subsequent item and test construction are also outlined in this article.
Publisher: The Endocrine Society
Date: 09-2004
DOI: 10.1210/JC.2004-0025
Publisher: Wiley
Date: 05-1999
DOI: 10.1046/J.1365-2265.1999.00716.X
Abstract: In the second trimester of pregnancy, inhibin A is significantly increased in maternal serum and decreased in amniotic fluid in Down's syndrome pregnancies compared to normal. We wished to further evaluate the levels of inhibin A, inhibin B, pro-alpha C inhibin, activin A and the binding protein follistatin in amniotic fluid in Down's syndrome and control pregnancies. Case-matched control study. 29 Down's syndrome and 290 chromosomally normal control pregnancies were identified from records and amniotic fluid, collected at second trimester amniocentesis, retrieved from routine storage for analysis. Inhibin A, inhibin B, pro-alpha C inhibin, total activin A and follistatin were measured using sensitive and specific enzyme linked immunosorbent assays. The median (10th-90th percentiles) amniotic fluid inhibin A level in the control pregnancies increased from 334 (122-553) ng/l at 14 weeks' to 695 (316-1475) ng/l at 19 weeks' gestation. The corresponding figures for inhibin B and the alpha-subunit precursor inhibin pro-alpha C were 632 (185-1354) and 2062 (1237-3381) ng/l, respectively at 14 weeks' and 2439 (748-5307) and 3115 (2021-6567) ng/l, respectively at 19 weeks' gestation. Total activin A increased from 3795 (1554-5296) at 14 weeks' to 5086 (3059-8224) at 18 weeks' gestation. Expressed as multiples of the median (MoM) the median (95% CI) amniotic fluid levels of inhibin A, inhibin B, pro-alpha C inhibin and acitivin A in the Down's syndrome s les were 0.77 (0.59-0.85), 0.94 (0.63-1.23), 0.77 (0.49-0.84) and 0.77 (0.53-0.87), respectively. Compared to controls the levels of inhibin A, pro-alpha C inhibin and activin A were significantly lower in Down's syndrome pregnancies (P < 0.01, Mann-Whitney U test). Follistatin levels in the controls declined slightly from 2106 (1421-3538) ng/l at 14 weeks' to 1600 (1281-2543) ng/l at 18 weeks' gestation. Levels in the Downs' syndrome pregnancies were similar to controls. The data suggest that the production, secretion or metabolism of the inhibin alpha- and beta A-subunits is altered in Down's syndrome pregnancies in the second trimester.
Publisher: JMIR Publications Inc.
Date: 02-11-2020
DOI: 10.2196/17980
Abstract: Virtual reality is increasingly being utilized by clinicians to facilitate analgesia and anxiolysis within an inpatient setting. There is however, a lack of a clinically relevant review to guide its use for this purpose. To systematically review the current evidence for the efficacy of virtual reality as an analgesic in the management of acute pain and anxiolysis in an inpatient setting. A comprehensive search was conducted up to and including January 2019 on PubMed, Ovid Medline, EMBASE, and Cochrane Database of Systematic reviews according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Search terms included virtual reality, vr, and pain. Primary articles with a focus on acute pain in the clinical setting were considered for the review. Primary outcome measures included degree of analgesia afforded by virtual reality therapy, degree of anxiolysis afforded by virtual reality therapy, effect of virtual reality on physiological parameters, side effects precipitated by virtual reality, virtual reality content type, and type of equipment utilized. Eighteen studies were deemed eligible for inclusion in this systematic review 67% (12/18) of studies demonstrated significant reductions in pain with the utilization of virtual reality 44% (8/18) of studies assessed the effects of virtual reality on procedural anxiety, with 50% (4/8) of these demonstrating significant reductions 28% (5/18) of studies screened for side effects with incidence rates of 0.5% to 8% 39% (7/18) of studies evaluated the effects of virtual reality on autonomic arousal as a biomarker of pain, with 29% (2/7) demonstrating significant changes 100% (18/18) of studies utilized a head mounted display to deliver virtual reality therapy, with 50% being in active form (participants interacting with the environment) and 50% being in passive form (participants observing the content only). Available evidence suggests that virtual reality therapy can be applied to facilitate analgesia for acute pain in a variety of inpatient settings. Its effects, however, are likely to vary by patient population and indication. This highlights the need for in idualized pilot testing of virtual reality therapy’s effects for each specific clinical use case rather than generalizing its use for the broad indication of facilitating analgesia. In addition, virtual reality therapy has the added potential of concurrently providing procedural anxiolysis, thereby improving patient experience and cooperation, while being associated with a low incidence of side effects (nausea, vomiting, eye strain, and dizziness). Furthermore, findings indicated a head mounted display should be utilized to deliver virtual reality therapy in a clinical setting with a slight preference for active over passive virtual reality for analgesia. There, however, appears to be insufficient evidence to substantiate the effect of virtual reality on autonomic arousal, and this should be considered at best to be for investigational uses, at present.
Publisher: Wiley
Date: 08-1997
DOI: 10.1111/J.1471-0528.1997.TB14356.X
Abstract: We have examined whether insulin dependent diabetes mellitus (IDDM) affects maternal serum levels of inhibin-A, a recently described prenatal marker of Down's syndrome, by comparing levels in 169 women with IDDM with levels in 432 nondiabetic pregnant women between 15 and 20 weeks of gestation. There was a small but significant increase in the inhibin-A level in the diabetic women only when levels were corrected for maternal weight: median MoM 1.17 (P < 0.01 vs controls, Student's t test). The underlying mechanism for this elevation in pregnancies complicated by IDDM currently remains obscure.
Publisher: S. Karger AG
Date: 2016
DOI: 10.1159/000444918
Abstract: Mechanical ventilation is a risk factor for cerebral inflammation and brain injury in preterm neonates. The risk increases proportionally with the intensity of treatment. Recent studies have shown that cerebral inflammation and injury can be initiated in the delivery room. At present, initiation of intermittent positive pressure ventilation (IPPV) in the delivery room is one of the least controlled interventions a preterm infant will likely face. Varying pressures and volumes administered shortly after birth are sufficient to trigger pathways of ventilation-induced lung and brain injury. The pathways involved in ventilation-induced brain injury include a complex inflammatory cascade and haemodynamic instability, both of which have an impact on the brain. However, regardless of the strategy employed to deliver IPPV, any ventilation has the potential to have an impact on the immature brain. This is particularly important given that preterm infants are already at a high risk for brain injury simply due to immaturity. This highlights the importance of improving the initial respiratory support in the delivery room. We review the mechanisms of ventilation-induced brain injury and discuss the need for, and the most likely, current therapeutic agents to protect the preterm brain. These include therapies already employed clinically, such as maternal glucocorticoid therapy and allopurinol, as well as other agents, such as erythropoietin, human amnion epithelial cells and melatonin, already showing promise in preclinical studies. Their mechanisms of action are discussed, highlighting their potential for use immediately after birth.
Publisher: Elsevier BV
Date: 09-2002
Abstract: In pregnancy the feto-placental unit is the major source of activin A. However, the role(s) of activin A in late pregnancy remain uncertain and controversial. In particular, whether activin A levels alter in association with labour is unclear. In a cross-sectional cohort study, maternal serum s les were collected from women at term prior to elective Caesarean section (n=11), during labour prior to a spontaneous vaginal delivery (n=31), an instrumental vaginal delivery (n=16) or an emergent Caesarean section (n=7). Umbilical artery blood s les were collected from 75 pregnancies, after an elective Caesarean section (n=9), a normal vaginal delivery (n=37), an instrumental vaginal delivery (n=15) or an emergent Caesarean section (n=14). Levels of activin A were measured and compared according to modes of delivery.Maternal, but not foetal, serum activin A was increased significantly in women who were delivered by an intrapartum Caesarean section compared to other modes of delivery. Foetal, but not maternal, serum activin A was significantly correlated with umbilical artery pH. Maternal serum activin A is increased in women undergoing an intrapartum Caesarean section compared to either a vaginal delivery or an elective Caesarean section. The mechanism(s) underlying this observation are not clear.
Publisher: Elsevier BV
Date: 04-1991
DOI: 10.1016/0952-3278(91)90092-J
Abstract: Human seminal plasma has uniquely high concentrations of PGE and 19-hydroxy PGE but the function of these PGs has not been elucidated. PGs of the E series have been shown to be paracrine and autocrine regulators of the function of immune cells and high levels of PGE have been shown consistently to suppress function in such cells. Human seminal plasma has a potent immunosuppressive effect and evidence is accumulating that this is largely due to PG components. In this study the effects of human seminal plasma on the killing activity of natural killer (NK) cells as judged by 51Cr release from K562 cells have been studied in groups of fertile and infertile men. Although there was no significant difference in the PGE, 19-hydroxy PGE or the NK cell inhibitory activity in the two groups, the inhibition of NK cell activity was closely correlated with the PGE and the 19-OH PGE content of the seminal plasma in the fertile group. This finding is further evidence that the major contribution to the immunosuppressive properties of human semen is provide by the high concentration of PGs of the E series in this fluid.
Publisher: Wiley
Date: 17-10-2007
DOI: 10.1111/J.1471-0528.2007.01511.X
Abstract: The aim of this study was to investigate whether maternal serum levels of angiopoietin-2 (Ang-2) and pregnancy-associated plasma protein A (PAPP-A) are associated with subsequent intrauterine growth restriction (IUGR). Ang-2 was measured in 29 nonpregnant and 44 pregnant women at 10-13 weeks of gestation. The median concentration of Ang-2 was 26.61 ng/ml in normal pregnant women compared with 1.71 ng/ml in nonpregnant controls (P < 0.01). Women who subsequently developed severe IUGR had lower levels of Ang-2 compared with normal pregnant controls (P < 0.01). PAPP-A levels were similar in all pregnant groups. These findings suggest that Ang-2 should be evaluated for its ability to predict pregnancies that later are affected by IUGR.
Publisher: Wiley
Date: 12-02-2021
DOI: 10.1111/AOGS.14074
Abstract: Preterm birth is a major cause of perinatal morbidity and mortality worldwide. In many countries preterm birth rates are increasing, largely as a result of increases in iatrogenic preterm birth, whereas in other countries rates are stable or even declining. The objective of the study is to describe trends in singleton preterm births in Victoria from 2007 to 2017 in relation to trends in perinatal mortality to identify opportunities for improvements in clinical care. We conducted a consecutive cross‐sectional study in all women with a singleton pregnancy giving birth at ≥20 weeks of pregnancy in Victoria, Australia, between 2007 and 2017, inclusive. Rates of preterm birth and perinatal mortality were calculated and trends were analyzed in all pregnancies, in pregnancies complicated by fetal growth problems, hypertension, (pre)ecl sia or prelabor rupture of membranes (PROM), and in (low‐risk) pregnancies not complicated by any of these conditions. There were 811 534 singleton births between 2007 and 2017. Preterm birth increased from 5.9% (4074 births) to 6.4% (4893 births P .001), due to an increase in iatrogenic preterm birth from 2.5% (1730 births) to 3.6% (2730 births P .001). Comparable trends were seen in pregnancies complicated by fetal growth problems and hypertension and in pregnancies not complicated by small for gestational age (SGA), hypertension, (pre)ecl sia or PROM (all P .001). In pregnancies complicated by SGA, hypertension, (pre)ecl sia or PROM the perinatal mortality rate from 20 weeks of gestation fell (13 to 12 per 1000 births P .001). In pregnancies not complicated by SGA, hypertension, (pre)ecl sia or PROM there was no significant change in the perinatal mortality from 28 weeks and no decrease in the preterm weekly prospective stillbirth risk. The singleton preterm birth rate in Victoria is increasing, driven by an increase in iatrogenic preterm birth, both in pregnancies complicated by SGA and hypertension, and in pregnancies not complicated by SGA, hypertension, (pre)ecl sia or PROM. While perinatal mortality decreased in the pregnancies complicated by SGA, hypertension, (pre)ecl sia or PROM, no significant reduction in perinatal mortality from 28 weeks or in preterm weekly prospective stillbirth risk was noted in the pregnancies not complicated by any of these conditions.
Publisher: Wiley
Date: 29-03-2016
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.WOMBI.2015.07.186
Abstract: Birth at home is a safe and appropriate choice for healthy women with a low risk pregnancy. However there is a small risk of emergencies requiring immediate, skilled management to optimise maternal and neonatal outcomes. We developed and implemented a simulation workshop designed to run in a home based setting to assist with emergency training for midwives and paramedical staff. The workshop was evaluated by assessing participants' satisfaction and response to key learning issues. Midwifery and emergency paramedical staff attending home births participated in a simulation workshop where they were required to manage birth emergencies in real time with limited availability of resources to suit the setting. They completed a pre-test and post-test evaluation form exploring the content and utility of the workshops. Content analysis was performed on qualitative data regarding the most important learning from the simulation activity. A total of 73 participants attended the workshop (midwifery=46, and paramedical=27). There were 110 comments, made by 49 participants. The most frequently identified key learning elements were related to communication (among midwives, paramedical and hospital staff and with the woman's partner), followed by recognising the role of other health care professionals, developing an understanding of the process and the importance of planning ahead. Home birth simulation workshop was found to be a useful tool by staff that provide care to women who are having a planned home birth. Developing clear communication and teamwork were found to be the key learning principles guiding their practice.
Publisher: Oxford University Press (OUP)
Date: 03-06-2007
Abstract: Pro-alphaC inhibins are luteal derived analytes peaking in the maternal serum as early as Day 16 after conception. We set out to verify a previous post hoc analysis which suggested that pro-alphaC levels measured this early are extremely sensitive in predicting clinical pregnancy success after unstimulated IVF with ovulatory cycles. Prospective observational study of 246 women undergoing frozen embryo transfer with ovulatory cycles. Serum pro-alphaC and beta-HCG levels at 14-17 days after conception were measured by enzyme-linked immunosorbent assay and grouped according to whether a clinical pregnancy occurred (demonstrable cardiac activity at > or =6 weeks' gestation). Of 34 (13.8%) women who achieved a clinical pregnancy, median (25th-75th centile) Days 14-17 pro-alphaC levels were 995 pg/ml (758-1463), 6- to 7-fold higher than levels observed in the remainder who did not fall pregnant (112.8 pg/ml (104-121) P < 0.0001). At a fixed 95% specificity, pro-alphaC was 100% sensitive in predicting clinical pregnancy. The best specificities achieved at 100% sensitivity were 94.8% for pro-alphaC, 96.7% for beta-HCG and 98.1% when both analytes were combined. Clinical pregnancy is always associated with a release of luteal derived pro-alphaC 14-17 days after conception. Pro-alphaC may play a possible biological role and be a useful clinical biomarker of luteal health.
Publisher: Wiley
Date: 05-09-2016
DOI: 10.1111/AJO.12517
Abstract: Postpartum haemorrhage (PPH) rates are increasing worldwide. The rate is particularly high in women undergoing an induced or augmented labour. In response to this, we altered our hospital's protocol for the management of the third stage of labour to recommend Syntometrine, in preference to oxytocin alone, for women being induced or augmented. We set out to assess the impact of the protocol change on the PPH rate. A random s le of 1200 women who had a singleton, term vaginal birth before and after the protocol change was taken. Exclusion criteria were then applied to match PPH risk status. Using a quasi-experimental study design, PPH rates were compared between women who had received oxytocin or Syntometrine for third stage management. Five hundred and forty-nine women received oxytocin prior to the protocol change and were compared with 333 women who received Syntometrine after protocol change. There was no difference in the PPH rate with respect to uterotonic used (P = 0.9). There was no evidence of an interaction between labour type, third stage uterotonic and PPH (P = 0.4). PPH rates were lowest for women who laboured spontaneously and received Syntometrine (19% oxytocin, 14% Syntometrine). The PPH rate was unchanged by uterotonic in women whose labour was augmented (34% for both). PPH was more common in women being induced who received Syntometrine (22% oxytocin, 27% Syntometrine). None of these differences were statistically significant. Compared to oxytocin, Syntometrine did not reduce the rate of PPH in women with augmented or induced labour. Other approaches to reducing PPH rates are required.
Publisher: Wiley
Date: 30-06-2019
Abstract: To validate the NHSLA maternity claims taxonomy at the level of a single maternity service and assess its ability to direct quality improvement. Qualitative descriptive study. Medico-legal claims between 1 January 2000 and 31 December 2016 from a maternity service in metropolitan Melbourne, Australia. All obstetric claims and incident notifications occurring within the date range were included for analysis. De-identified claims and notifications data were derived from the files of the insurer of Victorian public health services. Data included claim date, incident date and summary, and claim cost. All reported issues were coded using the NHSLA taxonomy and the lead issue identified. Rate of claims and notifications, relative frequency of issues, a revised taxonomy. A combined total of 265 claims and incidents were reported during the 6 years. Of these 59 were excluded, leaving 198 medico-legal events for analysis (1.66 events/1000 births). The costs for all claims was $46.7 million. The most common claim issues were related to management of labour (n = 63, $17.7 million), cardiotocographic interpretation (n = 43, $24.4 million), and stillbirth (n = 35, $656,750). The original NHSLA classification was not sufficiently detailed to inform care improvement programmes. A revised taxonomy and coding flowchart is presented. Systematic analysis of obstetric medico-legal claims data can potentially be used to inform quality and safety improvement. New taxonomy to target health improvement from maternity claims based on NHSLA Ten Years of Maternity Claims.
Publisher: Wiley
Date: 11-12-2022
DOI: 10.1002/IJGO.14049
Abstract: To assess pregnancy outcomes following first trimester combined screening for preterm preecl sia in Australia. We compared pregnancy outcomes of women with singleton pregnancies who underwent first trimester combined preecl sia screening with the Fetal Medicine Foundation algorithm between 2014 and 2017 in Melbourne and Sydney, Australia, with those from women who received standard care. The primary outcomes were preterm preecl sia and screening performance. Effect estimates were presented as risk ratios with 95% confidence intervals. A total of 29 618 women underwent combined screening and 301 566 women received standard care. Women who had combined screening were less likely to have preecl sia, preterm birth, small neonates, and low Apgar scores than the general population. Women with high-risk results (≥1 in 100) were more likely to develop preterm preecl sia (2.1% vs. 0.7%, risk ratio [RR] 3.04, 95% CI 2.46-3.77), while low-risk women (risk <1 in 100) had lower rates of preterm preecl sia (0.2% vs. 0.7%, RR 0.26, 95% CI 0.19-0.35) and other pregnancy complications. Screening detected 65.2% (95% CI 56.4-73.2%) of all preterm preecl sia cases, with improved performance after adjustment for treatment effect. First trimester screening for preecl sia in clinical practice identified a population at high risk of adverse pregnancy outcomes and low-risk women who may be suitable for less intensive antenatal care.
Publisher: Informa UK Limited
Date: 1995
Publisher: Public Library of Science (PLoS)
Date: 17-06-2021
DOI: 10.1371/JOURNAL.PONE.0253306
Abstract: Delayed umbilical cord cl ing (UCC) after birth is thought to cause placental to infant blood transfusion, but the mechanisms are unknown. It has been suggested that uterine contractions force blood out of the placenta and into the infant during delayed cord cl ing. We have investigated the effect of uterine contractions, induced by maternal oxytocin administration, on umbilical artery (UA) and venous (UV) blood flows before and after ventilation onset to determine whether uterine contractions cause placental transfusion in preterm lambs. At ~128 days of gestation, UA and UV blood flows, pulmonary arterial blood flow (PBF) and carotid arterial (CA) pressures and blood flows were measured in three groups of fetal sheep during delayed UCC maternal oxytocin following mifepristone, mifepristone alone, and saline controls. Each successive uterine contraction significantly (p .05) decreased UV (26.2±6.0 to 14.1±4.5 mL.min -1 .kg -1 ) and UA (41.2±6.3 to 20.7 ± 4.0 mL.min -1 .kg -1 ) flows and increased CA pressure and flow (47.1±3.4 to 52.8±3.5 mmHg and 29.4±2.6 to 37.3±3.4 mL.min -1 .kg -1 ). These flows and pressures were partially restored between contractions, but did not return to pre-oxytocin administration levels. Ventilation onset during DCC increased the effects of uterine contractions on UA and UV flows, with retrograde UA flow (away from the placenta) commonly occurring during diastole. We found no evidence that lification of uterine contractions with oxytocin increase placental transfusion during DCC. Instead they decreased both UA and UV flow and caused a net loss of blood from the lamb. Uterine contractions did, however, have significant cardiovascular effects and reduced systemic and cerebral oxygenation.
Publisher: Springer Science and Business Media LLC
Date: 30-07-2010
DOI: 10.1038/JP.2009.109
Abstract: To assess maternal serum activin A, an early phase response protein in systemic infection, as an early marker of intrauterine infection in women with preterm prelabour rupture of membranes (PPROM). A prospective cohort study of women with singleton pregnancies complicated by PPROM at 24 to 34 weeks' gestation. Serum was collected for activin A and cytokine measurements. Activin A was measured using commercial enzyme-linked immunosorbent assay. Cytokines were measured using commercial multiplex assay. Pregnancy outcomes including infection were determined by case-record review. Eighteen women with PPROM were studied, with seven developing intrauterine infection. Serum activin A in women with and without infection did not differ. Peripheral white cell count, interleukin (IL)-6 and IL-10 were higher (P=0.03, 0.05 and 0.009, respectively) and IL-7 lower (P=0.04) 72 h before delivery in women with infection. Activin A is not a clinically useful marker of intrauterine infection in women with PPROM.
Publisher: Wiley
Date: 2001
DOI: 10.1002/PD.127
Abstract: Inhibin A is a useful prenatal marker of Down syndrome. Currently, the available enzyme-linked immunosorbent assays (ELISAs) for inhibin A are based upon the same paired monoclonal antibodies. In the present study we have confirmed for one of those ELISAs that short-term s le storage as whole blood leads to a significant decline in detectable inhibin A and that this is most likely due to erythrocyte catalase interference with a critical oxidation step in the assay. While this interference can be eliminated by heating the s les pre-assay, this process is labour intensive. In the present study we have demonstrated that the addition of 3-amino-1,2,4-triazole (AT), a catalase 'suicide' inhibitor, also prevents the decline of inhibin A levels in s les stored as whole blood. We suggest that the addition of AT to s les prior to assay is a simple modification to the inhibin A ELISA that affords optimum performance.
Publisher: Oxford University Press (OUP)
Date: 07-05-2014
Publisher: Elsevier BV
Date: 08-2002
Abstract: In pregnancy the feto-placental unit is the major source of activin A. However, the role(s) of activin A in late pregnancy remain uncertain and controversial. In particular, whether activin A levels alter in association with labour is unclear. In a cross-sectional cohort study, maternal serum s les were collected from women at term prior to elective Caesarean section (n=11), during labour prior to a spontaneous vaginal delivery (n=31), an instrumental vaginal delivery (n=16) or an emergent Caesarean section (n=7). Umbilical artery blood s les were collected from 75 pregnancies, after an elective Caesarean section (n=9), a normal vaginal delivery (n=37), an instrumental vaginal delivery (n=15) or an emergent Caesarean section (n=14). Levels of activin A were measured and compared according to modes of delivery. Maternal, but not foetal, serum activin A was increased significantly in women who were delivered by an intrapartum Caesarean section compared to other modes of delivery. Foetal, but not maternal, serum activin A was significantly correlated with umbilical artery pH. Maternal serum activin A is increased in women undergoing an intrapartum Caesarean section compared to either a vaginal delivery or an elective Caesarean section. The mechanism(s) underlying this observation are not clear.
Publisher: Elsevier BV
Date: 10-2018
Publisher: Wiley
Date: 28-01-2009
DOI: 10.1002/PD.2210
Abstract: To compare women's understanding of different methods of expressing Down syndrome risks. A self-administered structured questionnaire given to 311 English-speaking women postpartum, at three maternity units. Understanding of numeric risk expression was assessed by women identifying whether a specified risk was higher, lower or the same as another nominated risk, expressed as two percentages, as two ratios or one of each. Perceptions of a high-risk result were obtained using display rankings of percentages and ratios. Response rate was 95% (294/311). Overall, women were poor comparing numeric risks whether expressed similarly (ratio vs. ratio or percentage vs. percentage) or not. When comparing similarly expressed risks, 66% (95% CI: 62-70%) of respondents were correct, considerably more than when asked to compare different risk expressions 30% (95% CI: 26-34%), P < 0.0001. Women were more tolerant of risk when expressed as a percentage than as a ratio (median high risk for percentage form was 5% (1:20) and for ratio form was 1:200 (0.5%). Women's understanding of Down syndrome risk is dependent upon how risks are expressed. These findings may usefully direct how risk should be reported to women having prenatal screening for Down syndrome.
Publisher: Springer Science and Business Media LLC
Date: 03-07-2017
DOI: 10.1038/S41598-017-04776-5
Abstract: Homeobox genes regulate embryonic and placental development, and are widely expressed in the human placenta, but their regulatory control by DNA methylation is unclear. DNA methylation analysis was performed on human placentae from first, second and third trimesters to determine methylation patterns of homeobox gene promoters across gestation. Most homeobox genes were hypo-methylated throughout gestation, suggesting that DNA methylation is not the primary mechanism involved in regulating HOX genes expression in the placenta. Nevertheless, several genes showed variable methylation patterns across gestation, with a general trend towards an increase in methylation over gestation. Three genes ( TLX1, HOXA10 and DLX5 ) showed inverse gains of methylation with decreasing mRNA expression throughout pregnancy, supporting a role for DNA methylation in their regulation. Proteins encoded by these genes were primarily localised to the syncytiotrophoblast layer, and showed decreased expression later in gestation. siRNA mediated downregulation of DLX5 , TLX1 and HOXA10 in primary term villous cytotrophoblast resulted in decreased proliferation and increased expression of differentiation markers, including ERVW-1 . Our data suggest that loss of DLX5, TLX1 and HOXA10 expression in late gestation is required for proper placental differentiation and function.
Publisher: Wiley
Date: 07-1997
DOI: 10.1111/J.1471-0528.1997.TB12035.X
Abstract: The effect of intramuscular dexamethasone administration in late pregnancy on the maternal peripheral white cell count was examined in 20 women. The mean total white cell count increased from a baseline of 11.3 x 10(9)/L (SD 2.3) to 16.2 x 10(9)/L (SD 4.6) on day 1, normalising thereafter. This 43% increase represented composite changes in the neutrophil and lymphocyte counts which, on average, increased by 62% and decreased by 22%, respectively. It is concluded that prenatal dexamethasone induces a significant neutrophilia on the first day following administration. This information may be helpful when monitoring for infection.
Publisher: S. Karger AG
Date: 2013
DOI: 10.1159/000346323
Abstract: Melatonin has erse physiological actions in addition to its well-recognized maintenance roles in circadian and seasonal timing. In particular, melatonin may have a direct protective action on the developing fetal brain. We examined the cellular processes by which melatonin provides protection following an acute late gestation hypoxic insult. 15 fetal sheep at 126 days' gestation were instrumented with a brachial artery catheter and a silastic cuff around the umbilical cord. At ∼130 days' gestation, the cuff was inflated for 10 min in 10 fetuses, causing complete umbilical cord occlusion (UCO). 5 UCO fetuses received intravenous melatonin maternally for 2 h, before and after UCO (UCO + melatonin). The remaining 5 fetuses had no UCO performed (sham-operated controls). At 48 h after UCO, the fetal brain was collected from each animal. Compared to controls, UCO caused significant hypoxia, hypercapnia and acidosis in UCO and UCO + melatonin fetuses. In the UCO-alone animals there were significant increases in pyknotic cell death, in the hippoc us ( -fold) and the cerebellum (3-fold). Maternal melatonin administration ameliorated cellular pyknosis in UCO fetuses. UCO was also associated with astrogliosis, increased albumin uptake, activated microglia and lipid peroxidation. Melatonin prevented these effects. There were no significant differences in the number of brain macrophages or microglia between any of the groups. Following acute severe hypoxia in the late gestation fetus, melatonin reduces neuronal lipid peroxidation and prevents loss of blood-brain barrier integrity and astrogliosis. These are likely key mechanisms underlying the neuroprotective actions of melatonin in the fetal brain.
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.PREGHY.2013.09.002
Abstract: Anti-angiogenic factors such as sFlt/sEng contribute to the pathology seen in preecl sia. Activin A, which is released by the placenta following exposure to oxidative stress and elevated in preecl sia, may interact with sFlt/sEng during the disease process. Using placental explant cultures, we determined that transcription of sFLT1, ENG and INHBA was upregulated following exposure to oxidative stress or IL-6. Explants treated with Activin A did not increase transcription of sFLT1, ENG. Conversely, treatment of placental explants with sFlt/sEng did not increase transcription of INHBA. These data may suggest that Activin A and sFlt/sEng contribute to preecl sia via separate pathways.
Publisher: S. Karger AG
Date: 2013
DOI: 10.1159/000346683
Abstract: Intrauterine infection, such as occurs in chorioamnionitis, is a principal cause of b /b reterm birth and is a strong risk factor for neurological morbidity and cerebral palsy. This study aims to examine whether human amnion epithelial cells (hAECs) can be used as a potential therapeutic agent to reduce brain injury induced by intra-amniotic administration of lipopolysaccharide (LPS) in preterm fetal sheep. Pregnant ewes underwent surgery at approximately 110 days of gestation (term is approx. 147 days) for implantation of catheters into the amniotic cavity, fetal trachea, carotid artery and jugular vein. LPS was administered at 117 days hAECs were labeled with carboxyfluorescein succinimidyl ester and administered at 0, 6 and 12 h, relative to LPS administration, into the fetal jugular vein, trachea or both. Control fetuses received an equivalent volume of saline. Brains were collected 7 days later for histological assessment of brain injury. Microglia (Iba-1-positive cells) were present in the brain of all fetuses and were significantly increased in the cortex, subcortical and periventricular white matter in fetuses that received LPS, indicative of inflammation. Inflammation was reduced in fetuses that received hAECs. In LPS fetuses, the number of TUNEL-positive cells was significantly elevated in the cortex, periventricular white matter, subcortical white matter and hippoc us compared with controls, and reduced in fetuses that received hAECs in the cortex and periventricular white matter. Within the fetal brains studied there was a significant positive correlation between the number of Iba-1-immunoreactive cells and the number of TUNEL-positive cells (R sup /sup = 0.19, p 0.001). The administration of hAECs protects the developing brain when administered concurrently with the initiation of intrauterine inflammation.
Publisher: Oxford University Press (OUP)
Date: 08-1998
Abstract: Tubal pregnancy is now commonly managed by laparoscopic salpingostomy or systemic methotrexate. A disadvantage of such conservative management is the need for appropriate follow-up, with serial measurement of serum concentrations of human chorionic gonadotrophin (HCG), to exclude persistent ectopic pregnancy (PEP). Concentrations of inhibin A, also a placental product, are significantly increased during pregnancy and the half-life of inhibin A is significantly shorter than that of HCG. To assess the suitability of inhibin A as a marker of PEP, we studied 16 women who had undergone surgery for a tubal pregnancy, measuring HCG and inhibin during follow-up. The mean +/- SEM time taken to achieve non-pregnant concentrations of inhibin A was significantly shorter than for HCG (4.2 +/- 0.8 days versus 21.6 +/- 4.4 days respectively P < 0.001 Wilcoxon signed rank test). However, in all women the inhibin A concentration increased rapidly after reaching a nadir, reflecting the return of ovarian function, complicating the interpretation of results. In four women inhibin A was almost undetectable preoperatively, while the corresponding HCG concentration was high. These data suggest that inhibin A will not be a useful marker for PEP but that it may provide a more accurate preoperative assessment of trophoblast viability than HCG, thereby improving management.
Publisher: John Wiley & Sons, Ltd
Date: 31-05-2013
Publisher: Wiley
Date: 30-03-2020
DOI: 10.1111/AJO.13156
Publisher: Elsevier BV
Date: 2009
DOI: 10.1016/J.AJOG.2008.08.029
Abstract: This study examined whether the type-5 phosphodiesterase inhibitor sildenafil citrate (Viagra Pfizer, New York, NY) could increase uterine blood flow in intrauterine growth restriction (IUGR), thereby improving fetal oxygenation and well being. In fetal sheep, we induced IUGR at 105-110 days (0.7 gestation) using single umbilical artery ligation (SUAL). In SUAL and control animals, we measured uterine blood flow (UBF) and blood gases before and after sildenafil administration. SUAL fetuses were hypoxemic compared with controls. Following sildenafil, UBF was significantly decreased in both SUAL and control ewes for approximately 40 minutes. In response to sildenafil, pO(2) was decreased in SUAL and control fetuses and both groups displayed significant hypotension and tachycardia. At postmortem SUAL fetal body weight was significantly reduced by 23% compared with controls. Sildenafil does not improve UBF or fetal well being in SUAL-induced IUGR pregnancies and should be used with caution in IUGR and healthy pregnancies because of its detrimental effects on uteroplacental perfusion and on the fetus.
Publisher: Wiley
Date: 05-04-2020
Publisher: The Endocrine Society
Date: 02-2006
DOI: 10.1210/EN.2005-1183
Abstract: Embryo implantation and trophoblast invasion are tightly regulated processes, involving sophisticated communication between maternal decidual and fetal trophoblast cells. Decidualization is a prerequisite for successful implantation and is promoted by a number of paracrine agents, including activin A. To understand the downstream mechanisms of activin-promoted decidualization, the effects of activin on matrix metalloproteinases (MMPs) (important mediators of decidualization) were investigated. Activin A stimulated endometrial production of proMMPs-2, -3, -7, -9, and active MMP-2. In contrast, inhibin A was a potent inhibitor of proMMP-2, and antagonized the effect of activin on MMPs. Activin is up-regulated with decidualization, and MMPs-2, -3, and -9 increase in parallel. Furthermore, proMMP-2 production is stimulated when decidualization is accelerated with activin, and suppressed when activin is neutralized, attenuating decidualization. These data support that activin A promotes decidualization through up-regulating MMPs. Previous in vitro evidence proposes further roles for activin and MMPs in promoting trophoblast invasion therefore, we examined their interrelationships in early human implantation sites. MMPs-7 and -9 were produced by static cytotrophoblast subpopulations, whereas MMP-2 was strikingly up-regulated in invasive extravillous cytotrophoblasts (EVT). Maternal decidua is the primary source of activin, where a role in stimulating MMP-2 in iEVTs can be envisaged. Inhibin was absent from cytotrophoblast populations, except for a dramatic up-regulation in endovascular EVT plugs, coinciding with a down-regulation of MMP-2. This suggests that inhibin may have a role in the cessation of vascular invasion. These data support that activin, via effects on MMPs, is an important factor in the maternal-fetal dialog regulating implantation.
Publisher: The Endocrine Society
Date: 02-2011
DOI: 10.1210/JC.2010-1405
Abstract: The pathogenic origin of preecl sia is defective placental development (placentation) and function. Preecl sia is not diagnosed until later in pregnancy, and reliable early detection is highly desirable. HtrA3 is a recently cloned gene with high expression during placentation in the mouse, rhesus monkey, and human. The present study examined the placental production and the serum profile of HtrA3 across gestation in women, the potential molecular mechanisms regulating HtrA3 production, and the association between maternal HtrA3 serum levels and preecl sia. Immunohistochemistry determined HtrA3 expression pattern and cellular localization in first-, second-, and third-trimester placenta. The maternal serum HtrA3 levels were analyzed by Western blotting. The regulation of placental HtrA3 production and the secretion by oxygen tension was investigated in first-trimester placental explants and trophoblast cells. Placental HtrA3 protein was maximally produced in the first trimester and then dramatically down-regulated, especially in the syncytiotrophoblast. HtrA3 was secreted into the maternal circulation with a serum profile reflecting placental production. Oxygen tension regulated HtrA3 low oxygen enhanced, whereas the transition from low to high oxygen decreased, HtrA3 protein production in syncytiotrophoblast. Maternal serum HtrA3 levels at approximately 13-14 wk of gestation were significantly higher in women who subsequently developed preecl sia. It appeared that HtrA3 down-regulation was delayed in preecl tic pregnancies. HtrA3 protein production is closely associated with changing in oxygen tension in the placenta. The decline in HtrA3 at the end of first trimester may reflect the placental low to high oxygen switch. Abnormally high levels of serum HtrA3 at approximately 13-14 wk of gestation is associated with preecl sia.
Publisher: Oxford University Press (OUP)
Date: 05-08-2018
DOI: 10.1002/SCTM.18-0079
Abstract: Bronchopulmonary dysplasia (BPD) is a chronic lung disease that mainly affects premature babies who require ventilator support. The pathogenesis of BPD is complex but includes vascular maldevelopment, alveolarization arrest, and lung inflammation. There is no cure for BPD. Clinical care is limited to supportive respiratory measures. A population of stem-like cells derived from placental membranes, human amnion epithelial cells (hAECs), has shown therapeutic promise in preclinical models of BPD. With a view to future efficacy trials, we undertook a first-in-human clinical trial of hAECs in babies with BPD to assess the safety of these cells. In a single-center, open-label phase I trial, we administered allogeneic hAECs (1 × 106 per kilogram bodyweight) by intravenous infusion to six premature babies with BPD. The primary outcomes of the study were focused on safety, including local site reaction, anaphylaxis, infection, features of rejection, or tumor formation. Outcomes to discharge from neonatal unit were studied. The hAECs were well tolerated. In the first baby, there was transient cardiorespiratory compromise during cell administration consistent with a pulmonary embolic event. Following changes to cell administration methods, including introduction of an inline filter, and reducing the cell concentration and the rate of cell infusion, no such events were observed in the subsequent five babies. We did not see evidence of any other adverse events related to cell administration. Allogeneic hAECs can be safely infused into babies with established BPD. Future randomized clinical trials to assess efficacy in this patient population are justified.
Publisher: Public Library of Science (PLoS)
Date: 06-06-2017
Publisher: Wiley
Date: 24-10-2002
DOI: 10.1002/PD.478
Abstract: Inhibin A, an established prenatal marker of Down syndrome (DS), exists in the maternal circulation in a number of isoforms. The present study explored whether specific inhibin A isoforms may be selectively increased in DS, offering the prospect of improved marker performance. Second trimester maternal serum, placental extracts and amniotic fluid (AF) pools from both normal and DS pregnancies were fractionated by a combined immunoaffinity (IA) chromatography, preparative polyacrylamide gel electrophoresis (Prep-PAGE) and electroelution procedure. Inhibins A, B and pro-alphaC were determined in the eluted fractions by specific enzyme-linked immunosorbent assays (ELISAs) and the profiles of immunoactivity (IA) characterized in terms of molecular weight (MW) and percentage recovery. The MW patterns of inhibin A and pro-alphaC in maternal serum and AF were similar between DS and control pregnancies, both showing peaks between 25-40 k and approximately 65 k. AF contained, in addition, a higher proportion of <30 k inhibins A and B, and <25 k pro-alphaC forms. There were large differences in the inhibin forms present in DS placentae, with more 70 k and less 30-40 k inhibin A than in controls. The present data suggest that the processing, cleavage or secretion of inhibin MW forms by the DS placenta differs from normal. However, these differences are not reflected in maternal serum and so improvements in serum screening will not be afforded by measuring specific inhibin A isoforms.
Publisher: MyJove Corporation
Date: 16-02-2018
DOI: 10.3791/57065
Publisher: American Thoracic Society
Date: 09-2010
Publisher: Wiley
Date: 13-03-2012
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.WOMBI.2018.08.172
Abstract: Interprofessional training programs for obstetric emergencies have been introduced for up-skilling birth unit staff in hospitals but not frequently used in training midwives and paramedicine staff for home birth emergency. Practical Obstetric Multiprofessional Training (PROMPT) has previously been described in the home birth setting using in-situ simulation training of home births for midwifery and paramedicine staff. The aim of this study was to evaluate the benefit of the home birth simulation in clinical practice and to explore how the simulation program prepared the midwives for a birth-related emergency in a publicly funded home birth program. Midwives conducting home births, the midwifery educator and the simulated woman in labour (n=9) attended an interview that explored how the midwives' learning through simulation affected their home birth clinical practice. The simulated woman and the facilitator who conducted the simulation for more than six years were also interviewed to comment on the observed change in performance in simulation. The interview transcripts were thematically analysed. The themes that were identified and agreed upon, were applying learning to clinical practice, learning in teams, valuing realism, facilitating simulation based education and managing variation. In-situ nature of simulation with home birth midwives and paramedical staff facilitated learning transfer and team-based approach to practice. The careful simulation design provided a breadth of experience in emergencies. Applying learning to prepare for clinical emergency situations changed the midwives' approach in managing home births. This provided evidence for a change in behaviour (Level 3 Kirkpatrick's framework) and transfer of learning, leading to changed protocols (Level 4a Kirkpatrick's framework).
Publisher: BMJ
Date: 02-2009
Abstract: To determine the risk factors associated with chlamydial infection in pregnancy and the sensitivity and specificity of these when used for selective screening. A prospective, cross-sectional study of pregnant women aged 16-25 years attending four major public antenatal services across Melbourne, Australia. Between October 2006 and July 2007, women were approached consecutively and asked to complete a questionnaire and to provide a first-pass urine specimen for Chlamydia trachomatis testing using PCR. Of 1180 eligible women, 1087 were approached and 1044 (88%) consented to participate. Among the 987 women for whom a questionnaire and a definitive diagnostic assay were available, the prevalence of chlamydia was 3.2% (95% CI 1.8 to 5.9). In a multiple logistic regression model, more than one sexual partner in the past year (AOR 11.5 95% CI 7.1 to 18.5) was associated with chlamydia infection. The use of any antibiotic within 3 months (AOR 0.2 95% CI 0.1 to 0.6) was associated with a decreased risk of infection. Screening restricted to women who reported more than one sexual partner in the past year would have detected 44% of infections in women aged 16-25 years and would have required only 7% of women to be screened. The addition of those women aged 20 years and under would have required 27% of women to be screened and detection of 72% of infections. Selective chlamydia screening of pregnant women based on risk factors can improve the yield from screening. However, the potential harm of missed infections among excluded women would need to be considered.
Publisher: Wiley
Date: 06-09-2011
DOI: 10.1111/J.1471-0528.2011.03133.X
Abstract: In current protocols for the medical management of ectopic pregnancies, the first indication of treatment response is obtained no sooner than day 7. We examined whether human chorionic gonadotrophin (βhCG) trends between days 0 and 4 after methotrexate provide an earlier indication of the likely outcome. Of 33 patients where serum βhCG dropped between days 0 and 4 after methotrexate, the ectopic pregnancy was resolved in 88% of cases without further treatment. Of 12 women where serum βhCG rose between days 0 and 4, only 42% had treatment success. A fall in βhCG between days 0 and 4 after treatment with methotrexate for ectopic pregnancy predicts a high likelihood of treatment success.
Publisher: SAGE Publications
Date: 08-2013
Abstract: With a view to developing a cell therapy for chronic lung disease, human amnion epithelial cells (hAECs) have been shown to prevent acute lung injury. Whether they can repair established lung disease is unknown. We aimed to assess whether hAECs can repair existing lung damage induced in mice by bleomycin and whether the timing of cell administration influences reparative efficacy. In addition, we aimed to characterize the effect of hAECs on fibroblast proliferation and activation, investigating possible mechanisms of reparative action. hAECs were administered intraperitoneally (IP) either 7 or 14 days after bleomycin exposure. Lungs were assessed 7 days after hAEC administration. Bleomycin significantly reduced body weight and induced pulmonary inflammation and fibrosis at 14 and 21 days. Delivery of hAECs 7 days after bleomycin had no effect on lung injury, whereas delivery of hAECs 14 days after bleomycin normalized lung tissue density, collagen content, and α-SMA production, in association with a reduction in pulmonary leucocytes and lung expression of TGF-β, PDGF-α, and PDGF-β. In vitro, hAECs reduced proliferation and activation of primary mouse lung fibroblasts. Our findings suggest that the timing of hAEC administration in the course of lung disease may impact on the ability of hAECs to repair lung injury.
Publisher: No publisher found
Date: 2007
Publisher: Wiley
Date: 09-1996
DOI: 10.1111/J.1471-0528.1996.TB09903.X
Abstract: To review the outcome of pregnancies complicated by placenta praevia over a three-year period (1991-1993) and to describe in detail the antenatal course and the events leading to delivery, assessing retrospectively whether there are clinical features predictive of outcome and whether outpatient management would be reasonable. A retrospective review of the case records of women with a pregnancy complicated by placenta praevia. A tertiary referral teaching hospital in Edinburgh. There were 15,930 deliveries in the study period. Fifty-eight women (0.4%) had a placenta praevia in the third trimester, 42 of whom (72%) had at least one episode of bleeding. Overall, 62% of the women had a major praevia with no differences in the grade of praevia between those women who did or did not have bleeding. Both diagnosis and delivery occurred significantly earlier in women with antepartum bleeding than in those without (median gestation at diagnosis 28.6 weeks versus 33.3 weeks (P < 0.01) and at delivery 36.0 weeks versus 37.1 weeks (P = 0.04), respectively). Delivery by emergency caesarean section was more common in women with bleeding (62% versus 38%). An increasing number of bleeding episodes experienced by in iduals was not associated with significant differences in outcomes. Rapid emergency delivery for bleeding was necessary for three women, in none of whom could the bleeding have been predicted. The clinical outcomes of placenta praevia are highly variable and cannot be predicted confidently from antenatal events. Nonetheless, in the majority of cases with or without bleeding and irrespective of the degree of praevia, outpatient management would appear safe and appropriate.
Publisher: Wiley
Date: 12-2008
Publisher: Wiley
Date: 16-03-2011
Publisher: Informa UK Limited
Date: 06-07-2012
DOI: 10.3109/14767058.2012.697940
Abstract: Clinical and experimental studies suggest that the growth-restricted fetus at increased risk of impaired cardiovascular function that likely contributes to both increased mortality rate and in survivors, to cardiovascular dysfunction apparent in childhood and later life. Fetal growth restriction is also associated with a high risk of preterm birth. Accordingly, the growth-restricted fetus is more likely than average to receive antenatal glucocorticoids to accelerate lung maturation in preparation for birth. However, glucocorticoids are powerful regulators of vascular tone and antenatal glucocorticoid administration to the intrauterine growth restriction (IUGR) fetus results in systemic cardiovascular changes that are not observed in the healthy normal grown fetus. These responses to glucocorticoids may disturb the IUGR fetus' ability to appropriately compensate to placental insufficiency. Indeed is it possible that in the setting of severe IUGR exogenous glucocorticoids are detrimental rather than beneficial to the fetus?
Publisher: SAGE Publications
Date: 07-2011
Abstract: Human amnion epithelial cells (hAECs) have attracted recent attention as a promising source of cells for regenerative therapies, with reports that cells derived from human term amnion possess multipotent differentiation ability, low immunogenicity, and anti-inflammatory properties. Specifically, in animal models of lung disease characterized by significant loss of lung tissue secondary to chronic inflammation and fibrosis, the transplantation of hAECs has been shown to reduce both inflammation and subsequent fibrosis. To further explore the mechanisms by which hAECs reduce pulmonary fibrosis and enhance lung regeneration, we utilized a bleomycin-induced model of pulmonary fibrosis and investigated the ability of hAECs to reduce fibrosis and thereby improve pulmonary function. We aimed to determine if hAECs, injected into the peritoneal cavity could migrate to the lung, engraft, and form functional lung epithelium, and whether hAECs could modulate the inflammatory environment in the bleomycin-injured lung. We demonstrated that, compared to bleomycin alone, IP administration of hAECs 24 h after bleomcyin, decreased gene expression of the proinflammatory cytokines TNF-α, TGF-β, IFN-γ, and IL-6 and decreased subsequent pulmonary fibrosis with less pulmonary collagen deposition, reduced levels of α-smooth muscle actin and decreased inflammatory cell infiltrate. We also showed that hAECs are able to prevent a decline in pulmonary function associated with bleomycin-induced lung damage. We were unable to detect any significant engraftment of hAECs in injured, or uninjured, lung after administration. The findings from this study support the further investigation of hAECs as a potential cell therapy for inflammatory and fibrogenic diseases.
Publisher: SAGE Publications
Date: 04-2017
Abstract: Intrauterine inflammation is a significant cause of injury to the developing fetal brain. Using a preterm fetal sheep model of in utero infection, we asked whether human amnion epithelial cells (hAECs) were able to reduce inflammation-induced fetal brain injury. Surgery was undertaken on pregnant sheep at ~105 days gestation (term is 147 days) for implantation of vascular catheters. Lipopolysaccharide (LPS 150 ng/kg bolus) or saline was administered IV at 109, 110, and 111 days. Sixty million fluorescent-labeled hAECs were administered at 110, 111, and 112 days gestation via the brachial artery catheter. Brains were collected at 114 days for histological assessment. hAECs were observed within the cortex, white matter, and hippoc us. Compared to control lambs, LPS administration was associated with significant and widespread fetal brain inflammation and injury as evidenced by increased number of activated microglia in the periventricular white matter ( p = 0.02), increased pyknosis, cell degeneration ( p = 0.01), and a nonsignificant trend of fewer oligodendrocytes in the subcortical and periventricular white matter. Administration of hAECs to LPS-treated animals was associated with a significant mitigation in both inflammation and injury as evidenced by fewer activated microglia ( p = 0.03) and pyknotic cells ( p = 0.03), significantly more oligodendrocytes in the subcortical and periventricular white matter ( p = 0.01 and 0.02, respectively), and more myelin basic protein-positive cells within the periventricular white matter ( p = 0.02). hAEC administration to fetal sheep exposed to multiple doses of LPS d ens the resultant fetal inflammatory response and mitigates associated brain injury.
Publisher: Wiley
Date: 17-06-2012
DOI: 10.1111/J.1471-0528.2012.03309.X
Abstract: To study the consequences of glucocorticoid treatment in fetal growth restriction (FGR) on cardiac function. Laboratory. Sheep. Growth restriction was induced in sheep fetuses using single umbilical artery ligation (SUAL) on days 105-110 of gestation (term 147). Control fetuses were not ligated. Betamethasone (BM) (11.4 mg intramuscularly) or saline was administered to ewes on days 5 and 6 after surgery. Ewes were anaesthetised on day 7, the fetuses were removed, and their hearts were mounted on a Langendorff apparatus. Balloon catheters were inserted into the right and left ventricles. Ventricular contractile function and infarct area following ischaemia/reperfusion. The SUAL resulted in FGR (body weight 77% of control). The FGR was associated with increases in basal left ventricular pressure development and rates of contraction and relaxation. Right ventricular contraction was unaffected. Following brief ischaemia/reperfusion, the infarct area in FGR hearts was increased four-fold compared with controls. Antenatal BM resulted in a proportional increase in heart size and coronary flow, especially in FGR fetuses, and left ventricular pressure and heart rate responses to β-adrenoceptor activation were increased. Fetal hearts rapidly adapt to FGR to maintain substrate delivery to the brain and heart. The FGR greatly enhanced the area of ischaemia, with implications for susceptibility in postnatal life. Antenatal BM treatment does not interfere with these cardiac changes but appears to increase left ventricle β-adrenoceptor responsiveness, which may render the offspring vulnerable to subsequent cardiac dysfunction.
Publisher: Informa UK Limited
Date: 05-2011
Abstract: Within-pair comparison of monozygotic (MZ) twins provides an ideal model for studying factors that regulate epigenetic profile, by controlling for genetic variation. Previous reports have demonstrated epigenetic variability within MZ pairs, but the contribution of early life exposures to this variation remains unclear. As epigenetic marks govern gene expression, we have used gene expression discordance as a proxy measure of epigenetic discordance in MZ twins at birth in two cell types. We found strong evidence of expression discordance at birth in both cell types and some evidence for higher discordance in twin pairs with separate placentas. Genes previously defined as being involved in response to the external environment showed the most variable expression within pairs, independent of cell type, supporting the idea that even slight differences in intrauterine environment can influence expression profile. Focusing on birthweight, previously identified as a predisposing factor for cardiovascular, metabolic and other complex diseases, and using a statistical model that estimated association based on within-pair variation of expression and birthweight, we found some association between birthweight and expression of genes involved in metabolism and cardiovascular function. This study is the first to examine expression discordance in newborn twins. It provides evidence of a link between birthweight and activity of specific cellular pathways and, as evidence points to gene expression profiles being maintained through cell ision by epigenetic factors, provides a plausible biological mechanism for the previously described link between low birthweight and increased risk of later complex disease.
Publisher: AMPCo
Date: 11-2019
DOI: 10.5694/MJA2.50387
Publisher: Wiley
Date: 23-03-2020
DOI: 10.1111/AJO.13147
Publisher: MyJove Corporation
Date: 12-08-2014
DOI: 10.3791/51755
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.PLACENTA.2017.10.008
Abstract: Maternal endothelial dysfunction underlying preecl sia arises from excessive placental release of anti-angiogenic factors, such as soluble fms-like tyrosine kinase-1 (sFlt1), soluble endoglin (sEng) and activin A. Resveratrol, an activator of the nuclear factor erythroid 2-related factor-2 (Nrf2) transcription factor, mediates the gene expression of antioxidant and vasoprotective factors that may counter the endothelial damage imposed by these anti-angiogenic factors. The objective of this study was to assess whether resveratrol could reduce placental oxidative stress and production of anti-angiogenic factors in vitro and/or improve in vitro markers of endothelial dysfunction via Nrf2 activation. We used in vitro term placental explants to assess the effects of resveratrol on placental oxidative stress and production of sFlt1, sEng and activin A. Using human umbilical vein endothelial cells we investigated the effects of resveratrol on markers of in vitro endothelial dysfunction, including the expression of intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), E-selectin and endothelin-1, and endothelial permeability. To confirm that resveratrol mediated its effects via Nrf2, we examined the impact of resveratrol on the same in vitro markers of endothelial and placental dysfunction following Nrf2 knockdown. Resveratrol significantly decreased placental oxidative stress and the production of sFlt1 and activin A. Resveratrol significantly mitigated tumor necrosis factor-α stimulated endothelial expression of ICAM1, VCAM1, E-selectin and endothelin-1 and prevented an increase in endothelial monolayer permeability. Nrf2 knockdown abolished some of the protective effects of resveratrol on endothelial cells, but not in primary trophoblast cells. Features of placental and endothelial dysfunction characteristic of preecl sia are improved by resveratrol in vitro, partially via the modulation of Nrf2.
Publisher: Oxford University Press (OUP)
Date: 17-04-2017
DOI: 10.1093/SLEEP/ZSX048
Abstract: Preterm birth and fetal growth restriction (FGR) are both associated with risk of hypertension in adulthood. Mechanisms leading to this pathology are unclear. In children aged 5-12 years, who were born preterm and FGR, we used sleep as a tool to assess autonomic control with assessment of cardiovascular structure and function. Eighteen children born preterm and FGR, 15 children born preterm with appropriate birth weights for gestational age (AGA), and 20 AGA term-born children were studied. Children underwent overnight polysomnography with the addition of continuous noninvasive blood pressure (Finometer™). Spectral measures of heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity were assessed and overnight urinary catecholamine levels measured. Echocardiographic studies (Vivid7, GE Healthcare) were performed and vascular compliance assessed (Miller Instruments™). Statistical comparisons were adjusted for age and body size. Compared to term children, preterm AGA children had increased high frequency HRV (p < .05) and BPV (p < .05) during sleep, reflecting increased parasympathetic activation and blood pressure changes related to respiration. Preterm FGR children had smaller left ventricular lengths, ascending aorta, and left ventricular outflow tract diameter (p < .05 for all) and vascular compliance was positively correlated with gestational age (r2 = 0.93, p < .05). FGR combined with preterm birth did not alter autonomic control but altered heart structure in children. In contrast, preterm birth alone altered autonomic control but had no change in heart structure. These changes in children born preterm and FGR may contribute, in part, to increased risk of cardiovascular disease later in life but by different mechanisms.
Publisher: Wiley
Date: 04-2017
DOI: 10.1111/AJO.12615
Publisher: Elsevier BV
Date: 08-2001
Publisher: Informa UK Limited
Date: 21-02-2018
DOI: 10.1080/14767058.2017.1289511
Abstract: In this review, we discuss the potential use of antimalarial drugs as an adjuvant therapy for preecl sia, focusing on the mechanisms of action of this class of drugs in the context of preecl sia. In particular, hydroxychloroquine has been shown to have various beneficial effects on patients with systemic lupus erythematosus. There are several pathways targeted by the antimalarial drugs that are similar to the pathophysiology of preecl sia and hence offering opportunities to develop novel therapies to treat the disease. Given the safety profile of hydroxychloroquine in pregnancy, there is merit in exploring the efficacy of this drug as an adjuvant therapy in women with early onset preecl sia.
Publisher: American Academy of Pediatrics (AAP)
Date: 10-2012
Abstract: Bronchopulmonary dysplasia (BPD) is a major cause of substantial lifelong morbidity in preterm infants. Despite a better understanding of the pathophysiology of BPD and significant research effort into its management, there remains today no effective treatment. Cell-based therapy is a novel approach that offers much promise in the prevention and treatment of BPD. Recent research supports a therapeutic role for cell transplantation in the management of a variety of acute and chronic adult and childhood lung diseases, with potential of such therapy to reduce inflammation and prevent acute lung injury. However, considerable uncertainties remain regarding cell therapies before they can be established as safe and effective clinical treatments for BPD. This review summarizes the current literature investigating cell therapies in lung disease, with particular focus on the various types of cells available and their specific properties in the context of a future therapy for BPD.
Publisher: Wiley
Date: 04-2017
Publisher: Wiley
Date: 15-04-2020
Publisher: BMJ
Date: 09-2013
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.BRAINRES.2017.10.010
Abstract: Power spectral analysis of the electroencephalogram (EEG) is a non-invasive method to examine infant brain maturation. Preterm fetal growth restricted (p-FGR) neonates display an altered EEG power spectrum compared to appropriate-for-gestational-age (AGA) peers, suggesting delayed brain maturation. Longitudinal studies investigating EEG power spectrum maturation in p-FGR infants are lacking, however. We thus aimed to investigate brain maturation using sleep EEG power spectral analysis in p-FGR infants compared to preterm and term AGA controls (p-AGA and t-AGA, respectively). EEG was recorded during spontaneous sleep in 13 p-FGR, 17 p-AGA and 19 t-AGA infants at 1 and 6 months post-term age. Infant sleep states (active and quiet sleep) were scored using standard criteria. Power spectral analysis of a single-channel EEG (C3-M2/C4-M1) was performed using Fast Fourier Transform. The EEG power spectrum was ided into delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), sigma (12-14 Hz) and beta (14-30 Hz) frequency bands. Relative (%) powers and the spectral edge frequency were calculated. The spectral edge frequency was significantly higher in p-FGR infants compared to p-AGA controls in quiet sleep at 1 month post-term age (p < .01). This was due to significantly reduced %-delta and significantly increased %-theta, %-alpha and %-beta power (p < .01 for all) compared to p-AGA infants. p-FGR infants also showed significantly increased %-beta power compared to t-AGA infants (p < .05). No group differences were observed in active sleep or at 6 months post-term age. In conclusion, p-FGR infants show altered sleep EEG power spectrum maturation compared to AGA peers. However, changes resolved by 6 months post-term age.
Publisher: Springer Science and Business Media LLC
Date: 11-03-2015
DOI: 10.1038/PR.2015.46
Abstract: Bronchopulmonary dysplasia (BPD) is one of the leading causes of morbidity and mortality in babies born prematurely, yet there is no curative treatment. In recent years, a number of inhibitors against TGFβ signaling have been tested for their potential to prevent neonatal injury associated with hyperoxia, which is a contributing factor of BPD. In this study, we assessed the contribution of activin A-a member of the TGFβ superfamily-to the development of hyperoxia-induced lung injury in neonatal mice. We placed newborn C57Bl6 mouse pups in continuous hyperoxia (85% O2) to mimic many aspects of BPD including alveolar simplification and pulmonary inflammation. The pups were administered activin A receptor type IIB-Fc antagonist (ActRIIB-Fc) at 5 mg/kg or follistatin at 0.1 mg/kg on postnatal days 4, 7, 10, and 13. Treatment with ActRIIB-Fc and follistatin protected against hyperoxia-induced growth retardation. ActRIIB-Fc also reduced pulmonary leukocyte infiltration, normalized tissue: airspace ratio and increased septal crest density. These findings were associated with reduced phosphorylation of Smad3 and decreased matrix metalloproteinase (MMP)-9 activity. This study suggests that activin A signaling may contribute to the pathology of bronchopulmonary dysplasia.
Start Date: 12-2013
End Date: 12-2016
Amount: $570,803.00
Funder: Australian Research Council
View Funded Activity