ORCID Profile
0000-0002-4892-6748
Current Organisation
Mater Medical Research Institute
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In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Animal developmental and reproductive biology | Cell physiology | Health Promotion | Biological Psychology (Neuropsychology, Psychopharmacology, | Psychology | Public Health and Health Services | Animal reproduction and breeding | Medical physiology
Clinical health not specific to particular organs, diseases and conditions | Health Education and Promotion | Communication not elsewhere classified |
Publisher: MDPI AG
Date: 29-12-2015
DOI: 10.3390/NU7010153
Publisher: SAGE Publications
Date: 03-12-2020
Abstract: Until relatively recently, processes of health application (app) design have been understudied and this has resulted in a lack of critical reflection on app creation, including curtailing opportunities to share insights and possible pitfalls that could inform best practice in the field. In response, this article contributes to a growing body of literature that addresses this lacuna by exploring the experiences of the research and design team that developed a health app for pregnant women attending a large tertiary hospital in South Australia. Our analysis pays particular attention to the designer–researcher–user nexus exhibited in the ‘co-design’ process and in doing so, draws on Rittel’s notion of ‘wicked problems’. Ultimately, we show that app design is a problem-solving process that is reflective of a high degree of sociality, fluidity, accommodations and compromises.
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1016/J.AJOG.2021.06.078
Abstract: A systematic review was conducted to determine placental outcomes following prenatal alcohol exposure in women. The search terms "maternal OR prenatal OR pregnant OR periconception" AND "placenta" AND "alcohol OR ethanol" were used across 5 databases (PubMed, Embase, Cochrane Library, Web of Science, and CINAHL) from inception until November 2020. Articles were included if they reported placental outcomes in an alcohol exposure group compared with a control group. Studies were excluded if placentas were from elective termination before 20 weeks' gestation, animal studies, in vitro studies, case studies, or coexposure studies. Study quality was assessed by 2 reviewers using the Newcastle-Ottawa Quality Assessment Scale. Title and abstract screening was conducted by 2 reviewers to remove duplicates and irrelevant studies. Remaining full text articles were screened by 2 reviewers against inclusion and exclusion criteria. Placental outcome data were extracted and tabulated separately for studies of placentation, placental weight, placental morphology, and placental molecular studies. Meta-analyses were conducted for outcomes reported by >3 studies. Database searching retrieved 640 unique records. Screening against inclusion and exclusion criteria resulted in 33 included studies. The quality assessment identified that 61% of studies were high quality, 30% were average quality, and 9% were low quality. Meta-analyses indicated that prenatal alcohol exposure increased the likelihood of placental abruption (odds ratio, 1.48 95% confidence interval, 1.37-1.60) but not placenta previa (odds ratio, 1.14 95% confidence interval, 0.84-1.34) and resulted in a reduction in placental weight of 51 g (95% confidence interval, -82.8 to -19.3). Reports of altered placental vasculature, placental DNA methylation, and gene expression following prenatal alcohol exposure were identified. A single study examined placentas from male and female infants separately and found sex-specific placental outcomes. Prenatal alcohol exposure increases the likelihood of placental abruption and is associated with decreased placental weight, altered placental vasculature, DNA methylation, and molecular pathways. Given the critical role of the placenta in determining pregnancy outcomes, further studies investigating the molecular mechanisms underlying alcohol-induced placental dysfunction are required. Sex-specific placental adaptations to adverse conditions in utero have been well documented thus, future studies should examine prenatal alcohol exposure-associated placental outcomes separately by sex.
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.PLACENTA.2009.12.008
Abstract: Workshops are an important part of the annual meeting of the International Federation of Placenta Associations (IFPA). At IFPA Meeting 2009 erse topics were discussed in twelve themed workshops. Topics covered included: immune response to pregnancy signaling between fetus and placenta bioactive lipids in placenta placenta in agricultural species epigenetics and placentation trophoblast deportation glucocorticoids and placental function endothelium placental transport genes and placenta uteroplacental blood flow and placental stem cells. This report is a full summary of the various topics covered.
Publisher: Elsevier
Date: 2012
Publisher: Elsevier BV
Date: 08-2019
Publisher: Springer Science and Business Media LLC
Date: 04-04-2014
Abstract: Asthma is the most prevalent chronic disease to complicate pregnancies worldwide, affecting around 12% of pregnant women in Australia. Oxidative stress and inflammation manifest during pregnancy however asthma in pregnancies further intensifies oxidative stress. Consumption of antioxidant-rich foods has been shown to be beneficial for asthma control in non-pregnant asthmatic adults. It has not been investigated whether antioxidant-rich foods can improve the elevated oxidative stress that occurs with asthma in pregnancy, thereby improving asthma control. The primary aim of this study is to determine whether increased consumption of antioxidant-rich foods for 12 weeks will improve maternal asthma control, compared to standard dietary intake during pregnancy. A 12 week, parallel randomized controlled trial will be conducted. One hundred and sixty eight pregnant women with mild, moderate, or severe asthma, currently using inhaled corticosteroids, and with poor diet quality, will be recruited at approximately12 weeks gestation. Following a 4 week run-in period, women will be randomized to either a 12 week antioxidant intervention (increased consumption of antioxidant-rich foods (≥5 servings/day vegetables, ≥2 servings/day fruit, ≥8 ½ servings/day grains (mostly wholegrains), 3–4 serving/week lean meat) or standard pregnancy care. The primary outcome is asthma control score (decrease of 0.5, the minimally clinically significant change). Secondary outcomes include plasma antioxidants, markers of oxidative stress, and time to, and number of, exacerbations. With two-tailed t-tests at 80% power, a s le size of 52 completions per group is required. Allowing for a 78% retention including a 20% removal of women from the analysis due to non-compliance, we will recruit 168 women. It is expected that this 12 week study will improve asthma control. This is significant because asthma is the most prevalent condition to complicate pregnancies and contributes to poor maternal, neonatal and infant health outcomes. Our research will provide the first evidence to show that, in pregnancy, consumption of antioxidant-rich foods is a key modifier of clinical asthma status. This research is crucial for contributing to the evidence base to inform future guidelines given existing clinical and research gaps. ACTRN12613000301763
Publisher: Elsevier BV
Date: 09-2014
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/741613
Abstract: Maternal asthma is a common disease to complicate human pregnancy. Epidemiological studies have identified that asthma during pregnancy increases the risk of a number of poor outcomes for the neonate including growth restriction, lower birthweight, preterm delivery, neonatal resuscitation, and stillbirth. Asthma therefore represents a significant health burden to society and could have an impact on the lifelong health of the children of women with asthma. Our research has identified that maternal asthma in pregnancy induces placental dysfunction and developmental perturbation in the fetus in a sex specific manner. These alterations in development could increase the risk of metabolic disease in adulthood of children of asthmatic mothers, especially females. In this paper, we will discuss the evidence currently available that supports the hypothesis that children of mothers with asthma may be at risk of lifelong health complications which include diabetes and hypertension.
Publisher: Informa UK Limited
Date: 26-02-2017
DOI: 10.1080/02770903.2016.1258080
Abstract: To determine the impact of self-reported maternal depression/anxiety on asthma control during pregnancy. Pregnant women with a doctor diagnosis of asthma (n = 189) were prospectively recruited at their antenatal booking visit, and the presence of maternal depression and anxiety was identified using self-report and routine questionnaire assessments. Data on exacerbations and asthma control were collected during gestation. Asthma control was assessed using the Juniper Asthma Control Questionnaire (ACQ) and women were classified as having recurrent uncontrolled asthma if their ACQ score was >1.5 during two or more consecutive study visits. Exacerbations were defined as events that led to increased treatment requirements, and doctor or hospital visits. There were 85 women with self-reported depression/anxiety and 104 women without self-reported depression/anxiety. The presence of depression/anxiety was associated with an increased likelihood (adjusted hazard ratio (HR) 1.67: 95% confidence interval (CI) 1.03-2.72) and incidence (adjusted incidence rate ratio (IRR) 1.71: 95% CI 1.13-2.58) of uncontrolled asthma during pregnancy, as well as an increased risk of recurrent uncontrolled asthma during 2 or more study visits (adjusted relative risk (RR) 1.98: 95% CI 1.00-3.91). No impact of depression/anxiety was observed with respect to the likelihood (adjusted HR 0.70: 95% CI 0.35-1.41) or incidence of exacerbations during pregnancy (adjusted IRR 0.66: 95% CI 0.35-1.26). This study provides evidence that the presence of maternal depression/anxiety is associated with an increased likelihood and incidence of uncontrolled asthma during pregnancy. Given the high prevalence of co-morbid depression/anxiety among asthmatics, further research investigating such associations is urgently required.
Publisher: Springer Science and Business Media LLC
Date: 15-03-2013
Publisher: Elsevier BV
Date: 03-2011
Publisher: The Endocrine Society
Date: 08-1994
DOI: 10.1210/JCEM.79.2.8045990
Abstract: The vasoactive effects of corticotropin-releasing hormone (CRH) in the human fetal-placental circulation in vitro have been investigated. Single lobules of term placentae were bilaterally perfused with constant flows of Krebs' solution (maternal and fetal, 5 ml/min, 95% O2, 5% CO2, 37 degrees C, pH 7.3) and changes in fetal-placental arterial perfusion pressure measured. Effects of human (hCRH) and ovine (oCRH) CRH were examined during submaximal vasoconstriction (100-120 mmHg) of the fetal-placental vasculature induced by prostaglandin F2 alpha (PGF2 alpha), (0.7-2 mumol/L). During infusion of hCRH or oCRH (24-7000 pmol/L) a concentration-dependent vasodilatation was observed. Human CRH and oCRH were equipotent as vasodilator agents (regression analysis P > 0.05 n = 5). The vasodilator response curves to human and ovine CRH were compared to prostacyclin (PGI2) (1.2-1180 nmol/L). Human and oCRH were 53 times more potent than PGI2 (regression analysis, P < 0.05 n = 5). These results indicate that CRH has powerful vasodilator properties in the human fetal-placental circulation and may play a role in control of placental vascular resistance to blood flow.
Publisher: Wiley
Date: 09-2014
DOI: 10.14814/PHY2.12145
Publisher: The Endocrine Society
Date: 12-2008
DOI: 10.1210/JC.2008-1077
Abstract: Differential promoter use and alternative splicing generate a variety of glucocorticoid receptor (GR) mRNA transcripts, potentially altering the cortisol responsiveness of gestational tissues during pregnancy and labor. We examined GR mRNA transcript expression in term placentae before and after labor, in association with fetal sex and after glucocorticoid treatment. RNA from 34 placentae and from eight placental explants incubated with glucocorticoids were analyzed for the GR mRNA variants GR-alpha, GR-beta, GR-P, and GR-gamma and the untranslated exon one variants 1A1, 1A2, 1A3, 1B, and 1C by quantitative RT-PCR. mRNA expression was assessed. All GR mRNA variants examined were detected in the human placenta, with GR-alpha and GR-1C mRNA having the highest expression of GR splice variants and exon 1 variants, respectively. GR-P mRNA abundance decreased with spontaneous labor (P < 0.01). GR-1A3 mRNA abundance changed with fetal sex, with a higher level in placentae of male fetuses (P < 0.05). GR-1C was the preferential promoter for GR-alpha, GR-gamma, and GR-P mRNA. GR-beta mRNA was preferentially associated with GR-1A1. GR-P mRNA transcription switched to the GR-1A1 promoter after labor and to the GR-1A3 promoter in placentae from male fetuses. Glucocorticoid treatment significantly reduced transcription from promoters GR-1B and -1C and decreased GR-alpha and GR-P mRNA abundance. The human placenta expresses a variety of GR mRNA transcripts. GR-alpha mRNA transcribed from the 1C promoter generates the majority of placental GR. However, alterations in promoter use and alternative splicing may modulate responses to cortisol during stressful events.
Publisher: Wiley
Date: 30-09-2016
DOI: 10.14814/PHY2.12941
Publisher: Informa UK Limited
Date: 12-09-2015
DOI: 10.3109/02770903.2015.1054403
Abstract: To describe the pattern and severity of rhinitis in pregnancy and the impact rhinitis has on asthma control and quality of life (QoL) in pregnant women with asthma. Two hundred and eighteen non-smoking pregnant women with asthma were participants in a randomised controlled trial of exhaled nitric oxide guided treatment adjustment. Rhinitis was assessed using a visual analogue scale (VAS) scored from 0 to 10 and classified as current (VAS > 2.5), moderate/severe versus mild (VAS > 6 vs <5), atopic versus non-atopic and pregnancy rhinitis. At baseline, women completed the 20-Item Sino-Nasal Outcome Test (SNOT20), asthma-specific (AQLQ-M) QoL questionnaires and the Six-Item Short-Form State Trait Anxiety Inventory (STAI-6). Asthma control was assessed using the asthma control questionnaire (ACQ). Perinatal outcomes were collected after delivery. Current rhinitis was present in 142 (65%) women including 45 (20%) women who developed pregnancy rhinitis. Women with current rhinitis had higher scores for ACQ (p = 0.004), SNOT20 (p < 0.0001) and AQLQ-M (p < 0.0001) compared to women with no rhinitis. Current rhinitis was associated with increased anxiety symptoms (p = 0.002), rhinitis severity was associated with higher ACQ score (p = 0.004) and atopic rhinitis was associated with poorer lung function (p = 0.037). Rhinitis symptom severity improved significantly during gestation (p < 0.0001). There was no impact on perinatal outcomes. Improved asthma control was associated with improvement in rhinitis. Rhinitis in pregnant women with asthma is common and associated with poorer asthma control, sino-nasal and asthma-specific QoL impairment and anxiety. In the context of active asthma management there was significant improvement in rhinitis symptoms and severity as pregnancy progressed.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.JRI.2017.07.002
Abstract: Allergy is a chronic disease that can develop as early as infancy, suggesting that early life factors are important in its aetiology. Variable associations between size at birth, a crude marker of the fetal environment, and allergy have been reported in humans and require comprehensive review. Associations between birth weight and allergy are however confounded in humans, and we and others have therefore begun exploring the effects of early life events on allergy in experimental models. In particular, we are using ovine models to investigate whether and how a restricted environment before birth protects against allergy, whether methyl donor availability contributes to allergic protection in IUGR, and why maternal asthma during pregnancy is associated with increased risks of allergic disease in children. We found that experimental intrauterine growth restriction (IUGR) in sheep reduced cutaneous responses to antigens in progeny, despite normal or elevated IgE responses. Furthermore, maternal methyl donor supplementation in late pregnancy partially reversed effects of experimental IUGR, consistent with the proposal that epigenetic pathways underlie some but not all effects of IUGR on allergic susceptibility. Ovine experimental allergic asthma with exacerbations reduces relative fetal size in late gestation, with some changes in immune populations in fetal thymus suggestive of increased activation. Maternal allergic asthma in mice also predisposes progeny to allergy development. In conclusion, these findings in experimental models provide direct evidence that a perturbed environment before birth alters immune system development and postnatal function, and provide opportunities to investigate underlying mechanisms and develop and evaluate interventions.
Publisher: Wiley
Date: 04-2022
DOI: 10.1111/AJO.13480
Publisher: Elsevier BV
Date: 06-2012
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.PLACENTA.2019.06.380
Abstract: Maternal asthma increases the risk of adverse pregnancy outcomes and may affect fetal growth and placental function by differential effects on the expression of glucocorticoid receptor (GR) isoforms, leading to altered glucocorticoid signalling. Our aim was to examine the effect of maternal asthma on placental GR profiles using a pregnant sheep model of asthma. Nine known GR isoforms were detected. There was a significant increase in the expression of placental GR isoforms that are known to have low trans-activational activity in other species including GR A, GR P and GRγ which may result in a pro-inflammatory environment in the presence of allergic asthma.
Publisher: Elsevier BV
Date: 06-2017
Publisher: BMJ
Date: 05-05-2021
DOI: 10.1136/BMJ.N893
Abstract: To determine the effectiveness of closed incision negative pressure wound therapy (NPWT) compared with standard dressings in preventing surgical site infection (SSI) in obese women undergoing caesarean section. Multicentre, pragmatic, randomised, controlled, parallel group, superiority trial. Four Australian tertiary hospitals between October 2015 and November 2019. Eligible women had a pre-pregnancy body mass index of 30 or greater and gave birth by elective or semi-urgent caesarean section. 2035 consenting women were randomised before the caesarean procedure to closed incision NPWT (n=1017) or standard dressing (n=1018). Allocation was concealed until skin closure. The primary outcome was cumulative incidence of SSI. Secondary outcomes included depth of SSI (superficial, deep, or organ/body space), rates of wound complications (dehiscence, haematoma, seroma, bleeding, bruising), length of stay in hospital, and rates of dressing related adverse events. Women and clinicians were not masked, but the outcome assessors and statistician were blinded to treatment allocation. The pre-specified primary intention to treat analysis was based on a conservative assumption of no SSI for a minority of women (n=28) with missing outcome data. Post hoc sensitivity analyses included best case analysis and complete case analysis. In the primary intention to treat analysis, SSI occurred in 75 (7.4%) women treated with closed incision NPWT and in 99 (9.7%) women with a standard dressing (risk ratio 0.76, 95% confidence interval 0.57 to 1.01 P=0.06). Post hoc sensitivity analyses to explore the effect of missing data found the same direction of effect (closed incision NPWT reducing SSI), with statistical significance. Blistering occurred in 40/996 (4.0%) women who received closed incision NPWT and in 23/983 (2.3%) who received the standard dressing (risk ratio 1.72, 1.04 to 2.85 P=0.03). Prophylactic closed incision NPWT for obese women after caesarean section resulted in a 24% reduction in the risk of SSI (3% reduction in absolute risk) compared with standard dressings. This difference was close to statistical significance, but it likely underestimates the effectiveness of closed incision NPWT in this population. The results of the conservative primary analysis, multivariable adjusted model, and post hoc sensitivity analysis need to be considered alongside the growing body of evidence of the benefit of closed incision NPWT and given the number of obese women undergoing caesarean section globally. The decision to use closed incision NPWT must also be weighed against the increases in skin blistering and economic considerations and should be based on shared decision making with patients. ANZCTR identifier 12615000286549.
Publisher: Elsevier BV
Date: 07-2014
Abstract: Maternal nutrition can have a profound effect on fetal growth, development, and subsequent infant birth weight. Preconception dietary patterns have not been assessed in relation to perinatal outcomes. The objectives of this study were to identify associations between maternal dietary patterns in the 12 mo before conception on fetal growth and preterm delivery. Preconception food frequency data were collected retrospectively in 309 women. Dietary patterns were derived using factor analysis. Perinatal outcomes were collected at delivery with birth weight data calculated into percentiles to assess small and large for gestational age and preterm delivery at <37 wk. Three dietary patterns were identified: 1) high-protein/fruit (characterized by fish, meat, chicken, fruit, and some whole grains) 2) high-fat/sugar/takeaway (takeaway foods, potato chips, refined grains) and 3) vegetarian-type (vegetables, legumes, whole grains). A 1-SD increase in the scores on the high-protein/fruit pattern was associated with decreased likelihood of preterm birth (adjusted OR: 0.31 95% CI: 0.13, 0.72 P = 0.007), whereas the reverse direction was apparent for the high-fat/sugar/takeaway pattern (adjusted OR: 1.54 95% CI: 1.10, 2.15 P = 0.011). A 1-SD increase in the scores on the high fat/sugar/takeaway pattern was also associated with shorter gestation (adjusted regression coefficient: -2.7 95% CI: -4.3, -1.1 P = 0.001) and birth length (adjusted regression coefficient: -0.5 95% CI: -0.8, -0.1 P = 0.004). Nutrition before pregnancy is associated with perinatal outcomes. A dietary pattern containing several protein-rich food sources, fruit, and some whole grains is associated with reduced likelihood for preterm delivery, whereas a dietary pattern mainly consisting of discretionary items is associated with preterm delivery, shorter birth length, and earlier gestation. Poor dietary behaviors in the periconceptional period could be altered to promote behavior change in dietary intake to improve perinatal outcomes and the long-term health of the child.
Publisher: Frontiers Media SA
Date: 13-10-2016
Publisher: European Respiratory Society (ERS)
Date: 09-2005
DOI: 10.1183/09031936.05.00135604
Abstract: During pregnancy, patients with asthma are at risk of poor outcomes, particularly when asthma is poorly controlled. The aim of this study was to determine the level of asthma self-management skills and knowledge among pregnant subjects and describe the implementation of an asthma education programme delivered in an antenatal clinic setting. Pregnant subjects with asthma were assessed by an asthma educator at 20 (n = 211) and 33 weeks gestation (n = 149). Lung function, symptoms, medication use, adherence, knowledge and inhaler technique were assessed. They were asked whether they had a written asthma action plan, or performed peak flow monitoring. Asthma was classified as mild, moderate or severe. At the first visit with the asthma educator, 40% of females reported nonadherence to inhaled corticosteroids, inhaler technique was assessed as inadequate in 16% and 42% had inadequate medication knowledge. Peak flow monitoring was performed by 3% and 15% had a written action plan. There were significant improvements in all aspects of asthma self-management following education. In females with severe asthma, night symptoms and reliever medication use significantly decreased after education. In conclusion, during pregnancy, patients with asthma have poor asthma knowledge and skills, and may benefit from self-management education as part of their obstetric care.
Publisher: MDPI AG
Date: 09-08-2023
Abstract: Alterations in the hypothalamic–pituitary–adrenal (HPA) axis and associated changes in circulating levels of glucocorticoids are integral to an organism’s response to stressful stimuli. Glucocorticoids acting via glucocorticoid receptors (GRs) play a role in fertility, reproduction, placental function, and foetal development. GRs are ubiquitously expressed throughout the female reproductive system and regulate normal reproductive function. Stress-induced glucocorticoids have been shown to inhibit reproduction and affect female gonadal function by suppressing the hypothalamic–pituitary–gonadal (HPG) axis at each level. Furthermore, during pregnancy, a mother’s exposure to prenatal stress or external glucocorticoids can result in long-lasting alterations to the foetal HPA and neuroendocrine function. Several GR isoforms generated via alternative splicing or translation initiation from the GR gene have been identified in the mammalian ovary and uterus. The GR isoforms identified include the splice variants, GRα and GRβ, and GRγ and GR-P. Glucocorticoids can exert both stimulatory and inhibitory effects and both pro- and anti-inflammatory functions in the ovary, in vitro. In the placenta, thirteen GR isoforms have been identified in humans, guinea pigs, sheep, rats, and mice, indicating they are conserved across species and may be important in mediating a differential response to stress. Distinctive responses to glucocorticoids, differential birth outcomes in pregnancy complications, and sex-based variations in the response to stress could all potentially be dependent on a particular GR expression pattern. This comprehensive review provides an overview of the structure and function of the GR in relation to female fertility and reproduction and discusses the changes in the GR and glucocorticoid signalling during pregnancy. To generate this overview, an extensive non-systematic literature search was conducted across multiple databases, including PubMed, Web of Science, and Google Scholar, with a focus on original research articles, meta-analyses, and previous review papers addressing the subject. This review integrates the current understanding of GR variants and their roles in glucocorticoid signalling, reproduction, placental function, and foetal growth.
Publisher: Elsevier BV
Date: 05-2021
DOI: 10.1016/J.PLACENTA.2021.03.013
Abstract: The human placenta expresses multiple glucocorticoid receptor (GR) isoforms that may be partially regulated by the untranslated 5' exon 1 GR gene promoter region which consists of 9 different promoters and 13 splice variants. The objective of this study was to determine which GR exon 1 variants are expressed in the human placenta and relate these findings to GR mRNA and protein expression. Placental extracts from pregnancies with or without the complication of maternal asthma and trophoblast cells exposed to an inflammatory challenge in vitro were examined using PCR and Western blot to measure GR exon 1 variants, GR splice variant mRNA and GR protein isoforms, respectively. All 9 GR exon 1 variants were detectable in the human placenta and included GR exons 1A, 1B, 1C, 1D, 1E, 1F, 1H, 1I and 1J. In the presence of maternal asthma and a male fetus there was preferential expression of GR exon 1B, 1C, IF and 1J (KW-ANOVA, P < 0.05) which were positively correlated with GRα D3 protein isoform. In female placentae from pregnancies complicated by asthma there was no upregulation of any exon 1 variant (KW-ANOVA, P < 0.05). Exposure of BeWo trophoblast cell line to an inflammatory challenge, lipopolysaccharide, in vitro, resulted in preferential expression of GR exon 1B, 1D, 1E and 1H and associated with GRα-D1 protein upregulation. The preferential expression of different GR exon 1 promoters drive the upregulation of GRα D isoforms and contribute to glucocorticoid resistance observed in male placentae of pregnancies complicated by asthma.
Publisher: European Respiratory Society (ERS)
Date: 30-07-2013
DOI: 10.1183/09031936.00054913
Abstract: Does cigarette smoking in pregnancy explain the increased risk of adverse perinatal outcomes that occur with maternal asthma or does it compound the effect? Using population based birth records, a retrospective analysis was conducted of all singleton pregnancies in South Australia over 10 years (1999-2008 n=172 305), examining maternal asthma, cigarette smoking and quantity of smoking to estimate odds ratios. Compared with nonasthmatic females who did not smoke during pregnancy, both asthmatic females who smoked and those who did not smoke during pregnancy had a significantly increased risk of gestational diabetes, antepartum haemorrhage, polyhydramnios, premature rupture of membranes, emergency Caesarean section, and the child being small for gestational age and having congenital abnormalities. These associations suggest that asthma, independently of maternal smoking, increases the risk of these adverse perinatal outcomes. Maternal smoking was itself associated with an increased risk of a number of poor neonatal outcomes, with a dose-response relationship observed. Notably, maternal asthma combined with cigarette smoking significantly increased the risk of preterm birth and urinary tract infections to a greater degree than with either exposure alone. Maternal asthma and cigarette smoking during pregnancy are both independently associated with adverse perinatal outcomes and, combined, compound the risk of preterm birth and urinary tract infections.
Publisher: Elsevier BV
Date: 09-2016
Publisher: The Endocrine Society
Date: 1999
DOI: 10.1210/JC.84.1.291
Publisher: MDPI AG
Date: 14-11-2021
DOI: 10.3390/NU13114068
Abstract: Premature infants have a fragile ecology of the gut microbiota, which is associated with many health problems and may be influenced by formula versus breast feeding. The present study investigated differences in the process of gut microbiota colonisation in preterm infants fed with breastmilk or formula with or without probiotics before 12 weeks. This cohort study recruited 138 premature infants 31 in the breastmilk (BM) group, 59 in the probiotics formula (PF) group and 48 in the non-probiotics formula (NPF) group, according to the feeding practice they received at birth. Gut bacterial composition was identified with 16S rRNA gene sequencing in faecal s les collected at 1 week, 6 weeks and 12 weeks after birth. The alpha ersity was higher in the PF group compared to the other groups at week 1 and 6 (both p 0.01) but showed no difference at week 12. The beta ersity of the three groups showed a trend towards similarity at the first two stages (p 0.001 and p = 0.009, respectively) and finally showed no difference at week 12. Canonical redundancy analysis showed that feeding type could explain the difference in gut microbiota composition at week one and six (both p 0.01). At genus level, Bifidobacterium was enriched in the PF group, while the Enterococcus and Streptococcus was enriched in the NPF group. In summary, formula with probiotics feeding after birth can affect gut microbiota colonisation and lead to a bacterial community with less potential pathogens.
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.PLACENTA.2022.02.015
Abstract: Maternal obesity is a significant risk factor for poor pregnancy outcomes. Obesity is linked to abnormalities in placental tissue at term. The purpose of this study was to correlate changes in placental stiffness, measured via ultrasound elastography, with maternal pre-pregnancy body mass index and gestational weight gain. Body Mass Index and gestation weight gain data was collected from 238 women. Elastography measurements were obtained via ultrasound at 24-, 28- and 36-weeks' gestation. An analysis using a linear mixed regression model assessed for the statistical significance of pre-pregnancy BMI, pregnancy weight gain and placental SWV (Shear Wave Velocity). Pre-pregnancy weight status has a significant impact on placental tissue stiffness detectable via ultrasound elastography. Placental tissue stiffness was highest in obese women, followed by overweight women. Obese women, on average, had a MeanSWV 0.11 m/s (95% CI (0.061-0.15) m/s, p < 0.001) above the healthy group throughout the 3rd trimester. Weight gain during pregnancy had a small impact on placental stiffness at the end of pregnancy. MeanSWV was 0.06 m/s (95% CI (0.03-0.10) m/s, p < 0.001) higher in the excessive weight gain group. Structural changes of the placenta detected via ultrasound elastography techniques are not exclusive to placental dysfunction conditions (pre-ecl sia and growth restriction) but are also associated with maternal obesity.
Publisher: Springer Science and Business Media LLC
Date: 03-2009
DOI: 10.1203/PDR.0B013E318193EDF1
Abstract: This study aimed to characterize early neonatal microvascular function after preecl tic pregnancy with respect to infant sex and in utero growth. Peripheral microvascular blood flow was examined prospectively from 6 to 72 h of age using laser Doppler flowmetry in a cohort of term infants of normotensive women and women with late-onset preecl sia. For male infants, those born to preecl tic women had greater microvascular blood flow at 6 h (p < 0.05) with no change over time. Male infants of normotensive women exhibited increasing blood flow with time (p = 0.005). Female infants of preecl tic mothers exhibited similar blood flow at 6 h of age to females of normotensive mothers, followed by significantly greater blood flow by 72 h (p < 0.001). Altered fetal microvascular structure and function in response to maternal preecl sia may result in sexually dimorphic patterns of fetal growth and account for alterations in neonatal microvascular adaptation after birth.
Publisher: Informa UK Limited
Date: 18-11-2011
DOI: 10.3109/02770903.2011.631239
Abstract: Little is known about the psychosocial impact and perceived teratogenic (fetal harm due to medication) risks of asthma treatment (inhaled/oral corticosteroids and β-agonist) during pregnancy. To assess the perception of asthma control, quality of life (QoL), and perceived risks of therapy in pregnant women with asthma. Pregnant women with asthma (n = 125) were recruited between 12 and 20 weeks gestation. QoL (generic: Short Form-12 Health Survey v1, and asthma specific: Asthma Quality of Life Questionnaire-Marks (AQLQ-M)) and psychological variables were assessed using the Perceived Control of Asthma Questionnaire (PCAQ), the Brief Illness Perception Questionnaire, and the Six-Item Short-Form State Trait Anxiety Inventory (STAI-6). Women's perceptions of the teratogenic risks of asthma therapy were also assessed and analyzed for adherence to maintenance inhaled corticosteroids (ICSs), poor asthma control, and QoL. Women reported good QoL (median AQLQ-M total score/maximum score = 0.88/10), moderate ability to deal with asthma symptoms (mean PCAQ score = 42.6/55), positive beliefs about their asthma and low anxiety (median STAI score = 26.7/80). Perceived teratogenic risks for asthma drugs were excessive and class dependent. Women perceived there was a 42% teratogenic risk for oral corticosteroid, a 12% risk for ICSs, and a 5% risk with short-acting β-agonist. Illness beliefs, emotional response to illness (p = .030), age ≥ 30 years (p = .046), and maintenance ICS use (p = .045) were significantly associated with uncontrolled asthma, while maintenance ICS use (p = .023), illness beliefs, consequences (p = .044), timeline (p = .016), and emotional response (p = .015) and anxiety (p ≤ .0001) were significantly associated with reduced QoL. In pregnancy, women with asthma experience good QoL but overestimate teratogenic risks of asthma medication. Maintenance ICS use, illness beliefs, and anxiety are associated with impaired QoL and asthma control.
Publisher: Elsevier BV
Date: 03-2022
DOI: 10.1016/J.PLACENTA.2022.02.010
Abstract: The mechanisms that contribute to continued male intrauterine growth in response to an adverse maternal environment, such as those brought on by maternal asthma, remain largely undefined but may, in part, be mediated by androgen-mediated signalling. We previously reported the expression of multiple AR protein isoforms in the human placenta and proposed the novel AR-45 isoform to be integral in mediating male-specific androgen-dependent signalling in the presence of maternal asthma. In the current study we have used an ex vivo approach to further understand sex-specific differences in placental androgen signalling in the presence and absence of inflammation using human term villous placental explants. Explants were cultured in the presence and absence of 0.1 nM dihydrotestosterone (DHT), 1 μg/ml lipopolysaccharide (LPS), or DHT + LPS for 24hr. Tissue was used for gene expression and subcellular AR protein isoform expression. Cytoplasmic and nuclear AR protein isoforms expression did not vary between culture conditions in either sex. AR-45 activity was upregulated in male placentae cultured in DHT, LPS and DHT + LPS only. There were no changes in the expression of androgen-mediated downstream targets in males in response to culture conditions, but females had significantly reduced IGF1R expression in response to LPS. Increased AR-45 activity in the presence of inflammation may drive continued male feto-placental growth via maintained expression of downstream growth targets. Our findings build on previous work suggesting an important role for AR-45 in regulating male-specific adaptations to placental inflammation and underscores the need to further characterise the function of this AR isoform.
Publisher: Informa UK Limited
Date: 18-04-2011
DOI: 10.3109/14767058.2011.569618
Abstract: Dysregulated vascular resistance contributes to hypotension following preterm birth with sex-specific differences in microvascular function conferring a male disadvantage. We hypothesized that glucocorticoid mediated, sex-specific differences in the endogenous catecholamine norepinephrine and endothelially derived endothelin-1 (ET-1) contribute to microvascular dysfunction in preterm neonates in the immediate newborn period. Umbilical and plasma ET-1 and normetanephrine, in 24 h urine s les, were determined at 24, 72, and 120 h of age in 24-34 week infants (n = 60). Microvascular blood flow was determined by laser Doppler flowmetry. In infants born within 72 h of antenatal glucocorticoid exposure, normetanephrine was higher in females than males (p = 0.048). Normetanephrine was inversely correlated with both microvascular blood flow at 24 h (p = 0.025) and CRIB II (p = 0.001). While umbilical arterial ET-1 was higher in females delivered <72 h after antenatal betamethasone (p = 0.006), plasma ET-1 did not correlate with microvascular blood flow or illness severity. Only sex and normetanephrine contributed significantly to both microvascular blood flow and endothelium dependant vasodilatation. These data support glucocorticoid mediated, sex-specific differences in mediators of vascular tone that may contribute to the impaired mechanisms compromising successful hemodynamic adaption to neonatal life and resulting in excess male morbidity and mortality.
Publisher: The American Association of Immunologists
Date: 02-2009
DOI: 10.4049/JIMMUNOL.182.3.1411
Abstract: In the presence of maternal asthma, we have previously reported reduced placental blood flow, decreased cortisol metabolism, and reductions in fetal growth in response to maternal asthma and asthma exacerbations. We have proposed that these changes in placental function and fetal development may be related to activation of proinflammatory pathways in the placenta in response to maternal asthma. In the present study, we examined the influence of maternal asthma severity, inhaled glucocorticoid treatment, maternal cigarette use, placental macrophage numbers, and fetal sex on placental cytokine mRNA expression from a prospective cohort study of pregnant women with and without asthma. Placental expression of TNF-α, IL-1β, IL-6, IL-8, and IL-5 mRNA were all increased significantly in placentae of female fetuses whose mothers had mild asthma, but no changes were observed in placentae of male fetuses. The proinflammatory cytokines TNF-α, IL-1β, and IL-6 were negatively correlated with female cord blood cortisol, but there were no such correlations in placentae from males. Multivariate analysis indicated the strongest predictor of both cytokine mRNA expression in the placenta and birth weight was fetal cortisol but only in females. Placental cytokine mRNA levels were not significantly altered by inhaled glucocorticoid use, placental macrophage numbers, cigarette use, moderate-severe asthma, or male sex. These data suggest that placental basal cytokine mRNA expression is sex specifically regulated in pregnancies complicated by asthma, and interestingly these changes are more prevalent in mild rather than severe asthma.
Publisher: Elsevier BV
Date: 11-2005
DOI: 10.1016/J.PLACENTA.2004.10.018
Abstract: Our previous work has demonstrated that alterations in placental function are associated with changes in fetal development in pregnancies complicated by asthma. The pathophysiology of asthma in adults and children and intrauterine growth restriction during pregnancy are associated with oxidative stress. Based on this information, we examined whether placental anti-oxidant pathways and markers of biological oxidation were altered in pregnancies complicated by asthma. Anti-oxidant enzyme activities of superoxide dismutase, glutathione peroxidase and thioredoxin reductase, thioredoxin concentrations, lipid and protein oxidation levels were measured in placentae of pregnancies complicated by asthma and compared to uncomplicated, non-asthmatic pregnancies. Placental tissue homogenates of pregnancies complicated by asthma demonstrated significantly increased levels of lipid peroxidation (25.7+/-1.8 micromol/mg protein versus 12.1+/-1.6 micromol/mg protein, P=0.008) and protein carbonyl concentrations (414.6+/-51.4 units/mg protein versus 222.3+/-32.6 units/mg protein, P=0.0032) when compared to non-asthmatic controls. The activities of the anti-oxidant proteins superoxide dismutase (2.17+/-0.09 units/mg protein versus 1.67+/-0.09 units/mg protein, P=0.014) and thioredoxin reductase (54.0+/-6.9 units/mg protein versus 28.7+/-6.0 units/mg protein, P=0.009) were significantly increased in the presence of maternal asthma. Placental thioredoxin levels (102.9+/-5.3 ng/mg protein versus 92.9+/-8.6 ng/mg protein, P=0.37) and glutathione peroxidase activity (27.3+/-2.2 mmol/min/mg protein versus 28.3+/-2.2 mmol/min/mg, P=0.83) were not significantly different in pregnancies complicated by asthma and non-asthmatic pregnancies. There was no effect of fetal sex, asthma severity or treatment for asthma on these pathways. Maternal asthma during pregnancy is associated with increased placental enzymatic anti-oxidant capacity and also increased protein oxidation suggesting there is a compensatory increase in anti-oxidant activity in response to increased oxidative stress.
Publisher: Elsevier BV
Date: 04-2016
Publisher: Informa UK Limited
Date: 16-09-2015
Publisher: The Endocrine Society
Date: 04-2006
DOI: 10.1210/ER.2005-0011
Abstract: The environment in which the fetus develops is critical for its survival and long-term health. The regulation of normal human fetal growth involves many multidirectional interactions between the mother, placenta, and fetus. The mother supplies nutrients and oxygen to the fetus via the placenta. The fetus influences the provision of maternal nutrients via the placental production of hormones that regulate maternal metabolism. The placenta is the site of exchange between mother and fetus and regulates fetal growth via the production and metabolism of growth-regulating hormones such as IGFs and glucocorticoids. Adequate trophoblast invasion in early pregnancy and increased uteroplacental blood flow ensure sufficient growth of the uterus, placenta, and fetus. The placenta may respond to fetal endocrine signals to increase transport of maternal nutrients by growth of the placenta, by activation of transport systems, and by production of placental hormones to influence maternal physiology and even behavior. There are consequences of poor fetal growth both in the short term and long term, in the form of increased mortality and morbidity. Endocrine regulation of fetal growth involves interactions between the mother, placenta, and fetus, and these effects may program long-term physiology.
Publisher: Future Medicine Ltd
Date: 2012
DOI: 10.2217/EBO.11.61
Publisher: American Academy of Pediatrics (AAP)
Date: 07-2009
Abstract: OBJECTIVE: With male gender as a strong predictor of cardiovascular instability, we hypothesized that gender-specific differences in circulating carbon monoxide levels contributed to dysregulated microvascular function in preterm male infants. METHODS: Infants born at 24 to 34 weeks of gestation (N = 84) were studied in a regional tertiary neonatal unit. Carboxyhemoglobin levels were measured through spectrophotometry in umbilical arterial blood and at 24, 72, and 120 hours after birth. Microvascular blood flow was determined through laser Doppler flowmetry. RESULTS: Carboxyhemoglobin levels demonstrated a strong inverse relationship with gestational age (r = −0.636 P & .001) and were higher in boys (P = .032). Repeated-measures analysis of variance showed a significant decrease in arterial carboxyhemoglobin levels over time (P & .001), with significant between-subjects effects for gestational age (P = .011) and gender (P = .025). Positive correlations with microvascular blood flow at 24 hours of age (r = 0.495 P & .001) and 120 hours of age (r = 0.548 P & .001) were observed. With controlling for gestational age, carboxyhemoglobin levels at 72 hours were greater for infants who died in the first week of life (P = .035). CONCLUSIONS: The gestational age- and gender-specific differences in carboxyhemoglobin levels and the relationship with dysregulated microvascular blood flow, a state related to greater illness severity and hypotension, are novel findings not confined solely to sick preterm infants. Both inducible heme oxygenase-dependent and non–heme oxygenase-dependent pathways may initially play a central role in carbon monoxide production, inducing pathophysiologic processes in a gender-specific manner.
Publisher: American Physiological Society
Date: 07-2002
DOI: 10.1152/AJPENDO.00497.2001
Abstract: We hypothesized that urocortin might be produced in the pituitary of the late-gestation ovine fetus in a manner that could contribute to the regulation of ACTH output. We used in situ hybridization and immunohistochemistry to identify urocortin mRNA and protein in late-gestation fetal pituitary tissue. Levels of urocortin mRNA rose during late gestation and were associated temporally with rising concentrations of pituitary proopiomelanocortin (POMC) mRNA. Urocortin was localized both to cells expressing ACTH and to non-ACTH cells by use of dual immunofluorescence histochemistry. Transfection of pituitary cultures with urocortin antisense probe reduced ACTH output, whereas added urocortin stimulated ACTH output from cultured pituitary cells. Cortisol infusion for 96 h in chronically catheterized late-gestation fetal sheep significantly stimulated levels of pituitary urocortin mRNA. We conclude that urocortin is expressed in the ovine fetal pituitary and localizes with, and can stimulate output of, ACTH. Regulation of urocortin by cortisol suggests a mechanism to override negative feedback and sustain feedforward of fetal hypothalamic-pituitary-adrenal function, leading to birth.
Publisher: Public Library of Science (PLoS)
Date: 07-01-2013
Publisher: Elsevier BV
Date: 08-2006
DOI: 10.1016/J.PLACENTA.2005.08.007
Abstract: Studies have shown that pregnancy can alter the pathophysiology of a pre-existing maternal disease such as asthma. However, the mechanisms that alter maternal asthma during pregnancy are presently unknown. Previous work has demonstrated that human bronchial smooth muscle (BSM) cells produce inflammatory factors in response to nonpregnant, atopic plasma. The aim of this study was to determine whether circulating pregnancy-derived factors in maternal and fetal plasma can stimulate inflammatory mediator release in BSM cells in the presence and absence of maternal asthma. Cultured human BSM cells were exposed to maternal and fetal plasma from normal pregnancies and pregnancies complicated by asthma. Inflammatory mediator release was determined by enzyme-linked immunosorbent assay (ELISA). Both maternal and fetal plasma from asthmatic and nonasthmatic in iduals significantly increased production of interleukin (IL)-6 (ANOVA, P<0.001), regulated upon activation, normal T-cell expressed and secreted (RANTES) (ANOVA, P<0.01), and soluble intercellular cell-adhesion molecule-1 (sICAM-1) (ANOVA, P<0.01). There was no difference in inflammatory mediator release in response to asthma and nonasthmatic plasma. Eotaxin release was increased by pregnant asthmatic plasma (ANOVA, P<0.05). The results of this study suggest that circulating pregnancy-related factors can activate asthma-associated mediators in BSM cells. This change in BSM function may be one mechanism that contributes to increased asthma severity during pregnancy.
Publisher: Frontiers Media SA
Date: 20-05-2021
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.PLACENTA.2016.12.017
Abstract: The physiological mechanisms that confer different outcomes in morbidity and mortality of the fetus exposed to stressful environments may be driven by significant differences in the expression and function of the placental glucocorticoid receptor (GR). The recent discovery that the placenta contains at least 8 different isoforms of the GR raises questions about the regulation and physiological relevance of the many GR variants expressed in the placenta. The current data also highlights that in idual differences in glucocorticoid sensitivity, variations in the effect of different complications of pregnancy on birth outcomes and sex differences in the response to stress, may all be dependent on a specific GR isoform expression profile. This review will investigate the current state of knowledge of GR isoforms in the placenta and discuss the potential role of these multiple isoforms in regulating glucocorticoid sensitivity.
Publisher: Elsevier BV
Date: 11-2012
DOI: 10.1016/J.PLACENTA.2012.08.004
Abstract: To examine whether syncytin-1 has immune regulatory functions and is carried by human placental exosomes. Further, to examine whether corticotropin-releasing hormone (CRH) can induce the production of syncytin-1. Human placental exosomes were isolated from placental explant, primary trophoblast and BeWo cell cultures. The presence of exosomes was confirmed by transmission electron microscopy and western blotting. Exosomal protein was probed with 3 separate antibodies targeting syncytin-1. Syncytin-1 immunosuppression was tested, using either a syncytin-1 recombinant ectodomain protein or a synthetic peptide with the human syncytin-1 immunosuppressive domain sequence, in an in vitro human blood culture system immune challenged with LPS or PHA. The inhibition of cytokine production by syncytin-1 was determined by ELISA of TNF-α, IFN-γ and CXCL10. BeWo cells were stimulated with CRH or vehicle for 24 h. mRNA and Protein was extracted from the cells for real-time PCR and western blotting analysis while exosomes were extracted from conditioned media for analysis by western blotting. Protein expression of syncytin-1 was detected in exosomes isolated from placental explants, primary trophoblast and BeWo cell cultures. Syncytin-1 recombinant ectodomain was also shown to inhibit the production of the Th1 cytokines TNF-α and IFN-γ as well as the chemokine, CXCL10 in human blood cells. Finally, this study showed that syncytin-1 can be stimulated by CRH. The presence of syncytin-1 in placental exosomes provides a mechanism for syncytin-1 to reach and interact with target cells of the maternal immune system and represents a novel mechanism of endogenous retroviral mediated immunosuppression that may be relevant for maternal immune tolerance.
Publisher: MDPI AG
Date: 14-08-2013
DOI: 10.3390/NU5083212
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: Elsevier BV
Date: 2007
DOI: 10.1016/J.PLACENTA.2005.12.010
Abstract: Pregnant women with asthma are frequently exposed to synthetic glucocorticoids and glucocorticoids are known to reduce fetal growth. The fetus is normally protected from the harmful effects of maternally derived glucocorticoids by the placental enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2). Whether 11beta-HSD2 inactivates the synthetic glucocorticoids used for asthma treatment during pregnancy (budesonide, beclomethasone dipropionate and fluticasone propionate) remains unknown. To investigate the relationship between steroid use during pregnancy and fetal growth and development, pregnant women with (n=119) and without asthma (n=84) were followed throughout pregnancy. Data on asthma medication use, neonatal size at birth, placental weight and cord blood cortisol and estriol were collected. Placental tissue s les were collected from non-asthmatic women (n=8) for metabolism studies. Placental 11beta-HSD2 activity was determined using beclomethasone dipropionate, budesonide, fluticasone propionate, prednisolone, dexamethasone and betamethasone as steroid substrates. Steroids and their oxidised metabolites were examined using thin layer chromatography and densitometry. Placental 11beta-HSD2 metabolised beclomethasone, prednisolone, dexamethasone and betamethasone, but not budesonide or fluticasone. No association between the use of inhaled steroids for asthma treatment during pregnancy and alterations in neonatal size, placental weight, gestational age at delivery, or umbilical vein estriol concentrations was demonstrated compared to non-asthmatic women. In conclusion, the use of inhaled steroids for asthma treatment does not affect fetal growth, despite differences in placental metabolism by 11beta-HSD2.
Publisher: Elsevier BV
Date: 11-2000
Publisher: European Respiratory Society (ERS)
Date: 04-2005
DOI: 10.1183/09031936.05.00085704
Abstract: Asthma is becoming increasingly prevalent worldwide. Numerous historical and prospective cohort studies have investigated the effects of maternal asthma on pregnancy outcome however, the data has been conflicting and many studies have not used standard classifications for asthma severity. Overall, the literature suggests that asthmatic females are more at risk of low birth weight neonates, pre-term delivery and complications such as pre-ecl sia, especially in the absence of actively managed asthma treated with inhaled corticosteroids. Pregnancy with a female foetus may particularly increase the risk of these outcomes. In addition, pregnancy has an effect on the course of asthma. The risk of an exacerbation requiring medical intervention may be as high as 50% in females with severe asthma and this may further increase the risk of poor outcomes, particularly low birth weight and pre-term delivery. The mechanisms responsible for changes in asthma with pregnancy, or alterations in pregnancy outcomes due to asthma have not been thoroughly explored. Maternal inflammatory pathways may contribute to reduced foetal growth through alterations in placental function. Asthma treatment, by reducing maternal inflammation and preventing exacerbations, is safe for use in pregnant females and contributes to improved outcomes for both mother and foetus.
Publisher: Public Library of Science (PLoS)
Date: 30-05-2014
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.PLACENTA.2013.11.010
Abstract: Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2013 there were twelve themed workshops, four of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of pregnancy pathologies and placental metabolism: 1) diabetes in pregnancy 2) lipids, fatty acids and the placenta 3) oxygen in placental development and pathologies 4) stem cells and pathologies.
Publisher: Elsevier BV
Date: 10-2020
DOI: 10.1016/J.GHIR.2009.07.004
Abstract: Fetal growth varies in a sex-specific manner in response to maternal asthma during pregnancy, but the mechanisms are unclear. We examined the influence of maternal asthma severity and associated exposures, inhaled glucocorticoid treatment, maternal cigarette use, and fetal sex on fetal growth and placental function during pregnancy and on the newborn insulin-like growth factor (IGF) axis. STUDY SUBJECTS AND DESIGN: Fetal growth was assessed in a prospective cohort of asthmatic and non-asthmatic women (n=145). At delivery, umbilical vein plasma was collected from male (n=61, controls n=16 and asthmatic n=45) or female (n=84, controls n=22 and asthmatic n=62) fetuses. Cord plasma insulin-like growth factor (IGF) binding protein (BP)-1, IGFBP-3, IGF-1 and IGF-2 were measured by radioimmunoassay and ELISA. Cord plasma IGF-1 was the main component of the neonatal IGF axis altered by asthma and cigarette use. IGF-1 was increased in the presence of mild asthma and a male fetus and decreased in the presence of a female fetus and maternal asthma with cigarette use. IGFBP-3 was also decreased in the female fetuses of pregnancies complicated by asthma and cigarette use. Inhaled glucocorticoid use for the treatment of asthma did not affect the IGF axis. The strongest overall predictor of female birth weight after accounting for asthma severity, inhaled glucocorticoid treatment and cigarette use was IGF-1. For males, the strongest predictor of birth weight was IGFBP-3. The data suggest male and female fetuses institute different strategies in response to adverse pregnancy conditions such as asthma and cigarette use.
Publisher: Elsevier BV
Date: 09-2013
Publisher: Elsevier BV
Date: 05-2010
DOI: 10.1016/J.PHYSBEH.2010.02.013
Abstract: Evidence suggests that exposure to bacterial endotoxin in early life can alter the production of pro-inflammatory cytokines in later life. This phenomenon may have significant consequences for pain and pain related behaviours as pro-inflammatory cytokines heighten pain sensitivity. This association has yet to be examined. As such, the aim of the present study was to characterize pain behaviours in adult rat offspring following prenatal endotoxin (PE) exposure. Pregnant F344 rats received endotoxin (200microg/kg, s.c.) or saline on gestational days 16, 18 and 20. Pain thresholds were assessed in the adult PE offspring (n=23) and control offspring (n=24) prior to and 4h following administration of lipopolysaccharide (LPS 100microg/kg, s.c.). Three assays of pain were employed - the hot plate, tail immersion and von Frey tests. Results demonstrated sex-specific effects of prenatal endotoxin on the offspring, with PE males displaying unaltered pain thresholds on the von Frey test post-LPS administration (p<0.01), while male control offspring (n=24) displayed the expected hyperalgesia. Male PE offspring also displayed increased pain thresholds on the tail immersion test (p<0.01), while no change in pain sensitivity was observed in control males following LPS exposure. No difference in response was observed between the female PE and control offspring on the von Frey test, however PE female offspring displayed increased thresholds on the tail immersion test compared to baseline - an effect not observed in the control female offspring. Pain sensitivity on the hot plate test was unaffected by prenatal exposure to endotoxin. These data suggest that prenatal exposure to products associated with bacterial infection have the capacity to alter pain responses, which are evident in the adult offspring.
Publisher: Informa UK Limited
Date: 22-10-2022
DOI: 10.1080/02770903.2021.1993249
Abstract: Asthma during pregnancy and extremes of body mass index (BMI) are independently associated with adverse pregnancy outcomes but the impact of the two conditions combined are currently unknown. The aim of this study was to determine the contribution of maternal BMI to adverse birth outcomes in pregnancies complicated by asthma. The study utilized the routinely collected perinatal data on births at the Mater Mother's Hospital Brisbane, Australia, from January 2008 to December 2019. BMI was grouped as underweight ( .5), normal weight (18.5- .99), overweight (25-29.99), and obese (≥30) and the population split by the presence and absence of maternal asthma. The comparison group was normal BMI, non-asthmatic pregnant women. A modified Poisson regression with robust variance was used to estimate the relative risk. In a retrospective cohort study of 110,057 pregnant women, 17.08% of women had asthma. Asthma and BMI were associated with an increased risk of poor fetal and neonatal outcomes. Asthma significantly increased the risk of stillbirth in underweight [adjusted RR: 2.22 (95% CI: 1.25-3.94] and obese [1.74 (1.11-2.71)] neonatal death in underweight [3.41 (1.89-6.16)] and obese [2.22 (1.37-3.59)] and perinatal death in underweight [2.34 (1.50-3.66)] and obese [1.92 (1.38-2.67)] women. Admission to the neonatal intensive care unit was increased in neonates of underweight [1.65 (1.44-1.89)] and obese [1.26 (1.14-1.40)] asthmatic women. Extremes of BMI, specifically underweight and obesity, increased the risk of adverse perinatal outcomes among asthmatic women highlighting the importance of accounting for BMI during pre-conception and pregnancy related management of asthmatic women.
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.HUMIMM.2022.02.002
Abstract: Expression of allergic diseases in very early childhood indicates that early life events play a significant role in childhood allergy development. The developmental origins of allergy hypothesis suggest events initiated in the in-utero period derived from the interaction between maternal, placental, and fetal factors may contribute to childhood allergy susceptibility. Environmental impacts on placental function and fetal programming are imperative in defining illness risk during pregnancy. Fetal programming, a process by which an injury delivered during a critical period of development, causes immediate adaptive responses with long-term consequences on an organism's structure or function. During pregnancy, the maternal immune response is skewed towards Th2-related humoral responses, hence increasing the susceptibility of childhood allergy development. Maternal atopic phenotype markedly increases the probability of her offspring developing an allergic predisposition. Combination of in utero events - which include maternal asthma or infection, and exposures to maternal allergy which changes the placental function - can alter placental cytokine expression and could predispose offspring to an allergic phenotype. All these events may affect embryology and fetal immune system development. Interestingly, the mechanism and role of the in-utero events on the developmental origins of allergy are not clearly understood this will be addressed in this review. (199 words).
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.PLACENTA.2014.01.012
Abstract: We have previously identified sex-specific differences in the fetal-placental response to cortisol. Our recent studies suggest that this differential response to cortisol is driven by differences in glucocorticoid receptor (GR) protein function rather than through changes in gene transcription or protein expression. This study was designed to define whether the human placenta expresses different isoforms of the GR and whether expression was altered by fetal sex and maternal asthma. Asthma and non-asthma pregnant women were prospectively recruited at their first antenatal visit and placentae collected at delivery. Placental GR expression was examined in relation to maternal asthma, fetal sex and birthweight. Twelve specific bands for the GR were identified at molecular weights of 94, 91, 81, 74, 69, 68, 65, 60, 55, 50, 48 and 38 kDa. The 12 isoforms were localised to the placental trophoblast and expression varied in relation to cellular location in either the cytoplasm or nucleus, fetal sex, fetal size and the presence and absence of maternal asthma. This is the first study to identify the presence of several protein isoforms of the GR in the human placenta. The data suggest glucocorticoid resistance observed in male placentae may be mediated through increased GRβ, GR A and GR P localisation to the nucleus. While female placentae may be more sensitive to cortisol in the presence of maternal asthma through a decrease in GRβ and an enhancement GRα activity via an interaction with GRα D3 and GRα C.
Publisher: Springer Science and Business Media LLC
Date: 07-08-2019
Publisher: Cambridge University Press
Date: 28-07-2005
Publisher: Elsevier BV
Date: 11-2008
DOI: 10.1016/J.JNEUROIM.2008.06.041
Abstract: The efficacy of the neonatal innate immune system to respond to bacterial exposure following maternal infection is of great interest, as the neonatal period is one of relative immune immaturity, and is associated with high rates of morbidity and mortality. This study aimed to determine the response to an in-vivo endotoxin challenge in the neonatal period following prenatal exposure to bacterial endotoxin. Pregnant Fischer 344 dams received either endotoxin or the vehicle on gestational days 16, 18 and 20 (term=23 days). The neonatal (5 day) offspring were then exposed to an endotoxin challenge blood was collected at baseline or at 4 h for analysis of blood cell counts, corticosterone, TNF alpha and IL-1 beta, levels. The neonatal rat pups responded to the challenge with significantly reduced corticosterone, TNF alpha and IL-1 beta levels compared to controls (p<0.003). Monocyte, neutrophil and eosinophil counts were also significantly reduced in the prenatal endotoxin offspring compared to controls (p<0.02). While the immune system is functionally immature in the neonatal period, these results suggest that prenatal infection may further reduce the capacity of the innate neonatal immune system to respond to endotoxin, leaving offspring more vulnerable to pathogenic invasion in neonatal life.
Publisher: Elsevier BV
Date: 08-2003
DOI: 10.1016/S0143-4004(03)00103-6
Abstract: 11beta-hydroxysteroid dehydrogenase type 1 and type 2 may be important in the process of human parturition and the regulation of fetal growth, by the modulation of cortisol concentrations in the fetal compartment. Changes in the expression and activity of these enzymes in late gestation have not been well described. This study has examined the gene expression of placental 11beta-HSD1 and 2, activity of 11beta-HSD2 and fetal cortisol concentrations during the final few weeks of human pregnancy and with the onset of labour. Placental 11beta-HSD2 activity decreased significantly between 38 and 40 weeks. There were no significant changes in mRNA abundance or protein expression with gestational age or labour. Placental 11beta-HSD1 mRNA abundance significantly increased with spontaneous labour. Fetal cortisol concentrations increased significantly with spontaneous labour. This study is the first to describe a decrease in 11beta-HSD2 activity in the last few weeks of human gestation. This decrease in type 2 activity, along with an increase in 11beta-HSD1 gene expression may be a mechanism by which cortisol concentrations rise at term to regulate fetal maturation and activate pathways associated with labour.
Publisher: Public Library of Science (PLoS)
Date: 24-07-2017
Publisher: Wiley
Date: 03-10-2021
DOI: 10.1111/AJO.13441
Abstract: Asthma is the most common respiratory illness in Aboriginal and Torres Strait Islander Australians. From the Mater Mothers routinely collected perinatal data in Brisbane we have identified that 24% of Indigenous and 17% of non‐Indigenous women have pregnancies complicated by asthma. Indigenous women with asthma are more likely to have poorer birth outcomes when compared to non‐Indigenous women with asthma, with neonatal death being doubled in asthmatic Indigenous women. These data indicate that asthma management during pregnancy is an unmet need for Indigenous women and essential if we are to avoid these devastating outcomes for Indigenous families.
Publisher: Wiley
Date: 08-2014
DOI: 10.1111/AJO.12230
Abstract: Obstetric anal sphincter injury (OASIS) following vaginal delivery increases the risk of anal incontinence (AI). Subsequent vaginal delivery and ageing increase the risk of worsening symptoms. Very little literature describes any in-depth understanding of what it is like to live with AI following a history of known OASIS. To describe and interpret women's experience of AI following OASIS and its impact on quality of life. An interpretive phenomenological study was conducted in a level 2 tertiary hospital in South Australia. Women with a history of OASIS and AI were purposefully recruited. The St Marks Vaizey score was utilised to identify symptom severity. Semi-structured open-ended interviews were conducted, and data were analysed utilising Van Manen thematic analysis. Participants (n = 10) aged 26-56 years. All women were symptomatic of AI following OASIS, and 80% had received a primary OASIS at their first vaginal delivery. The St Marks Vaizey score mean was 9.1 (range within 4-22). Three essential themes grieving for loss, silence, striving for normality with eight subthemes identified a significant sense of loss and psychological impact of AI for this group of women. Health professionals require a greater understanding of the negative impact of OASIS and AI on women's quality of life. This may improve the management, education and clinical care of this condition which may result as a consequence of OASIS.
Publisher: The Endocrine Society
Date: 11-2004
DOI: 10.1210/JC.2004-0540
Abstract: The prostaglandin (PG)-inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH) is highly expressed in the chorion leave. To assess the involvement of PGDH in the regulation of intrauterine PG levels, we have determined the mechanisms that control chorionic PGDH expression in women at term and preterm labor. PGDH gene activity decreased at term and during normal labor. PGDH mRNA abundance also decreased at term due to changing splice variant distribution. Gene activity predicted PGDH mRNA abundance preterm and after normal labor, but not at term before labor. PGDH mRNA decayed rapidly in cultured tissues and was stabilized by transcriptional arrest. PGDH protein levels varied without being significantly different between the patient groups. PGDH mRNA levels predicted PGDH protein levels at term, but not preterm and after labor. PGDH gene activity, mRNA variant, and immunoreactive protein levels were not different between the preterm labor and preterm not in labor groups. Thus, PGDH mRNA is transiently down-regulated before term labor by a posttranscriptional mechanism(s). Protein turnover controls PGDH protein abundance at preterm and after normal labor. At term, PGDH protein levels become dependent on the rapidly turning over PGDH mRNA. This may allow rapid changes in PGDH protein abundance and uterotonic PG concentrations promoting labor.
Publisher: Wiley
Date: 23-07-2018
DOI: 10.1111/OBR.12698
Publisher: Cold Spring Harbor Laboratory
Date: 28-11-2020
DOI: 10.1101/2020.11.24.20237529
Abstract: To compare the prevalence of live preterm birth rates during COVID-19 restriction measures with infants born during the same weeks in 2013-2019 in Queensland, Australia. Deidentified obstetric and neonatal data were extracted from the Mater Mothers’ electronic healthcare records database. This is a supra-regional tertiary perinatal centre. Logistic regressions were used to examine preterm birth rates during the beginning of COVID-19 restrictions (16 March-17 April “early” 6,955 births) and during the strictest part of COVID-19 restrictions (30 March-1 May “late” 6,953 births), according to gestational age subgroups and birth onset (planned or spontaneous). We adjusted for multiple covariates, including maternal age, body mass index, ethnicity, parity, socioeconomic status, maternal asthma, diabetes mellitus and/or hypertensive disorder. Stillbirth rates were also examined (16 March-1 May). A reduction in planned moderate/late preterm births was observed primarily during the early restriction period compared with the same calendar weeks in the previous seven years (29 versus an average of 64 per 1,000 births adjusted odds ratio [aOR] 0.39, 95% CI 0.22-0.71). There was no effect on extremely or very preterm infants, spontaneous preterm births, or stillbirth rates. Rolling averages from January to June revealed a two-week non-significant spike in spontaneous preterm births from late-April to early-May, 2020. Planned births for moderate/late preterm infants more than halved during early COVID-19 mitigation measures. Together with evidence from other nations, the COVID-19 pandemic provides a unique opportunity to identify causal and preventative factors for preterm birth.
Publisher: Elsevier BV
Date: 08-2014
Publisher: Springer Science and Business Media LLC
Date: 06-08-2016
DOI: 10.1038/PR.2016.160
Abstract: Microvascular dysregulation following preterm birth is associated with increased illness severity and hypotension, particularly in males. Sympathetic nervous vascular regulation is evident in females. We hypothesized that sympathetic dysfunction in male preterm infants may contribute to a failure of peripheral microvascular vasoconstriction. Microvascular blood flow of infants 24-43 wk gestational age was assessed at 6, 24, and 72 h of age by laser Doppler. Blood flow Fourier transformed frequency distribution spectra (low frequency/high frequency ratio) were used to assess the influence of sympathetic tone on microvascular regulation. Total sympathetic output was assessed as urinary normetanephrine. Microvascular sympathetic activity at 24 h postnatal age decreased in early preterm males, but not females. Peripheral sympathetic activity increased with advancing postnatal age in females, but decreased in males. In early preterm infants, total normetanephrine outputs increase significantly with postnatal age, in both sexes. Sympathetic activation following preterm birth is sexually dimorphic, with preterm males having reduced sympathetic tone and reduced upregulation of sympathetic tone following birth. There is evidence of a disconnect between central sympathetic activity and local peripheral microcirculatory sympathetic drive. This may relate to autonomic nervous immaturity and highlights the need to understand how preterm birth may affect autonomic function.
Publisher: Public Library of Science (PLoS)
Date: 03-02-2016
Publisher: Oxford University Press (OUP)
Date: 22-09-2015
Abstract: Reproductive disorders and infertility are associated with the risk of obstetric complications and have a negative impact on pregnancy outcome. Affected patients often require assisted reproductive technologies (ART) to conceive, and advanced maternal age is a further confounding factor. The challenge is to dissect causation, correlation and confounders in determining how infertility and reproductive disorders in idually or together predispose women to poor pregnancy outcomes. The published literature, to June 2015, was searched using PubMed, summarizing all evidences concerning the perinatal outcome of women with infertility and reproductive disorders and the potential mechanisms that may influence poor pregnancy outcome. Reproductive disorders (endometriosis, adenomyosis, polycystic ovary syndrome and uterine fibroids) and unexplained infertility share inflammatory pathways, hormonal aberrations, decidual senescence and vascular abnormalities that may impair pregnancy success through common mechanisms. Either in combination or alone, these disorders results in an increased risk of preterm birth, fetal growth restriction, placental pathologies and hypertensive disorders. Systemic hormonal aberrations, and inflammatory and metabolic factors acting on endometrium, myometrium, cervix and placenta are all associated with an aberrant milieu during implantation and pregnancy, thus contributing to the genesis of obstetric complications. Some of these features have been also described in placentas from ART. Reproductive disorders are common in women of childbearing age and rarely occur in isolation. Inflammatory, endocrine and metabolic mechanisms associated with these disorders are responsible for an increased incidence of obstetric complications. These patients should be recognized as ‘high risk’ for poor pregnancy outcomes and monitored with specialized follow-up. There is a real need for development of evidence-based recommendations about clinical management and specific obstetric care pathways for the introduction of prompt preventative care measures.
Publisher: Wiley
Date: 21-10-2014
Publisher: Springer Science and Business Media LLC
Date: 28-02-2018
Publisher: Wiley
Date: 14-05-2020
DOI: 10.1111/MICC.12622
Publisher: Informa UK Limited
Date: 31-01-2013
DOI: 10.3109/02770903.2012.757777
Abstract: To determine the relationship between psychosocial variables, future exacerbation risk during pregnancy, and perinatal outcomes. A secondary analysis of a randomized controlled trial of exhaled nitric oxide versus guideline-based treatment adjustment in pregnant women with asthma. Women were recruited between 12 and 20 weeks gestation and monitored for the remainder of the pregnancy. Psychosocial questionnaires including the Perceived Control of Asthma Questionnaire, the Brief Illness Perception Questionnaire, and the Six-Item Short-Form State Trait Anxiety Inventory were assessed at randomization. Exacerbations were defined as hospitalization, emergency visit, unscheduled doctor visit, or oral corticosteroid use for worsening asthma. Perinatal outcomes included preterm birth, small for gestational age, and cesarean section. Multiple logistic regressions were performed with predictor variables, including demographics and psychosocial and clinical variables. The 175 participants had a mean (SD) age = 28.5(5.4) years, forced expiratory volume in 1 second (FEV(1)%) predicted = 95.9(13.4), and asthma control score = 0.88(0.70). Greater perceived control of asthma reduced the odds of subsequent exacerbation (odds ratio (OR) [95%CI] 0.92 [0.85, 0.98], p = .016), cesarean without labor (0.84 [0.75, 0.94], p = .003), and preterm birth (0.84 [0.72, 0.97], p = .019), while increased anxiety increased the odds of subsequent exacerbation (1.05 [1.01, 1.08], p = .008). Women's perceptions of asthma control and their psychosocial state (anxiety) are related to future exacerbation risk, cesarean section, and preterm birth.
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.PLACENTA.2017.01.123
Abstract: Asthma is a highly prevalent chronic medical condition affecting an estimated 12% of pregnant, women each year, with prevalence of asthma greatest (up to 16%) among the socially disadvantaged. Maternal asthma is associated with significant perinatal morbidity and mortality including preterm births, neonatal hospitalisations and low birthweight outcomes each year. We have identified that the placenta adapts to the presence of chronic, maternal asthma during pregnancy in a sex specific manner that may confer sex differences in fetal outcome. The male fetus was at greater risk of a poor outcome than a female fetus in the presence of maternal asthma and an acute inflammatory event such as an asthma exacerbation. This review will examine the role of sex specific differences in placental function on fetal growth and survival.
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.PHRS.2017.12.019
Abstract: Maternal asthma represents a significant burden to in iduals and the healthcare system, affecting 1 in 10 pregnancies worldwide. Approximately 50% of asthmatic women experience a deterioration of asthma control at some stage during pregnancy, with a number requiring use of oral corticosteroids for the management of acute exacerbations. The presence of maternal asthma and exacerbations during pregnancy is a noted risk factor for a range of adverse perinatal outcomes including preterm birth, small-for-gestational age, pre-ecl sia, and gestational diabetes. These negative impacts highlight the need for evidence-based approaches for improving asthma management during pregnancy and subsequent perinatal outcomes. Despite this, relatively small progress has been made in enhancing the management of maternal asthma in the clinical setting. A major challenge in improving outcomes of asthmatic pregnancies is that there is no single simplified approach for improving outcomes, but rather the requirement to consider the dynamic relationship between a myriad of interrelated factors that ultimately determine an in idual's ability to maintain adequate asthma control. Understanding how these factors are impacted by pregnancy and how they can be addressed through various interventions is therefore important in optimising health outcomes. This review summarises key factors involved in influencing outcomes associated with maternal asthma. This includes an overview of the use of asthma medications in pregnancy, while also considering the impacts of interrelated aspects such as medication adherence, health-seeking behaviours, biological and lifestyle factors, co-morbidities, and asthma self-management strategies on asthma control. Addressing such factors through multidisciplinary approaches towards treatment have potential to improve the health of mothers and their offspring. Optimising asthma control should be a high priority within the antenatal setting, with women advised about the importance of good asthma control, managing asthma actively throughout pregnancy by utilising their asthma medications, and managing exacerbations in a timely and effective manner.
Publisher: Elsevier BV
Date: 08-2010
Publisher: Elsevier BV
Date: 08-2011
DOI: 10.1016/J.PLACENTA.2011.05.005
Abstract: Chronic maternal asthma is associated with reduced growth of the female fetus and normal growth of the male fetus. The mechanisms that control the differential effects of maternal asthma on the fetus have not been fully elucidated but alterations in placental function may play a role. In the current study we have used microarray platform to examine fetal sex-specific global changes in placental gene expression in pregnancies complicated by asthma as compared to non-asthmatic subjects. Placental RNA was extracted from 11 control subjects and 38 asthmatic subjects. Labeled cDNA was hybridized to an oligonucleotide chip with 1700 double spotted well-characterized human genes. Global gene expression data analysis and visualization were performed using the Binary Tree-Structured Vector Quantization (BTSVQ) software. Functional relationships of differentially expressed genes were assessed using protein-protein interaction database I2D, network analysis and visualization software NAViGaTOR and Ingenuity Pathway Analysis software. Overall, 65 genes were found to be altered in placentae of pregnancies complicated by asthma. Of these, only 6 genes were altered in male placentae. There were 59 gene changes in female placentae of asthmatic mothers relative to control placentae. Some of the sex-specific genes were associated with growth, inflammation and immune pathways. There are sex-specific alterations in placental gene expression in the presence of maternal asthma. Given that many of the identified genes in the female placentae were associated with or involved in cellular growth and tissue development, these may contribute to the sexually dimorphic difference in fetal growth in response to maternal asthma.
Publisher: Elsevier BV
Date: 08-2010
Publisher: Springer Science and Business Media LLC
Date: 29-07-2005
DOI: 10.1007/S00441-005-1117-5
Abstract: Human pregnancy is associated with sexually dimorphic differences in mortality and morbidity of the fetus with the male fetus experiencing the poorest outcome following complications such as pre-ecl sia, pre-term delivery and infection. The physiological mechanisms that confer these differences have not been well characterised in the human. Work conducted on the effect of maternal asthma during pregnancy, combining data collected from the mother, placenta and fetus has found some significant sex-related mechanistic differences associated with fetal growth in both normal pregnancies and pregnancies complicated by asthma. Specifically, sexually dimorphic differences have been found in placental glucocorticoid metabolism in male and female fetuses of normal pregnancies. In response to the presence of maternal asthma, only the female fetus alters placental glucocorticoid metabolism resulting in decreased growth. The male fetus does not alter placental function or growth in response to maternal asthma. As a result of the alterations in glucocorticoid metabolism in the female, downstream changes occur in pathways regulated by glucocorticoids. These data suggest that the female fetus adjusts placental function and reduces growth to compensate for maternal disease. However, the male fetus continues to grow in response to maternal asthma with no changes in placental function. This response by the male fetus may partially contribute to the increased risk of morbidity and mortality in this sex.
Publisher: The Endocrine Society
Date: 11-2003
Abstract: CRH plays a central role as a mediator of the hypothalamic-pituitary-adrenal axis and stress response and is a potent vasodilator. Previously, we have shown that CRH causes a gender-specific vasodilation in human skin, although the mechanism by which CRH operates is unclear. CRH causes mast cell degranulation in rat skin. As such, histamine and other mast cell-derived factors may be indirectly responsible for the vasodilatory effects of CRH, although CRH is also known to act directly on the vasculature. CRH-induced vasodilation in human skin was examined using laser Doppler flowmetry and iontophoresis in adult females. CRH (1 nM) was administered iontophoretically to the forearm, and blood flow was measured simultaneously in the same area by laser Doppler. CRH-induced dilation of the skin microvasculature was significantly reduced in the presence of the mast cell degranulation inhibitor, sodium cromoglycate, the histamine H(1)-antagonist, promethazine, or the H(2)-antagonist, ranitidine. CRH-induced dilation was also significantly reduced in the presence of the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester, or the cyclooxygenase inhibitor, piroxicam. These findings provide novel evidence that CRH-induced vasodilation in human skin occurs via mast cell degranulation and is principally mediated by histamine and, to a lesser extent, by prostacyclin and nitric oxide.
Publisher: Wiley
Date: 18-05-2023
DOI: 10.1111/AJO.13677
Abstract: There is growing evidence regarding the potential of closed incision negative pressure wound therapy (ci‐NPWT) to prevent surgical site infections (SSIs) in healing wounds by primary closure following a caesarean section (CS). To assess the cost‐effectiveness of ci‐NPWT compared to standard dressings for prevention of SSI in obese women giving birth by CS. Cost‐effectiveness and cost‐utility analyses from a health service perspective were undertaken alongside a multicentre pragmatic randomised controlled trial, which recruited women with a pre‐pregnancy body mass index ≥30 kg/m 2 giving birth by elective/semi‐urgent CS who received ci‐NPWT ( n = 1017) or standard dressings ( n = 1018). Resource use and health‐related quality of life (SF‐12v2) collected during admission and for four weeks post‐discharge were used to derive costs and quality‐adjusted life years (QALYs). ci‐NPWT was associated with AUD$162 (95%CI −$170 to $494) higher cost per person and an additional $12 849 (95%CI −$62 138 to $133 378) per SSI avoided. There was no detectable difference in QALYs between groups however, there are high levels of uncertainty around both cost and QALY estimates. There is a 20% likelihood that ci‐NPWT would be considered cost‐effective at a willingness‐to‐pay threshold of $50 000 per QALY. Per protocol and complete case analyses gave similar results, suggesting that findings are robust to protocol deviators and adjustments for missing data. ci‐NPWT for the prevention of SSI in obese women undergoing CS is unlikely to be cost‐effective in terms of health service resources and is currently unjustified for routine use for this purpose.
Publisher: Cambridge University Press (CUP)
Date: 24-04-2015
DOI: 10.1017/S1368980015001226
Abstract: To examine pre-conception dietary patterns in pregnant asthmatic women and to identify associations between maternal diet and asthma control during pregnancy. Cross-sectional study. Pre-conception food frequency data were collected retrospectively. Asthma control was assessed using the Global Initiative for Asthma guidelines. Dietary patterns were derived using factor analysis. Binary logistic regression analyses were used to test the association between uncontrolled asthma and each dietary pattern ( Z -score), with values presented as odds ratio and 95 % confidence interval. Antenatal clinic in a tertiary hospital, Adelaide, Australia, May 2009–July 2013. One hundred and fifty-eight asthmatic pregnant women. Three dietary patterns were identified: (i) ‘high protein/fruit’ (strong food group loadings for fish, meat, chicken, fruit) (ii) ‘high fat/sugar/takeaway’ (takeaway foods, crisps, refined grains) and (iii) ‘vegetarian-type’ (vegetables, fruit, soya milk, whole grains). A 1 sd increase in score on the high fat/sugar/takeaway pattern was associated with increased likelihood of uncontrolled asthma (adjusted OR=1·54 95 % CI 1·07, 2·23 P= 0·022). Women with uncontrolled asthma ( n 115) had higher energy-adjusted intakes of saturated fat, monounsaturated fat, carbohydrate, sugar and fibre compared with women with controlled asthma ( n 43, all P ≤0·05). Pre-pregnancy dietary patterns may influence maternal asthma control. Our work highlights the importance of achieving a healthy diet before pregnancy that is low in saturated fat, sugar and takeaway foods, and therefore higher in lean meats, poultry and fish, as well as fruits, vegetables and whole grains. A healthy dietary pattern should be encouraged in all asthmatic women who are of childbearing age, and should additionally be promoted before pregnancy and beyond.
Publisher: Elsevier BV
Date: 09-2017
Publisher: Bentham Science Publishers Ltd.
Date: 02-11-2020
DOI: 10.2174/1874467213666200303130153
Abstract: Vitamin D insufficiency and deficiency can be associated with adverse effects on pregnancy outcomes, which may include recurrent pregnancy loss through the mechanisms that are yet unknown. The aim of this study was to evaluate the effect of 1,25VitD3 on regulatory T cells (Tregs) and T helper17 (Th17) cell populations In vitro in unexplained recurrent pregnancy loss (URPL) patients and healthy women. S les from 20 non-pregnant women with a history of URPL were compared to 20 normal non-pregnant women. Peripheral blood mononuclear cells (PBMC) were ided into 3 wells for each subject: in the presence of 1, 25 VitD3 (50 nM, for 16 hours), PHA (positive control) (10μM), and without any treatment (as a baseline or negative control). The percentage of regulatory T cells and Th17 cells was measured by flow cytometry at baseline and then after cell culture experiments. Our study indicated that the percentage of Tregs in patients with URPL was significantly lower than the control group (2.42 ± 0.27 vs. 3.41 ± 0.29, P= 0.01). The percentage of Th17 cells was significantly greater in URPL patients compared to the control group (2.91 ± 0.33 vs. 1.18± 0.15, P=0.001). 1, 25VitD3 treatment significantly increased the percentage of Tregs from the baseline in the URPL group compared to that in the control group (1.23 ± 0.03 vs. 1.00 ± 0.03, P= 0.01). Vitamin D deficiency may be a contributor to recurrent pregnancy loss and suggests supplementation of women with Vit D pre-pregnancy may be protective against URPL.
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.PLACENTA.2021.10.008
Abstract: Morphological changes to the placenta occur as the demands of the foetus increase throughout gestation. Physical activity during pregnancy is known to benefit both the mother and infant, however the impact of antenatal exercise training on placental development is less known. The aim of this systematic review and meta-analysis was to investigate the effects of exercise training during pregnancy on measures of placental composition. Six electronic databases were searched from inception to June 2021 for studies comparing regular antenatal exercise with either usual maternal care or no exercise for its effect on measures of placental morphological composition. Meta-analyses were performed for placental weight and the placental weight to birthweight (PWBW) ratio. Seven randomised controlled trials and two cohort studies were included in the systematic review and meta-analysis (n = 9). There was no significant difference in placental weight (mean difference (MD) = -9.07g, p = 0.42) or the PWBW ratio (MD = 0.00, p = 0.32) between exercise and control groups. Parenchymal tissue volume was higher, represented by an increase in villous tissue, and non-parenchymal volume was lower in women who exercised regularly compared to those that were not exercising during pregnancy. Exercise training during pregnancy may not alter placental weight or the PWBW ratio. However, findings from this review indicate that antenatal exercise training can promote advantageous morphological changes to placental tissues.
Publisher: BMJ
Date: 13-07-2010
Abstract: Fetal growth inhibition is a known sequelae of in utero glucocorticoid exposure and has long-term consequences for adult health. Sex-specific fetal growth patterns are observed in pregnancies with maternal asthma and may be due to differential sensitivity of the placenta to glucocorticoids. It is currently unknown whether expression of the placental glucocorticoid receptor (GR) becomes altered with asthma or the use of inhaled corticosteroids. Pregnant women with mild asthma (n=52), moderate-severe asthma (n=71) and without asthma (n=51) were recruited at John Hunter Hospital, Newcastle, Australia. At delivery, placentae and cord blood were collected, and fetal sex and birth weight were recorded. Placental GR heterogeneous nuclear RNA (hnRNA), mRNA and protein were measured and cord blood cortisol concentrations were assessed. Placental GR gene activity increased with cortisol exposure but decreased with inhaled corticosteroid treatment (p=0.05). With maternal asthma, female birth weight centiles were inversely associated with cortisol (r=-0.286, p=0.017) and, despite a decrease in placental GR mRNA (p=0.003), placental GRalpha protein levels were unchanged. In males, no change to cortisol, birth weight or placental GR were evident in pregnancies with asthma. Together, these results indicate that in pregnancies complicated by asthma, placental GR gene activity, but not mRNA expression or protein levels, is dependent on cortisol and inhaled corticosteroid treatment. The sex-specific associations between cortisol and birth weight observed in pregnancies with asthma are not due to altered GR expression however, they may be due to differential glucocorticoid sensitivity via preferential transcription of GR isoforms or post-translational modifications.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2006
Publisher: Springer Science and Business Media LLC
Date: 21-11-2019
DOI: 10.1186/S12905-019-0840-0
Abstract: There is limited research defining the true prevalence of anal incontinence (AI) in women of childbearing age. Understanding the limitations of the current assessment tools in the identification of AI is paramount for identifying the prevalence of AI and improving the care and management for women of childbearing age. The aim of this research was to explore and develop an understanding of women’s experiences in disclosing AI when completing a new bowel-screening questionnaire when compared to two established AI tools. A phenomenological qualitative research study was undertaken in a maternity setting in a large tertiary hospital. Parous women in the first trimester of a subsequent pregnancy were recruited to complete a specifically designed screening tool (BSQ), St Marks Faecal incontinence score (Vaizey) and Cleveland (Wexner) score. Qualitative semi-structured interviews were utilised to identify experiences in disclosing AI. Women ( n = 16, 22–42 years) with a history of anal incontinence either following the first birth ( n = 12) or the second ( n = 4) provided differing responses between the three assessment tools. All women answered the BSQ while the Vaizey and Wexner scores were more difficult to complete due to clinical language and participants level of comprehension. Women identified three major themes that were barriers for disclosing incontinence, which included social expectations, trusted space and confusion. There are barriers for disclosing AI in the pregnant and post-natal population, which can be improved with the use of an easy assessment tool. The BSQ may facilitate discussion on AI between the patient and health professional leading to earlier identification and improvement in short and long-term health outcomes.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.PLACENTA.2017.06.009
Abstract: A significant proportion of children born preterm will experience some level of neurodevelopmental impairment. Changes in placental function have been observed with many antenatal conditions that are risk factors for preterm birth and/or poor neurodevelopment including fetal growth restriction and in-utero inflammation. This review will highlight placental factors that have been studied to understand the underlying mechanisms and identify biomarkers that lead to poor child neurodevelopmental outcomes. These include changes in gross morphological and histopathological structure and the placental inflammatory response to prenatal infection. Further, we will describe the placenta's role as both a barrier to maternally-derived bioactive substances critical for normal fetal brain development, such as cortisol, and a source of neuroactive steroids and neurotrophins known to have critical functions in neuronal proliferation, axonal growth, myelination and the regulation of apoptosis. Finally, emerging data supporting the potential utility of novel placental biomarkers in the early prediction of poor neurodevelopmental outcome in infants born both preterm and term will be discussed. These include the assessment of genetic variants (e.g. single nucleotide polymorphisms in placental tissue) and epigenetic biomarkers (e.g. placental microRNAs and placental DNA methylation). With the placenta the key tissue regulating the fetal environment, integration of observed changes in placental function with genetic and epigenetic variations may advance our ability to predict future infant health. Ultimately, this may facilitate targeted allocation of health resources with the aim of improving lifelong neurodevelopmental capability.
Publisher: Public Library of Science (PLoS)
Date: 16-05-2018
Publisher: Elsevier BV
Date: 08-2010
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.PLACENTA.2017.01.114
Abstract: Normal placental function is essential for optimal fetal growth. Transport of glucose from mother to fetus is critical for fetal nutrient demands and can be stored in the placenta as glycogen. However, the function of this glycogen deposition remains a matter of debate: It could be a source of fuel for the placenta itself or a storage reservoir for later use by the fetus in times of need. While the significance of placental glycogen remains elusive, mounting evidence indicates that altered glycogen metabolism and/or deposition accompanies many pregnancy complications that adversely affect fetal development. This review will summarize histological, biochemical and molecular evidence that glycogen accumulates in a) placentas from a variety of experimental rodent models of perturbed pregnancy, including maternal alcohol exposure, glucocorticoid exposure, dietary deficiencies and hypoxia and b) placentas from human pregnancies with complications including preecl sia, gestational diabetes mellitus and intrauterine growth restriction (IUGR). These pregnancies typically result in altered fetal growth, developmental abnormalities and/or disease outcomes in offspring. Collectively, this evidence suggests that changes in placental glycogen deposition is a common feature of pregnancy complications, particularly those associated with altered fetal growth.
Publisher: Elsevier BV
Date: 08-2010
Publisher: Elsevier BV
Date: 10-2012
Publisher: Elsevier BV
Date: 09-2020
Publisher: Elsevier BV
Date: 04-2008
DOI: 10.1016/J.PLACENTA.2008.01.011
Abstract: Asthma is the most common respiratory disease to complicate pregnancy. Although adverse effects on the fetus have been documented, there is a paucity of information regarding the effects of asthma, and its treatment, on placental morphology. The aim of this study was to test for volumetric differences in placental composition between non-asthmatic pregnancies and those associated with maternal asthma grouped according to asthma severity and glucocorticoid (GC) treatment. Each placenta was weighed and random s les of tissue were fixed in formalin-saline, embedded in wax and analysed by design-based stereology. Volume densities of parenchymal compartments (peripheral villi and maternal intervillous space) and residual non-parenchyma were estimated by test point counting and converted to absolute volumes by taking into account placental size. Relative and absolute lengths of villi and capillaries were also estimated and used to derive secondary quantities related to villous capillarization and maturation. Between-group comparisons were drawn by two-way analysis of variance with group and fetal sex as the principal factors. Compared to non-asthmatic controls, asthmatics had reduced absolute volumes of fetal capillaries which was most marked in those with moderate/severe asthma and those using low and high doses of inhaled GCs. Changes in the total length and mean cross-sectional area of capillaries and peripheral villi were also observed. Lengths were greater in mild asthmatics and lowest in those with high GC usage. Calibre areas were lower in mild asthmatics and villous calibres in the high GC group were greater than those in asthmatics not taking GCs. Those making greatest use of inhaled GCs also had villi which were hypovascularized in terms of capillary:villus length ratios. The findings suggest that the morphometric differences in fetoplacental vascularity are likely to be due to the effects of asthma and use of inhaled GCs rather than the effects of maternal or fetal hypoxic stress.
Publisher: Informa UK Limited
Date: 2002
DOI: 10.1076/APAB.110.1.94.897
Abstract: The first target autoantigen to have been identified in lymphocytic hypophysitis is a 49 kDa protein, identified as alpha-enolase. Pituitary autoimmunity is strongly associated with pregnancy and we have shown that pituitary autoantibodies from patients with peripartum lymphocytic hypophysitis also recognise enolase in the placenta. Enolase exists in different forms as a number of isoenzymes, which are homo- or heterodimers of three subunits, alpha, beta and gamma. alphaalpha-enolase is ubiquitous, betabeta-enolase is muscle-specific and gammagamma-enolase, which is restricted to neuronal tissue and neuroendocrine cells, is known as neuron-specific enolase (NSE). NSE is expressed in normal human pituitary and pituitary neoplasms. The current study investigated which isoforms of enolase in pituitary and placenta reacted with the sera of patients with lymphocytic hypophysitis. Immunoblotting of two-dimensional gels of human pituitary cytosolic proteins showed that autoantibodies in patient sera react with both an acidic form, and more neutral forms of enolase. Immunoblotting with a monoclonal antibody to NSE confirmed the identity of the acidic enolase isoform as the gammagamma-isoform in both pituitary and placental s les. Gamma-enolase, i.e. NSE, was detected by immunohistochemistry in term placenta in decidua, syncytiotrophoblasts, anchoring villi and terminal villi. Our study is the first to describe the cellular localisation of NSE in normal human placenta, thus establishing a direct link between pituitary and placental autoantigens. This link provides a theoretical basis for the strong prediliction of lymphocytic hypophysitis to occur during or after pregnancy.
Publisher: Informa UK Limited
Date: 20-04-2023
Publisher: Elsevier BV
Date: 02-2012
DOI: 10.1016/J.PLACENTA.2011.11.005
Abstract: Pregnancy induces a number of alterations to maternal physiology to accommodate the increased demands made by the developing fetus and placenta. These alterations appear at least in part to be driven by products derived from the feto-placental unit, including microchimeric cells, as well as placental exosomes and microparticles, inducing changes to maternal physiology both during pregnancy and beyond. Further, increasing evidence suggests that some of these alterations are dependent on the sex of the fetus. Pre-ecl sia and asthma represent two common pregnancy complications that have provided valuable insight into how the feto-placental unit influences maternal physiology in a sex-specific manner. Pregnancy-induced alterations in maternal physiology may expose pre-existing subclinical pathologies and provide insight into future maternal health and disease. While most pregnancy-induced alterations to the maternal system are reversed following delivery, some can persist after parturition leading to cardiovascular, metabolic and autoimmune disease and increased risk of early mortality.
Publisher: Informa UK Limited
Date: 11-2008
Publisher: Springer Science and Business Media LLC
Date: 12-2006
DOI: 10.1016/J.JSGI.2006.06.006
Abstract: Peripheral microvascular function is altered in preecl sia (PE). Recent studies suggest that maternal physiology varies with fetal sex. We wanted to examine if there were sex-specific differences in maternal peripheral microvascular function in normal pregnancy and pregnancy complicated by PE. Peripheral microvascular responses were examined using the noninvasive technique of laser Doppler flowmetry in normotensive healthy pregnant women and in women diagnosed with PE. We measured baseline perfusion, response to thermal hyperemia, post-occlusive reperfusion, and vasodilatation in response to corticotropin-releasing hormone (CRH), a potent vasodilator in human skin. At 31 to 40 weeks' gestation those women with a male fetus exhibited increased vasodilatation in response to CRH (P <.05) and greater baseline perfusion (P <.05) than those pregnant with a female fetus. PE women pregnant with a male fetus demonstrated a significantly reduced vasodilatation in response to CRH (P <.05), reduced baseline perfusion (P <.05), and reduced response to thermal hyperemia (P <.05) compared to normotensive women pregnant with a male fetus. Microvascular function was not significantly different between preecl tic and normotensive women with a female fetus. These data show that there are differences in maternal peripheral microvascular function in relation to fetal sex.
Publisher: Elsevier BV
Date: 09-2015
Publisher: Elsevier BV
Date: 08-2007
DOI: 10.1016/J.JCHROMB.2007.05.041
Abstract: In the present work, human male and female fetal cord blood s les were purified, selectively extracted and separated to examine a fraction of steroids ranging from polar estetrol to relatively non-polar progesterone using solid phase extraction based on C-18 tubes and beta-cyclodextrin driven temperature dependent inclusion chromatography. Resulting UV diode array chromatographic patterns revealed the presence of 27 peaks. Chromatographic patterns of UV detected steroids were analyzed using principal components analysis which revealed differences between male/female and labour/not-in-labour clusters. Quantitative analysis of nine identified steroids including: estetrol, 17beta-estradiol, estrone, estriol, cortisol, cortisone, progesterone, 20 alpha-hydroxyprogesterone and 17 alpha-hydroxyprogesterone were not significantly different between males and females. Significant differences between male and female fetuses were related to as yet unidentified compounds. Four peaks were significantly different with labour which corresponded with cortisol, cortisone and two unidentified compounds. This protocol may distinguish significant differences between clinical groups that are not readily identifiable using univariate measurements of single steroids or different low molecular mass biomarkers. Moreover, we have provided new evidence that despite the absence of testosterone there are number of steroids and low molecular mass compounds that differ between male and female fetuses.
Publisher: Oxford University Press (OUP)
Date: 11-1995
Abstract: Clifton VL, Owens PC, Robinson PJ, Smith R. Identification and characterization of a corticotrophinreleasing hormone receptor in human placenta. Eur J Endocrinol 1995 :591–7. ISSN 0804–4643 Corticotrophin-releasing hormone (CRH) causes vasodilatation in the human fetal–placental circulation and has paracrine actions in placental tissue, suggesting that CRH receptors may be present in the human placenta. We have now identified and characterized placental CRH binding sites and compared them to those described previously in human myometrium and rat pituitary. Radiolabelled ovine CRH binding to placental membranes was pH-, time-, temperature- and alent cation-dependent and was reversible in the presence of 1 μmol/l unlabelled ovine CRH. Scatchard analysis of placentae delivered vaginally or by elective caesarean section revealed dissociation constants (K d ) of 214.5 ± 84 pmol/l (N = 8) and 45.4 ± 23.9 pmol/l (N = 9), respectively. The K d for caesarean placental binding sites was similar to that of human myometrium (59.6 pmol/l, N = 3) and rat pituitary (82.5 pmol/l, N = 3) receptors. However, in vaginally delivered placentae the CRH binding sites had a much lower affinity (p 0.05). The receptor densities (B max ) of vaginally delivered and caesarean-delivered placentae were 28.6 ± 9.6 and 6.1 ± 2.8 fmol/mg, respectively (p 0.05). Chemical cross-linking studies using disuccinimidyl suberate indicated that the molecular weight of the CRH receptor in the placenta and rat pituitary is 75 kD. We conclude that there is a high-affinity population of CRH binding sites in the human placenta that are physicochemically similar to pituitary and myometrial CRH receptors. The CRH receptor properties in the placenta change in response to labour, when CRH levels in maternal blood are highest, suggesting that placental CRH may regulate its receptor. R Smith, Endocrinology Unit, John Hunter Hospital, Locked Bag 1, Hunter Regional Mail Centre, Newcastle, NSW 2310, Australia
Publisher: Elsevier BV
Date: 09-2016
Publisher: American Thoracic Society
Date: 12-2003
Publisher: American Thoracic Society
Date: 15-08-2001
DOI: 10.1164/AJRCCM.164.4.2009119
Abstract: Asthma during pregnancy is associated with low-birthweight neonates at term but the mechanisms that cause this outcome are presently unknown. Changes in placental vascular function resulting from asthma or its treatment could contribute to altered fetal growth. We have prospectively followed women with asthma and a control group of women without asthma during their pregnancies, classified them based on asthma severity and glucocorticoid intake, and monitored fetal development and placental blood flow using Doppler ultrasound at 18 and 30 wk gestation. The placentae from these women were collected after delivery and vascular responses to dilator and constrictor agonists assessed using an in vitro placental perfusion method. At 18 wk gestation, umbilical artery flow velocity waveforms were significantly reduced in the moderate and severe asthmatic groups and in those women using high-dose inhaled glucocorticoid for the treatment of their asthma (ANOVA, p 0.05). Corticotropin-releasing hormone (CRH), a potent vasodilator that acts via the nitric oxide pathway, caused a dose-dependent vasodilatory response in all placentae in vitro. However, CRH-induced dilation was significantly reduced in moderate and severe asthmatics (ANOVA, p < 0.05). Vasoconstrictor responses to potassium chloride and prostaglandin F(2alpha) were reduced in placentae from moderate and severe asthmatic women (ANOVA, p < 0.05). These studies demonstrate significant differences in placental vascular function in pregnancies complicated by asthma, which may relate directly to the asthma or be a consequence of the associated glucocorticoid treatment. These changes in vascular function in asthmatic pregnancies may contribute to the low-birthweight outcome observed in this condition.
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.PLACENTA.2017.02.021
Abstract: Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2016 there were twelve themed workshops, four of which are summarized in this report. These workshops addressed challenges, strengths and limitations of techniques and model systems for studying the placenta, as well as future directions for the following areas of placental research: 1) placental imaging 2) sexual dimorphism 3) placenta and development of other organs 4) trophoblast cell lines.
Publisher: Elsevier BV
Date: 08-2008
DOI: 10.1016/J.CYTO.2008.05.008
Abstract: The mechanisms contributing to worsening of asthma during pregnancy have not been well characterized. Both asthma and pregnancy are conditions associated with a skewing of the immune response from T helper (Th) 1 toward a Th2 response. We hypothesise that worsening of asthma during pregnancy may be due to an enhanced production of circulating proinflammatory cytokines and chemokines and this may be modified by the use of inhaled glucocorticoid treatment. Peripheral blood was collected from asthmatic (n=35) and control non-asthmatic patients (n=13) in the third trimester (30-37 weeks) of pregnancy. Fetal blood was collected from the umbilical vein of the placenta after delivery from normal (n=24) and pregnancies complicated by asthma (n=24). Plasma s les were assayed for IL-6, -8, eotaxin and RANTES using conventional ELISA. In addition, a range of Th1 and Th2 cytokines measured using Luminex system. There were no significant differences in the levels of maternal IL-6, IL-8, eotaxin and RANTES between asthmatics and nonasthmatics. The results of this study suggest that the presence of asthma does not result in an enhanced circulation of Th2 related cytokines and chemokines during the third trimester of pregnancy. Furthermore peripheral blood cytokine concentrations appear unaffected by inhaled glucocorticoid treatment. Cord plasma eotaxin concentrations were increased in pregnancies complicated by asthma, compared with control. This is the first study to show increased eotaxin production in the feto-placental unit of asthmatic pregnancies and may be one mechanism by which allergy susceptibility is increased in the offspring of asthmatic women.
Publisher: MDPI AG
Date: 26-03-2021
DOI: 10.3390/APP11072992
Abstract: The availability of 2-Dimensional Shear Wave Elastography (2D-SWE) technology on modern medical ultrasound systems is becoming increasingly common. The technology is now being used to investigate a range of soft tissues and related pathological conditions. This work investigated the reliability of a single commercial 2D-SWE system using a tissue-mimicking elastography phantom to understand the major causes of intra-system variability. Sources of shear wave velocity (SWV) measurement variability relates to imaging depth, target stiffness, s ling technique and the operator. Higher SWV measurement variability was evident with increasing depth and stiffness of the phantom targets. The influence of the operator was minimal, and variations in s ling technique had little impact on the SWV.
Publisher: Springer Science and Business Media LLC
Date: 19-08-2023
DOI: 10.1007/S00737-022-01257-1
Abstract: Antenatal depression (AND) affects 1 in 10 fathers, potentially negatively impacting maternal mental health and well-being during and after the transition to parenthood. However, few studies have assessed the social predictors of paternal AND or their possible associations with maternal mental health. We analysed data from 180 couples participating in the Queensland Family Cohort longitudinal study. Both parents completed surveys measuring mental health, relationship quality, social support, and sleep quality at 24 weeks of pregnancy. Mothers also completed the same surveys 6 weeks’ postpartum. Antenatal depression, stress, and anxiety were highest among fathers reporting lower social support and higher sleep impairment. Maternal AND, stress, and anxiety were higher among mothers reporting higher physical pain and poor sleep quality. Postnatally, mothers reporting lower social support also reported higher depression, anxiety, stress, and psycho-social well-being. While there were no significant associations between AND among fathers and maternal antenatal or postnatal depression, an exploratory analysis revealed that mothers whose partners reported lower antenatal social support also reported lower postnatal social support and higher postnatal depression. Our findings highlight the importance of including data among fathers to achieve a whole family approach to well-being during the transition to parenthood.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2013
Publisher: Elsevier BV
Date: 02-2012
DOI: 10.1016/J.CLNU.2011.09.006
Abstract: One of the most prevalent complications of pregnancy is asthma which is associated with an increased incidence of intrauterine growth restriction. The mechanisms that affect fetal development in pregnancies complicated by asthma are not clearly defined. Antioxidants are particularly important during pregnancy due to their protective role against a state of high oxidative stress as gestation progresses. The current study was designed to characterise the circulating profile of tocopherols and carotenoids in pregnant women with asthma to determine whether asthma severity and dietary intake were associated with an altered antioxidant profile. Maternal dietary intake and plasma and erythrocyte concentrations of tocopherols and carotenoids were examined in women with (n = 84) and without asthma (n = 47) at 18, 30 and 36 weeks gestation. Tocopherol and carotenoid levels were related to fetal and birth outcomes. Pregnant women with moderate/severe asthma were found to have increased plasma concentrations of total carotenoids (P < 0.05), lutein (P < 0.05 and α-tocopherol (P < 0.02) late in gestation compared to those women with mild asthma and healthy pregnant controls. Moderate/severe asthmatics had higher erythrocyte α-tocopherol quinone levels early in gestation relative to the controls (P < 0.02) but this marker of oxidative stress decreased as gestation progressed. Tocopherols and carotenoids were positively associated with birth weight centile (P < 0.05). These findings suggest that the maternal system adjusts antioxidant pathways in response to the presence of a high oxidative load induced by asthma during pregnancy in an attempt to ensure continued fetal growth in an adverse environment.
Publisher: Elsevier BV
Date: 02-2006
DOI: 10.1016/J.CHROMA.2005.11.119
Abstract: Clinical and metabolomic investigations of complex human fluids require cost-effective methodologies that can rapidly assess the steroid hormone milieu of in idual s les. The efficiency of quantification of many steroids is limited using immunoassays as these methods can only measure a single component of biological s les and are dependent upon the specificity of the antiserum used in the protocol. In this study, we optimised the solid-phase extraction protocol for the extraction of a range of steroids of varied polarity from estetrol to progesterone from human plasma. The final SPE procedure for efficient extraction of steroids was a washing mixture of 5 ml of 30% methanol and an elution solvent of 2 ml of 100% methanol using 0.5 g C-18 cartridges. This protocol resulted in a high recovery rate, ranging from 85.2 to 99.9% for both the internal standard (7,8-dimethoxyflavone) and steroids of interest. We also improved the separation methodology of our previous work using temperature dependent inclusion chromatography with a mobile phase composition of 35% acetonitrile and 12 mM of beta-cyclodextrin at 29 degrees C. Under these conditions most of the fluid components including estetrol were detected in the first 10 min with progesterone appearing at 43 min. This method is simplistic, inexpensive and reproducible with the capabilities of accurate quantification of steroids. Therefore it could have numerous clinical and metabolomic applications.
Publisher: European Respiratory Society (ERS)
Date: 2016
DOI: 10.1183/23120541.00054-2015
Abstract: There exists a paucity of data for socially disadvantaged populations describing patterns and predictors of asthma control status and exacerbations during pregnancy, and their relationship to adverse perinatal outcomes. Asthmatic women (n=189) were followed prospectively during pregnancy, with visits at 12, 20, 28 and 36 weeks gestation. Data on loss of control, recurrent uncontrolled asthma and moderate/severe exacerbations were collected at each visit and their relationship to perinatal outcomes examined following stratification for fetal sex. 50% of asthmatic women experienced a loss of control or moderate/severe exacerbation during pregnancy, with 22% of women experiencing a moderate/severe exacerbation. Factors associated with an increased risk of women experiencing recurrent uncontrolled asthma during pregnancy included smoking (relative risk 2.92, 95% CI 1.53–5.58), inhaled corticosteroid use at the beginning of pregnancy (relative risk 2.40, 95% CI 1.25–4.60) and increasing maternal age (relative risk 1.06, 95% CI 1.01–1.11). No factors were associated with moderate/severe exacerbations. Asthma control rather than exacerbations during pregnancy appeared to be most strongly correlated with perinatal outcomes. Following stratification by fetal sex, the presence of recurrent uncontrolled asthma was associated with an increased risk of being small for gestational age in women pregnant with females (33.3% versus 9.5% p=0.018). In contrast, there was a nonsignificant increased risk of preterm birth in women with recurrent uncontrolled asthma that were pregnant with males (25.0% versus 11.8% p=0.201) These results suggest that the key to improving perinatal outcomes lies in improving asthma control as early as possible in pregnancy and monitoring throughout pregnancy, rather than focusing on preventing exacerbations alone.
Publisher: Informa UK Limited
Date: 02-09-2020
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.FERTNSTERT.2015.12.127
Abstract: To investigate the possible correlation between maternal characteristics, in utero and early neonatal life exposures, and the development of endometriosis in adult life. Case-control study. University hospital. A group of 161 patients with endometriosis and a control group of 230 women undergoing laparoscopy for benign adnexal diseases and free of endometriosis. All women included in the study were requested to answer a series of questions about their mothers' gestational data and on their own perinatal and early postnatal lives. Odds ratio, adjusted odds ratios, and 95% confidence intervals for the associations between maternal characteristics during the patient's pregnancy, in utero exposure to obstetrical and perinatal complications, and the type of feeding received during the neonatal period with the development of endometriosis in adult life. Mothers of women with endometriosis were significantly more likely to be affected by endometriosis or uterine fibroids, with a higher incidence of smoking during pregnancy. Women with endometriosis were more frequently born prematurely, with a significantly lower birth weight, and their mothers experienced preecl sia during their pregnancies more often than control subjects. They were also more frequently formula fed than breast fed in early life. However, only prematurity and formula feeding were retained in the multivariate analysis model. Among intrauterine and early neonatal exposures, prematurity and formula feeding were risk factors for the development of endometriosis in adult life. Further studies should evaluate the underlying biologic mechanisms.
Publisher: The Endocrine Society
Date: 10-1995
Publisher: Informa UK Limited
Date: 08-06-2019
DOI: 10.1080/02770903.2018.1471709
Abstract: Asthma exacerbations and medication non-adherence are significant clinical problems during pregnancy. While asthma self-management education is effective, the number of education sessions required to maximise asthma management knowledge and inhaler technique and whether improvements persist postpartum, are unknown. This paper describes how asthma knowledge, skills, and inhaled corticosteroid (ICS) use have changed over time. Data were obtained from 3 cohorts of pregnant women with asthma recruited in Newcastle, Australia between 2004 and 2017 (N = 895). Medication use, adherence, knowledge, and inhaler technique were compared between cohorts. Changes in self-management knowledge/skills and women's perception of medication risk to the fetus were assessed in 685 women with 5 assessments during pregnancy, and 95 women who had a postpartum assessment. At study entry, 41%, 29%, and 38% of participants used ICS in the 2004, 2007, and 2013 cohorts, respectively (p = 0.017), with 40% non-adherence in each cohort. Self-management skills of pregnant women with asthma did not improve between 2004 and 2017 and possession of a written action plan remained low. Maximum improvements were reached by 3 sessions for medications knowledge and one session for inhaler technique, and were maintained postpartum. ICS adherence was maximally improved after one session, but not maintained postpartum. Perceived risk of asthma medications on the fetus was highest for corticosteroid-containing medication and was significantly reduced following education. There was a high prevalence of non-adherence and poor self-management skills in all cohorts. More awareness of the importance of optimal asthma management during pregnancy is warranted, since no improvements were observed over the past decade.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2009
Publisher: Elsevier BV
Date: 09-2020
Publisher: BMJ
Date: 03-04-2007
Abstract: To characterise the relationships between peripheral microvascular blood flow and measures of physiological and cardiovascular function in preterm infants in the immediate newborn period. Prospective observational cohort study. Tertiary neonatal intensive care unit, New South Wales, Australia. Ninety-six preterm neonates (24-36 weeks' gestation) admitted to the neonatal intensive care unit. Relationship between laser Doppler-derived basal microvascular blood flow, functional echocardiographic measurements of cardiovascular status, mean arterial blood pressure and clinical illness severity at 24, 72 and 120 h of age. At 24 h of age, multiple linear regression revealed a significant positive relationship, independent of gestational age, between baseline microvascular blood flow and clinical risk index for babies (CRIB II) score (r2 = 0.442). Microvascular blood flow was inversely related to mean arterial blood pressure (r2 = -0.563), and correlated positively with left ventricular output (r2 = 0.435). Microvascular blood flow continued to exhibit a significant inverse relationship with mean arterial blood pressure (r2 = -0.4) at 72 h of age, but by 120 h no significant relationships were evident. This is the first study to show that baseline microvascular blood flow in premature infants exhibits significant relationships with clinical illness severity and cardiovascular function in the immediate postnatal period. The effects of temporal and functional changes in the microvasculature on cardiovascular adaptation warrant further detailed study.
Publisher: MDPI AG
Date: 09-08-2019
DOI: 10.3390/NU11081851
Abstract: Background: Periconceptional nutrition may have an important function in programming the immune function and allergies, however, there is a lack of studies assessing pre-conception food intake and childhood allergic disorders. The aim of the current study was to identify maternal pre-conception dietary components that may be associated with allergic disorders in children up to 3 years of age. Methods: Pregnant women attending their first antenatal visit and who were aged years were invited to participate. Pre-conception food frequency data was retrospectively collected at 18 weeks’ gestation. Childhood eczema, current wheeze, and rhinitis was assessed at 36 months of age using a questionnaire and doctor diagnosis (n = 234). Linear discriminant analysis (LDA) was used to explore the combination of dietary food components that best discriminated between allergy status in children. Results: Maternal pre-conception food intake such as low and high fat dairy, fresh fruit, unsaturated spreads, and take-away foods, were protective for any allergy assessed. Non-oily fish was protective for eczema and current wheeze saturated spreads (e.g., butter) was protective for eczema, current wheeze, and rhinitis poultry and fruit juice were adversely associated with each allergy. Conclusions: Pre-conception food intakes demonstrate inconsistent and somewhat contrary relationships to the development of child allergies. Whether and how maternal food intake impacts the underlying fetal programming and the mechanisms of childhood allergy warrants further investigation.
Publisher: Elsevier BV
Date: 05-2012
Publisher: Elsevier BV
Date: 2005
DOI: 10.1016/J.PLACENTA.2004.04.002
Abstract: Oxidative stress occurs when cellular levels of reactive oxygen species exceed anti-oxidant capabilities and has been implicated in the pathogenesis of pre-ecl sia. In this study we have examined the tissue levels of endogenous anti-oxidant proteins (superoxide dismutase, glutathione peroxidase, thioredoxin reductase and thioredoxin) and the level of lipid and protein oxidation in placental s les from normal and pre-ecl tic pregnancies. Pre-ecl tic tissue homogenates demonstrated significantly increased levels of lipid peroxidation (20.68 +/- 7.811 microM protein versus 5.33 +/- 4.03 microM/mg protein, P < 0.001) and a trended increase in protein carbonyl concentration (248.1 +/- 97.71 units/mg protein versus 209.7 +/- 82.6 U/mg protein) when compared to controls. The levels and activities of the anti-oxidant proteins superoxide dismutase (2.48 +/- 0.6 U/mg protein versus 2.02 +/- 0.51 U/mg protein, P <0.02), thioredoxin reductase (19.25 +/- 9.81 U/mg protein versus 13.02 +/- 5.66 U/mg protein,P = 0.02), thioredoxin (107.00 +/- 18.11 ng/mg protein versus 91.12 +/- 21.18 ng/mg protein, P = 0.02) and glutathione peroxidase (17.33 +/- 6.63 mmol/min/mg protein versus 11.50 +/- 3.11 mmol/min/mg, P < 0.02) were all found to be significantly reduced when comparing pre-ecl tic placental tissue homogenates to gestational age-matched control placentae from non-pre-ecl tic pregnancies. The results of this study demonstrate a decreased enzymatic anti-oxidant capacity and increased oxidation in placental tissue from pre-ecl tic women, which may contribute to the pathogenesis of this complex disorder.
Publisher: Informa UK Limited
Date: 2002
DOI: 10.1076/APAB.110.1.146.892
Abstract: Corticotrophs were long thought to be a static, homogeneous population of cells that respond positively to hypothalamic stimulation, are inhibited by glucocorticoid feedback and secrete a single biologically active peptide, ACTH(1-39). Our current understanding is that this is an oversimplification and corticotrophs are a dynamic and more complex group of cells. The biosynthetic precursors of ACTH and other cleavage products of proopiomelanocortin (POMC) have been found to be secreted by anterior pituitary cells, to circulate and to have biological activity. POMC and the biosynthetic intermediate, pro-ACTH, exert activity antagonistic to ACTH(1-39) on glucocorticoid secretion by adrenal cells, and other derivatives of POMC are mitogenic to adrenocortical cells. In terms of responses to hypothalamic and peripheral factors, corticotrophs are functionally heterogeneous. This is reflected in the sensitivity of in idual subtypes of corticotrophs to CRH, vasopressin and glucocorticoids. There is a functional plasticity amongst the various types of corticotrophs. During gestation, in fetal sheep, changes occur in the overall ACTH-secretory responses to CRH relative to vasopressin, the proportions of total corticotrophs that respond to the respective peptides and the average secretory response of in idual cells. Corticotrophs also respond to locally produced pituitary factors. Local actions of leukaemia inhibitory factor are demonstrated by the effects of immunoneutralization of the peptide in pituitary cells. Urocortin and preproTRH(178-199) are locally produced peptides with potent stimulatory and inhibitory actions on corticotrophs, respectively. The specific roles of these peptides are under investigation.
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.WOMBI.2016.05.009
Abstract: Indirect and direct trauma following vaginal birth can negatively impact on the pelvic floor function increasing the risk of anal incontinence. It is often difficult for women to openly disclose that they have anal incontinence and there are limited data collection tools available for the identification of these women in a clinical setting. This study aims to describe the prevalence of undisclosed anal incontinence in antenatal and postnatal women with pelvic floor dysfunction. Retrospective cohort study of 230 antenatal and postnatal women referred to a Continence Nursing Service in a large tertiary hospital in South Australia, Australia, with pelvic floor dysfunction. A criteria list was utilised to access the primary reason for referral, anal incontinence assessments and attendance to an appointment. Anal incontinence was identified in 26% of women (n=59). Anal incontinence was the primary reason for referral amongst 8 women, with the remaining 51 women identified as having anal incontinence following clinical screening via phone consultation. Eighty six percent of women stated they had not previously disclosed anal incontinence to health professionals. Overall, 71% of symptomatic women (n=28 antenatal and n=14 postnatal women) attended appointments to a service specialising in pelvic floor dysfunction. Women presenting with urinary incontinence or other markers of pelvic floor dysfunction should be actively screened for anal incontinence as the prevalence of this condition is high amongst childbearing women.
Publisher: Elsevier BV
Date: 08-2019
Publisher: BMJ
Date: 13-07-2010
Abstract: Smoking and severe asthma exacerbations in pregnancy are risk factors for low birth weight babies. No studies have assessed the clinical implications of smoking on asthma exacerbations in pregnancy. Pregnant women with current asthma (n=80) were prospectively assessed at clinic visits (18, 30, 36 weeks), during exacerbations and with fortnightly phone calls. The asthma control questionnaire was administered at each contact and exacerbations classified as severe (requiring medical intervention) or mild (self-managed). Medications, self-management skills, smoking history, fractional exhaled nitric oxide (FENO), exhaled carbon monoxide (ECO) and lung function were assessed. Pregnant women without asthma (controls, n=46) were assessed prospectively at clinic visits. Women with asthma were more likely to smoke (34% current smokers) than women without asthma (15% current smokers). In women with asthma, the median (IQR) exacerbation rate during pregnancy was 2.0 (1.0-3.0) in current smokers, 2.0 (1.0-3.0) in ex-smokers and 1.5 (1.0-2.0) in never smokers. The asthma control score during exacerbations was higher in current smokers (median (IQR) 2.17 (1.17-2.7)) compared with never smokers (1.17 (0.8-2.17), p=0.056). An adjusted linear regression model found that smoking was significantly associated with higher asthma control score during exacerbation (P=0.04). birth weights were lower among children of smokers than non-smokers (p=0.023 control group, p=0.086 asthma group). During pregnancy, asthma exacerbations are more common and more severe in current smokers than never smokers. The risk of effects of maternal asthma on the fetus may be greater among smokers.
Publisher: Springer Science and Business Media LLC
Date: 07-2005
DOI: 10.1016/J.JSGI.2005.01.024
Abstract: We conducted a comparative proteomic analysis of placental and umbilical cord blood proteins using surface-enhanced laser desorption ionization-time of flight mass spectrometry (SELDI-TOF MS) to examine the associations among asthma, fetal gender, and protein profiles. Placental tissue and umbilical vein plasma were collected from 10 healthy and 20 asthmatic women. Placental proteins were extracted using phosphate-buffered saline containing protease inhibitors. S les were applied to the surfaces of strong anion exchange (SAX2), weak cation exchange (WCX2) and immobilized metal affinity capture (IMAC-Cu(2+)) chips. Mass analysis was conducted using a Ciphergen Protein Biology System IIc (Freemont, CA), and differences in in idual peak intensities between groups were determined. Fourteen placental peaks were significantly different between asthmatic and non-asthmatic women (seven more highly expressed and seven less highly expressed). Ten umbilical cord blood peak differences were identified, with four peaks more highly expressed and six peaks less highly expressed in asthmatics. Four placental and three umbilical cord blood proteins differed significantly between male and female fetuses. Two placental and five umbilical cord blood peaks were specifically increased in a subgroup of s les collected from asthmatic women who did not use inhaled glucocorticoids and were pregnant with a female fetus, a group previously found to have altered placental function. This study demonstrates the abilities of the SELDI technique as a tool for protein profiling in tissue or plasma. Further work to positively identify the candidate peptides found in this study may provide a greater understanding of the placental mechanisms leading to alterations in fetal growth in patients with bronchial asthma.
Publisher: Bioscientifica
Date: 09-2013
DOI: 10.1530/REP-13-0239
Abstract: Docosahexaenoic acid (DHA) supplementation in pregnancy may confer some clinical benefits however, this compound can exert pro-oxidant effects. In this study, we investigated the effects of DHA on pro-oxidant/antioxidant balance in term and preterm placental explants, assessing oxidative stress marker concentrations, antioxidant capacity and pro-inflammatory cytokine production. Term ( n =8) and preterm ( n =9) placental explants were exposed to lipopolysaccharide (LPS, 1 ng/ml), DHA (1, 10 and 100 μM), and DHA and LPS simultaneously or pre-treated with DHA for 24 h prior to LPS treatment. The production of malondialdehyde (MDA, lipid peroxidation), 8-hydroxy-2-deoxy guanosine (8-OHdG, oxidative DNA damage) and pro-inflammatory cytokines (tumour necrosis factor α (TNFα), interleukin 6 and interferon-γ) and total antioxidant capacity were measured. DHA at a concentration of 100 μM induced oxidative stress in term placentas, while at all the three concentrations, it induced oxidative stress in preterm placentas. DHA and LPS resulted in reduced MDA levels in term ( P .005) and preterm ( P =0.004) placentas and reduced 8-OHdG levels in preterm placentas ( P =0.035). DHA pre-treatment, but not co-treatment with LPS, reduced 8-OHdG levels ( P .001) in term placentas. DHA increased antioxidant capacity only in term placentas ( P .001), with lower antioxidant capacity being observed overall in preterm placentas compared with term placentas ( P ≤0.001). In term placentas, but not in preterm ones, DHA co-treatment and pre-treatment reduced LPS-induced TNFα levels. The ability of DHA to alter placental pro-oxidant/antioxidant balance is dependent on the DHA concentration used and the gestational age of the placental tissue. DHA has a greater capacity to increase oxidative stress in preterm placentas, but it offers greater protection against inflammation-induced oxidative stress in term placentas. This appears to be a result of DHA altering placental antioxidant capacity. These data have implications for the timing and concentration of DHA supplementation in pregnancy.
Publisher: Elsevier BV
Date: 09-2021
DOI: 10.1016/J.PLACENTA.2021.07.303
Abstract: The human placenta has a defined lifespan and placental aging is a key feature as pregnancy progresses. Placental aging and mitochondrial dysfunction are known to play a key role in pregnancy pathophysiology. Premature aging of the placenta has also been linked with placental dysfunction resulting in poor fetal development and premature birth. The expression of key mitochondrial-related genes were analysed in a series of publicly available databases then expression changes were validated in placental s les collected from term, pre-term, post-term pregnancies and pregnancies complicated by fetal growth restriction (FGR). Gene and protein expression levels of MFN1, MFN2, TFAM, TOMM20, OPA3 and SIRT4 were measured in placental tissues via qPCR and western blotting. Initial analysis found that key mitochondrial transcripts related to biogenesis, bioenergetics and mitophagy clustered by pregnancy trimester. A refined list of 13 mitochondrial-related genes were investigated in additional external datasets of pregnancy complications. In the new cohort, protein expression of MFN1 was decreased in FGR and MFN2 is decreased in post-term placenta. Analysis of placental tissues revealed that TOMM20 gene and protein expression was altered in FGR and post-term placenta. MFN1 and MFN2 play a major role in mitochondrial dynamics, and alterations in these markers have been highlighted in early unexplained miscarriage. TOMM20 is an importer protein that plays a major role in mitophagy and changes have also been identified in age-related diseases. Significant changes in MFN1, MFN2 and TOMM20 indicate that mitochondrial regulators play a critical role in placental aging and placental pathophysiology.
Publisher: Informa UK Limited
Date: 09-2011
DOI: 10.1586/ECI.11.51
Abstract: Maternal infection and inflammation are common events during pregnancy. This article documents evidence that suggests such inflammation compromises the development of the fetal innate immune response, in support of an in utero origins hypothesis of neonatal and childhood inflammatory disease. The potential for this response to exhibit sex specificity is also explored, based on evidence of sexually dimorphic placental responses to maternal inflammation.
Publisher: Elsevier BV
Date: 10-2011
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 29-05-2023
Publisher: Wiley
Date: 12-1989
DOI: 10.1038/ICB.1989.53
Abstract: The lack of progress in development of vaccines to stimulate local protection in the urinary tract is attributable in part to the lack of information regarding mechanisms of local immunity and to the difficulty in antigen administration at this site. Experiments reported in this paper indicate that the urinary tract in rats forms part of an effector network linking mucosal organs (the common mucosal immune system). Concomitant immunization of the intestine and urinary tract with ovalbumin resulted in the appearance at both sites of antiovalbumin-containing cells (ACC) of IgA specificity. The gut origin of ACC in the urinary tract was confirmed by demonstrating in similarly immunized rats abrogation of the urinary tract response by chronic drainage of the thoracic lymphatic duct during the post-challenge period and by demonstrating the appearance of radiolabelled ACC in the urinary tract after injection of labelled autologous thoracic duct lymphocytes collected during the post-challenge period. These experiments indicate a role for oral immunization in enhancing the local antibody response in the urinary tract against invading pathogens.
Publisher: Wiley
Date: 12-07-2022
DOI: 10.1111/AJO.13406
Abstract: Reports from around the world suggest that rates of preterm birth decreased during COVID‐19 lockdown measures. To compare the prevalence of preterm birth and stillbirth rates during COVID‐19 restriction measures with infants born at the same maternity centre during the same weeks in 2013–2019. Deidentified data were extracted from the Mater Mothers’ healthcare records database. This is a supra‐regional tertiary perinatal centre. Logistic regressions were used to examine singleton live preterm birth rates during the beginning of COVID‐19 restrictions (16 March‐17 April ‘early’ 6955 births) and during the strictest part of COVID‐19 restrictions (30 March‐1 May ‘late’ 6953 births), according to gestational age subgroups and birth onset (planned or spontaneous). We adjusted for multiple covariates, including maternal age, body mass index, ethnicity, parity, socioeconomic status, maternal asthma, diabetes mellitus and/or hypertensive disorder. Singleton stillbirth rates were also examined between 16 March–1 May. Planned moderate/late preterm births declined by more than half during early COVID‐19 restrictions compared with the previous seven years (29 vs an average of 64 per 1000 births adjusted odds ratio 0.39, 95% CI 0.22–0.71). There was no effect on extremely or very preterm infants, spontaneous preterm births, or stillbirth rates. Rolling averages from January to June revealed a two‐week non‐significant spike in spontaneous preterm births from late April to early May, 2020. Together with evidence from other nations, the pandemic provides a unique opportunity to identify causal and preventative factors for preterm birth.
Publisher: Frontiers Media SA
Date: 08-09-2022
Publisher: Bioscientifica
Date: 07-2005
DOI: 10.1677/JOE.1.06030
Abstract: Females have a significantly greater life expectancy than males, which in part may be due to the cardio-protective effects of the female sex hormone, estrogen, on vascular function. However, the sex-specific mechanisms contributing to these differences are complex and not fully understood. Previously we have reported that corticotropin-releasing hormone (CRH) has potent dilator effects in the female skin circulation via mast cell degranulation. Furthermore the dilator response to CRH was more enhanced in females than in age-matched males, suggesting that estrogens may be involved. In this study we examined whether CRH-induced dilation and endothelial cell-dependent dilation in the skin circulation of pre-menopausal females were associated with changes in estrogen during the menstrual cycle. CRH-induced dilation (1 nM) was enhanced in the presence of high circulating concentrations of estrogen and a positive correlation was identified between CRH-induced dilation and plasma estrogen concentrations. Endothelial cell-dependent dilation was examined using acetylcholine. Acetylcholine-induced dilation (1 nM) was not correlated with circulating concentrations of estrogen. These data suggest the variation in CRH-induced dilation in the skin microvasculature during the menstrual cycle may be due to estrogenic effects on mast cell function and not due to direct changes in endothelial cell function.
Publisher: MDPI AG
Date: 10-01-2020
Abstract: Small-for-gestational-age (SGA) infants are fetuses that have not reached their genetically programmed growth potential. Low birth weight predisposes these infants to an increased risk of developing cardiovascular, metabolic and neurodevelopmental conditions in later life. However, our understanding of how this pathology occurs is currently incomplete. Previous research has focused on understanding the transcriptome, epigenome and bacterial signatures separately. However, we hypothesise that interactions between moderators of gene expression are critical to understanding fetal growth restriction. Through a review of the current literature, we identify that there is evidence of modulated expression/methylation of the placental genome and the presence of bacterial DNA in the placental tissue of SGA infants. We also identify that despite limited evidence of the interactions between the above results, there are promising suggestions of a relationship between bacterial signatures and placental function. This review aims to summarise the current literature concerning fetal growth from multiple avenues and propose a novel relationship between the placental transcriptome, methylome and bacterial signature that, if characterised, may be able to improve our current understanding of the placental response to stress and the aetiology of growth restriction.
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.EJOGRB.2015.11.038
Abstract: We sought to investigate the impact of introducing an antenatal asthma management service (AMS) on asthma control during pregnancy and subsequent perinatal outcomes. Prospective, observational cohort study of pregnant asthmatic women attending a tertiary hospital antenatal clinic. Asthmatic women were recruited from the antenatal clinic and were followed prospectively with visits at 12, 20, 28 and 36 weeks gestation. A new nurse-led AMS was introduced offering asthma self-management education and support. Outcomes were compared between women recruited before and after the AMS was introduced (n=89 and 80, respectively) and included prevalence of exacerbations during pregnancy, asthma control throughout pregnancy and perinatal outcomes, including preterm birth and small-for-gestational-age (SGA). The relative risk for exacerbations (0.69 CI: 0.33-1.42), loss of control (0.67 CI 0.46-0.99) and persistent uncontrolled asthma (0.48 CI 0.26-0.9) were all reduced with attendance to AMS during pregnancy. AMS was associated with non-statistically significant reductions in asthma exacerbations (19.1-15.0% p=0.480) and uncontrolled asthma at ≥ 2 study visits (21.3-11.3% p=0.078). These findings demonstrate the potential impact of an AMS in improving asthma control during pregnancy, supporting the need for an adequately powered RCT to determine its clinical- and cost-effectiveness.
Publisher: Cold Spring Harbor Laboratory
Date: 21-01-2023
DOI: 10.1101/2023.01.20.524893
Abstract: In recent years, pregnant people infected with the SARS-CoV-2 virus have shown a higher incidence of “preecl sia-like syndrome”. Preecl sia is a systematic syndrome that affects 5-8 % of pregnant people worldwide and is the leading cause of maternal mortality and morbidity. It is unclear what causes preecl sia, and is characterised by placental dysfunction, leading to poor placental perfusion, maternal hypertension, proteinuria, thrombocytopenia, or neurological disturbances. In this study, we used whole-transcriptome, digital spatial profiling of placental tissues to analyse the expression of genes at the cellular level between placentae from pregnant participants who contracted SARS-CoV-2 in the third trimester of their pregnancy and those prior to the start of the pandemic. Our focused analysis of the trophoblast and villous core stromal cell populations revealed tissue-specific pathways enriched in the SARS-CoV-2 placentae that align with a pre-ecl sia signature. Most notably, we found enrichment of pathways involved in vascular tension, blood pressure, inflammation, and oxidative stress. This study illustrates how spatially resolved transcriptomic analysis of placental tissue can aid in understanding the underlying pathogenic mechanisms of SARS-CoV-2 in pregnancy that are thought to induce “preecl sia-like syndrome”. Moreover, our study highlights the benefits of using digital spatial profiling to map the crosstalk between trophoblast and villous core stromal cells linked to pathways involved in “preecl sia-like syndrome” presenting in pregnant people with SARS-CoV-2.
Publisher: Springer Science and Business Media LLC
Date: 11-04-2010
Publisher: Elsevier BV
Date: 09-2017
Publisher: Elsevier BV
Date: 08-2011
DOI: 10.1016/J.BBI.2011.03.014
Abstract: Stressful events during the perinatal period in both humans and animals have long-term consequences for the development and function of physiological systems and susceptibility to disease in adulthood. One form of stress commonly experienced in the neonatal period is exposure to bacterial and viral infections. The current study investigated the effects of live Chlamydia muridarum bacterial infection at birth followed by re-infection in adulthood on hippoc al glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) and stress response outcomes. Within 24 h of birth, neonatal mice were infected intranasally with C. muridarum (400 inclusion-forming units [ifu]) or vehicle. At 42 days, mice were re-infected (100 ifu) and euthanized 10 days later. In males, infection in adulthood alone had the most impact on the parameters measured with significant increases in GR protein compared to adult infection alone and significant increases MR protein and circulating corticosterone compared to other treatment groups. Neonatal infection alone induced the largest alterations in the females with results showing reciprocal patterns for GR protein and TH protein. Perinatal infection resulted in a blunted response following adult infection for both males and females across all parameters. The present study demonstrates for the first time that males and females respond differently to infection based on the timing of the initial insult and that there is considerable sex differences in the hippoc al phenotypes that emerge in adulthood after neonatal infection.
Publisher: Springer International Publishing
Date: 2015
Publisher: American Physiological Society
Date: 04-2014
DOI: 10.1152/AJPREGU.00432.2013
Abstract: Prenatal and early childhood exposures are implicated as causes of allergy, but the effects of intrauterine growth restriction on immune function and allergy are poorly defined. We therefore evaluated effects of experimental restriction of fetal growth on immune function and allergic sensitization in adolescent sheep. Immune function (circulating total red and white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, and the antibody response to Clostridial vaccination) and responses to house dust mite (HDM) allergen and ovalbumin (OVA) antigen sensitization (specific total Ig, IgG 1 , and IgE antibodies, and cutaneous hypersensitivity) were investigated in adolescent sheep from placentally restricted (PR, n = 23) and control ( n = 40) pregnancies. Increases in circulating HDM-specific IgE ( P = 0.007) and OVA-specific IgE ( P = 0.038) were greater in PR than control progeny. PR did not alter total Ig, IgG 1 , or IgM responses to either antigen. PR increased OVA-specific but not HDM-specific IgA responses in females only ( P = 0.023). Multiple birth increased Ig responses to OVA in a sex-specific manner. PR decreased the proportion of positive cutaneous hypersensitivity responders to OVA at 24 h ( P = 0.030) but had no effect on cutaneous responses to HDM. Acute wheal responses to intradermal histamine correlated positively with birth weight in singletons ( P = 0.023). Intrauterine growth restriction may suppress inflammatory responses in skin downstream of IgE induction, without impairment in antibody responses to a nonpolysaccharide vaccine. Discord between cutaneous and IgE responses following sensitization suggests new mechanisms for prenatal allergy programming.
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.BBI.2014.10.014
Abstract: The immune and nociceptive systems are shaped during the neonatal period where they undergo fine-tuning and maturation. Painful experiences during this sensitive period of development are known to produce long-lasting effects on the immune and nociceptive responses. It is less clear, however, whether inflammatory pain responses are primed by neonatal exposure to mild immunological stimuli, such as with lipopolysaccharide (LPS). Here, we examine the impact of neonatal LPS exposure on inflammatory pain responses, peripheral and hippoc al interleukin-1β (IL-1β), as well as mast cell number and degranulation in preadolescent and adult rats. Wistar rats were injected with LPS (0.05mg/kg IP, Salmonella enteritidis) or saline on postnatal days (PNDs) 3 and 5 and later subjected to the formalin test at PNDs 22 and 80-97. At both time-points, and one-hour after formalin injection, blood and hippoc us were collected for measuring circulating and central IL-1β levels using ELISA and Western blot, respectively. Paw tissue was also isolated to assess mast cell number and degree of degranulation using Toluidine Blue staining. Behavioural analyses indicate that at PND 22, LPS-challenged rats displayed enhanced flinching (p<.01) and licking (p<.01) in response to formalin injection. At PNDs 80-97, LPS-challenged rats exhibited increased flinching (p<.05), an effect observed in males only. Furthermore, neonatal LPS exposure enhanced circulating IL-1β and mast cell degranulation in preadolescent but not adult rats following formalin injection. Hippoc al IL-1β levels were increased in LPS-treated adult but not preadolescent rats in response to formalin injection. These data suggest neonatal LPS exposure produces developmentally regulated changes in formalin-induced behavioural responses, peripheral and central IL-1β levels, as well as mast cell degranulation following noxious stimulation later in life. These findings highlight the importance of immune activation during the neonatal period in shaping immune response and pain sensitivity later in life. This is of clinical relevance given the high prevalence of bacterial infection during the neonatal period, particularly in the vulnerable population of preterm infants admitted to neonatal intensive care units.
Publisher: Wiley
Date: 08-2008
Publisher: SAGE Publications
Date: 12-2016
Abstract: Few studies have investigated breastfeeding outcomes among women exposed to antidepressants. This study aimed to evaluate the association between antidepressant use in late gestation and maternal psychiatric illness on breastfeeding rates at discharge from hospital. The authors conducted a retrospective cohort study of 32,662 women delivering live-born singletons between January 2001 and December 2008. Electronic hospital records were used to obtain data on antidepressant exposure during late gestation and whether mothers were breastfeeding at discharge from hospital following delivery. Five hundred seventy-five women received a dispensing for an antidepressant in late gestation (exposed), 1,552 did not receive a dispensing for an antidepressant but had a reported psychiatric illness (disease comparison), and 30,535 served as nonexposed controls. Exposed women were significantly less likely to be breastfeeding their infants at discharge from hospital compared with nonexposed women, adjusted odds ratio ( AOR) = 0.63, 95% confidence interval (CI) [0.50-0.80], but no statistically significant difference was observed when compared with women in the disease comparison group, AOR = 0.83, 95% CI [0.65-1.07]. In stratified analyses, compared with women in the disease comparison group, exposed women were significantly less likely to be breastfeeding their infants at discharge from hospital if their neonate was delivered at term, AOR = 0.73, 95% CI [0.55-0.98], but not preterm, AOR = 1.24, 95% CI [0.66-2.32]. While antidepressant use is associated with a reduction in breastfeeding rates, this association appears to be strongly influenced by factors such as underlying maternal psychiatric illness. Overall, these results highlight that these women may benefit from additional education and support to improve breastfeeding rates.
Publisher: Elsevier BV
Date: 03-2007
DOI: 10.1016/J.BBR.2006.12.008
Abstract: Prenatal exposure of animals to bacterial endotoxin is an experimental model of systemic maternal infection in the human pregnancy. Previous studies in the rat have demonstrated that such exposure is associated with long term alterations to hypothalamic pituitary adrenal (HPA) axis development. Typically, these animals display an elevated HPA response to stress in adulthood. As neural development is more similar in the human and the guinea pig than the rat, this study adopted a guinea pig model of pregnancy to explore the effects of endotoxin exposure on the HPA axis in the offspring. The offspring of dams exposed to endotoxin exhibited an attenuated cortisol response to the novel environment stress in the weaning period. The degree to which this cortisol response was both buffered by the mother's presence, and habituated to on repeated exposure, differed significantly between the prenatal treatment groups. In adulthood, a diminished cortisol response to the immune challenge was only evident in the female offspring, while both male and female offspring exhibited altered febrile responses. The results of the present study indicate that prenatal bacterial exposure in the guinea pig results in offspring with lower cortisol responses to stress in later life. These findings contrast past research that has used the rat to model pregnancy. As such, the use of the guinea pig to model infection may provide a useful alternative model of human pregnancy to explore programming effects.
Publisher: Wiley
Date: 04-2006
Publisher: Elsevier BV
Date: 04-2012
Publisher: CSIRO Publishing
Date: 2009
DOI: 10.1071/RD08224
Abstract: 5α-Reduced steroids, including allopregnanolone, suppress neuronal activity and can have neuroprotective effects in the fetus. 5α-Reductases in the placenta may contribute precursors to brain allopregnanolone synthesis. Preterm birth and glucocorticoids, administered for fetal lung maturation or for maternal asthma, may influence reductase expression. The aims of the present study were to evaluate placental 5α-reductase isoform expression during late gestation and to examine fetal sex differences and the effects of glucocorticoid therapies on the expression of these enzymes. Expression of the two 5α-reductase isoenzymes was measured in placental s les, whereas cortisol concentrations were measured in cord blood, from two cohorts. The first cohort consisted of women who delivered preterm and received betamethasone treatment (n = 41) the second cohort consisted of women who delivered at term and were either healthy controls (n = 30) or asthmatics who had used glucocorticoids (n = 24). Placental expression of both isoenzymes increased with advancing gestation and there were marked sex differences in levels of 5α-reductase I (P 0.05), but not of 5α-reductase II. The expression of both enzymes was positively correlated with cortisol levels (P 0.05), but there was no effect of recent glucocorticoid exposure. These findings suggest that the preterm neonate may have lower developmental exposure to 5α-reduced steroids and may lack steroid-mediated neuroprotection depending on fetal sex.
Publisher: The Endocrine Society
Date: 04-2002
DOI: 10.1210/JC.87.4.1660
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 1997
Publisher: The Endocrine Society
Date: 04-1996
DOI: 10.1210/JC.81.4.1406
Publisher: Wiley
Date: 03-07-2019
DOI: 10.1113/JP277952
Publisher: Elsevier BV
Date: 12-2014
Publisher: The Endocrine Society
Date: 10-1995
DOI: 10.1210/JCEM.80.10.7559870
Abstract: This study has used an in vitro perfusion method to investigate the mechanism by which CRH causes vasodilatation in the human fetal-placental circulation. In normal term placentas, vasodilatory responses to human CRH (24-7000 pmol/L) were examined during submaximal vasoconstriction (100-120 mm Hg) of the fetal-placental vasculature induced by prostaglandin F2 alpha (0.7-2 mumol/L), KCl (50-100 mmol/L), or the thromboxane A2 mimetic, U46619 (0.05-0.5 mumol/L). Infusion of CRH caused a concentration-dependent vasodilatation that was similar in the presence of each constrictor agent (P > 0.05). The CRH antagonist, alpha-helical CRH-(9-41) (200 pmol/L), and a polyclonal CRH antiserum significantly inhibited CRH-induced vasodilatation during constriction with prostaglandin F2 alpha (P < 0.05). Vasodilatory responses to CRH were attenuated by the nitric oxide synthase inhibitor, N omega-nitro-L-arginine (100 mumol/L P < 0.05), and the guanylate cyclase inhibitor, LY 83583 (1 mumol/L P 0.05). In placentas of women with increased fetal vascular resistance, as demonstrated by Doppler ultrasound waveforms in vivo, CRH-induced vasodilatation was significantly reduced (P < 0.05). These results indicate that in the human fetal-placental circulation, CRH causes a vasodilatory response via a nitric oxide-/cGMP-dependent pathway. CRH may play a role in the control of vascular resistance to blood flow in the normal human placenta, and there may be a deficiency in the CRH signaling pathway of placentas with increased fetal vascular resistance.
Publisher: The Endocrine Society
Date: 08-1994
DOI: 10.1210/JC.79.2.666
Publisher: Elsevier BV
Date: 08-2011
DOI: 10.1016/J.CHROMA.2011.06.065
Abstract: The goal of this paper is to demonstrate the separation and detection capability of eco-friendly micro-TLC technique for the classification of spirulina and selected herbs from pharmaceutical and food products. Target compounds were extracted using relatively low-parachor liquids. A number of the spirulina s les which originated from pharmaceutical formulations and food products, were isolated using a simple one step extraction with small volume of methanol, acetone or tetrahydrofuran. Herb s les rich in chlorophyll dyes were analyzed as reference materials. Quantitative data derived from micro-plates under visible light conditions and after iodine staining were explored using chemometrics tools including cluster analysis and principal components analysis. Using this method we could easily distinguish genuine spirulina and non-spirulina s les as well as fresh from expired commercial products and furthermore, we could identify some biodegradation peaks appearing on micro-TLC profiles. This methodology can be applied as a fast screening or fingerprinting tool for the classification of genuine spirulina and herb s les and in particular may be used commercially for the rapid quality control screening of products. Furthermore, this approach allows low-cost fractionation of target substances including cyanobacteria pigments in raw biological or environmental s les for preliminary chemotaxonomic investigations. Due to the low consumption of the mobile phase (usually less than 1 mL per run), this method can be considered as environmentally friendly analytical tool, which may be an alternative for fingerprinting protocols based on HPLC machines and simple separation systems involving planar micro-fluidic or micro-chip devices.
Publisher: BMJ
Date: 02-2006
Publisher: Informa UK Limited
Date: 25-10-2023
DOI: 10.1080/02770903.2022.2134794
Abstract: Asthma and obesity are both inflammatory complications of pregnancy and when combined contribute to an increased risk of uncontrolled asthma during pregnancy and poor perinatal outcomes. Our previous work has identified the presence of maternal asthma is associated with a proinflammatory milieu in the placenta and reduced fetal growth. The current study was designed to determine the relationships between immunomodulatory metabolic pathways and inflammation and establish whether these pathways are associated with uncontrolled asthma in obese pregnant women. Fifty-three obese (BMI >30) pregnant women were recruited prospectively. Participants were classified as having no asthma, controlled asthma, and uncontrolled asthma based on a doctor diagnosis and assessment using the Asthma Control Questionnaire (ACQ). Circulating plasma concentrations of metabolic hormones leptin, adiponectin, insulin, glucose, and extracellular vesicle (EVs) associated cytokines were measured at 18- and 36-weeks gestation. Concentrations of metabolic and inflammatory markers among obese participants with or without asthma were not significantly different throughout gestation. However total adiponectin concentrations increased as gestation progressed in obese, non-asthmatic women but did not increase in women with asthma. Plasma adiponectin and leptin levels in women with uncontrolled asthma were positively correlated with EV inflammatory markers including GM-CSF, IL-6, TNFα and IFNγ protein. This study demonstrated that most metabolic markers remain unchanged with the presence and severity of asthma in obese pregnant women. However, differences in the associations between metabolic and inflammatory pathways were observed in women with asthma and may be one of the mechanisms contributing to uncontrolled asthma in obese pregnant women.
Publisher: Informa UK Limited
Date: 06-02-2011
DOI: 10.3109/10253890.2010.532576
Abstract: During the perinatal period, the developing brain is sensitive to environmental events. Deleterious programing resulting from infection, dietary restriction, or psychological stress has been observed and affects adult immune and endocrine systems as well as behavior. In this study, we determined whether neonatal infection permanently alters immune and glucocorticoid receptor signaling pathways in the adult hippoc us. A Chlamydia muridarum respiratory infection was induced in male and female mice at birth. Mice were allowed to recover and microarray analysis was conducted on RNA from adult hippoc al tissue. In males, neonatal infection induced an up-regulation of genes associated with cellular development, nervous system development and function, such as cyclin-dependent kinase inhibitor 1A. After neonatal infection, adult females exhibited a T-helper 2 immune bias with genes such as major histocompatibility complex, class II, DQ beta 1 up-regulated. Expression of prolactin, vasopressin, hypocretin, corticotrophin-releasing hormone-binding protein, and oxytocin were confirmed by quantitative real-time polymerase chain reaction. This study shows that neonatal infection differentially alters the gene expression profiles of both female and male mice along immune and neuroendocrine pathways.
Publisher: Bioscientifica
Date: 08-2017
DOI: 10.1530/JOE-17-0171
Abstract: Maternal dexamethasone exposure in the mouse impairs placental development and programs adult disease in a sexually dimorphic manner. Glucocorticoids bind to different glucocorticoid receptor (GR) isoforms to regulate gene transcription and cellular signaling. We hypothesized that sexually dimorphic placental responses to glucocorticoids are due to differences in GR isoforms present in the placenta. Pregnant C57Bl6 mice were exposed to saline or dexamethasone from E12.5 until E14.5 (1 µg/kg/h) before the collection of placentae. Cytoplasmic and nuclear protein fractions were extracted from placentae of male and female fetuses for Western blot analysis of GR isoforms. Eight known isoforms of the GR were detected in the mouse placenta including the translational isoforms GRα-A, B, C and D1–3 and the splice variants GRA and GRP. The expression of GRA, GRP and each of the GRα isoforms were altered by dexamethasone in relation to fetal sex and cellular location. Placentae of female fetuses had higher GRα-A and GRP expression in the cytoplasm than males, and GRα-C was more highly expressed in the nucleus of females than that in males. Dexamethasone significantly increased the cytoplasmic expression of GRα-A, but reduced the expression of GRα-C in placentae of males. Dexamethasone increased the expression of the GRα-C-regulated genes Sgk1 and Bcl2l11 , particularly in females. The cleaved caspase-3 staining in placental sections indicated GRα-C may mediate sex differences in dexamethasone-induced apoptosis. These findings may underlie the sex-specific placental adaptations that regulate different growth profiles in males and females and different risks for programmed disease outcomes in offspring.
Publisher: Wiley
Date: 21-11-2020
Abstract: The female reproductive tract represents a continuum between the vagina and the upper genital tract. New evidence from cultivation-independent studies suggests that the female upper genital tract is not sterile however, the significance of this for reproductive health and disease remains to be elucidated fully. Further, diagnosis and treatment of infectious reproductive tract pathologies using cultivation-independent technologies represents a largely unchartered area of modern medical science. The challenge now is to design well-controlled experiments to account for the ease of contamination known to confound molecular-based studies of low-biomass niches, including the uterus and placenta. This will support robust assessment of the potential function of microorganisms, microbial metabolites, and cell-free bacterial DNA on reproductive function in health and disease. TWEETABLE ABSTRACT: Molecular microbial studies of low-biomass niches require stringent experimental controls to reveal causal relations in reproductive health and disease.
Publisher: Elsevier BV
Date: 09-2016
Publisher: European Respiratory Society (ERS)
Date: 02-2018
Publisher: Wiley
Date: 17-10-2012
DOI: 10.1002/DEV.20615
Abstract: The current study investigated the effects of neonatal infection with Chlamydia muridarum bacteria on glucocorticoid (GR) and mineralocorticoid (MR) receptors in the adult mouse hippoc us. In male adults infected at birth, circulating corticosterone was significantly increased when compared to same sex controls while neonatal infection resulted in female adults with significantly increased GR mRNA compared to same sex controls. When comparing males and females after neonatal infection, males had significantly less GR protein than females. Interestingly, after control treatment, males had significantly more GR mRNA, MR mRNA, and GR protein with significantly lower corticosterone than females. Neonatal respiratory infection significantly impacts adult hippoc al GR and MR, and circulating corticosterone in a sex-specific manner potentially altering stress responsivity.
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.PLACENTA.2016.01.003
Abstract: Workshops are an important part of the IFPA annual meeting, as they allow for discussion of specialized topics. At the IFPA meeting 2015 there were twelve themed workshops, three of which are summarized in this report. These workshops were related to various aspects of placental biology but collectively covered areas of pregnancy pathologies and placental metabolism: 1) nanomedicine applications and exosome biology 2) xenobiotics and endocrine disruptors and pregnancy 3) lipid mediators and placental function.
Publisher: CSIRO Publishing
Date: 1993
DOI: 10.1071/RD9930135
Abstract: A group of 29 re-anastomosed men were examined with respect to semen quality, anti-sperm antibody titres in serum and seminal plasma, presence of anti-sperm antibodies on sperm, and success rate in inducing pregnancy. Results indicated no association between pre-reversal serum anti-sperm antibody titres and post-reversal semen quality, but a pregnancy induction rate of zero was associated with serum anti-sperm antibody titres greater than 160. It is recommended that men considering reversal, with anti-sperm antibody titres of this level, should receive counselling about the possibility of post-reversal infertility.
Publisher: Elsevier BV
Date: 10-2021
DOI: 10.1016/J.PLACENTA.2021.09.001
Abstract: Research into the role of ultrasound elastography to assess compromised placental tissue is ongoing. There is particular interest in evaluating its potential in the investigation of changes associated with uteroplacental dysfunction. To date, there is limited data on how different maternal and fetal considerations, such as advancing gestational age, amniotic fluid Index (AFI) and maternal body mass index (BMI) may influence shear wave velocity (SWV) measurements. This study aimed to evaluate longitudinal changes in SWV throughout gestation and model these changes with other developing fetal and maternal physiological and biological characteristics. The study utilised 238 singleton pregnancies and collected longitudinal data at repeated intervals in the 3rd trimester representing 629 in idual data points. Linear mixed model regression analysis was used to identify significant predictors for SWV. From a total of ten variables selected for modelling, only gestational age, AFI, BMI, and s le depth were found to be significant predictors of placental SWV, and gestational age and AFI were found to have only a minimal impact on SWV. Sophisticated statistical modelling demonstrates that many of the expected maternal and fetal changes in the 3rd trimester have no or minimal impact on placental SWV. Understanding which factors influence placental SWV is essential to ascertain the technique's utility in managing pregnancies complicated by placental dysfunction in the future.
Publisher: Elsevier BV
Date: 08-2019
Publisher: Frontiers Media SA
Date: 15-09-2021
DOI: 10.3389/FIMMU.2021.743022
Abstract: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The virus primarily affects the lungs where it induces respiratory distress syndrome ranging from mild to acute, however, there is a growing body of evidence supporting its negative effects on other system organs that also carry the ACE2 receptor, such as the placenta. The majority of newborns delivered from SARS-CoV-2 positive mothers test negative following delivery, suggesting that there are protective mechanisms within the placenta. There appears to be a higher incidence of pregnancy-related complications in SARS-CoV-2 positive mothers, such as miscarriage, restricted fetal growth, or still-birth. In this review, we discuss the pathobiology of COVID-19 maternal infection and the potential adverse effects associated with viral infection, and the possibility of transplacental transmission.
Publisher: Elsevier BV
Date: 03-2021
Publisher: American Physiological Society
Date: 2018
DOI: 10.1152/AJPREGU.00549.2016
Abstract: Perinatal exposures are associated with altered risks of childhood allergy. Human studies and our previous work suggest that restricted growth in utero (IUGR) is protective against allergic disease. The mechanisms are not clearly defined, but reduced fetal abundance and altered metabolism of methyl donors are hypothesized as possible underlying mechanisms. Therefore, we examined whether late-gestation maternal dietary methyl donor and cofactor supplementation of the placentally restricted (PR) sheep pregnancy would reverse allergic protection in progeny. Allergic outcomes were compared between progeny from control pregnancies (CON n = 49), from PR pregnancies without intervention (PR n = 28), and from PR pregnancies where the dam was fed a methyl donor plus cofactor supplement from day 120 of pregnancy until delivery (PR + Methyl n = 25). Both PR and PR + Methyl progeny were smaller than CON supplementation did not alter birth size. PR was protective against cutaneous hypersensitivity responses to ovalbumin (OVA P 0.01 in singletons). Cutaneous hypersensitivity responses to OVA in PR + Methyl progeny were intermediate to and not different from the responses of CON and PR sheep. Cutaneous hypersensitivity responses to house dust mites did not differ between treatments. In singleton progeny, upper dermal mast cell density was greater in PR + Methyl than in PR or CON (each P 0.05). The differences in the cutaneous allergic response were not explained by treatment effects on circulating immune cells or antibodies. Our results suggest that mechanisms underlying in utero programming of allergic susceptibility by IUGR and methyl donor availability may differ and imply that late-gestation methyl donor supplementation may increase allergy risk.
Publisher: MDPI AG
Date: 15-06-2021
DOI: 10.3390/IJMS22126386
Abstract: It is well understood that sex differences exist between females and males even before they are born. These sex-dependent differences may contribute to altered growth and developmental outcomes for the fetus. Based on our initial observations in the human placenta, we hypothesised that the male prioritises growth pathways in order to maximise growth through to adulthood, thereby ensuring the greatest chance of reproductive success. However, this male-specific “evolutionary advantage” likely contributes to males being less adaptable to shifts in the in-utero environment, which then places them at a greater risk for intrauterine morbidities or mortality. Comparatively, females are more adaptable to changes in the in-utero environment at the cost of growth, which may reduce their risk of poor perinatal outcomes. The mechanisms that drive these sex-specific adaptations to a change in the in-utero environment remain unclear, but an increasing body of evidence within the field of developmental biology would suggest that alterations to placental function, as well as the feto-placental hormonal milieu, is an important contributing factor. Herein, we have addressed the current knowledge regarding sex-specific intrauterine growth differences and have examined how certain pregnancy complications may alter these female- and male-specific adaptations.
Publisher: Wiley
Date: 20-06-2017
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.PLACENTA.2013.01.013
Abstract: The beneficial effects of antenatal glucocorticoid therapy on fetal lung maturation require their passage across the placental glucocorticoid barrier, composed of glucocorticoid metabolising enzymes, such as 11 beta hydroxysteroid dehydrogenase (11βHSD), and proteins that efflux glucocorticoids, such as P-glycoprotein (P-gp). We have shown that 11βHSD2 activity is responsive to antenatal glucocorticoids, however the effect on placental P-gp remains unknown. Since antenatal glucocorticoids have a greater prophylactic effect in females compared to males, we also assessed whether this therapy induced sexually dimorphic effects on P-gp expression, as well as on placental inflammatory processes mediated by corticosteroids. Placentas were collected from 53 women presenting in threatened preterm labour, and processed to assess cytokine and P-gp mRNA expression, as well as P-gp localisation using immunohistochemistry. Placental cytokine, P-gp mRNA and protein expression were not altered by timing of antenatal glucocorticoids or fetal sex. However, both P-gp mRNA and protein expression were significantly reduced in placentas from infants born small for gestational age (SGA) compared to appropriately grown infants (p < 0.05), suggesting a role for P-gp in its pathogenesis via the provision of a net increase in fetal exposure to bioactive exogenous glucocorticoids. While this study identified no change in placental P-gp following antenatal glucocorticoids, it has provided evidence that P-gp plays an important role in cases of SGA. This supports the known mechanistic relationship between antenatal glucocorticoids, fetal development and the postnatal phenotype. Given that P-gp also confers fetal protection from a number of drugs, this finding warrants further investigation to improve clinical management of the SGA fetus.
Publisher: MDPI AG
Date: 04-07-2023
DOI: 10.20944/PREPRINTS202306.2241.V1
Abstract: Alterations in the hypothalamic-pituitary-adrenal (HPA) axis and associated changes in circulating levels of glucocorticoids are integral to an organism's response to stressful stimuli. Glucocorticoids acting via glucocorticoid receptors (GR) play a role in fertility, reproduction, placental function, and fetal development. GRs are ubiquitously expressed throughout the female reproductive system and regulate normal reproductive function. Stress induced glucocorticoids have been shown to inhibit reproduction and affect female gonadal function by supressing the hypothalamic-pituitary-gonadal (HPG) axis at each level. Furthermore, during pregnancy, a mother's exposure to prenatal stress or external glucocorticoids can result in long-lasting alterations to the fetal HPA and neuroendocrine function. Several GR isoforms generated via alternative splicing or translation initiation from the GR gene have been identified in the mammalian ovary and uterus. The GR isoforms identified include the splice variants, GR& alpha and GR& beta , GR& gamma and GR-P. Glucocorticoids can exert both stimulatory and inhibitory effects and both pro- and anti-inflammatory functions in the ovary, in vitro. In the placenta, thirteen GR isoforms have been identified in human, guinea pig, sheep, rat and mouse indicating it is conserved across species and may be important in mediating a differential response to stress. Distinctive responses to glucocorticoids, differential birth outcomes in pregnancy complications, and sex-based variations in the response to stress could all potentially be dependent on a particular GR expression pattern. This review provides an overview of the structure and function of the GR in relation to female fertility and reproduction and discusses the changes in GR and glucocorticoid signalling during pregnancy. This review will delve into the existing understanding of GR isoforms and explore the possible roles that these distinct isoforms may have in regulating glucocorticoid signalling, along with their impact on gonadal activity, placental function, and fetal growth.
Publisher: Elsevier BV
Date: 03-1995
Publisher: AMPCo
Date: 09-2014
DOI: 10.5694/MJA13.11142
Abstract: To assess the impact of Aboriginal status, active cigarette smoking and smoking cessation during pregnancy on perinatal outcomes. Retrospective cohort study from 1 January 1999 to 31 December 2008. All singleton births in South Australia. Population-based birth records of pregnancies to Aboriginal women (n = 4245) and non-Aboriginal women (n = 167 746). Adjusted odds ratios (aORs) and 95% CIs for adverse maternal and neonatal outcomes according to Aboriginal status and maternal smoking in pregnancy. Active cigarette smoking during pregnancy was associated with an increased risk of adverse perinatal outcomes, including premature labour (Aboriginal, 1-10 cigarettes per day: aOR, 1.69 95% CI, 1.28-2.23 non-Aboriginal, 1-10 cigarettes per day: aOR, 1.46 95% CI, 1.34-1.58), preterm birth (Aboriginal, 1-10 cigarettes per day: aOR, 1.40 95% CI, 1.14-1.73 non-Aboriginal, 1-10 cigarettes per day: aOR, 1.48 95% CI, 1.39-1.57), intrauterine growth restriction (Aboriginal, 1-10 cigarettes per day: aOR, 2.33 95% CI, 1.77-3.08 non-Aboriginal, 1-10 cigarettes per day: aOR, 2.65 95% CI, 2.48-2.83) and small for gestational age (Aboriginal, 1-10 cigarettes per day: aOR, 2.49 95% CI, 2.06-3.00 non-Aboriginal, 1-10 cigarettes per day: aOR, 2.29 95% CI, 2.20-2.40). For both Aboriginal and non-Aboriginal women who smoked 11 or more cigarettes per day the aOR for these outcomes increased. Smoking cessation in the first trimester reduced these risks to levels comparable with non-smokers. The risk of each adverse outcome was greater in Aboriginal than non-Aboriginal women for all smoking categories however, interactions between Aboriginal status and smoking were not significant, indicating an equal contribution of smoking to poor outcomes in both populations. Smoking cessation or reduction during pregnancy would significantly improve outcomes in both Aboriginal and non-Aboriginal women. This should be made a clear priority to improve pregnancy outcomes for all women.
Publisher: Elsevier BV
Date: 10-2007
DOI: 10.1016/J.JNEUROIM.2007.07.021
Abstract: Growing evidence suggests that maternal health during the prenatal period is a critical determinant of adult immuno-competence. This study aimed to characterise the innate immune response to bacterial exposure in rat offspring following maternal exposure to a pro-inflammatory stimulus. The offspring's innate immune responses were investigated at four developmental timepoints in the rat by determination of immune cell subtypes and TNF-alpha and IL-1beta response to in-vivo LPS exposure. The pre-weaned offspring of exposed dams demonstrated no immune response to the LPS challenge, whereas control offspring responded with a typical elevation in cytokine levels. In pubescence no differences were observed between the responses of the control and exposed offspring. In adulthood and senescence, offspring of endotoxin treated dams had significantly less monocytes in circulation than control offspring and differential sex effects were only evident in these older animals. The developmental profile of immune functioning following prenatal immune activation has not previously been demonstrated. This study highlights the prenatal period as one of importance in determining later immune function.
Publisher: S. Karger AG
Date: 2016
DOI: 10.1159/000443961
Abstract: b i Background: /i /b Around 30-40% of the world's population will experience allergy, the most common and earliest-onset noncommunicable disease. With a steady rise in the incidence of allergic disease over recent decades, up to 18% of children will suffer a respiratory, food or skin allergy before their 18th birthday. There is compelling evidence that the risk of developing allergy is influenced by early life events and particularly in utero exposures. b i Methods: /i /b A comprehensive literature review was undertaken which outlines prenatal risk factors and potential mechanisms underlying the development of allergy in childhood. b i Results: /i /b Exposures including maternal cigarette smoking, preterm birth and Caesarean delivery are implicated in predisposing infants to the later development of allergy. In contrast, restricted growth in utero, a healthy maternal diet and a larger family size are protective, but the mechanisms here are unclear and require further investigation. b i Conclusion: /i /b To ameliorate the allergy pandemic in young children, we must define prenatal mechanisms that alter the programming of the fetal immune system and also identify specific targets for antenatal interventions.
Publisher: Elsevier BV
Date: 11-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2021
Publisher: American Thoracic Society
Date: 05-2011
DOI: 10.1164/AJRCCM-CONFERENCE.2011.183.1_MEETINGABSTRACTS.A6414
Publisher: Wiley
Date: 30-03-2023
Abstract: Modifiable behaviours during the first 1000 days of life influence developmental trajectories of adult chronic diseases. Despite this, sub‐optimal dietary intakes during pregnancy and excessive gestational weight gain are common. Very little is known about partners' dietary patterns and the influence on women's pregnancy dietary patterns. We aimed to examine dietary intake during pregnancy among women and their partners, and gestational weight gain patterns in the Queensland Family Cohort pilot study. The Queensland Family Cohort is a prospective, observational study piloted at a Brisbane (Australia) tertiary maternity hospital from 2018 to 2021. Participant characteristics, weight gain, dietary and nutrient intake were assessed. Data were available for 194 pregnant women and their partners. Poor alignment with Australian Guide to Healthy Eating recommendations was observed. Highest alignment was for fruit (40% women) and meat/alternatives (38% partners) and lowest for breads/cereals ( % women) and milk/alternatives (13% partners). Fewer women (4.4%–60.3%) than their partners (5.4%–92.3%) met guidelines for all micronutrient intakes from food alone, particularly folic acid, iodine, and iron. Women were more likely to meet daily recommendations for fruit, vegetables, dairy, bread/cereals, and meat/alternatives when their partners also met recommendations. Women with a higher pre‐pregnancy body mass index were more likely to gain above recommended weight gain ranges. In this contemporary cohort of pregnant women and their partners, sub‐optimal dietary patterns and deficits in some nutrients were common. There is an urgent need for evidence‐informed public health policy and programs to improve diet quality during pregnancy due to intergenerational effects.
Publisher: Springer Science and Business Media LLC
Date: 08-01-2014
Abstract: Pregnancy presents a unique situation for the management of asthma as it can alter the course of asthma severity and its treatment, which in turn can affect pregnancy outcomes. Despite awareness of the substantial adverse effects associated with asthma during pregnancy, little has been done to improve its management and reduce associated perinatal morbidity and mortality. The aim of this randomized controlled trial is to evaluate the clinical and cost effectiveness of an Antenatal Asthma Management Service. Design: Multicentre, randomized controlled trial. Inclusion criteria: Women with physician diagnosed asthma, which is not currently in remission, who are less than 20 weeks gestation with a singleton pregnancy and do not have a chronic medical condition. Trial entry and randomization: Eligible women with asthma, stratified by treatment site, disease severity and parity, will be randomized into either the ‘Standard Care Group’ or the ‘Intervention Group’. Study groups: Both groups will be followed prospectively throughout pregnancy. Women in the ‘Standard Care Group’ will receive routine obstetric care reflecting current clinical practice in Australian hospitals. Women in the ‘Intervention Group’ will receive additional care through the nurse-led Antenatal Asthma Management Service, based in the antenatal outpatient clinic. Women will receive asthma education with a full assessment of their asthma at 18, 24, 30 and 36 weeks gestation. Each antenatal visit will include a 60 min session where asthma management skills are assessed including: medication adherence and knowledge, inhaler device technique, recognition of asthma deterioration and possession of a written asthma action plan. Furthermore, subjects will receive education about asthma control and management skills including trigger avoidance and smoking cessation counseling when appropriate. Primary study outcome: Asthma exacerbations during pregnancy. S le size: A s le size of 378 women will be sufficient to show an absolute reduction in asthma exacerbations during pregnancy of 20% (alpha 0.05 two-tailed, 90% power, 5% loss to follow-up). The integration of an asthma education program within the antenatal clinic setting has the significant potential to improve the participation of pregnant women in the self-management of their asthma, reduce asthma exacerbations and improve perinatal health outcomes. ACTRN12613000244707
Publisher: Wiley
Date: 09-2021
Abstract: The Queensland Family Cohort Pilot Study follows 450 women over the course of their pregnancy and after giving birth, collecting a wealth of information on socioeconomic characteristics, health, healthcare use and biological s les. The focus of this paper is to demonstrate how these data may be used to measure inequality of opportunity, between advantaged and disadvantaged populations, for mothers, partners and babies, in terms of their mental health and use of scarce health care resources. This paper provides the foundation for future analyses when a wider Queensland study is proposed to collect data from 12,500 families.
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.PSYNEUEN.2013.11.016
Abstract: The neonatal period is characterized by significant plasticity where the immune, endocrine, and nociceptive systems undergo fine-tuning and maturation. Painful experiences during this period can result in long-term alterations in the neurocircuitry underlying nociception, including increased sensitivity to mechanical or thermal stimuli. Less is known about the impact of neonatal exposure to mild inflammatory stimuli, such as lipopolysaccharide (LPS), on subsequent inflammatory pain responses. Here we examine the impact of neonatal LPS exposure on inflammatory pain sensitivity and HPA axis activity during the first three postnatal weeks. Wistar rats were injected with LPS (0.05mg/kg IP, Salmonella enteritidis) or saline on postnatal days (PNDs) 3 and 5 and later subjected to the formalin test at PNDs 7, 13, and 22. One hour after formalin injection, blood was collected to assess corticosterone responses. Transverse spinal cord slices were also prepared for whole-cell patch cl recording from lumbar superficial dorsal horn neurons (SDH). Brains were obtained at PND 22 and the hypothalamus was isolated to measure glucocorticoid (GR) and mineralocorticoid receptor (MR) transcript expression using qRT-PCR. Behavioural analyses indicate that at PND 7, no significant differences were observed between saline- or LPS-challenged rats. At PND 13, LPS-challenged rats exhibited enhanced licking (p<.01), and at PND 22, increased flinching in response to formalin injection (p<.05). LPS-challenged rats also displayed increased plasma corticosterone at PND 7 and PND 22 (p<.001) but not at PND 13 following formalin administration. Furthermore, at PND 22 neonatal LPS exposure induced decreased levels of GR mRNA and increased levels of MR mRNA in the hypothalamus. The intrinsic properties of SDH neurons were similar at PND 7 and PND 13. However, at PND 22, ipsilateral SDH neurons in LPS-challenged rats had a lower input resistance compared to their saline-challenged counterparts (p<.05). These data suggest neonatal LPS exposure produces developmentally regulated changes in formalin-induced behavioural responses, corticosterone levels, and dorsal horn neuron properties following noxious stimulation later in life. These findings highlight the importance of immune activation during the neonatal period in shaping pain sensitivity later in life. This programming involves both spinal cord neurons and the HPA axis.
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1016/J.PLACENTA.2011.08.010
Abstract: Glucocorticoids (GC) are known to influence fetal ROS production and anti-oxidant defences yet little attention has focused on the potential for effects in the placenta. We hypothesised that antenatal GC exposure alters placental pro-oxidant-anti-oxidant balance sex-specifically, based upon the known relationship between male sex and poor pregnancy outcome. Placentae were collected from 60 women who delivered between 24 and 31 completed weeks gestation and placental oxidative and nitrative stress (protein carbonyl, lipid hydroperoxide, and nitrotyrosine concentration) and anti-oxidant enzyme activity (glutathione peroxidase, thioredoxin reductase, and superoxide dismutase) measured. A pro-oxidant state was observed in placentae of male compared to female infants born within 72 h of antenatal GC exposure, with higher levels of protein carbonyl content (p = 0.04), lipid hydroperoxide (p < 0.01) and nitrotyrosine content (p = 0.02), and lower levels of glutathione peroxidase activity (p = 0.01). A pro-oxidant state continued to be observed in placentae of males compared to females born outside of 72 h, with higher protein carbonyl content (p = 0.04) and lower glutathione peroxidase activity (p = 0.01) than females, however no differences in placental lipid hydroperoxide and nitrotyrosine content were observed. These sex-specific alterations in products of placental oxidative stress could not purely be explained by differences in clinical illness severity (CRIB2 score). Therefore, these sex-specific alterations in placental pro-oxidant-antioxidant balance in response to antenatal betamethasone exposure, independent of illness severity, could contribute to the patho-physiologic processes underlying oxygen radical diseases of the newborn, conditions known to exhibit a male excess.
Publisher: Elsevier BV
Date: 10-2022
DOI: 10.1016/J.PLACENTA.2022.08.004
Abstract: The pathological decrease of fetal growth during gestation can lead to subsequent poor health outcomes for the fetus. This process is commonly controlled by the placenta, the interface between mother and baby during gestation. Sex-specific gene expression has been implicated in placental function, therefore, there is a need to determine if it is important during reduced fetal growth. We therefore aimed to characterise placental gene expression at term to evaluate sex-specific genetic changes that occur in small for gestational age (SGA) infants. RNA-sequencing of twelve human placental tissue s les collected from pregnancies yielding either term appropriate for gestational age (AGA) or SGA infants identified at delivery. Candidate genes associated with fetal size and fetal sex were identified using differential gene expression and weighted gene co-expression network analyses. Single-cell sequencing data was used for candidate validation and to estimate candidate transcript expression in specific placental cell populations. Differential gene expression and weighted gene co-expression network analyses identified 403 candidate transcripts associated with SGA infants. One hundred and three of these transcripts showed sex-specific expression. . Published placental sequencing datasets were used to validate the key expression results from the twelve placental s les initially studied the sex-independent transcript expression for genes involved in cell cycle processes in males (7 transcripts) and endoplasmic reticulum stress in females (17 transcripts). This study identified the activation of multiple molecular mechanisms involved in the placental response to an adverse environmental stressor. Mechanisms such as disrupted protein synthesis were shared between infant biological sex when comparing AGA to SGA, whilst other pathways such as cell cycle and endoplasmic reticulum stress appear as independent/specific to either males or females when investigating reduced fetal growth. This data suggests that sexual dimorphism is an important consideration when examining placental dysfunction and poor fetal growth.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 31-03-2021
Publisher: Cambridge University Press (CUP)
Date: 05-10-2015
DOI: 10.1017/S2040174415007151
Abstract: The objective was to investigate the association between early and late maternal smoking during pregnancy on offspring body mass index (BMI). We undertook a retrospective cohort study using linked records from the Women’s and Children’s Health Network in South Australia. Among a cohort of women delivering a singleton, live-born infants between January 2000 and December 2005 ( n =7658), 5961 reported not smoking during pregnancy, 297 reported quitting smoking during the first trimester of pregnancy, and 1400 reported continued smoking throughout pregnancy. Trained nurses measured the height and weight of the children at preschool visits in a state-wide surveillance programme. The main outcome measure was age- and sex-specific BMI z-score. At 4 to 5 years, mean ( s.d. ) BMI z-score was 0.40 (1.05), 0.60 (1.07) and 0.65 (1.18) in children of mothers who reported never smoking, quitting smoking and continued smoking during pregnancy, respectively. Compared with the group of non-smokers, both quitting smoking and continued smoking were associated with an increase in child BMI z-score of 0.15 (95% confidence interval: 0.01–0.29) and 0.21 (0.13–0.29), respectively. A significant dose–response relationship was also observed between the number of cigarettes smoked per day on average during the second half of pregnancy and the increase in offspring BMI z-score ( P .001). In conclusion, any maternal smoking in pregnancy, even if mothers quit, is associated with an increase in offspring BMI at 4 to 5 years of age.
Publisher: Elsevier BV
Date: 04-2004
Publisher: Elsevier BV
Date: 12-2021
Publisher: Elsevier BV
Date: 02-2001
Publisher: American Physiological Society
Date: 08-2009
DOI: 10.1152/AJPREGU.00175.2009
Abstract: Placental 11β-hydroxysteroid dehydrogenase-2 (11βHSD2) limits fetal glucocorticoid exposure and is associated with physiological stability in the premature newborn infant. Antenatal betamethasone alters 11βHSD2 activity and confers sex-specific advantages in neonatal outcome. We investigated the influence of betamethasone and sex on 11βHSD2 activity, neonatal adrenal function and clinical course in 24- to 36-wk gestation neonates from birth to day 5 of life. Univariate analyses demonstrated an interaction between timing of betamethasone exposure and sex for 11βHSD2 activity rate ( P = 0.02) and umbilical arterial cortisol ( P = 0.01). For infants born 72 h following antenatal betamethasone, females had higher 11βHSD2 activity ( P 0.01) and umbilical arterial cortisol ( P = 0.01) than males. Females born 72 h of betamethasone exposure had higher day 1 urinary cortisol, if exposed to perinatal stress, than males ( P 0.01). For infants born 72 h after betamethasone exposure, 11βHSD2 activity was negatively correlated with Clinical Illness Severity Score score ( r = −0.79 P = 0.01) and positively correlated with mean arterial blood pressure ( r = 0.8 P = 0.01) only in females. Sex-specific placental 11BHSD2 autoregulation following antenatal betamethasone exposure may limit adrenal suppression in females influencing physiological stability following preterm birth. A lack of adjustment in 11βHSD2 and adrenal response may contribute to the increased incidence of poor outcome observed in preterm males.
Publisher: Wiley
Date: 10-1992
DOI: 10.1038/ICB.1992.38
Abstract: In previous studies we have demonstrated that the male urinary tract forms part of the common mucosal immune system, and that the gut contributes to local defences at this site. The question arises as to the extent to which the reproductive tract also forms part of the common mucosal immune system. Rats were immunized by a variety of routes designed to stimulate a local response in the intestine and/or the reproductive tract. Rats immunized only by the intratesticular (i.t.) route yielded no antibody-containing (ACC) response in any of the tissues examined. Intestinal immunization using intraperitoneal priming followed by intraduodenal challenge (i.p./i.d.) yielded a substantial IgA-specific ACC response in the jejunum, but no ACC were detectable in any of the reproductive tract tissues. However, when intestinal and testicular immunizations were combined, large numbers of IgA-specific antibodies were detected in all tissues examined. Chronic drainage of the thoracic lymphatic duct throughout the post-challenge period abrogated the ACC response in all tissues of the reproductive tract, indicating that the ACC appearing at these sites after immunization were of gut origin. The IgA-specific anti-OVA antibody detectable in serum, saliva and testis homogenate reflected the ACC counts in histological sections. The studies reported here confirm that the male reproductive tract does form part of a common mucosal immune system and that gut-associated lymphoid tissues may contribute cellular precursors for ACC, particularly those of IgA specificity, appearing in the tract after local challenge.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Wiley
Date: 12-2009
Publisher: BMJ
Date: 06-2021
DOI: 10.1136/BMJOPEN-2020-044463
Abstract: The perinatal–postnatal family environment is associated with childhood outcomes including impacts on physical and mental health and educational attainment. Family longitudinal cohort studies collect in-depth data that can capture the influence of an era on family lifestyle, mental health, chronic disease, education and financial stability to enable identification of gaps in society and provide the evidence for changes in government in policy and practice. The Queensland Family Cohort (QFC) is a prospective, observational, longitudinal study that will recruit 12 500 pregnant families across the state of Queensland (QLD), Australia and intends to follow-up families and children for three decades. To identify the immediate and future health requirements of the QLD population pregnant participants and their partners will be enrolled by 24 weeks of gestation and followed up at 24, 28 and 36 weeks of gestation, during delivery, on-ward, 6 weeks postpartum and then every 12 months where questionnaires, biological s les and physical measures will be collected from parents and children. To examine the impact of environmental exposures on families, data related to environmental pollution, household pollution and employment exposures will be linked to pregnancy and health outcomes. Where feasible, data linkage of state and federal government databases will be used to follow the participants long term. Biological s les will be stored long term for future discoveries of biomarkers of health and disease. Ethical approval has been obtained from the Mater Research Ethics (HREC/16/MHS/113). Findings will be reported to (1) QFC participating families (2) funding bodies, institutes and hospitals supporting the QFC (3) federal, state and local governments to inform policy (4) presented at local, national and international conferences and (5) disseminated by peer-review publications.
Publisher: Springer Science and Business Media LLC
Date: 04-06-2022
DOI: 10.1186/S12884-022-04795-9
Abstract: There are very few developed countries where physical isolation and low community transmission has been reported for COVID-19 but this has been the experience of Australia. The impact of physical isolation combined with low disease transmission on the mental health of pregnant women is currently unknown and there have been no studies examining the psychological experience for partners of pregnant women during lockdown. The aim of the current study was to examine the impact of the first COVID-19 lockdown in March 2020 and post lockdown from August 2020 on the mental health of pregnant women or postpartum women and their partners. Pregnant women and their partners were prospectively recruited to the study before 24 weeks gestation and completed various questionnaires related to mental health and general wellbeing at 24 weeks gestation and then again at 6 weeks postpartum. The Depression, Anxiety and Stress Scale (DASS-21) and the Edinburgh Postnatal Depression Scale (EPDS) were used as outcome measures for the assessment of mental health in women and DASS-21 was administered to their partners. This analysis encompasses 3 time points where families were recruited before the pandemic (Aug 2018-Feb 2020), during lockdown (Mar-Aug 2020) and after the first lockdown was over (Sept-Dec 2020). There was no significant effect of COVID-19 lockdown and post lockdown on depression or postnatal depression in women when compared to a pre-COVID-19 subgroup. The odds of pregnant women or postpartum women experiencing severe anxiety was more than halved in women during lockdown relative to women in the pre-COVID-19 period (OR = 0.47 95%CI: 0.27–0.81 P = 0.006). Following lockdown severe anxiety was comparable to the pre-COVID-19 women. Lockdown did not have any substantial effects on stress scores for pregnant and postpartum women. However, a substantial decrease of over 70% in the odds of severe stress was observed post-lockdown relative to pre-COVID-19 levels. Partner’s depression, anxiety and stress did not change significantly with lockdown or post lockdown. A reproductive age population appear to be able to manage the impact of lockdown and the pandemic with some benefits related to reduced anxiety.
Publisher: Wiley
Date: 15-09-2015
Abstract: To investigate the association between antidepressant use in late gestation and postpartum haemorrhage (PPH). Retrospective cohort study. Tertiary teaching hospital in Adelaide, Australia. A total of 30 198 women delivering between 2002 and 2008. Relative risks adjusted for maternal sociodemographics and comorbidities (aRRs) were calculated for PPH, comparing women with late-gestation exposure to antidepressants (n = 558), women with a psychiatric illness but no antidepressant use (n = 1292), and women with neither antenatal exposures (n = 28 348). Additional sensitivity analyses were undertaken, examining associations with severe PPH and postpartum anaemia. The primary outcome was PPH, defined as a recorded blood loss of ≥500 mL for vaginal deliveries and ≥1000 mL for caesarean sections. Secondary outcomes included severe PPH (≥1000 mL blood loss, irrespective of method of delivery), and the presence of postpartum anaemia (identified from hospital medical records). Compared with unexposed controls, women exposed to antidepressants had an increased risk of PPH (aRR 1.53 95% confidence interval, 95% CI 1.25-1.86), whereas no increased risk was observed for women with a psychiatric illness but no antidepressant use (aRR 1.04 95% CI 0.89-1.23). In sensitivity analyses, late gestation antidepressant exposure was associated with an increased risk of severe PPH (aRR 1.84 95% CI 1.39-2.44), as well as postpartum anaemia (aRR 1.80 95% CI 1.46-2.22). Exposure to antidepressants in late gestation was associated with a significantly increased risk of PPH. Although potential confounding by unmeasured factors cannot be ruled out, these findings suggest a direct effect of antidepressant exposure on PPH. Late gestation antidepressant exposure is associated with a significantly increased risk of postpartum haemorrhage.
Publisher: Springer Science and Business Media LLC
Date: 30-10-2010
DOI: 10.1007/S00011-009-0102-Y
Abstract: Pregnancy can influence the course of maternal asthma, but the mechanisms are presently unknown. The aim of the present study was to access maternal immune cell profiles in the presence and absence of asthma and to determine the effect of pregnancy-derived factors on epithelial cell function. Cells from the human bronchial epithelial cell line BEAS-2B were treated with plasma from pregnant or nonpregnant asthmatic and nonasthmatic subjects. Cell culture supernatants were collected after 24 h and assayed for IL-6, IL-8, eotaxin, RANTES and sICAM-1 protein using ELISA. Maternal immune cell count and peripheral blood chemotactic response to plasma from pregnant and non-pregnant asthmatic subjects were also assessed. The presence of maternal asthma during pregnancy was associated with increased monocyte and neutrophil numbers, increased BEAS-2B cell production of IL-8 and sICAM-1 (P < 0.05) and increased chemotactic capacity relative to pregnant women without asthma. The results of this study suggest that circulating pregnancy-related factors enhance chemotactic mediators in epithelial cells in the presence of asthma. This may be one mechanism that contributes to pregnancy-induced changes in asthma.
Publisher: Wiley
Date: 2006
DOI: 10.1111/J.1440-1843.2006.00782.X
Abstract: The course of asthma may be altered during pregnancy with at least one-third of women experiencing a worsening of asthma and 20% having an exacerbation during pregnancy. This study used the novel proteomic technique, surface-enhanced laser desorption ionization-time of flight mass spectrometry to determine if the presence of asthma during pregnancy was associated with alterations in plasma proteins. Plasma collected from healthy (n = 23) and asthmatic (n = 27) pregnant women at 18 and 30 weeks gestation was applied to strong anion exchange (SAX2), weak cation exchange (WCX2) and immobilized metal affinity capture (IMAC-Cu(2+)) chips. Mass analysis was conducted using Ciphergen Protein Biology System IIc and significant differences in in idual peak intensities between groups determined. At 18 weeks gestation, 91 peaks were significantly different between pregnant women with and without asthma, representing 28% of the total peaks identified. At 30 weeks gestation, 51 peaks were significantly different. There were two peaks that were significantly different between groups at both 18 and 30 weeks gestation and expressed at a similar level at both time points. One was increased in asthmatics (MW = 6444 Da) whereas the other decreased in asthmatics compared with non-asthmatic women (MW = 1846 Da). This study demonstrated that there are differences in protein patterns between pregnant women with and without asthma. Other techniques are needed to define the molecular species and classify pathophysiological significance. Surface-enhanced laser desorption ionization-time of flight mass spectrometry has potential as a tool to monitor disease progression in situations such as pregnancy.
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.PLACENTA.2019.03.006
Abstract: The role of steroids throughout pregnancy and their effect on placental physiology is well established, especially for estrogens, progestogens, and glucocorticoids however, the role of androgens - particularly within the context of placental physiology - remains largely unexplored. Androgens are often defined as the male sex-steroids and are fundamental for the defeminisation and masculinisation of male fetuses. Therefore, the placenta may adapt to these steroids in a sex-specific manner, with males being more receptive to changes in these steroids concentrations, when compared with females however, their involvement in female intrauterine development has been investigated in several studies and may suggest females have a level of responsiveness to these steroids. While the former may be true, studies have reported sex-specific differences in the expression and activity of factors involved in androgen biosynthesis and bioavailability, with males consistently demonstrating greater degrees of altered protein and gene expression when compared with females. Understanding the placental androgen axis is essential as many pregnancy comorbidities are associated with elevated concentrations of androgens and perturbed intrauterine development or growth. Indeed, it appears that specific pathophysiologies of pregnancy can modulate the activity of key factors involved in the placental androgen axis and this may contribute to the etiology of sex-specific developmental outcomes from certain pregnancy complications. This review will provide insight into what is currently known regarding androgen signalling and the human placenta, and how this complex system may regulate sex-specific growth and developmental outcomes in normal and adverse pregnancies.
Publisher: Elsevier BV
Date: 08-2010
Publisher: Future Science Ltd
Date: 12-2007
DOI: 10.2144/000112594
Abstract: We describe a procedure for the simultaneous extraction of proteins and nucleic acids from the same experimental s le allowing for direct correlations between genetic, genomic, and proteomic data. This approach, using commercially available column-based nucleic acid extraction kits, requires no hazardous chemicals and is a quick, reliable, and consistent method for concomitant protein extraction. Buffer choice is critical to completely solubilize all proteins in the s le. Proteins solubilized in radioimmunoprecipitation assay (RIPA) buffer did not represent the entire profile when compared with conventionally extracted proteins using the same buffer at the one-dimensional (1-D) sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) level, however, proteins extracted from the columns and solubilized in a two-dimensional (2-D) electrophoresis lysis buffer showed a similar profile to conventionally extracted proteins when analyzed at both the 1-D and the 2-D level. We further showed that proteins extracted using these methods were compatible with Western blot analysis. This technique provides a simple and effective way to analyze protein and nucleic acids simultaneously from the same s le without affecting yield and quality.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.EJOGRB.2016.07.487
Abstract: To examine the patterns and predictors of inter-pregnancy body mass index (BMI) change and its impact on perinatal outcomes in the second pregnancy. Retrospective cohort study. Tertiary teaching hospital in Adelaide, Australia. Women with their first and second consecutive, singleton deliveries occurring between 2000 and 2012 (N=5371). Inter-pregnancy weight change calculated based on difference between BMI at respective antenatal booking visits. Association between inter-pregnancy weight change and perinatal outcomes investigated using multivariate generalised linear models, with stratification according to initial maternal BMI category in first pregnancy. Gestational diabetes (GDM) pregnancy induced hypertensive disorders small-for-gestational age (SGA) preterm birth large-for-gestational age (LGA) and macrosomia (>4500g). On average, women with a normal BMI gained 1kg/m(2) between first and second pregnancies, while women who were overweight or obese gained 1.37kg/m(2). Among women with a normal BMI in their first pregnancy, a BMI increase of ≥4kg/m(2) was associated with increased risk of developing GDM (aRR 1.97 95% CI 1.22-3.19), a macrosomic (aRR 4.06 95% CI 2.25-7.34) or LGA infant (aRR 1.31 0.96-1.78) in the second pregnancy, while a reduction in BMI (≤-2kg/m(2)) was associated with an increased risk of SGA (aRR 1.94 1.19-3.16). Among women who were overweight or obese in their first pregnancy, a BMI increase of ≥2-4 and ≥4kg/m(2) was associated with increased risks of developing GDM in the second pregnancy (aRR 1.39 95% CI 1.01-1.91 and aRR 1.64 95% CI 1.16-2.31 ptrend<0.001), while no associations were observed for a BMI increase and risk of a macrosomic, SGA, or LGA infant. In contrast, reduction in BMI (≤-2kg/m(2)) was associated with a reduced risk of GDM (aRR 0.58 95% CI 0.37-0.90) and SGA (aRR 0.47 95% CI 0.25-0.87). Increases in BMI between pregnancies is associated with an increased risk for perinatal complications, even in normal-weight women, while a reduction in BMI is associated with improved perinatal outcomes among women who are overweight/obese. Inter-pregnancy weight control is an important target to reduce the risk of an adverse perinatal outcome in a subsequent pregnancy.
Publisher: Elsevier BV
Date: 09-2011
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1016/J.PLACENTA.2011.03.004
Abstract: The mechanisms that contribute to adverse outcomes for the neonate in pregnancies complicated by asthma may be mediated via changes in placental immune function. This study was designed to determine whether the presence of maternal asthma during pregnancy alters the placental pro-inflammatory immune response in vitro. A prospective cohort study of women with asthma (n = 22) and control (n = 11) subjects had placentae collected immediately after delivery. Placental explants were exposed to an immune challenge, lipopolysaccharide, in the presence and absence of cortisol in vitro. Cytokines, glucocorticoid receptor α (GR α) and p38 MAPK protein were measured. Placentae of control pregnancies had an increase in pro-inflammatory cytokine production over a 24 h period. Placentae from pregnancies complicated by maternal asthma had a reduced pro-inflammatory cytokine response to an immune challenge relative to the controls especially in relation to the production of interleukin (IL)-1β and TNFα regardless of fetal sex. Cortisol inhibition of placental cytokine production was dependent on timing of exposure, fetal sex and presence and absence of asthma. GRα and p38 MAPK protein expression did not appear to contribute to differences in response to endotoxin or cortisol. Maternal asthma during pregnancy induces a hyposensitive inflammatory state in the placenta which is regulated by cortisol in a sexually dimorphic manner.
Publisher: American Thoracic Society
Date: 15-03-2011
Publisher: Springer Science and Business Media LLC
Date: 04-2020
Publisher: Elsevier BV
Date: 12-2015
Publisher: MDPI AG
Date: 30-01-2023
DOI: 10.3390/NU15030696
Abstract: Breastmilk is thought to influence the infant gut by supplying prebiotics in the form of human milk oligosaccharides and potentially seeding the gut with breastmilk microbes. However, the presence of a breastmilk microbiota and origins of these microbes are still debated. As a pilot study, we assessed the microbes present in expressed breastmilk at six-weeks postpartum using shotgun metagenomic sequencing in a heterogenous cohort of women who delivered by vaginal (n = 8) and caesarean delivery (n = 8). In addition, we estimated the microbial load of breastmilk at six-weeks post-partum with quantitative PCR targeting the 16S rRNA gene. Breastmilk at six-weeks postpartum had a low microbial mass, comparable with PCR no-template and extraction controls. Microbes identified through metagenomic sequencing were largely consistent with skin and oral microbes, with four s les returning no identifiable bacterial sequences. Our results do not provide convincing evidence for the existence of a breastmilk microbiota at six-weeks postpartum. It is more likely that microbes present in breastmilk are sourced by ejection from the infant’s mouth and from surrounding skin, as well as contamination during s ling and processing.
Publisher: Springer Science and Business Media LLC
Date: 06-01-2021
DOI: 10.1007/S43032-020-00413-1
Abstract: Maternal alcohol consumption during pregnancy results in elevated vulnerability to intrauterine growth restriction, preterm birth, miscarriage, and stillbirth. Many of the detrimental effects of fetal alcohol exposure may be mediated through placental dysfunction however, the exact mechanisms remain unknown. Here, we aimed to determine the effect of maternal alcohol exposure prior to and during early pregnancy on placental glucocorticoid receptor (GR) isoforms, associated GR regulated genes, and infant outcomes. Participants carrying singleton fetuses (n = 113) were recruited during early pregnancy. Amount and type of alcohol consumed over the last 12 months were obtained at 18 weeks of gestation. The level of drinking was separated into none (0 g/day), low ( 100 g/day). At delivery, placental weight, infant sex, birthweight, and head circumference were recorded. Placental GR isoforms and genes involved in downstream signalling pathways were quantified. The majority of women (70.8%) consumed alcohol. Of these, most consumed low (48.8%) or moderate (37.5%) amounts. Placental weight was unaffected by alcohol consumption, but infants born to heavy drinkers tended to be lighter at birth. In female, but not male, placentae, maternal alcohol consumption resulted in increased GRαC and decreased GRαD1 cytoplasmic expression. In both female and male placentae, a d ened inflammatory response was evident with maternal alcohol consumption, involving downregulated IL6R and upregulated POU2F2 gene expression, respectively. Maternal alcohol consumption in the months prior to, and/or during early, pregnancy alters placental GR isoform and expression of some inflammatory genes in a sex-specific manner.
Publisher: Elsevier BV
Date: 12-2012
DOI: 10.1016/J.PLACENTA.2012.09.010
Abstract: The increase in oxidative stress during pregnancy is associated with increased placental antioxidant enzyme activity and may additionally be limited by the uncoupling proteins (UCPs). There is little data on the expression and localisation of UCP2 in the human preterm placenta or on its role in the regulation of placental oxidative stress. Placentae were collected from women with singleton pregnancies who delivered between 24 and 36 weeks gestation (n = 54) and from a term reference group who delivered following uncomplicated pregnancy (n = 11). UCP2 expression and localisation was determined by quantitative real-time RTPCR using Taqman gene expression assays and immunohistochemistry. Placental lipid hydroperoxide and nitrotyrosine content was determined by ELISA. UCP2 mRNA expression increased from 24 to 41 weeks gestation (p < 0.001) and was positively correlated with placental weight (p = 0.004). While UCP2 expression was lower in small for gestational age infants (p = 0.045) it did not differ with respect to timing of antenatal betamethasone exposure nor with placental lipid hydroperoxide or nitrotyrosine content. UCP2 staining was identified in the cytotrophoblast in 34% of s les and in the syncytiotrophoblast in 63% of s les. Cytotrophoblast staining was more frequent in later gestations (p = 0.03) with syncytiotrophoblast UCP2 staining was not altered by gestation. In the preterm group, no association was observed with time since antenatal betamethasone exposure or placental lipid hydroperoxide or nitrotyrosine content. The current data supports gestation dependant alterations in UCP2 mRNA expression and immunohistochemical localisation in the human placenta but no evidence for an important role for UCP2 in protection against placental oxidative damage.
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.EJOGRB.2018.03.059
Abstract: This systematic review evaluates the utility of maternal Placental Growth Factor (PlGF) when measured in late pregnancy (>20 weeks) as a predictor of adverse obstetric and perinatal outcomes. Pubmed and Embase were searched using the term "placental growth factor" in combination with relevant perinatal outcomes. Studies were included if they measured PlGF levels in pregnant women after 20 + 0 weeks gestation and reported relevant adverse obstetric or perinatal outcomes related to placental insufficiency (excluding pre-ecl sia). Twenty-six studies were eligible for inclusion with 21 studies investigating the relationship between PlGF and small for gestational age (SGA) and 7 studies investigating PlGF for the prediction of other adverse perinatal outcomes. In all studies, maternal PlGF levels were significantly lower in the SGA group compared to controls. Other outcomes investigated included caesarean section (CS) for fetal compromise, low Apgar score, neonatal intensive care unit (NICU) admission, neonatal acidosis, stillbirth, and intrapartum fetal compromise. The results generally showed a significant association between low PlGF levels and CS for fetal compromise, NICU admission and stillbirth. Low maternal PlGF levels in late pregnancy are strongly associated with SGA. Findings across studies were variable in relation to PlGF and the prediction of other adverse intrapartum and perinatal outcomes, however there was a consistent association between low PlGF levels and CS for fetal compromise, NICU admission and stillbirth. This review suggests that the use of PlGF for the prediction of adverse outcomes is promising. Its predictive value may potentially be enhanced if used in combination with other biomarkers or biophysical measures of fetal well-being.
Publisher: Springer Science and Business Media LLC
Date: 03-01-2017
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.PLACENTA.2009.11.010
Abstract: There are known sex specific differences in fetal and neonatal morbidity and mortality. There are also known differences in birthweight centile with males generally being larger than females at birth. These differences are generally ignored when studying obstetric complications of pregnancy and the mechanisms that confer these differences between the sexes are unknown. Current evidence suggests sex specific adaptation of the placenta may be central to the differences in fetal growth and survival. Our research examining pregnancies complicated by asthma has reported sexually dimorphic differences in fetal growth and survival with males adapting placental function to allow for continued growth in an adverse maternal environment while females reduce growth in an attempt to survive further maternal insults. We have reported sex differences in placental cytokine expression, insulin-like growth factor pathways and the placental response to cortisol in relation to the complication of asthma during pregnancy. More recently we have identified sex specific alterations in placental function in pregnancies complicated by preterm delivery which were associated with neonatal outcome and survival. We propose the sexually dimorphic differences in growth and survival of the fetus are mediated by the sex specific function of the human placenta. This review will present evidence supporting this hypothesis and will argue that to ignore the sex of the placenta is no longer sound scientific practice.
Publisher: Elsevier BV
Date: 11
DOI: 10.1016/J.PLACENTA.2021.01.003
Abstract: Maternal asthma is known to impact intrauterine growth outcomes, which may be mediated, in part, by altered androgen signalling. Our aim was to explore whether the sheep placenta expresses androgen receptor (AR) isoforms and determine if the differential expression of AR protein isoforms is altered by maternal asthma. Four known AR isoforms were detected (AR-FL, AR-v1, AR-v7, and AR-45), and their expression and subcellular distribution was altered in the presence of maternal allergic asthma. These findings underscore the importance for in vivo models of maternal asthma to delineate molecular patterns that may contribute to feto-placental growth and development.
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.EJOGRB.2015.02.034
Abstract: A histologic response of histologic chorioamnionitis (HCA) is defined as an intrauterine inflammatory condition characterized by acute granulocyte infiltration into the fetal-maternal or the fetal tissues. Prevalence of HCA is inversely correlated with gestational age, occurring in 50% of preterm birth and in up to 20% of deliveries at term. Regardless of these standard definitions, understanding HCA is challenging as it reflects a heterogeneous condition. A histologic response of HCA from term placentas often does not correspond to a clinical presentation in this context, the present review aims to analyze main characteristics of this condition, in particular focusing on mechanisms and birth outcomes.
Publisher: Springer Science and Business Media LLC
Date: 04-2008
Publisher: Frontiers Media SA
Date: 30-09-2020
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.PLACENTA.2019.03.012
Abstract: Numerous studies show that males have increased intrauterine growth compared to females, and that pregnancy complications may further these growth differences, but the regulatory mechanisms underlying these differences remain unknown. We propose that these growth outcomes may be due to sex-specific differences in androgen sensitivity - giving rise to altered growth signalling pathways - mediated by the differential expression of placental androgen receptor (AR) variants. Placental protein and mRNA were used to identify AR protein variant levels and AR-downstream target gene expression, and were then analysed against neonatal measurements. Dihydrotestosterone (DHT)-induced AR protein variant expression and downstream growth factors were examined in vitro. Four known AR variants (AR-FL, AR-V1, AR-V7, and AR-45), and three unknown proteins (120, 90 and 55 kDa) immunoreactive to the anti-AR antibody were identified in human placentae. Male placentae from controlled asthmatic pregnancies had increased AR-45 and decreased AR-V1 and AR-V7 nuclear expression. Increased nuclear AR-45 expression was associated with increased insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R), and IGF-binding protein 5 (IGFBP-5) mRNA expression and normal male growth. AR-45 mRNA and protein did not change in the presence of uncontrolled maternal asthma and associated with an increase in small for gestational (SGA) male fetuses. In vitro DHT stimulation increased AR-45 protein and IGF-1R and IGFBP-5 mRNA expression. Collectively, our data shows altered AR protein expression and downstream signalling targets may contribute to sex-specific fetal growth outcomes in response to an adverse environment, and that AR-45 appears central in mediating these changes.
Publisher: Elsevier BV
Date: 06-2019
Publisher: Elsevier BV
Date: 07-2015
Start Date: 09-2011
End Date: 12-2014
Amount: $150,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 04-2010
End Date: 07-2013
Amount: $150,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 03-2023
End Date: 03-2026
Amount: $478,327.00
Funder: Australian Research Council
View Funded Activity