ORCID Profile
0000-0002-6408-8238
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Research Topics
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.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Signal Processing | Electrical and Electronic Engineering | Diagnostic Applications | Learning, Memory, Cognition And Language | Image Processing | Clinical Sciences | Biological Psychology (Neuropsychology, Psychopharmacology, | Psychology | Sensory Processes, Perception And Performance | Biomedical Engineering | Rehabilitation And Therapy: Hearing And Speech | Biomechanical Engineering | Linguistic Processes (Incl. Speech Production And Comprehension) | Medical Physics
ANZSRC Socio-Economic Objective (SEO)
Information processing services | Child health | Diagnostic methods | Behavioural and cognitive sciences | Hearing, vision, speech and their disorders | Clinical health not specific to particular organs, diseases and conditions | "Occupational, speech and physiotherapy" | Medical instrumentation | Evaluation of health outcomes | Integrated systems |
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Publications
Neurodevelopmental outcomes at 7 years' corrected age in preterm infants who were fed high-dose docosahexaenoic acid to term equivalent
Publisher: BMJ
Date: 18-03-2015
Early prediction of typical outcome and mild developmental delay for prioritisation of service delivery for very preterm and very low birthweight infants: a study protocol
Publisher: BMJ
Date: 07-2016
Detection of neonatal EEG burst-suppression using a time-frequency approach
Publisher: IEEE
Date: 12-2014
Perfluorocarbon Dosing when Starting Partial Liquid Ventilation: Haemodynamics and Cerebral Blood Flow in Preterm Lambs
Publisher: S. Karger AG
Date: 22-09-2009
DOI: 10.1159/000239768
Abstract: i Background: /i Very preterm neonates can have severe lung disease and are prone to brain injury if cerebral blood flow fluctuates. Partial liquid ventilation (PLV) may benefit the lung disease, but it is unknown whether the administration of intratracheal perfluorocarbon when starting PLV affects haemodynamics or cerebral blood flow. i Objectives: /i To determine if haemodynamics or cerebral blood flow are affected in preterm lambs receiving a dose of perfluorocarbon when starting PLV. i Methods: /i Sixteen preterm lambs were randomised to either PLV or conventional mechanical ventilation. An intratracheal loading dose of 30 ml/kg of perfluorocarbon liquid (PLV group) or air (sham group) was instilled over 20 min. Data were collected continuously for 30 min from the start of dosing. i Results: /i Cortical cerebral blood flow velocity, measured continuously with laser Doppler, was increased in the PLV group during the administration of perfluorocarbon and immediately thereafter (p = 0.0026) the highest mean increase in the PLV group was 27%. There was no difference in cortical cerebral blood flow variability (p = 0.96). There was a slightly lower mean arterial blood pressure in the PLV group the heart rate did not differ between groups. The Pa i CO /i sub /sub was higher in the PLV group at 30 min – the difference between groups was not statistically significant (difference between means = 5.5 mm Hg, 95% confidence interval –2.7 to 13.7). i Conclusions: /i Preterm lambs receiving a dose of tracheal perfluorocarbon at the start of PLV have an increased cortical cerebral blood flow velocity, but no change in cortical cerebral blood flow variability.
Glial glutamate transporter expression patterns in brains from multiple mammalian species
Publisher: Wiley
Date: 12-2004
DOI: 10.1002/GLIA.20139
Abstract: It is generally assumed that rodent brains can be used as representative models of neurochemical function in other species, such as humans. We have compared the distributions of the predominant glial glutamate transporters in rodents, rabbits, cats, pigs, monkeys, and humans. We identify similarities but also significant differences between species. GLT-1v, which is abundantly expressed by rodent astrocytes, is expressed only in a rare subset of astrocytes of cats and humans, and appears to be absent from brains of rabbits and monkeys. Conversely, in the pig brain GLT-1v is expressed only by oligodendrocytes. GLAST and GLT-1alpha expression differed significantly between species while rodents and rabbits exhibited uniform expression patterns in cortex, higher species, including cats, pigs, monkeys, and humans, exhibited heterogeneities in cortical and hippoc al expression. Patches devoid of labeling intermingling with patches of strong labeling were evident in areas such as temporal cortex and frontal cortex. In addition, we noted that in human motor cortex, there were inconsistencies in labeling for the C-terminal of GLT-1alpha and common domains of GLT-1, suggesting that the C-terminal region may be missing or that an unidentified splicing is present in many human astrocytes. Collectively our data suggest that assumptions as to the roles of glutamate transporters in any species may need to be tested empirically.
Erratum to: Parenting and Prematurity: Understanding Parent Experience and Preferences for Support
Publisher: Springer Science and Business Media LLC
Date: 20-03-2015
Oscillations in Cardiovascular Function During Acute Hypoxia in the Newborn Piglet Are Associated With Less Neurological Damage and Occur More Frequently in Females
Publisher: Springer Science and Business Media LLC
Date: 05-2009
A passive DSP approach to fetal movement detection for monitoring fetal health
Publisher: IEEE
Date: 07-2012
Neonatal seizures are associated with redistribution and loss of GABA
Publisher: Wiley
Date: 09-2016
DOI: 10.1111/JNC.13746
Abstract: Seizures are a common manifestation of hypoxic-ischaemic brain injury in the neonate. In status epilepticus models alterations to GABA
Measuring Time-Varying Information Flow in Scalp EEG Signals: Orthogonalized Partial Directed Coherence
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 03-2014
Human primed endothelial colony forming cells exert neuroprotective effects in the growth restricted newborn piglet
Publisher: Cold Spring Harbor Laboratory
Date: 17-02-2021
DOI: 10.1101/2021.02.15.431307
Abstract: The fetal brain is particularly vulnerable to the detrimental effects of fetal growth restriction (FGR) with subsequent abnormal neurodevelopment being common. There are no current treatments to protect the FGR newborn from lifelong neurological disorders. This study examines whether pure fetal mesenchymal stem cells and endothelial colony forming cells (ECFC) from the human term placenta are neuroprotective through modulating neuroinflammation and supporting the brain vasculature. We determined that one dose of these primed ECFCs (pECFC) on the first day of life to the newborn FGR piglet improved damaged vasculature, restored the neurovascular unit, reduced brain inflammation and improved adverse neuronal and white matter changes present in the FGR newborn piglet brain. These findings could not be reproduced using mesenchymal stromal cells alone. These results demonstrate pECFC treatment exerts beneficial effects on multiple cellular components in the FGR brain and act as a neuroprotectant. Stem cell treatment improves brain outcomes in the growth restricted newborn
Hypoxic/Ischemic models in newborn piglet: Comparison of constant FiO2 versus variable FiO2 delivery
Publisher: Elsevier BV
Date: 07-2006
DOI: 10.1016/J.BRAINRES.2006.04.119
Abstract: A comparison of a constant (continuous delivery of 4% FiO2) and a variable (initial 5% FiO2 with adjustments to induce low litude EEG (LAEEG) and hypotension) hypoxic/ischemic insult was performed to determine which insult was more effective in producing a consistent degree of survivable neuropathological damage in a newborn piglet model of perinatal asphyxia. We also examined which physiological responses contributed to this outcome. Thirty-nine 1-day-old piglets were subjected to either a constant hypoxic/ischemic insult of 30- to 37-min duration or a variable hypoxic/ischemic insult of 30-min low peak litude EEG (LAEEG <5 microV) including 10 min of low mean arterial blood pressure (MABP <70% of baseline). Control animals (n = 6) received 21% FiO2 for the duration of the experiment. At 72 h, the piglets were euthanased, their brains removed and fixed in 4% paraformaldehyde and assessed for hypoxic/ischemic injury by histological analysis. Based on neuropathology scores, piglets were grouped as undamaged or damaged piglets that did not survive to 72 h were grouped separately as dead. The variable insult resulted in a greater number of piglets with neuropathological damage (undamaged = 12.5%, damaged = 68.75%, dead = 18.75%) while the constant insult resulted in a large proportion of undamaged piglets (undamaged = 50%, damaged = 22.2%, dead = 27.8%). A hypoxic insult varied to maintain peak litude EEG <5 microV results in a greater number of survivors with a consistent degree of neuropathological damage than a constant hypoxic insult. Physiological variables MABP, LAEEG, pH and arterial base excess were found to be significantly associated with neuropathological outcome.
NSE and S100 after Hypoxia in the Newborn Pig
Publisher: Springer Science and Business Media LLC
Date: 11-2005
MAP2 provides reliable early assessment of neural injury in the newborn piglet model of birth asphyxia
Publisher: Elsevier BV
Date: 06-2008
DOI: 10.1016/J.JNEUMETH.2008.02.011
Abstract: Reduction in microtubule-associated-protein-2 (MAP2) immunoreactivity is a sensitive and quantifiable early marker of neural injury in rats. This study assessed the reliability of MAP2 as an early marker of neural injury following hypoxia/ischaemia in neonatal piglets, and compared the effects of perfusion and immersion fixation on MAP2 immunoreactivity. Hypoxia was induced in newborn piglets (n=23) by reducing the FiO2 to 4% for 0, 25, 35 or 50 min. Six hours after the end of hypoxia piglets were killed, and the brain removed and immunolabelled for MAP2. Significant reductions in MAP2 immunoreactivity were seen in cortex, hippoc us, basal ganglia and thalamus. Reductions correlated with duration of hypoxia, pH at the end of hypoxia, cerebral function monitor litude and cerebral impedance 6h after hypoxia, and with early histological evidence of ischaemic changes. Regions with reduced immunoreactivity correlated with areas where damage is present in later histological examination in this model. Immersion fixation with postmortem delays up to 30 min did not affect MAP2 immunoreactivity compared to perfusion-fixed tissue. Results indicate that MAP2 immunoreactivity 6h after hypoxia/ischaemia is a reliable marker of neural injury in the neonatal piglet.
Docosahexaenoic acid supplementation of preterm infants and parent-reported symptoms of allergic disease at 7 years corrected age: follow-up of a randomized controlled trial
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1093/AJCN/NQZ010
Abstract: Docosahexaenoic acid (DHA, 22:6n-3) supplementation in the prenatal period is associated with a reduction in the incidence of some symptoms of allergic disease. Infants born preterm are at increased risk of allergic disease, but it is unknown if DHA supplementation reduces the risk of childhood allergies. The aim of this study was to determine if supplementation of infants born at <33 wk gestation with high-DHA compared with standard-DHA enteral feeds decreases the incidence and severity of parent-reported allergic disease symptoms at a corrected age (CA) of 7 y. This study was a follow-up of an Australian multicenter randomized controlled trial. Infants were given high-DHA (∼1% total fatty acids) or standard-DHA (∼0.3% total fatty acids) enteral feeds from 2-4 d of postnatal age until 40 wk postmenstrual age. Parent-reported incidence of respiratory allergic disease symptoms including wheeze and rhinitis at 7 y CA were the main outcomes. Other outcomes included the incidence of eczema symptoms severity of any symptoms and the incidence of wheeze, rhinitis, rhinoconjunctivitis, and eczema from birth to 7 y CA. Data were available for 569 of 657 (87%) children originally randomized. Symptoms of wheeze or rhinitis at 7 y CA did not differ between high- and standard-DHA groups [wheeze: RR: 1.10 95% CI: 0.73, 1.65 P = 0.66 rhinitis: RR: 1.09 95% CI: 0.81, 1.46 P = 0.59]. There was no difference in other allergic disease symptoms at 7 y CA or in the severity of symptoms. Parent-reported symptoms of wheeze, rhinitis, rhinoconjunctivitis, or eczema from birth to 7 y CA did not differ between the groups. High-dose DHA supplementation of infants born at <33 wk gestation did not alter allergic disease symptoms or severity at 7 y CA, or from birth to 7 y CA compared with standard-dose DHA. This trial was registered with the Australian New Zealand Clinical Trials Registry as ANZCTR 12606000327583 (www.anzctr.org.au).
Noninvasive measurement of cerebral bioimpedance for detection of cerebral edema in the neonatal piglet
Publisher: Elsevier BV
Date: 07-2002
DOI: 10.1016/S0006-8993(02)02744-0
Abstract: The association of sustained cerebral edema with poor neurological outcome following hypoxia-ischaemia in the neonate suggests that measurement of cerebral edema may allow early prediction of outcome in these infants. Direct measurements of cerebral impedance have been widely used in animal studies to monitor cerebral edema, but such invasive measurements are not possible in the human neonate. This study investigated the ability of noninvasive cerebral impedance measurements to detect cerebral edema following hypoxia-ischaemia. One-day-old piglets were anaesthetized, intubated and ventilated. Hypoxia was induced by reducing the inspired oxygen concentration to 4-6% O(2). Noninvasive cerebral bioimpedance was measured using gel electrodes attached to the scalp. Cerebral bioimpedance was also measured directly by insertion of two silver-silver chloride electrodes subdurally. Noninvasive and invasive measurements were made before, during and after hypoxia. Whole body impedance was measured to assess overall fluid movements. Intracranial pressure was measured continuously via a catheter inserted subdurally, as an index of cerebral edema. There was good agreement between noninvasive and invasive measurements of cerebral impedance although externally obtained responses were attenuated. Noninvasive measurements were also well correlated with intracranial pressure. Whole body impedance changes did not account for increases in noninvasively measured cerebral impedance. Results suggest that noninvasive cerebral impedance measurements do reflect intracranial events, and are able to detect cerebral edema following hypoxia-ischaemia in the neonate.
A Nonlinear Model of Newborn EEG with Nonstationary Inputs
Publisher: Springer Science and Business Media LLC
Date: 20-04-2010
DOI: 10.1007/S10439-010-0041-3
Abstract: Newborn EEG is a complex multiple channel signal that displays nonstationary and nonlinear characteristics. Recent studies have focussed on characterizing the manifestation of seizure on the EEG for the purpose of automated seizure detection. This paper describes a novel model of newborn EEG that can be used to improve seizure detection algorithms. The new model is based on a nonlinear dynamic system the Duffing oscillator. The Duffing oscillator is driven by a nonstationary impulse train to simulate newborn EEG seizure and white Gaussian noise to simulate newborn EEG background. The use of a nonlinear dynamic system reduces the number of parameters required in the model and produces more realistic, life-like EEG compared with existing models. This model was shown to account for 54% of the linear variation in the time domain, for seizure, and 85% of the linear variation in the frequency domain, for background. This constitutes an improvement in combined performance of 6%, with a reduction from 48 to 4 model parameters, compared to an optimized implementation of the best performing existing model.
Prevention of Gestational Diabetes
Publisher: American Diabetes Association
Date: 31-03-2010
DOI: 10.2337/DC09-2336
Abstract: To examine the feasibility of an in idualized exercise program to prevent gestational diabetes mellitus (GDM) in obese pregnant women. The study was a pilot randomized controlled trial with obese pregnant women (intervention group, in idualized exercise program [n = 25] control group, usual care [n = 25]). Average weekly energy expenditure (MET hours per week and kilocalories per week) of exercise-specific activity was assessed during pregnancy using the Pregnancy Physical Activity Questionnaire. Fasting glucose and insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were assessed at baseline and 20, 28, and 36 weeks' gestation. Of the women in the intervention group, 16 of 22 (73%) achieved more than 900 kcal/week of exercise-based activity at 28 weeks compared with 8 of 19 women in the control group (42%), P = 0.047. However, insulin resistance (HOMA-IR) did not differ between the groups. This intervention was feasible and prompted a modest increase in physical activity. However, we are not confident that this intervention would be sufficient to prevent GDM.
Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: A randomized controlled trial
Publisher: American Medical Association (AMA)
Date: 20-10-2010
Abstract: Uncertainty about the benefits of dietary docosahexaenoic acid (DHA) for pregnant women and their children exists, despite international recommendations that pregnant women increase their DHA intakes. To determine whether increasing DHA during the last half of pregnancy will result in fewer women with high levels of depressive symptoms and enhance the neurodevelopmental outcome of their children. A double-blind, multicenter, randomized controlled trial (DHA to Optimize Mother Infant Outcome [DOMInO] trial) in 5 Australian maternity hospitals of 2399 women who were less than 21 weeks' gestation with singleton pregnancies and who were recruited between October 31, 2005, and January 11, 2008. Follow-up of children (n = 726) was completed December 16, 2009. Docosahexaenoic acid-rich fish oil capsules (providing 800 mg/d of DHA) or matched vegetable oil capsules without DHA from study entry to birth. High levels of depressive symptoms in mothers as indicated by a score of more than 12 on the Edinburgh Postnatal Depression Scale at 6 weeks or 6 months postpartum. Cognitive and language development in children as assessed by the Bayley Scales of Infant and Toddler Development, Third Edition, at 18 months. Of 2399 women enrolled, 96.7% completed the trial. The percentage of women with high levels of depressive symptoms during the first 6 months postpartum did not differ between the DHA and control groups (9.67% vs 11.19% adjusted relative risk, 0.85 95% confidence interval [CI], 0.70-1.02 P = .09). Mean cognitive composite scores (adjusted mean difference, 0.01 95% CI, -1.36 to 1.37 P = .99) and mean language composite scores (adjusted mean difference, -1.42 95% CI, -3.07 to 0.22 P = .09) of children in the DHA group did not differ from children in the control group. The use of DHA-rich fish oil capsules compared with vegetable oil capsules during pregnancy did not result in lower levels of postpartum depression in mothers or improved cognitive and language development in their offspring during early childhood. anzctr.org.au Identifier: ACTRN12605000569606.
Intrapartum oximetry of the fetus
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2007
DOI: 10.1213/01.ANE.0000268493.90073.F3
Abstract: Fetal monitoring during labor aims to identify fetal problems which, if uncorrected, may result in morbidity or death. A nonreassuring or abnormal fetal heart rate trace by cardiotocography (CTG) does not necessarily equate with fetal hypoxia and/or acidosis. However, in the absence of more objective data, the use of CTG often results in variable, but inappropriately high, operative delivery rates (forceps, vacuum, or cesarean delivery) for nonreassuring fetal status in many hospitals. The addition of fetal pulse oximetry (FPO) has the potential to improve the assessment of fetal well-being during labor. In this review we consider several aspects of FPO. Several factors, such as sensor to skin contact, uterine contractions, fetal hair, and caput succedaneum, influence the performance and use of FPO. Issues such as clinicians' perspectives of FPO sensor placement, maternal perspectives of FPO during labor, and an economic analysis have all favored FPO. Several randomized controlled trials (RCTs) of FPO reported a reduction in cesarean delivery for nonreassuring fetal status when FPO was added to conventional CTG monitoring, with no difference in overall cesarean delivery rates. One large RCT reported no difference in mode of birth for any indication. Several issues relevant to the future of FPO have been addressed by these RCTs, the major issue being that it makes no difference to cesarean rates. It may be argued that FPO has a valid clinical use in monitoring the fetus with congenital heart block. Additionally, in situations of nonreassuring fetal status and dystocia, FPO may provide the necessary reassurance until adequate resources for cesarean delivery are available.
Are parenting interventions effective in improving the relationship between mothers and their preterm infants?
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.INFBEH.2013.12.009
Abstract: To systematically review the efficacy of parenting interventions in improving the quality of the relationship between mothers and preterm infants. Randomized or quasi-randomized controlled trials (RCT) of parenting interventions for mothers of preterm infants where mother-infant relationship quality outcomes were reported. Databases searched: The Cochrane Library, PubMed, CINAHL, PsycINFO and Web of Science. Seventeen studies met the inclusion criteria, 14 with strong methodological quality. Eight parenting interventions were found to improve the quality of the mother-preterm infant relationship. Heterogeneity of the interventions calls for an integrated new parenting program focusing on cue-based, responsive care from the mother to her preterm infant to improve the quality of the relationship for these mother-preterm infant dyads.
Neonatal Seizure Detection and Localization using Time-Frequency Analysis of Multichannel EEG
Publisher: IEEE
Date: 2007
Parenting and Prematurity: Understanding Parent Experience and Preferences for Support
Publisher: Springer Science and Business Media LLC
Date: 24-05-2013
Neonatal EEG at scalp is focal and implies high skull conductivity in realistic neonatal head models
Publisher: Elsevier BV
Date: 08-2014
DOI: 10.1016/J.NEUROIMAGE.2014.04.007
Abstract: The potential improvements in spatial resolution of neonatal EEG used in source localization have been challenged by the insufficiencies in realistic neonatal head models. Our present study aimed at using empirical methods to indirectly estimate skull conductivity the model parameter that is known to significantly affect the behavior of newborn scalp EEG and cause it to be markedly different from that of an adult. To this end, we used 64 channel EEG recordings to study the spatial specificity of scalp EEG by assessing the spatial decays in focal transients using both litudes and between-c'hannels linear correlations. The findings showed that these litudes and correlations decay within few centimeters from the reference channel/electrode, and that the nature of the decay is independent of the scalp area. This decay in newborn infants was found to be approximately three times faster than the corresponding decay in adult EEG analyzed from a set of 256 channel recordings. We then generated realistic head models using both finite and boundary element methods along with a manually segmented magnetic resonance images to study the spatial decays of scalp potentials produced by single dipole in the cortex. By comparing the spatial decays due to real and simulated EEG for different skull conductivities (from 0.003 to 0.3S/m), we showed that a close match between the empirical and simulated decays was obtained when the selected skull conductivity for newborn was around 0.06-0.2S/m. This is over an order of magnitude higher than the currently used values in adult head modeling. The results also showed that the neonatal scalp EEG is less smeared than that of an adult and this characteristic is the same across the entire scalp, including the fontanel region. These results indicate that a focal cortical activity is generally only registered by electrodes within few centimeters from the source. Hence, the conventional 10 to 20 channel neonatal EEG acquisition systems give a significantly spatially under s led scalp EEG and may, consequently, give distorted pictures of focal brain activities. Such spatial specificity can only be reconciled by appreciating the anatomy of the neonatal head, especially the still unossified skull structure that needs to be modeled with higher conductivities than conventionally used in the adults.
Using skin for drug delivery and diagnosis in the critically ill
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.ADDR.2014.10.004
Abstract: Skin offers easy access, convenience and non-invasiveness for drug delivery and diagnosis. In principle, these advantages of skin appear to be attractive for critically ill patients given potential difficulties that may be associated with oral and parenteral access in these patients. However, the profound changes in skin physiology that can be seen in these patients provide a challenge to reliably deliver drugs or provide diagnostic information. Drug delivery through skin may be used to manage burn injury, wounds, infection, trauma and the multisystem complications that rise from these conditions. Local anaesthetics and analgesics can be delivered through skin and may have wide application in critically ill patients. To ensure accurate information, diagnostic tools require validation in the critically ill patient population as information from other patient populations may not be applicable.
Intrauterine growth restriction due to uteroplacental vascular insufficiency leads to increased hypoxia-induced cerebral apoptosis in newborn piglets
Publisher: Elsevier BV
Date: 07-2006
DOI: 10.1016/J.BRAINRES.2006.04.129
Abstract: Uteroplacental vascular insufficiency in humans is a common cause of intrauterine growth restriction (IUGR) and is associated with an increased incidence of perinatal asphyxia and neurodevelopmental disorders compared to normal weight newborns. Experimental models that provide an opportunity to analyze the pathogenesis of these relationships are limited. Here, we used neonatal pigs from large litters in which there were piglets of normal birth weight (for controls) and of low birth weight (for uteroplacental vascular insufficiency). Hypoxia was induced in paired littermates by reducing the fraction of inspired oxygen to 4% for 25 min. Brain tissue was collected 4 h post-hypoxia. Cerebral levels of apoptosis were quantified morphologically and verified with caspase-3 activity and TUNEL. Expression of Bcl-2, Bcl-XL and Bax proteins was investigated using immunohistochemistry. Cellular positivity for Bcl-2 was consistently higher in the non-apoptotic white matter of the hypoxic IUGR animals compared with their littermates and reached significance at P < 0.05 in several pairs of littermates. Alterations in Bax showed a trend towards higher expression in the hypoxic IUGR littermates but rarely reached significance. The IUGR piglets showed a significantly greater amount of apoptosis in response to the hypoxia than the normal weight piglets, suggesting an increased vulnerability to apoptosis in the IUGR piglets.
Pre- and post-term growth in pre-term infants supplemented with higher-dose DHA: a randomised controlled trial
Publisher: Cambridge University Press (CUP)
Date: 29-03-2011
DOI: 10.1017/S000711451000509X
Abstract: The effect of the dietary n -3 long-chain PUFA, DHA (22 : 6 n -3), on the growth of pre-term infants is controversial. We tested the effect of higher-dose DHA (approximately 1 % dietary fatty acids) on the growth of pre-term infants to 18 months corrected age compared with standard feeding practice (0·2–0·3 % DHA) in a randomised controlled trial. Infants born 33 weeks gestation ( n 657) were randomly allocated to receive breast milk and/or formula with higher DHA or standard DHA according to a concealed schedule stratified for sex and birth-weight ( 1250 and ≥ 1250 g). The dietary arachidonic acid content of both diets was constant at approximately 0·4 % total fatty acids. The intervention was from day 2 to 5 of life until the infant's expected date of delivery (EDD). Growth was assessed at EDD, and at 4, 12 and 18 months corrected age. There was no effect of higher DHA on weight or head circumference at any age, but infants fed higher DHA were 0·7 cm (95 % CI 0·1, 1·4 cm P = 0·02) longer at 18 months corrected age. There was an interaction effect between treatment and birth weight strata for weight ( P = 0·01) and length ( P = 0·04). Higher DHA resulted in increased length in infants born weighing ≥ 1250 g at 4 months corrected age and in both weight and length at 12 and 18 months corrected age. Our data show that DHA up to 1 % total dietary fatty acids does not adversely affect growth.
Use of the Ages and Stages Questionnaire to predict outcome after hypoxic‐ischaemic encephalopathy in the neonate
Publisher: Wiley
Date: 24-09-2008
DOI: 10.1111/J.1440-1754.2008.01388.X
Abstract: Infants who suffer hypoxic-ischaemic encephalopathy (HIE) at birth are at increased risk of developmental disability. In this at-risk population, reliable, inexpensive and early identification of those children who are likely to require formal developmental assessment and intervention is needed. To evaluate the ability of the Ages and Stages Questionnaire (ASQ) to detect developmentally delayed children in an Australian population of infants who suffered HIE at birth. Fifty-five children who survived HIE were followed until 12-14 months of age. Test characteristics were calculated to examine the ability of the ASQ to appropriately identify developmentally delayed infants against this study's 'gold standard': the Bayley Scales of Infant Development II. Comparing the ASQ with the Bayley Scales of Infant Development II, the questionnaire had the following test characteristics: sensitivity 92%, specificity 95%, positive predictive value 92%, negative predictive value 95% when used to detect severe developmental delay and sensitivity 67%, specificity 93%, positive predictive value 92%, negative predictive value 68% when used to detect both severe and mild developmental delay. However, the ASQ used at standard cut-offs failed to detect any of the children with mild delay. The ASQ is extremely effective for the detection of severe developmental delay in children who have suffered HIE at birth. Its capacity to identify those with milder delay is limited. The ability of the test to detect only those with severe developmental delay means that the ASQ is of little value as a screening tool in this population.
Human fetal intrapartum oxygen saturation monitoring: Agreement between readings from two sensors on the same fetus
Publisher: Elsevier BV
Date: 05-1996
DOI: 10.1016/S0002-9378(96)70612-9
Abstract: Our purpose was to assess the level of agreement between oxygen saturation values obtained from two identical sensors used on different sides of the face of the same human fetus during labor. Two identical fetal pulse oximeter sensors were placed on 12 fetuses during uncomplicated labor at < or = 38 weeks' gestation. Oxygen saturation, fetal heart rate, and uterine activity were recorded. The agreement between synchronous values of oxygen saturation was assessed by calculating the mean difference and SD of the difference. The SD of a single sensor was estimated as the SD of the difference ided by the square root of 2. The mean oxygen saturation value returned from one sensor was 49.2% and from the other 49.9% the mean difference was -0.7%. The SD of the difference was 7.5%, and the 95% limits (+/- 2 SDs of the difference) were -15.5% to 14.1%. The SD from a single sensor was estimated as 5.3%. There was no clinically significant difference between the oxygen saturation values returned from two identical sensors on the one fetus. The magnitude of the SD from a single sensor must be taken into account when an arbitrary "cutoff" or "action" oxygen saturation value in a clinical setting or trial is defined.
Umbilical Cord Blood Cell Clearance Post-Infusion in Immune-Competent Children with Cerebral Palsy
Publisher: S. Karger AG
Date: 19-10-2023
DOI: 10.1159/000527612
Abstract: Umbilical cord blood cells have therapeutic potential for neurological disorders, through a paracrine mechanism of action. A greater understanding of the safety and immunological effects of allogeneic donor cord blood cells in the context of a healthy recipient immune system, such as in cerebral palsy, is needed. This study aimed to determine how quickly donor cord blood cells were cleared from the circulation in children with cerebral palsy who received a single intravenous infusion of 12/12 human leucocyte antigen (HLA) matched sibling cord blood cells. Twelve participants with cerebral palsy aged 2-12 years received cord blood cell infusions as part of a phase I trial of umbilical blood infusion for cerebral palsy. Digital droplet PCR analysis of DNA copy number variants specific to donor and recipient was used to assess donor DNA clearance at five timepoints post infusion, a surrogate measure of cell clearance. Donor cells were cleared from 3 months post-infusion in 11/12 participants. When detected, donor DNA was at a fraction of 0.01 - 0.31% of total DNA with no signs of graft-versus-host disease (GvHD) in any participant. The donor DNA clearance times provided by this study have important implications for understanding safety of allogeneic cord blood cell infusion for cerebral palsy and translational tissue engineering or regenerative medicine research in other disorders.
A Pig Model of the Preterm Neonate: Anthropometric and Physiological Characteristics
Publisher: Public Library of Science (PLoS)
Date: 09-07-2013
Intrapartum fetal scalp lactate sampling for fetal assessment in the presence of a non-reassuring fetal heart rate trace
Publisher: Wiley
Date: 05-2015
Therapeutic potential to reduce brain injury in growth restricted newborns
Publisher: Wiley
Date: 23-05-2018
DOI: 10.1113/JP275428
Ibuprofen inhibits neuroinflammation and attenuates white matter damage following hypoxia–ischemia in the immature rodent brain
Publisher: Elsevier BV
Date: 07-2011
DOI: 10.1016/J.BRAINRES.2011.06.001
Abstract: Damage to major white matter tracts is a hallmark mark feature of hypoxic-ischemic (HI) brain injury in the preterm neonate. There is, however, no therapeutic intervention to treat this injury. Neuroinflammation is thought to play a prominent role in the pathogenesis of the HI-induced white matter damage but identification of the key mediators that constitute the inflammatory response remain to be fully elucidated. Cyclooxygenase enzymes (COX-1 and COX-2) are candidate neuroinflammatory mediators that may contribute to the HI-induced demise of early oligodendrocyte progenitors and myelination. We investigated whether ibuprofen, a non-steroidal anti-inflammatory drug that inhibits COX enzymes, can attenuate neuroinflammation and associated white matter damage incurred in a rodent model of preterm HI. On postnatal day 3 (P3), HI was produced (right carotid artery ligation and 30 min 6% O(2)). An initial dose of ibuprofen (100mg/kg, s.c.) was administered 2h after HI followed by a maintenance dose (50mg/kg, s.c.) every 24h for 6 days. Post-HI ibuprofen treatment significantly attenuated the P3 HI-induced increases in COX-2 protein expression as well as interleukin-1beta (IL-1β) and tumour necrosis factor-alpha (TNF-α) levels in the brain. Ibuprofen treatment also prevented the HI-induced loss O4- and O1-positive oligodendrocyte progenitor cells and myelin basic protein (MBP)-positive myelin content one week after P3 HI. These findings suggest that a repeated, daily, ibuprofen treatment regimen administered after an HI insult may be a potential therapeutic intervention to prevent HI-induced damage to white matter progenitors and early myelination in the preterm neonate.
Analysis of the time-varying cortical neural connectivity in the newborn EEG: A time-frequency approach
Publisher: IEEE
Date: 05-2011
Post‐insult minocycline treatment attenuates hypoxia‐ischemia‐induced neuroinflammation and white matter injury in the neonatal rat: a comparison of two different dose regimens
Publisher: Wiley
Date: 04-03-2008
DOI: 10.1016/J.IJDEVNEU.2008.02.005
Abstract: An increase in the number of activated microglia in the brain is a key feature of neuroinflammation after a hypoxic-ischemic insult to the preterm neonate and can contribute to white matter injury in the brain. Minocycline is a potent inhibitor of microglia and may have a role as a neuroprotective agent that ameliorates brain injury after hypoxia-ischemia in neonatal animal models. However to date large doses, pre-insult administration and short periods of treatment after hypoxia-ischemia have mostly been investigated in animal models making it difficult to translate minocycline's potential applicability to protect the human preterm neonatal brain exposed to hypoxia-ischemia. We investigated whether repeated doses of minocycline can minimize white matter injury and neuroinflammation one week after hypoxia-ischemia (right carotid artery ligation and 30 min 6% O(2)) in the post-natal day 3 rat pup. Two dosage regimens of minocycline were administered for one week a high dose of 45 mg/kg 2h after hypoxia-ischemia then 22.5 mg/kg daily or a low dose 22.5 mg/kg 2h after hypoxia-ischemia then 10 mg/kg. Post-natal day 3 hypoxia-ischemia significantly reduced myelin content, numbers of O1- and O4-positive oligodendrocyte progenitor cells and increased activated microglia one week later on post-natal day 10. The low dose minocycline regimen was as effective as the high dose in ameliorating neuroinflammation after post-natal day 3 hypoxia-ischemia. However only the high dose regimen significantly attenuated reductions in O1- and O4-positive oligodendrocyte progenitor cells and myelin content. The low dose only significantly attenuated the reduction in O1-positive oligodendrocyte cell counts. Repeated, daily, post-insult treatment with minocycline abolished neuroinflammation and may provide neuroprotection to white matter for up to one week after hypoxia-ischemia in a rodent preterm model. The present findings suggest the potential clinical relevance of a repeated, daily minocycline treatment strategy, administered after a hypoxia-ischemia insult, as a therapeutic intervention for hypoxia-ischemia-affected preterm neonates.
Differential effects of neonatal hypoxic–ischemic brain injury on brainstem serotonergic raphe nuclei
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.BRAINRES.2010.01.065
Abstract: Serotonergic fibres have a pervasive innervation of hypoxic-ischemic (HI)-affected areas in the neonatal brain and serotonin (5-HT) is pivotal in numerous neurobehaviours that match many HI-induced deficits. However, little is known about how neonatal HI affects the serotonergic system. We therefore examined whether neonatal HI can alter numbers of serotonergic raphe neurons in specific sub- isions of the midbrain and brainstem since these nuclei are the primary sources of serotonin throughout the central nervous system (CNS). We utilised an established neonatal HI model in the postnatal day 3 (P3) rat pup (right common carotid artery ligation+30min 6% O2) and determined the effects of P3 HI on 5-HT counts in 5 raphe sub- isions in the midbrain and brainstem one and six weeks later. After P3 HI, numbers of 5-HT-positive neurons were significantly decreased in the dorsal raphe dorsal, dorsal raphe ventrolateral and dorsal raphe caudal nuclei on P10 but only in the dorsal raphe dorsal and dorsal raphe ventrolateral nuclei on P45. In contrast, P3 HI did not alter counts in the dorsal raphe interfascicular and raphe magnus nuclei. We also discovered that P3 HI significantly reduces brainstem SERT protein expression the key regulator of 5-HT in the CNS. In conclusion, neonatal HI injury caused significant disruption of the brainstem serotonergic system that can persist for up to six weeks after the insult. The different vulnerabilities of serotonergic populations in specific raphe nuclei suggest that certain raphe nuclei may underpin neurological deficits in HI-affected neonates through to adulthood.
Prediction of outcome following hypoxia/ischaemia in the human infant using cerebral impedance
Publisher: Elsevier BV
Date: 02-2009
DOI: 10.1016/J.CLINPH.2008.11.008
Abstract: Changes in cerebral impedance in the newborn piglet are able to discriminate, within 1-2 h of acute hypoxia, between animals which will have a good neurological outcome, and those who have suffered more severe hypoxia resulting in poor outcome. The aim of this study was to determine if cerebral impedance could be used to identify those human infants with an encephalopathy following acute hypoxia who subsequently have a poor neurological outcome. It is these infants who may benefit most from neural rescue treatment. Twenty-four newborn term infants with evidence of severe acute intrapartum hypoxia and encephalopathy were studied. Bioimpedance spectroscopy was commenced as soon as possible after birth and repeated every 30 min until the infant was 12 h old. Neurodevelopmental outcome was assessed at 12 months of age. Although cerebral impedance was different to control values, there was no significant difference in cerebral impedance between hypoxic babies with normal and those with abnormal development. Cerebral impedance was increased in hypoxic babies, as predicted from animal data, but the method was not suitable for discrimination of outcome. Cerebral impedance is not useful for early identification of infants who subsequently have a poor outcome after acute intrapartum hypoxia and who may benefit from neural rescue treatment.
School-age outcomes of very preterm infants after antenatal treatment with magnesium sulfate vs placebo
Publisher: American Medical Association (AMA)
Date: 17-09-2014
Abstract: Antenatal magnesium sulfate given to pregnant women at imminent risk of very preterm delivery reduces the risk of cerebral palsy in early childhood, although its effects into school age have not been reported from randomized trials. To determine the association between exposure to antenatal magnesium sulfate and neurological, cognitive, academic, and behavioral outcomes at school age. The ACTOMgSO4 was a randomized clinical trial conducted in 16 centers in Australia and New Zealand, comparing magnesium sulfate with placebo given to pregnant women (n = 535 magnesium n = 527 placebo) for whom imminent birth was planned or expected before 30 weeks' gestation. Children who survived from the 14 centers who participated in the school-age follow-up (n = 443 magnesium n = 424 placebo) were invited for an assessment at 6 to 11 years of age between 2005 and 2011. Mortality, cerebral palsy, motor function, IQ, basic academic skills, attention and executive function, behavior, growth, and functional outcomes. Main analyses were imputed for missing data. Of the 1255 fetuses known to be alive at randomization, the mortality rate to school age was 14% (88/629) in the magnesium sulfate group and 18% (110/626) in the placebo group (risk ratio [RR], 0.80 95% CI, 0.62-1.03, P = .08). Of 867 survivors available for follow-up, outcomes at school age (corrected age 6-11 years) were determined for 669 (77%). Comparing the magnesium sulfate and placebo groups revealed no statistically significant difference in proportions with cerebral palsy (23/295 [8%] and 21/314 [7%], respectively odds ratio [OR], 1.26 95% CI, 0.84-1.91 P = .27) or abnormal motor function (80/297 [27%] and 80/300 [27%], respectively OR, 1.16 95% CI, 0.88-1.52 P = .28). There was also little difference between groups on any of the cognitive, behavioral, growth, or functional outcomes. Magnesium sulfate given to pregnant women at imminent risk of birth before 30 weeks' gestation was not associated with neurological, cognitive, behavioral, growth, or functional outcomes in their children at school age, although a mortality advantage cannot be excluded. The lack of long-term benefit requires confirmation in additional studies. anzctr.org.au Identifier: ACTRN12606000252516.
A time-frequency based approach for generalized phase synchrony assessment in nonstationary multivariate signals
Publisher: Elsevier BV
Date: 05-2013
Review: The blood-brain barrier; protecting the developing fetal brain
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.PLACENTA.2016.12.005
Abstract: While placental function is fundamental to normal fetal development, the blood-brain barrier provides a second checkpoint critical to protecting the fetal brain and ensuring healthy brain development. The placenta is considered the key barrier between the mother and fetus, regulating delivery of essential nutrients, removing waste as well as protecting the fetus from potentially noxious substances. However, disturbances to the maternal environment and subsequent adaptations to placental function may render the placenta ineffective for providing a suitable environment for the developing fetus and to providing sufficient protection from harmful substances. The developing brain is particularly vulnerable to changes in the maternal/fetal environment. Development of the blood-brain barrier and maturation of barrier transporter systems work to protect the fetal brain from exposure to drugs, excluding them from the fetal CNS. This review will focus on the role of the 'other' key barrier during gestation - the blood-brain barrier - which has been shown to be functional as early as 8 weeks' gestation.
Developmental Expression and Distribution of GABA<sub>A</sub> Receptor α<sub>1</sub>-, α<sub>3</sub>- and β<sub>2</sub>-Subunits in Pig Brain
Publisher: S. Karger AG
Date: 2011
DOI: 10.1159/000326630
Abstract: The principal function of the γ-aminobutyric acid (GABA) system in the adult brain is inhibition however, in the neonatal brain, GABA provides much of the excitatory drive. As the brain develops, transmembrane chloride gradients change and the inhibitory role of GABA is initiated and continues throughout juvenile and adult life. Previous studies have shown that GABA sub A /sub receptor subunit expression is developmentally regulated, and it is thought that the change in GABA function from excitation to inhibition corresponds to the changeover in expression of ‘immature’ to ‘mature’ subunit isoforms. We examined the protein expression pattern and distribution of GABA type A (GABA sub A /sub ) receptor α sub /sub -, α sub /sub - and β sub /sub -subunits in the parietal cortex and hippoc us of the developing piglet brain. Four perinatal ages were studied 14 days preterm (P–14), 10 days preterm (P–10), day of birth (P0) and at postnatal day 7 (P7). Animals were obtained by either caesarean section or spontaneous birth. Protein expression levels and subunit localization were analysed by Western blotting and immunohistochemistry, respectively. In the cortex and hippoc us, GABA sub A /sub receptor α sub /sub -subunit showed greatest expression at P7 when compared to all other age groups (p 0.05). In contrast, α sub /sub expression in the cortex was elevated in preterm brain, peaking at P0, followed by a significant reduction by P7 (p 0.05) a similar trend was observed in the hippoc us. GABA sub A /sub receptor β sub /sub -subunit protein expression appeared relatively constant across all time points studied in both the cortex and hippoc us. Immunolabelling of the α sub /sub -, α sub /sub - and β sub /sub -subunits was observed throughout all cortical layers at every age. GABA sub A /sub receptor α sub /sub -subunit appeared to show specific localization to layers V and VI whilst labelling for the β sub /sub -subunit was observed in layer IV. In the hippoc us of all animals, the α sub /sub - and β sub /sub -subunits were shown to immunolabel various cells and processes in the dentate gyrus (DG), CA1 and CA3 the α sub /sub -subunit was barely observed except at the stratum moleculare of the DG. We report for the first time the ontogenesis of GABA sub A /sub receptor subunits α sub /sub , α sub /sub and β sub /sub in the perinatal pig brain.
Detecting fetal movements using non-invasive accelerometers
Publisher: IEEE
Date: 05-2010
Effect of Delayed Cord Clamping on Cerebral Oxygenation in Very Preterm Infants
Publisher: S. Karger AG
Date: 10-09-2018
DOI: 10.1159/000492712
Abstract: b i Background and Objective: /i /b The mechanism of reported benefits of delayed cord cl ing (DCC) are unclear. We aimed to determine whether DCC compared to immediate cord cl ing (ICC) in very preterm infants improves cerebral oxygenation in the first 24 h. b i Study Design: /i /b This is a prospective study of a subset of infants at & #x3c 30 weeks of gestation who were randomised to DCC (≥60 s) or ICC (& #x3c 10 s) and required an indwelling arterial catheter. Regional cerebral oxygenation (rScO sub /sub ), blood pressure, PI, and peripheral saturation were measured and cerebral fractional tissue oxygen extraction (cFTOE) calculated for the following 3 time intervals: 3–6, 6–12, and 12–28 h of age. Functional ultrasound measures including superior vena cava flow, right ventricular output, ductus arteriosus size and shunt and anterior cerebral artery resistive index were determined. b i Results: /i /b The mean (±SD) gestation and birth weight of the 51 study infants were 27 ± 1 weeks and 1,046 ± 241 g respectively. Twenty infants received DCC and 31 received ICC. Baseline demographics were similar between the 2 groups. Comparing DCC and ICC infants, there was no difference in rScO sub /sub or cFTOE at any time point. Three out of 20 infants did not receive DCC due to clinical concerns. A sensitivity analysis revealed that cord cl ing ≥30 s was significantly associated with increased rScO sub /sub and decreased cFTOE at all 3 time points after adjusting for gestation. b i Conclusion: /i /b Although DCC was not associated with changes in cerebral oxygenation overall, sensitivity analysis suggested a possible effect of an increased rScO sub /sub and a decreased cFTOE with ≥30 s of DCC.
Determinants of Body Fat in Infants of Women With Gestational Diabetes Mellitus Differ With Fetal Sex
Publisher: American Diabetes Association
Date: 14-11-2011
DOI: 10.2337/DC11-0728
Abstract: Neonatal adiposity is a well-recognized complication of gestational diabetes mellitus (GDM). This study aimed to identify factors influencing adiposity in male and female infants of women treated for GDM. This was a prospective study of 84 women with GDM. Daily blood glucose levels (BGLs) were retrieved from glucose meters, and overall mean fasting and mean 2-h postprandial BGLs were calculated for each woman. Infant body composition was measured at birth, and regression analysis was used to identify significant predictors of infant body fat separately in male and female infants. Maternal fasting BGL was the major predictor of adiposity in male infants but had little relationship to adiposity in female infants. In male infants, percent fat was increased by 0.44% for each 0.1 mmol/L increase in mean maternal fasting BGL. Maternal BMI was the primary predictor in female infants but had little effect in males. In female infants, percent fat was increased by 0.11% for each 1 kg/m2 increase in maternal prepregnancy BMI. Fetal sex may influence the impact that treatment strategies for GDM have on infant adiposity.
Women's evaluations of their experience in a multicenter randomized controlled trial of intrapartum fetal pulse oximetry (the FOREMOST trial)
Publisher: Wiley
Date: 24-05-2006
DOI: 10.1111/J.0730-7659.2006.00086.X
Abstract: Fetal pulse oximetry improves the assessment of fetal well-being during labor. The objective of this study was to evaluate women's satisfaction with their experience with this additional technology. We surveyed women participating in the FOREMOST trial, a randomized controlled trial comparing the addition of fetal pulse oximetry (FPO) to conventional cardiotocograph (CTG) monitoring (intervention group), versus CTG-only (control group), in the presence of nonreassuring fetal status during labor. Our survey evaluated 3 aspects of women's experience: labor, fetal monitoring, and participation in the research. The survey was administered within a few days of giving birth and repeated 3 months later. No differences were found between the intervention and control groups for women's evaluations of their labor, fetal monitoring, research, or overall experiences when surveyed on both occasions. Within each study group, a small but statistically significant decline occurred in women's scores for their experience of labor and overall experience from the initial survey close to the time of giving birth, to 3 months later. The magnitude of differences in responses over time was similar for the both groups. Women were more satisfied after a spontaneous or assisted vaginal birth than after cesarean section. Length of time the research midwife was present had a significant positive effect on women's ratings of their experience several days after giving birth (p = 0.006), but no effect at 3 months. The addition of fetal pulse oximetry for the assessment of fetal well-being during labor did not affect childbearing women's perceptions of fetal monitoring or their labor. Women evaluated their experience in the research process positively overall. Small changes occurred in women's perception of their satisfaction over time.
Prem Baby Triple P: A randomised controlled trial of enhanced parenting capacity to improve developmental outcomes in preterm infants
Publisher: Springer Science and Business Media LLC
Date: 04-03-2015
Reply:
Publisher: American Society of Neuroradiology (ASNR)
Date: 23-11-2017
DOI: 10.3174/AJNR.A5478
Endogenous angiotensins and catecholamines do not reduce skin blood flow or prevent hypotension in preterm piglets
Publisher: Wiley
Date: 12-2014
DOI: 10.14814/PHY2.12245
Assessment of Structural Connectivity in the Preterm Brain at Term Equivalent Age Using Diffusion MRI and T2 Relaxometry: A Network-Based Analysis
Publisher: Public Library of Science (PLoS)
Date: 07-08-2013
Selective Losses of Brainstem Catecholamine Neurons After Hypoxia-Ischemia in the Immature Rat Pup
Publisher: Springer Science and Business Media LLC
Date: 04-2008
Kalman filter-based time-varying cortical connectivity analysis of newborn EEG
Publisher: IEEE
Date: 08-2011
Accelerometer-based fetal movement detection
Publisher: IEEE
Date: 08-2011
Long-term losses of amygdala corticotropin-releasing factor neurons are associated with behavioural outcomes following neonatal hypoxia-ischemia
Publisher: Elsevier BV
Date: 04-2010
DOI: 10.1016/J.BBR.2010.01.007
Abstract: Neuronal losses are observed in the brain after neonatal hypoxia-ischemia (HI) however few studies have examined the effects of HI on specific neuronal phenotypes and their possible contribution to behavioural outcomes. In the present study we examined whether postnatal day 3 (P3) HI alters numbers of corticotropin-releasing factor (CRF) and neuropeptide-Y (NPY) neurons in the paraventricular nucleus of the hypothalamus (PVN), the bed nucleus of the stria terminalis (BNST) and the amygdala, 1 (P10) and 6 (P45) weeks after P3 HI. A significant reduction in the number of CRF-positive neurons in the PVN, central nucleus of the amygdala (CeA) and BNST ipsilateral to the carotid ligation 1 and 6 weeks after P3 HI was observed. There was also a significant reduction in the number of NPY-positive neurons in the PVN, amygdala and BNST ipsilateral to the carotid ligation 1 week after P3 HI. However after 6 weeks, only the number of PVN NPY-positive neurons decreased significantly. At 6 weeks post-insult, the number of CeA CRF-positive neurons was inversely associated with locomotor activity and exploratory behaviour in an open field. In contrast, no significant correlations between neuronal counts and early neurodevelopment tests performed on P10 were observed. Thus after P3 HI persistent losses of CRF- and NPY-positive neurons occur and the loss of CeA CRF neurons may provide a central anatomical mechanism underlying neurobehavioural deficits observed 6 weeks after P3 HI.
S-Adenosyl-L-methionine restores photoreceptor function following acute retinal ischemia
Publisher: Cambridge University Press (CUP)
Date: 11-2009
DOI: 10.1017/S0952523809990241
Abstract: The survival and function of retinal neurons is dependent on mitochondrial energy generation and its intracellular distribution by creatine kinase. Post ischemic disruption of retinal creatine synthesis, creatine kinase activity, or transport of creatine into neurons may impair retinal function. S-adenosyl- l -methionine (SAMe) is required for creatine synthesis, phosphatidylcholine and glutathione synthesis, and transducin methylation. These reactions are essential for photoreceptor function but may be downregulated after ischemia due to a reduction in SAMe. Our aim was to determine whether administration of SAMe after ischemia could improve retinal function. Unilateral retinal ischemia was induced in adult rats by increasing the intraocular pressure to 110 mm Hg for 60 min. Immediately after the ischemic insult, SAMe was injected into the vitreous (100 μ m ), followed by oral administration (69 mg/kg/day) for 5 or 10 days. Retinal function (electroretinography), histology, and creatine transporter (CRT-1) expression were analyzed. Photoreceptoral responses (Rm P3 , S ), rod and cone bipolar cell responses (PII), and oscillatory potentials were reduced by the ischemia/reperfusion insult. Although SAMe treatment ameliorated the ischemia-induced histological damage by day 5, there was no improvement in retinal function and the intensity of CRT-1 labeling in ischemic retinas was markedly reduced. However, 10 days after ischemia, a recovery in CRT-1 immunolabeling was evident and SAMe supplementation significantly restored photoreceptor function and rod PII responses. In conclusion, these data suggest that creatine transport and methylation reactions, such as creatine synthesis, may be compromised by an ischemic insult contributing to retinal dysfunction and injury. Oral SAMe supplementation after retinal ischemia may provide an effective, safe, and accessible neuroprotective strategy.
Neurodevelopmental Outcomes of Preterm Infants Fed High-Dose Docosahexaenoic Acid: A Randomized Controlled Trial
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2009
Erythropoietin protects against apoptosis and increases expression of non-neuronal cell markers in the hypoxia-injured developing brain
Publisher: Wiley
Date: 14-03-2011
DOI: 10.1002/PATH.2862
Abstract: Erythropoietin (EPO) is a cytokine hormone with cytoprotective effects in many tissues including the brain. Although the benefits of administration of recombinant human EPO (rhEPO) for neonatal hypoxic brain injury have been demonstrated in neuronal tissue, the effect on non-neuronal cell populations is unclear. We tested the hypothesis that rhEPO would not only protect neuronal cells but also glial cells at a stage of brain development where their maturation was particularly sensitive, and also protect the vasculature. This was evaluated in a rat model of hypoxic injury. 1000 IU/kg rhEPO was delivered intraperitoneally at the start of 4 h hypoxia or normoxia. Treatment groups of neonatal rats (day of birth, at least N = 10 per group) were as follows: normoxia normoxia plus rhEPO hypoxia (8% FiO(2) delivered in temperature-controlled chambers) and hypoxia plus rhEPO. Day of birth in rats is equivalent to human gestation of 28-32 weeks. The effects of rhEPO administration, especially to non-neuronal cell populations, and the associated molecular pathways, were investigated. Apoptosis was increased with hypoxia and this was significantly reduced with rhEPO (p < 0.05). The neuronal marker, microtubule-associated protein-2, increased in expression (p < 0.05) when apoptosis was significantly reduced by rhEPO. In addition, compared with hypoxia alone, rhEPO-treated hypoxia had the following significant protein expression increases (p < 0.05): the intermediate filament structural protein nestin myelin basic protein (oligodendrocytes) and glial fibrillary acidic protein (astrocytes). In conclusion, rhEPO protects the developing brain via anti-apoptotic mechanisms and promotes the health of non-neuronal as well as neuronal cell populations at a time when loss of these cells would have long-lasting effects on brain function.
Cerebral impedance and neurological outcome following a mild or severe hypoxic/ischemic episode in neonatal piglets
Publisher: Elsevier BV
Date: 04-2003
DOI: 10.1016/S0006-8993(03)02295-9
Abstract: Multi-frequency bio-impedance has the potential to identify infants at risk of poor neurodevelopmental outcome following hypoxia by detecting cerebral edema. This study investigated the relationship between the severity of an hypoxic/ischemic episode, neurological outcome following the hypoxia and non-invasively measured cerebral bioelectrical impedance in piglets. One-day-old piglets were anaesthetised and ventilated. Hypoxia was induced by reducing the inspired oxygen concentration to 3-5%. Severe hypoxia was defined as hypoxia resulting in at least 30 min of low litude EEG (<5 microV) as well as hypotension and acidosis. Cerebral bio-impedance was measured before, during and for up to 6 h post-hypoxia. Neurological outcome was determined by a neurology score at 24 and 48 h after hypoxia, and by histological examination of the brain at 72 h. There was no increase in cerebral impedance in control animals. Following mild hypoxia cerebral impedance increased transiently. Following severe hypoxia, cerebral impedance increased and remained elevated. Cerebral impedance following severe hypoxia was significantly higher than after mild hypoxia at 10 min and from 2 to 6 h after resuscitation. Cerebral impedance measurements made up to 1 h and between 3 and 6 h after resuscitation were significantly correlated with neurological outcome. Results indicate that non-invasive cerebral impedance measurements are able to discriminate early between those in iduals who have suffered a mild, acute hypoxic episode, and those who have suffered a severe hypoxic episode. The technique has the potential to predict which in iduals will have a poor neurological outcome.
PREMM: preterm early massage by the mother: protocol of a randomised controlled trial of massage therapy in very preterm infants
Publisher: Springer Science and Business Media LLC
Date: 27-08-2016
Prem Baby Triple P a new parenting intervention for parents of infants born very preterm: Acceptability and barriers
Publisher: Elsevier BV
Date: 12-2011
DOI: 10.1016/J.INFBEH.2011.06.004
Abstract: Over 10% of preterm infants develop major disabilities, 50% develop behavioural problems and 40% need special education (Huddy et al., 2001 Webster, 2003). Prem Baby Triple P is a new variant of the Positive Parenting Program (Triple P) adapted specifically for parents of very preterm infants. The aim of this study is to assess the acceptability of Prem Baby Triple P to parents of infants born preterm and to test whether parental attributions and parental perception of infant health/developmental status are barriers to intervention acceptability. One hundred and twenty-three parents of preterm infants participated, 83 parents of very preterm infants and 40 parents of preterm infants. In addition, 32 parents of term infants participated as a comparison group. The acceptability of Prem Baby Triple P was moderately high and did not differ significantly across the three groups. Parental attributions were not found to be barriers to intervention acceptability and parental perceptions that their infant is less healthy/developmentally delayed facilitated Prem Baby Triple P acceptance in parents of infants born very preterm. This suggests that the planned Prem Baby Triple P content is acceptable to parents of infants born very preterm and sensitised to medical and developmental issues. These findings, as social validation data, will contribute towards the further development of Prem Baby Triple P and a future randomised controlled trial.
Non-invasivemonitoring of fetal movements using time-frequency features of accelerometry
Publisher: IEEE
Date: 05-2014
Blood Biomarkers in the Fetally Growth Restricted and Small for Gestational Age Neonate: Associations with Brain Injury
Publisher: S. Karger AG
Date: 10-05-2023
DOI: 10.1159/000530492
Abstract: Fetal growth restriction (FGR) and small for gestational age (SGA) infants have increased risk of mortality and morbidity. Although both FGR and SGA infants have low birthweights for gestational age, a diagnosis of FGR also requires assessments of umbilical artery Doppler, physiological determinants, neonatal features of malnutrition, and in utero growth retardation. Both FGR and SGA are associated with adverse neurodevelopmental outcomes ranging from learning and behavioral difficulties to cerebral palsy. Up to 50% of FGR, newborns are not diagnosed until around the time of birth, yet this diagnosis lacks further indication of the risk of brain injury or adverse neurodevelopmental outcomes. Blood biomarkers may be a promising tool. Defining blood biomarkers indicating an infant’s risk of brain injury would provide the opportunity for early detection and therefore earlier support. The aim of this review was to summarize the current literature to assist in guiding the future direction for the early detection of adverse brain outcomes in FGR and SGA neonates. The studies investigated potential diagnostic blood biomarkers from cord and neonatal blood or serum from FGR and SGA human neonates. Results were often conflicting with heterogeneity common in the biomarkers examined, timepoints, gestational age, and definitions of FGR and SGA used. Due to these variations, it was difficult to draw strong conclusions from the results. The search for blood biomarkers of brain injury in FGR and SGA neonates should continue as early detection and intervention is critical to improve outcomes for these neonates.
Clinical tools used in young infants born very preterm to predict motor and cognitive delay (not cerebral palsy): a systematic review
Publisher: Wiley
Date: 13-11-2020
DOI: 10.1111/DMCN.14730
Seizures Are Associated with Blood-Brain Barrier Disruption in a Piglet Model of Neonatal Hypoxic-Ischaemic Encephalopathy
Publisher: S. Karger AG
Date: 2018
DOI: 10.1159/000499365
Abstract: Seizures in the neonatal period are most often symptomatic of central nervous system (CNS) dysfunction and the most common cause is hypoxic-ischaemic encephalopathy (HIE). Seizures are associated with poor long-term outcomes and increased neuropathology. Blood-brain barrier (BBB) disruption and inflammation may contribute to seizures and increased neuropathology but are incompletely understood in neonatal HIE. The aim of this study was to investigate the impact of seizures on BBB integrity in a preclinical model of neonatal hypoxic-ischaemic (HI) injury. Piglets (age: & #x3c h) were subjected to a 30-min HI insult followed by recovery to 72 h post-insult. Amplitude-integrated electroencephalography (aEEG) was performed and seizure burden and background aEEG pattern were analysed. BBB disruption was evaluated in the parietal cortex and hippoc us by means of immunohistochemistry and Western blot. mRNA and protein expression of tight-junction proteins (zonula-occludens 1 [ZO1], occludin [OCLN], and claudin-5 [CLDN5]) was assessed using quantitative polymerase chain reaction (qPCR) and Western blot. In addition, mRNA from genes associated with BBB disruption vascular endothelial growth factor (VEGF) and matrix metalloproteinase 2 (MMP2) as well as inflammatory cytokines and chemokines was assessed with qPCR. Piglets that developed seizures following HI (HI-Sz) had significantly greater injury, as demonstrated by poorer aEEG background pattern scores, lower neurobehavioural scores, and greater histopathology. HI-Sz animals had severe IgG extravasation into brain tissue and uptake into neurons as well as significantly greater levels of IgG in both brain regions as assessed by Western blot. IgG protein in both brain regions was significantly associated with seizure burden, aEEG pattern scores, and neurobehavioural scores. There was no difference in mRNA expression of the tight junctions, however a significant loss of ZO1 and OCLN protein was observed in the parietal cortex. The inflammatory genes TGFβ, IL1β, IL8, IL6, and TNFα were significantly upregulated in HI-Sz animals. MMP2 was significantly increased in animals with seizures compared with animals without seizures. Increasing our understanding of neuropathology associated with seizure is vital because of the association between seizure and poor outcomes. Investigating the BBB is a major untapped area of research and a potential avenue for novel treatments.
Inotropes do not increase cardiac output or cerebral blood flow in preterm piglets.
Publisher: Springer Science and Business Media LLC
Date: 04-08-2016
DOI: 10.1038/PR.2016.156
Abstract: The preterm newborn is at high risk of developing cardiovascular compromise during the first day of life and this is associated with increased risk of brain injury. Standard treatments are volume expansion and administration of inotropes, typically dopamine and/or dobutamine, but there is limited evidence that inotropes improve clinical outcomes. This study investigated the efficacy of dopamine and dobutamine for the treatment of cardiovascular compromise in the preterm newborn using a piglet model. Preterm and term piglets were assigned to either dopamine, dobutamine or control infusions. Heart rate, left ventricular contractility, cardiac output, blood pressure, and cerebral and regional blood flows were measured during baseline, low (10 µg/kg/h), and high (20 µg/kg/h) dose infusions. At baseline, preterm piglets had lower cardiac contractility, cardiac output, blood pressure, and cerebral blood flow compared to term piglets. The response of preterm piglets to either dopamine or dobutamine administration was less than in term piglets. In both preterm and term piglets, cardiac output and cerebral blood flow were unaltered by either inotrope. In order to provide better cardiovascular support, it may be necessary to develop treatments that target receptors with a more mature profile than adrenoceptors in the preterm newborn.
Perioperative predictors of developmental outcome following cardiac surgery in infancy
Publisher: Cambridge University Press (CUP)
Date: 08-2004
DOI: 10.1017/S104795110400407X
Abstract: At 1 year we assessed the neurodevelopmental outcomes in infants undergoing cardiac surgery, seeking to explore the predictive value of perioperative markers of cerebral injury. We prospectively enroled 47 neurodevelopmentally normal infants prior to planned cardiac surgery. Postoperative monitoring consisted of 10-channel video synchronised, continuous electroencephalography from 6 to 30 h, Doppler assessment of cerebral blood flow in the anterior cerebral artery at 1, 2, 3 and 5 h, and measurement of serum S-100B at 0 and 24 h. Neurodevelopmental assessments were performed using the second edition of the Bayley Scale of Infant Development. Follow-up at 1 year was available on 35 infants. The mean age of these patients at surgery had been 57 ± 15 days. We observed clinical seizures in 1 patient, with 3 other patients having electroencephalographic abnormalities. At follow-up of 1 year, neurodevelopmental scores were lower than preoperative scores, with mean mental scores changing from 103 ± 5 to 94 ± 13 (p = 0.001), and mean motor scores changing from 99 ± 8 to 89 ± 20 (p = 0.004). No association was found between electroencephalographic abnormalities, reduced cerebral blood flow, or elevation of serum S-100B levels and impaired neurodevelopmental outcome at 1 year. Infants with electroencephalographic abnormalities had elevation of the levels of S-100B in the serum (p = 0.02). At 1 year of follow-up, infants undergoing cardiac surgery demonstrated a reduction in the scores achieved using the second edition of the Bayley Scale of Infant Development. They require ongoing assessment of their progress. Electroencephalographic abnormalities, cerebral blood flow, or levels of S-100B in the serum were not useful perioperative markers for predicting a poor neurodevelopmental outcome in the clinical setting.
Folic Acid Supplementation and Spontaneous Preterm Birth: Adding Grist to the Mill?
Publisher: Public Library of Science (PLoS)
Date: 12-05-2009
Increased progression to kidney fibrosis after erythropoietin is used as a treatment for acute kidney injury
Publisher: American Physiological Society
Date: 15-03-2014
DOI: 10.1152/AJPRENAL.00241.2013
Abstract: Treatment of renal ischemia-reperfusion (IR) injury with recombinant human erythropoietin (rhEPO) reduces acute kidney injury and improves function. We aimed to investigate whether progression to chronic kidney disease associated with acute injury was also reduced by rhEPO treatment, using in vivo and in vitro models. Rats were subjected to bilateral 40-min renal ischemia, and kidneys were studied at 4, 7, and 28 days postreperfusion for renal function, tubular injury and repair, inflammation, and fibrosis. Acute injury was modulated using rhEPO (1,000 or 5,000 IU/kg, intraperitoneally) at the time of reperfusion. Renal tubular epithelial cells or fibroblasts in culture were subjected to hypoxia or oxidative stress, with or without rhEPO (200 IU/ml), and fibrogenesis was studied. The results of the in vivo model confirmed functional and structural improvement with rhEPO at 4 days post-IR ( P 0.05). At 7 days post-IR, fibrosis and myofibroblast stimulation were increased with IR with and without rhEPO ( P 0.01). However, at 28 days post-IR, renal fibrosis and myofibroblast numbers were significantly greater with IR plus rhEPO ( P 0.01) compared with IR only. Mechanistically, rhEPO stimulated profibrotic transforming growth factor-β, oxidative stress (marker 8-hydroxy-deoxyguanosine), and phosphorylation of the signal transduction protein extracellular signal-regulated kinase. In vitro, rhEPO protected tubular epithelium from apoptosis but stimulated epithelial-to-mesenchymal transition and also protected and activated fibroblasts, particularly with oxidative stress. In summary, although rhEPO was protective of renal function and structure in acute kidney injury, the supraphysiological dose needed for renoprotection contributed to fibrogenesis and stimulated chronic kidney disease in the long term.
Phosphorylation of GFAP is Associated with Injury in the Neonatal Pig Hypoxic-Ischemic Brain
Publisher: Springer Science and Business Media LLC
Date: 19-04-2012
DOI: 10.1007/S11064-012-0774-5
Abstract: Glial fibrillary acidic protein (GFAP) is an intermediate filament protein expressed in the astrocyte cytoskeleton that plays an important role in the structure and function of the cell. GFAP can be phosphorylated at six serine (Ser) or threonine (Thr) residues but little is known about the role of GFAP phosphorylation in physiological and pathophysiological states. We have generated antibodies against two phosphorylated GFAP (pGFAP) proteins: p8GFAP, where GFAP is phosphorylated at Ser-8 and p13GFAP, where GFAP is phosphorylated at Ser-13. We examined p8GFAP and p13GFAP expression in the control neonatal pig brain and at 24 and 72 h after an hypoxic-ischemic (HI) insult. Immunohistochemistry demonstrated pGFAP expression in astrocytes with an atypical cytoskeletal morphology, even in control brains. Semi-quantitative western blotting revealed that p8GFAP expression was significantly increased at 24 h post-insult in HI animals with seizures in frontal, parietal, temporal and occipital cortices. At 72 h post-insult, p8GFAP and p13GFAP expression were significantly increased in HI animals with seizures in brain regions that are vulnerable to cellular damage (cortex and basal ganglia), but no changes were observed in brain regions that are relatively spared following an HI insult (brain stem and cerebellum). Increased pGFAP expression was associated with poor neurological outcomes such as abnormal encephalography and neurobehaviour, and increased histological brain damage. Phosphorylation of GFAP may play an important role in astrocyte remodelling during development and disease and could potentially contribute to the plasticity of the central nervous system.
Seizure detection algorithm for neonates based on wave-sequence analysis
Publisher: Elsevier BV
Date: 06-2006
DOI: 10.1016/J.CLINPH.2006.02.016
Abstract: The description and evaluation of the performance of a new real-time seizure detection algorithm in the newborn infant. The algorithm includes parallel fragmentation of EEG signal into waves wave-feature extraction and averaging elementary, preliminary and final detection. The algorithm detects EEG waves with heightened regularity, using wave intervals, litudes and shapes. The performance of the algorithm was assessed with the use of event-based and liberal and conservative time-based approaches and compared with the performance of Gotman's and Liu's algorithms. The algorithm was assessed on multi-channel EEG records of 55 neonates including 17 with seizures. The algorithm showed sensitivities ranging 83-95% with positive predictive values (PPV) 48-77%. There were 2.0 false positive detections per hour. In comparison, Gotman's algorithm (with 30s gap-closing procedure) displayed sensitivities of 45-88% and PPV 29-56% with 7.4 false positives per hour and Liu's algorithm displayed sensitivities of 96-99%, and PPV 10-25% with 15.7 false positives per hour. The wave-sequence analysis based algorithm displayed higher sensitivity, higher PPV and a substantially lower level of false positives than two previously published algorithms. The proposed algorithm provides a basis for major improvements in neonatal seizure detection and monitoring.
Prediction of fat-free mass and percentage of body fat in neonates using bioelectrical impedance analysis and anthropometric measures: validation against the PEA POD
Publisher: Cambridge University Press (CUP)
Date: 15-09-2011
DOI: 10.1017/S0007114511004624
Abstract: Accurate assessment of neonatal body composition is essential to studies investigating neonatal nutrition or developmental origins of obesity. Bioelectrical impedance analysis or bioimpedance analysis is inexpensive, non-invasive and portable, and is widely used in adults for the assessment of body composition. There are currently no prediction algorithms using bioimpedance analysis in neonates that have been directly validated against measurements of fat-free mass (FFM). The aim of the study was to evaluate the use of bioimpedance analysis for the estimation of FFM and percentage of body fat over the first 4 months of life in healthy infants born at term, and to compare these with estimations based on anthropometric measurements (weight and length) and with skinfolds. The present study was an observational study in seventy-seven infants. Body fat content of infants was assessed at birth, 6 weeks, 3 and 4·5 months of age by air displacement plethysmography, using the PEA POD body composition system. Bioimpedance analysis was performed at the same time and the data were used to develop and test prediction equations for FFM. The combination of weight+sex+length predicted FFM, with a bias of 100 g and limits of agreement of 6–13 %. Before 3 months of age, bioimpedance analysis did not improve the prediction of FFM or body fat. At 3 and 4·5 months, the inclusion of impedance in prediction algorithms resulted in small improvements in prediction of FFM, reducing the bias to 50 g and limits of agreement to 9 %. Skinfold measurements performed poorly at all ages.
Neurodevelopmental Outcomes of Preterm Infants Fed High-Dose Docosahexaenoic Acid
Publisher: American Medical Association (AMA)
Date: 14-01-2009
Abstract: Uncertainty exists about the benefit of dietary docosahexaenoic acid (DHA) on the neurodevelopment of preterm infants. To determine the effect of meeting the estimated DHA requirement of preterm infants on neurodevelopment at 18 months' corrected age. Randomized, double-blind controlled trial enrolling infants born at less than 33 weeks' gestation from April 2001 to October 2005 at 5 Australian tertiary hospitals, with follow-up to 18 months. High-DHA (approximately 1% total fatty acids) enteral feeds compared with standard DHA (approximately 0.3% total fatty acids) from day 2 to 4 of life until term corrected age. Bayley Mental Development Index (MDI) at 18 months' corrected age. A priori subgroup analyses were conducted based on randomization strata (sex and birth weight or = 1250 g). Of the 657 infants enrolled, 93.5% completed the 18-month follow-up. Bayley MDI scores did not differ between the high- and standard-DHA groups (mean difference, 1.9 95% confidence interval [CI], -1.0 to 4.7). The MDI among girls fed the high-DHA diet was higher than girls fed standard DHA in unadjusted and adjusted analyses (unadjusted mean difference, 4.7 95% CI, 0.5-8.8 adjusted mean difference, 4.5 95% CI, 0.5-8.5). The MDI among boys did not differ between groups. For infants born weighing less than 1250 g, the MDI in the high-DHA group was higher than with standard DHA in the unadjusted comparison (mean difference, 4.7 95% CI, 0.2-9.2) but did not reach statistical significance following adjustment for gestational age, sex, maternal education, and birth order (mean difference, 3.8 95% CI, -0.5 to 8.0). The MDI among infants born weighing at least 1250 g did not differ between groups. A DHA dose of approximately 1% total fatty acids in early life did not increase MDI scores of preterm infants overall born earlier than 33 weeks but did improve the MDI scores of girls. anzctr.org.au Identifier: ACTRN12606000327583.
Early detection of developmental delay in infants born very preterm or with very low birthweight
Publisher: Wiley
Date: 17-09-2022
DOI: 10.1111/DMCN.15381
Abstract: This study aimed to identify early clinical biomarkers from birth to 16 weeks corrected age to predict typical outcome and developmental delay in infants born very preterm or with very low birthweight. A prospective cohort of infants on the Sunshine Coast, Australia, was assessed using the Premie‐Neuro Examination, the General Movement Assessment (GMA), the Alberta Infant Motor Scale, and the Infant Sensory Profile 2. At 24 months corrected age, delay was identified using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley‐III) and Neurosensory Motor Developmental Assessment (NSMDA). One hundred and four infants were recruited 79 completed outcome assessments (43 females, 36 males mean gestational age 30 weeks [SD 1 week 6 days], mean birthweight 1346 g [SD 323]). The incidence of developmental delay (motor or cognitive) was 6.3%. Suboptimal quality of fidgety general movements (temporal organization) at 16 weeks corrected age demonstrated the best predictive accuracy (Bayley‐III motor: sensitivity 100% [95% confidence interval {CI} 3–100], specificity 75% [95% CI 63–84], area under the curve [AUC] 0.87) Bayley‐III cognitive: sensitivity 100% [95% CI 3–100], specificity 75% [95% CI 64–84], AUC 0.88) NSMDA motor: sensitivity 100% [95% CI 40–100], specificity 81% [95% CI 70–90], AUC 0.91 [95% CI 0.86–0.95]). GMA trajectories that combined abnormal writhing general movements at 4 to 5 weeks corrected age with suboptimal quality of fidgety movement at 16 weeks corrected age were strongly predictive of developmental delay, superior to all other clinical tools, and perinatal and demographic variables investigated ( p = 0.01, Akaike information criterion method 18.79 [score corrected for small s le size], accounting for 93% of the cumulative weight). Only the GMA had sufficient predictive validity to act as a biomarker for both conditions: typical outcome and developmental delay (motor or cognitive). GMA trajectories that assessed both writhing general movements at 4 to 5 weeks corrected age and quality of fidgety movement at 16 weeks corrected age predicted adverse neurodevelopmental outcome, accurately differentiating between infants with typical outcomes and those at increased risk for motor or cognitive delay.
Effect of cooling and re-warming on cerebral and whole body electrical impedance
Publisher: IOP Publishing
Date: 17-02-2004
DOI: 10.1088/0967-3334/25/2/001
Abstract: Cerebral electrical impedance is useful for the detection of cerebral edema following hypoxia in newborn infants. Thus it may be useful for determining neurological outcome or monitoring treatment. Hypothermia is a promising new therapy currently undergoing trials, but will alter impedance measurements. This study aimed to define the relationship between temperature and both cerebral and whole body electrical impedance, and to derive correction factors for adjustment of impedance measurements during hypothermia. In eight anaesthetized 1-2 day old piglets rectal, tympanic and scalp temperatures were monitored continuously. Following baseline readings at a rectal temperature of 39 degrees C, piglets were cooled to 32 degrees C. Four piglets were re-warmed. Cerebral and whole body impedance were measured at each 0.5 degrees C as rectal temperature decreased. There was a strong linear relationship between both cerebral and whole body impedance and each of the temperatures measured. There was no difference in the relationship between impedance and rectal, tympanic or scalp temperatures. The relationship for impedance and rectal temperature was the same during cooling and re-warming. Using the correction factors derived it will be possible to accurately monitor cerebral and whole body fluid distribution during hypothermic treatment.
GABAA receptor expression and white matter disruption in intrauterine growth restricted piglets
Publisher: Wiley
Date: 20-02-2017
DOI: 10.1016/J.IJDEVNEU.2017.02.004
Abstract: Intrauterine growth restriction (IUGR) is one of the most common causes of perinatal mortality and morbidity. White matter and neuronal injury are major pathophysiological features of the IUGR neonatal brain. GABA
A Randomized Trial of Baby Triple P for Preterm Infants: Child Outcomes at 2 Years of Corrected Age
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.JPEDS.2019.01.024
Abstract: To determine the efficacy of a hospital-based intervention that transitions into existing community support, in enhancing developmental outcomes at 2 years of corrected age in infants born at less than 32 weeks. In total, 323 families of 384 infants born <32 weeks were randomized to receive intervention or care-as-usual. The intervention teaches parents coping skills, partner support, and effective parenting strategies over 4 hospital-based and 4 home-phone sessions. At 2 years of corrected age maternally reported child behavior was assessed by the Infant and Toddler Social Emotional Adjustment Scale. Observed child behavior was coded with the Revised Family Observation Schedule. Cognitive, language, and motor skills were assessed with the Bayley Scales of Infant and Toddler Development III. Mean gestational age of infants was 28.5 weeks (SD = 2.1), and mothers' mean age was 30.6 years (SD = 5.8). A total of 162 families (n = 196 infants) were allocated to intervention and 161 families (n = 188 infants) received care-as-usual. There was no significant adjusted difference between treatment groups on dysregulation (0.2 95% CI -2.5 to 3.0, P = .9) externalizing (0.3 95% CI -1.6 to 2.2, P = .8), internalizing (-1.5 95% CI -4.3 to 1.3, P = .3), observed aversive (0.00 -0.04 to 0.04, P = .9), or nonaversive behavior (-0.01 95% CI -0.05 to 0.03, P = .7). Intervention children scored significantly higher on cognition (3.5 95% CI 0.2-6.8, P = .04) and motor skill (5.5 95% CI 2.5-8.4, P < .001), and approached significance on language (3.8 95% CI -0.3 to 7.9, P = .07). Baby Triple P for Preterm Infants increases cognitive and motor skills but does not impact behavior. The results are evidence that hospital-based interventions can improve some developmental outcomes for infants <32 weeks. ACTRN 12612000194864.
EEG background features that predict outcome in term neonates with hypoxic ischaemic encephalopathy: A structured review
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.CLINPH.2015.05.018
Abstract: Hypoxic ischaemic encephalopathy is a significant cause of mortality and morbidity in the term infant. Electroencephalography (EEG) is a useful tool in the assessment of newborns with HIE. This systematic review of published literature identifies those background features of EEG in term neonates with HIE that best predict neurodevelopmental outcome. A literature search was conducted using the PubMed, EMBASE and CINAHL databases from January 1960 to April 2014. Studies included in the review described recorded EEG background features, neurodevelopmental outcomes at a minimum age of 12 months and were published in English. Pooled sensitivities and specificities of EEG background features were calculated and meta-analyses were performed for each background feature. Of the 860 articles generated by the initial search strategy, 52 studies were identified as potentially relevant. Twenty-one studies were excluded as they did not distinguish between different abnormal background features, leaving 31 studies from which data were extracted for the meta-analysis. The most promising neonatal EEG features are: burst suppression (sensitivity 0.87 [95% CI (0.78-0.92)] specificity 0.82 [95% CI (0.72-0.88)]), low voltage (sensitivity 0.92 [95% CI (0.72-0.97)] specificity 0.99 [95% CI (0.88-1.0)]), and flat trace (sensitivity 0.78 [95% CI (0.58-0.91)] specificity 0.99 [95% CI (0.88-1.0)]). Burst suppression, low voltage and flat trace in the EEG of term neonates with HIE most accurately predict long term neurodevelopmental outcome. This structured review and meta-analysis provides quality evidence of the background EEG features that best predict neurodevelopmental outcome.
Intrapartum fetal scalp lactate sampling for fetal assessment in the presence of a non-reassuring fetal heart rate trace
Publisher: John Wiley & Sons, Ltd
Date: 18-10-2006
Generalized Mean Phase Coherence for asynchrony abnormality detection in multichannel newborn EEG
Publisher: IEEE
Date: 07-2012
EEG amplitude and correlation spatial decay analysis for neonatal head modelling
Publisher: IEEE
Date: 07-2012
An improved survival model of hypoxia/ischaemia in the piglet suitable for neuroprotection studies
Publisher: Elsevier BV
Date: 11-2001
DOI: 10.1016/S0006-8993(01)03011-6
Abstract: The purpose of this study was to develop a newborn piglet model of hypoxia/ischaemia which would better emulate the clinical situation in the asphyxiated human neonate and produce a consistent degree of histopathological injury following the insult. One-day-old piglets (n=18) were anaesthetised with a mixture of propofol (10 mg/kg/h) and alfentinal (55.5 microg/kg/h) i.v. The piglets were intubated and ventilated. Physiological variables were monitored continuously. Hypoxia was induced by decreasing the inspired oxygen (FiO(2)) to 3-4% and adjusting FiO(2) to maintain the cerebral function monitor peak litude at < or =5 microV. The duration of the mild insult was 20 min while the severe insult was 30 min which included 10 min where the blood pressure was allowed to fall below 70% of baseline. Control piglets (n=4 of 18) were subjected to the same protocol except for the hypoxic/ischaemic insult. The piglets were allowed to recover from anaesthesia then euthanased 72 h after the insult. The brains were perfusion-fixed, removed and embedded in paraffin. Coronal sections were stained by haematoxylin/eosin. A blinded observer examined the frontal and parietal cortex, hippoc us, basal ganglia, thalamus and cerebellum for the degree of damage. The total mean histology score for the five areas of the brain for the severe insult was 15.6+/-4.4 (mean +/-S.D., n=7), whereas no damage was seen in either the mild insult (n=4) or control groups. This 'severe damage' model produces a consistent level of damage and will prove useful for examining potential neuroprotective therapies in the neonatal brain.
Baby Triple P for Parents of a Very Preterm Infant: A Case Study
Publisher: Springer Science and Business Media LLC
Date: 04-10-2016
Prematurity and parental self-efficacy: The Preterm Parenting & Self-Efficacy Checklist
Publisher: Elsevier BV
Date: 12-2012
DOI: 10.1016/J.INFBEH.2012.07.009
Abstract: There is a lack of research investigating parental self-efficacy in parents of infants born preterm as well as a paucity of parental self-efficacy measures that are domain-specific and theoretically grounded. This study aimed to compare parental self-efficacy in parents of infants born term, preterm and very preterm as well as to test whether parental self-efficacy mediates the relationship between psychological symptoms and parental competence. In order to achieve this, a new measure of parental self-efficacy and parental competence relevant for the preterm population and consistent with Bandura's (1977, 1986, 1989) conceptualisation of self-efficacy was developed. Participants included 155 parents, 83 of whom were parents of very preterm (GA<32 weeks), 40 parents of preterm (GA<37 weeks) and 32 parents of term born infants. Parents completed the Preterm Parenting & Self-Efficacy Checklist (the new measure), Family Demographic Questionnaire, Depression Anxiety Stress Scale and Self-Efficacy Questionnaire. This initial study indicates that the Preterm Parenting & Self-Efficacy Checklist has adequate content validity, construct validity, internal consistency and split half reliability. Contrary to expectations, parents of very preterm infants did not report significantly lower overall levels of parental self-efficacy or significantly higher levels of psychological symptoms compared to parents of preterm and term infants. Parental self-efficacy about parenting tasks mediated the relationship between psychological symptoms and self perceived parental competence as predicted. Clinical implications of the results and suggestions for future research are discussed.
Validation of an MRI Brain Injury and Growth Scoring System in Very Preterm Infants Scanned at 29- to 35-Week Postmenstrual Age
Publisher: American Society of Neuroradiology (ASNR)
Date: 18-05-2017
DOI: 10.3174/AJNR.A5191
Associations between serum cortisol, cardiovascular function and neurological outcome following acute global hypoxia in the newborn piglet
Publisher: Informa UK Limited
Date: 2009
DOI: 10.1080/10253890802372414
Abstract: Perinatal asphyxia is a significant contributor to neonatal brain injury. However, there is significant variability in neurological outcome in neonates after global hypoxia-ischemia. The aims of this study were to identify which physiological response/s during global hypoxia-ischemia influence the severity of brain injury and to assess their relative importance. Hypoxia/hypercapnia was induced in 20 anaesthetized piglets by reducing the inspired oxygen fraction to 10% and the ventilation rate from 30 to 10 breaths per minute for 45 min. Neurological outcome was assessed using functional markers including cerebral function litude (via electroencephalography) and cerebral impedance, and the structural marker microtubule associated protein-2 by immunohistochemistry at 6 h post hypoxia. Significant variability in neurological outcome was observed following the constant hypoxia/hypercapnia insult. There was a high degree of variability in cardiovascular function (mean arterial blood pressure and heart rate) and serum cortisol concentrations in response to hypoxia. More effective maintenance of cardiovascular function and higher serum cortisol concentrations were associated with a better outcome. These two variables were strongly associated with neurological outcome, and together explained 68% of the variation in the severity of neurological outcome. The variability in the cardiovascular and cortisol responses to hypoxia may be a more important determinant of neurological outcome then previously recognized.
Seizures are associated with brain injury severity in a neonatal model of hypoxia–ischemia
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.NEUROSCIENCE.2009.11.067
Abstract: Hypoxia-ischemia is a significant cause of brain damage in the human newborn and can result in long-term neurodevelopmental disability. The loss of oxygen and glucose supply to the developing brain leads to excitotoxic neuronal cell damage and death such over-excitation of nerve cells can also manifest as seizures. The newborn brain is highly susceptible to seizures although it is unclear what role they have in hypoxic-ischemic (H/I) injury. The aim of this study was to determine an association between seizures and severity of brain injury in a piglet model of perinatal H/I and, whether injury severity was related to type of seizure, i.e. sub-clinical (electrographic seizures only) or clinical (electrographic seizures+physical signs). Hypoxia (4% O(2)) was induced in anaesthetised newborn piglets for 30 min with a final 10 min period of hypotension animals were recovered and survived to 72 h. Animals were monitored daily for seizures both visually and with electroencephalogram (EEG) recordings. Brain injury was assessed with magnetic resonance imaging (MRI), (1)H-MR spectroscopy ((1)H-MRS), EEG and by histology (haematoxylin and eosin). EEG seizures were observed in 75% of all H/I animals, 46% displayed clinical seizures and 29% sub-clinical seizures. Seizure animals showed significantly lower background litude EEG across all post-insult days. Presence of seizures was associated with lower cortical apparent diffusion coefficient (ADC) scores and changes in (1)H-MRS metabolite ratios at both 24 and 72 h post-insult. On post-mortem examination animals with seizures showed the greatest degree of neuropathological injury compared to animals without seizures. Furthermore, clinical seizure animals had significantly greater histological injury compared with sub-clinical seizure animals this difference was not apparent on MRI or (1)H-MRS measures. In conclusion we report that both sub-clinical and clinical seizures are associated with increased severity of H/I injury in a term model of neonatal H/I.
Reduced blood volume decreases cerebral blood flow in preterm piglets
Publisher: Wiley
Date: 02-07-2018
DOI: 10.1113/JP275583
Orthogonalized partial directed coherence for functional connectivity analysis of newborn EEG
Publisher: Springer Berlin Heidelberg
Date: 2012
Investigating Brain Age Deviation in Preterm Infants: A Deep Learning Approach
Publisher: Springer International Publishing
Date: 2018
Fetal pulse oximetry for fetal assessment in labour
Publisher: Wiley
Date: 07-10-2014
Fetal pulse oximetry for fetal assessment in labour
Publisher: John Wiley & Sons, Ltd
Date: 18-04-2007
Increased cerebral lactate during hypoxia may be neuroprotective in newborn piglets with intrauterine growth restriction
Publisher: Elsevier BV
Date: 11-2007
DOI: 10.1016/J.BRAINRES.2007.08.037
Abstract: Intrauterine growth restriction (IUGR) can increase susceptibility to perinatal hypoxic brain injury for reasons that are unknown. Previous studies of the neonatal IUGR brain have suggested that the cerebral mitochondrial capacity is reduced but the glycolytic capacity increased relative to normal weight (NW) neonates. In view of these two factors, we hypothesized that the generation of brain lactate during a mild hypoxic insult would be greater in neonatal IUGR piglets compared to NW piglets. Brain lactate/N-acetylaspartate (NAA) ratios and apparent diffusion coefficients (ADCs) were determined by proton magnetic resonance spectroscopy and imaging of the brain before, during and after hypoxia in seven neonatal piglets with asymmetric IUGR and six NW piglets. During hypoxia, IUGR piglets had significantly higher brain lactate/NAA ratios than NW piglets (P=0.046). The lactate response in the IUGR piglets correlated inversely with apoptosis in the thalamus and frontal cortex of the brain measured 4 h post hypoxia (Pearson's r=0.86, P<0.05). Apoptosis in IUGR piglets with high brain lactate was similar to that in the NW piglets whereas IUGR piglets with low brain lactate had significantly higher apoptosis than NW piglets (P=0.019). ADCs in the high lactate IUGR piglets were significantly lower during hypoxia than in all the other piglets. This signifies increased diffusion of water into brain cells during hypoxia, possibly in response to increased intracellular osmolality caused by high intracellular lactate concentrations. These findings support previous studies showing increased susceptibility to hypoxic brain injury in IUGR neonates but suggest that increased glycolysis during hypoxia confers neuroprotection in some IUGR piglets.
Passive detection of accelerometer-recorded fetal movements using a time-frequency signal processing approach
Publisher: Elsevier BV
Date: 02-2014
Magnetic resonance diffusion tractography of the preterm infant brain: A systematic review
Publisher: Wiley
Date: 16-09-2014
DOI: 10.1111/DMCN.12250
Abstract: Preterm birth is associated with an increased risk of adverse neurodevelopmental outcomes. Diffusion magnetic resonance imaging (dMRI) combined with tractography can be used to assess non-invasively white matter microstructure and brain development in preterm infants. Our aim was to conduct a systematic review of the current evidence obtained from tractography studies of preterm infants in whom MRI was performed up to term-equivalent age. Databases were searched for dMRI tractography studies of preterm infants. Twenty-two studies were assessed. The most frequently assessed tracts included the corticospinal tract, the corpus callosum, and the optic radiations. The superior longitudinal fasciculus, and the anterior and superior thalamic radiations were investigated less frequently. A clear relationship exists between diffusion metrics and postmenstrual age at the time of scanning, although the evidence of an effect of gestational age at birth and white matter injury is conflicting. Sex and laterality may play an important role in the relationship between diffusion metrics, early clinical assessment, and outcomes. Studies involving infants of all gestational ages are required to elucidate the relationship between gestational age and diffusion metrics, and to establish the utility of tractography as a predictive tool. There is a need for more robust acquisition and analysis methods to improve the accuracy of assessing development of white matter pathways.
Brain microstructure and morphology of very preterm-born infants at term equivalent age: Associations with motor and cognitive outcomes at 1 and 2 years.
Publisher: Elsevier BV
Date: 11-2020
Structural remodeling of gray matter astrocytes in the neonatal pig brain after hypoxia/ischemia
Publisher: Wiley
Date: 15-07-2009
DOI: 10.1002/GLIA.20911
Abstract: Astrocytes play a vital role in the brain their structural integrity and sustained function are essential for neuronal viability, especially after injury or insult. In this study, we have examined the response of astrocytes to hypoxia/ischemia (H/I), employing multiple methods (immunohistochemistry, iontophoretic cell injection, Golgi-Kopsch staining, and D-aspartate uptake) in a neonatal pig model of H/I. We have identified morphological changes in cortical gray matter astrocytes in response to H/I. Initial astrocytic changes were evident as early as 8 h post-insult, before histological evidence for neuronal damage. By 72 h post-insult, astrocytes exhibited significantly fewer processes that were shorter, thicker, and had abnormal terminal swellings, compared with astrocytes from control brains that exhibited a complex structure with multiple fine branching processes. Quantification and image analysis of astrocytes at 72 h post-insult revealed significant decreases in the average astrocyte size, from 686 microm(2) in controls to 401 microm(2) in H/I brains. Sholl analysis revealed a significant decrease (>60%) in the complexity of astrocyte branching between 5 and 20 microm from the cell body. D-Aspartate uptake studies revealed that the H/I insult resulted in impaired astrocyte function, with significantly reduced clearance of the glutamate analog, D-aspartate. These results suggest that astrocytes may be involved in the pathophysiological events of H/I brain damage at a far earlier time point than first thought. Developing therapies that prevent or reverse these astrocytic changes may potentially improve neuronal survival and thus might be a useful strategy to minimize brain damage after an H/I insult.
Maturation of Corpus Callosum Anterior Midbody Is Associated with Neonatal Motor Function in Eight Preterm-Born Infants
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/359532
Abstract: Background . The etiology of motor impairments in preterm infants is multifactorial and incompletely understood. Whether corpus callosum development is related to impaired motor function is unclear. Potential associations between motor-related measures and diffusion tensor imaging (DTI) of the corpus callosum in preterm infants were explored. Methods . Eight very preterm infants (gestational age of 28–32 weeks) underwent the Hammersmith neonatal neurological examination and DTI assessments at gestational age of 42 weeks. The total Hammersmith score and a motor-specific score (sum of Hammersmith motor subcategories) were calculated. Six corpus callosum regions of interest were defined on the mid-sagittal DTI slice—genu, rostral body, anterior midbody, posterior midbody, isthmus, and splenium. The fractional anisotropy (FA) and mean diffusivity (MD) of these regions were computed, and correlations between these and Hammersmith measures were sought. Results . Anterior midbody FA measures correlated positively with total Hammersmith (rho = 0.929 , P = 0.001 ) and motor-specific scores (rho = 0.857 , P = 0.007 ). Total Hammersmith scores also negatively correlated with anterior midbody MD measures (rho = − 0.714 , P = 0.047 ). Discussion . These results suggest the integrity of corpus callosum axons, particularly anterior midbody axons, is important in mediating neurological functions. Greater callosal maturation was associated with greater motor function. Corpus callosum DTI may prove to be a valuable screening or prognostic marker.
Safety of sibling cord blood cell infusion for children with cerebral palsy
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.JCYT.2022.01.003
Abstract: Cerebral palsy (CP) is a nonprogressive neurological disorder and the most common physical disability of childhood. There is no cure for CP, but stem cells have the potential to improve brain injury and hence function. This phase 1 clinical trial investigated the safety of the intravenous infusion of full-matched sibling cord blood cells for children with CP aged 1 to 16 years. Preliminary efficacy outcomes were also investigated. Twelve participants received 12/12 HLA-matched sibling cord blood cell infusions. One treatable serious adverse reaction to cryoprotectant was observed, and no adverse reactions occurred beyond 24 h after infusion. Gross motor function measure (GMFM-66) scores did not improve compared with baseline beyond what could be expected from developmental levels, and participants had varied changes in the Quality of Upper Extremity Skills Test (QUEST) and Vineland Adaptive Behavior Scales (VABS-II) scores. In conclusion, matched sibling cord blood cell infusion for children with CP is relatively safe when conducted in an appropriate facility. Australian and New Zealand Clinical Trials Registry (ACTRN12616000403437) and Clinicaltrials.gov (NCT03087110).
Classification of fetal movement accelerometry through time-frequency features
Publisher: IEEE
Date: 12-2014
Neurovascular unit alterations in the growth restricted newborn are improved following ibuprofen treatment
Publisher: Cold Spring Harbor Laboratory
Date: 17-02-2021
DOI: 10.1101/2021.02.15.431329
Abstract: Fetal brain development is particularly vulnerable to the effects of fetal growth restriction (FGR) and abnormal neurodevelopment is common in the FGR infant. Adverse outcomes range from behavioural and learning disorders through to cerebral palsy. Unfortunately, no treatment exists to protect the FGR newborn brain. Recent evidence suggests inflammation may play a key role in the mechanism responsible for the progression of brain impairment in the FGR newborn, including disruption to the neurovascular unit (NVU). We explored whether ibuprofen, a non-steroidal anti-inflammatory drug, could reduce NVU disruption and brain impairment in the FGR newborn. We used a preclinical piglet model of growth restriction in which FGR occurs spontaneously. Newborn FGR (birthweight th centile) and normally grown piglets were collected on day of birth and oral ibuprofen was administered daily for 3 days (20mg/kg/day, day 1 and 10mg/kg/day days 2 and 3). FGR brains demonstrated an inflammatory state, with changes to glial morphology (astrocytes and microglia), and blood brain barrier disruption, assessed by IgG and albumin leakage into the brain parenchyma and a decrease in blood vessel density. Loss of interaction between astrocytic end-feet and blood vessels was evident in the microvasculature where leakage was present, suggestive of structural deficits to the NVU. Ibuprofen treatment reduced the pro-inflammatory response in FGR piglets, reducing levels of pro-inflammatory cytokines and number of activated microglia and astrocytes associated with blood vessels. Ibuprofen treatment also attenuated albumin and IgG leakage. There were no alterations to angiogenesis, or blood vessel proliferation in treated-FGR piglets. These findings suggest postnatal administration of ibuprofen on day of birth modulates the inflammatory state, allowing for stronger interaction between vasculature and astrocytic end-feet to restore NVU integrity. These changes to the FGR brain microenvironment may be key to neuroprotection.
Developmental Changes in Expression of GABA<sub>A</sub> Receptor Subunits α<sub>1</sub>, α<sub>2</sub>, and α<sub>3</sub> in the Pig Brain
Publisher: S. Karger AG
Date: 2017
DOI: 10.1159/000468926
Abstract: GABA is a major neurotransmitter in the mammalian brain. In the mature brain GABA exerts inhibitory actions via the GABA sub A /sub receptor (GABA sub A /sub R) however, in the immature brain GABA provides much of the excitatory drive. We examined the expression of 3 predominant GABA sub A /sub α-subunit proteins in the pig brain at various pre- and postnatal ages. Brain tissue was collected from piglets born via caesarean section at preterm ages 91, 97, 100, and 104 days' gestational age (GA), at term equivalent (114 days' GA, caesarean section) and at term, postnatal day 0 (P0) (spontaneous delivery, term = 115 days). Tissue was obtained from piglets at P4 and P7. Adult tissue from sows was collected postmortem after caesarean section. In all cortical regions and basal ganglia (1) α sub /sub exhibited a significant increase in protein expression at 100 days' GA, (2) α sub /sub expression decreased with age after 100 days' GA, (3) α sub /sub increased with age, with peak expression at P7 in cortices, hippoc us, and thalamus, and (4) α sub /sub protein expression remained relatively constant across the ages examined. The subunit expression of α sub /sub was most abundant at preterm ages, with α sub /sub the predominant subunit expressed postnatally. Immunofluorescent labelling revealed α sub /sub expression on the somatic membranes of pyramidal cells in the cortex and hippoc us, and in the cerebellar Purkinje cells. Positive α sub /sub labelling was apparent on interneurones in the cortex and hippoc us. The switch between dominant α-subunits may coincide with the functional change in GABAergic neurotransmission from excitation to inhibition. Brain growth in the pig closely reflects that in the term human, making the pig a valuable non-primate model for studying development and the effects of insults on the perinatal brain.
GLAST1b, the exon-9 skipping form of the glutamate-aspartate transporter EAAT1 is a sensitive marker of neuronal dysfunction in the hypoxic brain
Publisher: Elsevier BV
Date: 10-2007
DOI: 10.1016/J.NEUROSCIENCE.2007.08.011
Abstract: In normal brain, we previously demonstrated that the exon-9 skipping form of glutamate-aspartate transporter (GLAST which we refer to as GLAST1b) is expressed by small populations of neurons that appear to be sick or dying and suggested that these cells were subject to inappropriate local glutamate-mediated excitation. To test this hypothesis we examined the expression of GLAST1b in the hypoxic pig brain. In this model glial glutamate transporters such as GLAST and glutamate transporter 1 (GLT-1) are down-regulated in susceptible regions, leading to regional loss of glutamate homeostasis and thus to brain damage. We demonstrate by immunohistochemistry that in those brain regions where astroglial glutamate transporters are lost, GLAST1b expression is induced in populations of neurons and to a lesser extent in some astrocytes. These neurons were also immunolabeled by antibodies against the carboxyl-terminal region of GLAST but did not label with antibodies directed against the amino-terminal region. Our Western blotting data indicate that GLAST1b expressed by neurons lacks the normal GLAST amino-terminal region and may be further cleaved to a smaller approximately 30-kDa fragment. We propose that GLAST1b represents a novel and sensitive marker for the detection of neurons at risk of dying in response to hypoxic and other excitotoxic insults and may have wider applicability in experimental and clinical contexts.
Diffusion MRI of the neonate brain: acquisition, processing and analysis techniques
Publisher: Springer Science and Business Media LLC
Date: 18-08-2012
DOI: 10.1007/S00247-012-2427-X
Abstract: Diffusion MRI (dMRI) is a popular noninvasive imaging modality for the investigation of the neonate brain. It enables the assessment of white matter integrity, and is particularly suited for studying white matter maturation in the preterm and term neonate brain. Diffusion tractography allows the delineation of white matter pathways and assessment of connectivity in vivo. In this review, we address the challenges of performing and analysing neonate dMRI. Of particular importance in dMRI analysis is adequate data preprocessing to reduce image distortions inherent to the acquisition technique, as well as artefacts caused by head movement. We present a summary of techniques that should be used in the preprocessing of neonate dMRI data, and demonstrate the effect of these important correction steps. Furthermore, we give an overview of available analysis techniques, ranging from voxel-based analysis of anisotropy metrics including tract-based spatial statistics (TBSS) to recently developed methods of statistical analysis addressing issues of resolving complex white matter architecture. We highlight the importance of resolving crossing fibres for tractography and outline several tractography-based techniques, including connectivity-based segmentation, the connectome and tractography mapping. These techniques provide powerful tools for the investigation of brain development and maturation.
Time-frequency characterization of tri-axial accelerometer data for fetal movement detection
Publisher: IEEE
Date: 12-2011
The Breathing for Life Trial: A randomised controlled trial of fractional exhaled nitric oxide (FENO)-based management of asthma during pregnancy and its impact on perinatal outcomes and infant and childhood respiratory health
Publisher: Springer Science and Business Media LLC
Date: 17-05-2016
Alarm settings for the Marquette 8000 pulse oximeter to prevent hyperoxic and hypoxic episodes
Publisher: Wiley
Date: 04-1999
DOI: 10.1046/J.1440-1754.1999.00317.X
Abstract: To determine safe and appropriate alarm limits for the Marquette 8000 pulse oximeter to prevent hyperoxic and hypoxic episodes in neonates. It is necessary to define these limits for each brand of oximeter because of the variance in nonuser adjustable calibration algorithms used in pulse oximeters. Oxygen saturation values obtained from a Marquette 8000 pulse oximeter (SpO2) were compared with simultaneous arterial blood gas PaO2 values obtained from blood gas analysis, for 322 s les in 24 consecutive neonates (median 30 weeks' gestation). In order to prevent 95% of hyperoxic episodes (PaO2 > 90 mmHg), the upper alarm limit was 95% SpO2. Similarly, to prevent 95% of hypoxic episodes (PaO2 < 40 mmHg), the lower alarm limit was 95% SpO2. A sensitivity lower than 95% had to be accepted to develop an alarm range which prevented both hyperoxic and hypoxic episodes. To maintain PaO2 values between 40 and 90 mmHg, an appropriate alarm range of 94-97% SpO2 (90% sensitivity, 28% specificity) was established. The relative merits of high sensitivity versus high specificity should be considered when determining appropriate alarm limits. Alarm limits which represent a balance between sensitivity and specificity will minimise false alarms and provide a clinically practical range. It would be useful for this type of information to be available for each brand of oximeter, to assist the user in determining appropriate alarm settings.
Loss of glial glutamate transporters and induction of neuronal expression of GLT-1B in the hypoxic neonatal pig brain
Publisher: Elsevier BV
Date: 10-2004
DOI: 10.1016/J.DEVBRAINRES.2004.06.019
Abstract: The homeostasis of glutamate is critical to normal brain function deficiencies in the regulation of extracellular glutamate are thought to be a major determinant of damage in hypoxic brains. Extracellular levels of glutamate are regulated mainly by plasmalemmal glutamate transporters. We have evaluated the distribution of the glutamate transporter GLAST and two splice variants of GLT-1 in the hypoxic neonatal pig brain using this as model of neonatal humans. In response to severe hypoxic insults, we observe a rapid loss of two glial glutamate transporters from specific brain regions, such as the CA1 region of the hippoc us, but not the dentate gyrus. The spatial distribution of loss accords with patterns of damage in these brains. Conversely, we demonstrate that hypoxia evokes the expression of a splice variant of GLT-1 in neurons. We suggest that this expression may be induced in response to elevated extracellular glutamate around these neurons, and that this splice variant may represent a useful marker for direct quantification of the extent of likely neuronal damage in hypoxic brains.
Automatic seizure detection based on the combination of newborn multi-channel EEG and HRV information
Publisher: Springer Science and Business Media LLC
Date: 07-10-2012
Clinicians' perceptions of placing a fetal oximetry sensor
Publisher: Wiley
Date: 12-2000
DOI: 10.1046/J.1440-1762.2000.00379.X
Abstract: The aim of this study was to determine clinicians' perceptions of placing a fetal oximetry sensor. A survey was developed seeking details of staff category, birth suite experience, previous sensor placement, ease of application and use of epidural analgesia. Following staff feedback, the survey was revised from asking clinicians to rate women's comfort during sensor placement, to a visual analogue scale (VAS) of the clinician's assessment of the women's pain during sensor placement. Survey validity was sought from experts during development and for specific questions using item-total correlation in this analysis. Ease of sensor placement (n = 131) was rated as good or excellent 71% of the time. Clinicians rated women's comfort during sensor placement as good or excellent in 90% of cases. Median pain VAS was 0 (range 0-7.5). Item-total correlations of survey questions were all significant. Fetal oximetry sensor placement was rated well by clinicians in this purpose-designed survey.
Missing out on precious time: Extending paid parental leave for parents of babies admitted to neonatal intensive or special care units for prolonged periods
Publisher: Wiley
Date: 27-11-2022
DOI: 10.1111/JPC.15836
Abstract: In Australia, approximately 18% of newborn babies are admitted to a neonatal intensive or special care nursery. While most babies admitted to a neonatal intensive or special care nursery are discharged home within a few weeks, around 6% of babies spend more than 2 weeks in hospital. For the parents of these babies, much of their leave entitlements (Australian Government Paid Parental Leave Scheme is up to18 weeks for the primary care giver and up to 2 weeks for partners) are used before their baby comes home from hospital. The time babies and parents spend together in the early developmental period, during the hospitalisation and when the baby is discharged home, is crucial for optimal child development and bonding. Yet care givers who have a baby admitted to neonatal intensive or special care for extended periods are not currently entitled to any extra parental leave payments in Australia. We recommend the Australian Paid Parental Leave Act is changed to allow primary carers access to 1 week of extra parental leave pay for every week in hospital (for babies admitted to hospital for more than 2 weeks), up to a maximum of 14 weeks. For fathers and partners of these babies, we recommend an additional 2 weeks of extra Dad and Partner Pay. The net cost, taking into account likely productivity benefits, would be less than 1.5% of the current cost of the scheme and would improve health and socio‐economic outcomes for the baby, family and society.
Measurement of extracellular fluid volume in the neonate using multiple frequency bio-impedance analysis
Publisher: IOP Publishing
Date: 05-2000
DOI: 10.1088/0967-3334/21/2/305
Abstract: Bioelectrical impedance analysis may be useful for cot-side monitoring of fluid balance in the neonatal intensive care unit (NICU). However the presence of cardio-respiratory monitoring equipment, non-ideal electrode placement and inability to obtain accurate crown-heel measurements may interfere with the ability to obtain reliable impedance data in this setting. This study aimed to investigate the effects of these factors on impedance analysis and to develop a prediction equation for extracellular fluid volume in the neonate. The study found that cardio respiratory monitoring had no significant effect on multi-frequency impedance measurements. Placement of current delivering electrodes on the ventral rather than dorsal surfaces improved separation of current and voltage electrodes but did not alter impedance results. Contralateral measurements were not significantly different to ipsilateral measurements. In 24 infants, extracellular fluid volume was measured using corrected bromide space (CBS) and simultaneous impedance analysis was performed. There was good correlation between CBS and the impedance quotient FF2/Ro where F is foot length and R0 is resistance at zero frequency. The study concludes that despite many potential difficulties associated with impedance analysis in the NICU, reliable measurements of impedance can be obtained and further work to validate prediction equations for ECF is warranted.
Morphological changes in white matter astrocytes in response to hypoxia/ischemia in the neonatal pig
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.BRAINRES.2010.01.010
Abstract: White matter damage is a significant problem in the human pre-term baby. Damage to white matter is usually associated with injury or insults to babies born prematurely, typically before 32weeks' gestation, however there is increasing evidence of both grey and white matter damage occurring after 32weeks' gestation. Astrocytes play a vital role in white matter, regulating molecules such as glutamate in the extracellular space and preventing excitotoxic damage to neighbouring oligodendrocytes and axons. We have previously described dramatic changes in grey matter astrocytes in response to a hypoxic/ischemic (H/I) insult around the time of birth. In this study, we have used GFAP immunohistochemistry and Golgi-Kopsch staining to examine the morphology of white matter astrocytes in control neonatal pig brains, and in the brains of animals exposed to the same (perinatal) H/I insult. We demonstrate that the areal percentage of the section occupied by GFAP-immunoreactive processes and cell bodies is significantly decreased (by 46%, P<0.0001) in subcortical white matter from H/I brains. This loss of GFAP was accompanied by alterations in astrocyte morphology and an overall decrease in the size (field of section occupied by an in idual astrocyte) of white matter astrocytes from 649microm(2) to 426microm(2), as revealed by Golgi-Kopsch staining and image analysis. These data suggest that astrocytes may contribute to the pathology of white matter damage following an H/I insult around the time of birth, and suggest that astrocytes may offer a novel target for therapies to improve outcomes after H/I.
Effect of the dose volume of perfluorocarbon when starting partial liquid ventilation
Publisher: Wiley
Date: 03-09-2010
DOI: 10.1111/J.1440-1754.2010.01828.X
Abstract: Very preterm neonates are prone to brain injury if cerebral blood flow fluctuates. Partial liquid ventilation (PLV) may benefit any lung disease but giving 30 mL/kg of perfluorocarbon when starting PLV increases cortical cerebral blood flow velocity. We aimed to determine if varying the initial dose of perfluorocarbon alters the effect on cerebral blood flow velocity when starting PLV. In this randomised, controlled trial with historical comparison 24 preterm lambs received one of three loading doses of intratracheal perfluorocarbon liquid over 20 min when starting PLV: 20, 30 or 40 mL/kg. Data on respiratory mechanics, haemodynamics and cerebral blood flow velocity, measured with laser Doppler, were collected continuously for 30 min from the start of dosing. Cortical cerebral blood flow velocity increased over time in all three groups (two-way ANOVA, P= 0.007). There was no difference between groups (two-way ANOVA, P= 0.26). There was no difference between groups in cortical cerebral blood flow velocity variability (P= 0.68), blood pressure (P= 0.96) or heart rate (P= 0.46). The was no statistically significant difference in PaCO(2) between groups measured at baseline and at 30 min after starting PLV (P= 0.51). Cortical cerebral blood flow velocity and its variability are not affected by varying doses of tracheal perfluorocarbon (20, 30 or 40 mL/kg) at the start of PLV in preterm lambs.
The effect of intrapartum fetal pulse oximetry, in the presence of a nonreassuring fetal heart rate pattern, on operative delivery rates: A multicenter, randomized, controlled trial (the FOREMOST trial)
Publisher: Elsevier BV
Date: 03-2006
DOI: 10.1016/J.AJOG.2005.08.051
Abstract: The objective of the study was to compare operative delivery rates for nonreassuring fetal status between 2 groups of laboring women: those having conventional cardiotocograph monitoring and those having cardiotocograph monitoring plus fetal pulse oximetry. The intrapartum fetal oximetry prospective, multicenter, randomized, controlled trial (the FOREMOST trial) was conducted in 4 Australian maternity hospitals. The primary outcome was operative birth rates for nonreassuring fetal status. There was a statistically significant 23% relative risk reduction in operative delivery for nonreassuring fetal status in the fetal pulse oximetry + cardiotocograph group (n = 75 of 305, 25%), compared with those in the cardiotocograph-only group (n = 95/295, 32%) (relative risk 0.77, 95% confidence interval 0.599, 0.999, P = .048). There were no significant between-group differences in overall operative births (fetal pulse oximetry + cardiotocograph group 73%, cardiotocograph-only group 71%, relative risk 1.04, 95% confidence interval 0.94, 1.15, P = .478) or neonatal outcomes. The use of fetal pulse oximetry to augment fetal well-being assessment during labor resulted in a statistically significant reduction in the operative intervention for nonreassuring fetal status, compared with the use of conventional cardiotocograph monitoring alone. This reduction was achieved with no significant difference in neonatal outcomes.
Short-Term Dose–Response Characteristics of 2-Iminobiotin Immediately Postinsult in the Neonatal Piglet After Hypoxia-Ischemia
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2013
DOI: 10.1161/STROKEAHA.112.677922
Abstract: To determine the optimal dose of 2-iminobiotin (2-IB) for the treatment of moderate to severe asphyxia in a neonatal piglet model of hypoxia-ischemia. Newborn piglets were subjected to a 30-minute hypoxia-ischemia insult and randomly treated with vehicle or 2-IB (0.1 mg/kg, 0.2 mg/kg, or 1.0 mg/kg). aEEG background and seizure activity were scored after hypoxia-ischemia every 4 h until 24 h and at 48 h and neurobehavioral scores were obtained. Brain tissue was collected and processed for analysis of caspase-3 activity, histology, and tyrosine nitration. A dose range of 0.1 to 1.0 mg/kg/dose of 2-IB improved short-term outcome as demonstrated by an increased survival with a normal aEEG and decreased nitrotyrosine staining in the 2-IB–treated animals, indicating decreased cellular damage. Neurobehavior, caspase-3 activity in thalamus, and histology scores were not significantly different. Based on survival with a normal aEEG, 0.2 mg/kg 2-IB is likely to be the most appropriate dose for use in future clinical trials in neonates with perinatal hypoxia-ischemia.
Diagnostic accuracy of early magnetic resonance imaging to determine motor outcomes in infants born preterm: a systematic review and meta‐analysis
Publisher: Wiley
Date: 29-11-2017
DOI: 10.1111/DMCN.13611
Abstract: To examine the diagnostic ability of early magnetic resonance imaging (MRI <36wks postmenstrual age) to detect later adverse motor outcomes or cerebral palsy (CP) in infants born preterm. Studies of infants born preterm with MRI earlier than 36 weeks postmenstrual age and quantitative motor data or a diagnosis of CP at or beyond 1 year corrected age were identified. Study details were extracted and meta-analyses performed where possible. Quality of included studies was evaluated with the QUADAS-2 (a revised tool for the quality assessment of diagnostic accuracy studies). Thirty-one articles met the inclusion criteria, five of which reported diagnostic accuracy and five reported data sufficient for calculation of diagnostic accuracy. Early structural MRI global scores detected a later diagnosis of CP with a pooled sensitivity of 100% (95% confidence interval [CI] 86-100) and a specificity of 93% (95% CI 59-100). Global structural MRI scores determined adverse motor outcomes with a pooled sensitivity of 89% (95% CI 44-100) and a specificity of 98% (95% CI 90-100). White matter scores determined adverse motor outcomes with a pooled sensitivity of 33% (95% CI 20-48) and a specificity of 83% (95% CI 78-88). Early structural MRI has reasonable sensitivity and specificity to determine adverse motor outcomes and CP in infants born preterm. Greater reporting of diagnostic accuracy in studies examining relationships with motor outcomes and CP is required to facilitate clinical utility of early MRI. Early magnetic resonance imaging (MRI) has reasonable sensitivity and specificity to determine later adverse motor outcomes and cerebral palsy (CP). Detection of infants who progressed to CP was stronger than motor outcomes. Global MRI scores determined adverse motor outcomes more accurately than white matter scores. Few studies report diagnostic accuracy of early MRI findings. Diagnostic accuracy is required to draw clinically meaningful conclusions from early MRI studies.
Effect of maternal epidural analgesia on fetal intrapartum oxygen saturation
Publisher: Georg Thieme Verlag KG
Date: 2002
DOI: 10.1055/S-2002-25312
Abstract: The use of maternal epidural analgesia in labor may be associated with nonreassuring fetal heart rate (FHR) patterns. Fetal oxygen saturation (FSpO2) monitoring may improve assessment of fetal well-being during this time. Mean FSpO2 values were compared over seven 5-minute epochs: 5 minutes prior to an epidural event (combined insertion of epidural/top-up epidural analgesia and infusion pump bolus), to 30 minutes following the event, including possible effects of maternal position and FHR pattern on FSpO2 values. Mean FSpO2 values were significantly different between the 5 minutes prior (49.5%) versus 16-20 minutes (44.3%, p <0.05), 21-25 minutes (43%, p <0.01), and 26-30 minutes (43.8%, p <0.05) epochs and 6-10 minutes (48.3%) versus 21-25 minutes (43%, p <0.05) epochs, but were not influenced by FHR pattern or maternal position. There were no differences in mean FSpO2 values following administration of an epidural infusion bolus. We conclude that fetal oxygenation was affected following initial or top-up epidural analgesia and that fetal intrapartum pulse oximetry may be useful in assessing fetal status following these events.
Diagnostic accuracy of the Hammersmith Neonatal Neurological Examination in predicting motor outcome at 12 months for infants born very preterm
Publisher: Wiley
Date: 22-01-2023
DOI: 10.1111/DMCN.15512
Abstract: To evaluate the predictive validity of the Hammersmith Neonatal Neurological Examination (HNNE) performed early (at 32 weeks postmenstrual age) and at term‐equivalent age (TEA) for 12‐month motor outcomes in infants born very preterm. This was a diagnostic study using data from a prospective birth cohort. A total of 104 infants born preterm at less than 31 weeks gestational age (males n = 61 mean = 28 weeks 1 day [SD 1 week 6 days], range 23 weeks 1 day–30 weeks 6 days) underwent HNNE early and at TEA, which were scored by comparison with term data. Motor outcomes at 12 months corrected age were determined using the Bayley Scales of Infant and Toddler Development, Third Edition (scores ≤85). Cut‐off points were determined using receiver operating characteristic curves. Sixteen (15%) infants born preterm had motor impairment at 12 months corrected age. The HNNE total score cut‐off points with the best combination of sensitivity and specificity at early and TEA assessments were 15.2 or lower (sensitivity 77%, 95% confidence interval [CI] = 46%–95% specificity 74%, 95% CI = 63%–83%) and 23.5 or lower (sensitivity 67%, 95% CI = 38%–88% specificity 66%, 95% CI = 54%–76%) respectively. The most predictive subscale at the early assessment was reflexes (sensitivity 86%, 95% CI = 57%–98% specificity 62%, 95% CI = 51%–72% cut‐off point ≤3) at TEA, it was spontaneous movements (sensitivity 73%, 95% CI = 45%–92% specificity 60%, 95% CI = 48%–70% cut‐off point ≤2). The HNNE provides moderate predictive accuracy for motor outcome at 12 months corrected age in infants born very preterm. Although modest at both time points, early assessment had stronger predictive ability for motor outcomes than TEA when scored using term data, highlighting the value of performing the HNNE earlier in the neonatal period. Performing HNNE earlier may assist risk stratification when planning follow‐up services.
Automating Quantitative Measures of an Established Conventional MRI Scoring System for Preterm-Born Infants Scanned between 29 and 47 Weeks’ Postmenstrual Age
Publisher: American Society of Neuroradiology (ASNR)
Date: 19-08-2021
DOI: 10.3174/AJNR.A7230
Brain Outcomes in Runted Piglets: A Translational Model of Fetal Growth Restriction
Publisher: S. Karger AG
Date: 2022
DOI: 10.1159/000523995
Abstract: Fetal growth restriction (FGR) is associated with long-term neurodevelopmental disabilities including learning and behavioral disorders, autism, and cerebral palsy. Persistent changes in brain structure and function that are associated with developmental disabilities are demonstrated in FGR neonates. However, the mechanisms underlying these changes remain to be determined. There are currently no therapeutic interventions available to protect the FGR newborn brain. With the wide range of long-term neurodevelopmental disorders associated with FGR, the use of an animal model appropriate to investigating mechanisms of injury in the FGR newborn is crucial for the development of effective and targeted therapies for babies. Piglets are ideal animals to explore how perinatal insults affect brain structure and function. FGR occurs spontaneously in the piglet, unlike other animal models that require surgical or chemical intervention, allowing brain outcomes to be studied without the confounding impacts of experimental interventions. The FGR piglet mimics many of the human pathophysiological outcomes associated with FGR including asymmetrical growth restriction with brain sparing. This review will discuss the similarities observed in brain outcomes between the FGR human and FGR piglet from a magnetic resonance imaging in the living and a histological perspective. FGR piglet studies provide the opportunity to determine and track mechanisms of brain injury in a clinically relevant animal model of FGR. Findings from these FGR piglet studies may provide critical information to rapidly translate neuroprotective interventions to clinic to improve outcomes for newborn babies.
PPREMO: a prospective cohort study of preterm infant brain structure and function to predict neurodevelopmental outcome
Publisher: Springer Science and Business Media LLC
Date: 16-09-2015
Mother-Very Preterm Infant Relationship Quality: RCT of Baby Triple P
Publisher: Springer Science and Business Media LLC
Date: 20-09-2016
EFFICACY OF PREVENTATIVE PARENTING INTERVENTIONS FOR PARENTS OF PRETERM INFANTS ON LATER CHILD BEHAVIOR: A SYSTEMATIC REVIEW AND META‐ANALYSIS
Publisher: Wiley
Date: 20-10-2014
DOI: 10.1002/IMHJ.21480
Abstract: The aim of this systematic review was to determine the efficacy of parenting interventions for parents of preterm infants to improve child behavior. Randomized controlled trials (RCTs) of parenting interventions for parents of preterm infants were included. Searchers were conducted of PubMed from 1951 to April 2013, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 1982 to April 2013, Scopus from 1966 to April 2013, PsycINFO from 1840 to April 2013, the Web of Science, and the Cochrane Library. Twelve RCTs were identified that assessed child behavior. Of these studies, only data from three were able to be pooled for meta-analysis: the Infant Health and Development Program (IHDP) at 3 years, the Mother-Infant Transaction Program (modified MITP-M) at 5 years, and the Victorian Infant Brain Studies (VIBeS Plus) at 4 years. Outcome from this analysis revealed a small, but significant, effect on child behavior favoring the intervention (95% CI: 0.08-0.32 p = .001). There is evidence that preterm parenting interventions can improve child behavior. Streamlined interventions such as MITP-M and VIBeS Plus that have a strong focus on the mother-infant relationship may have greatest potential.
Review: Neuroinflammation in intrauterine growth restriction
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.PLACENTA.2016.11.012
Abstract: Disruption to the maternal environment during pregnancy from events such as hypoxia, stress, toxins, inflammation, and reduced placental blood flow can affect fetal development. Intrauterine growth restriction (IUGR) is commonly caused by chronic placental insufficiency, interrupting supply of oxygen and nutrients to the fetus resulting in abnormal fetal growth. IUGR is a major cause of perinatal morbidity and mortality, occurring in approximately 5-10% of pregnancies. The fetal brain is particularly vulnerable in IUGR and there is an increased risk of long-term neurological disorders including cerebral palsy, epilepsy, learning difficulties, behavioural difficulties and psychiatric diagnoses. Few studies have focused on how growth restriction interferes with normal brain development in the IUGR neonate but recent studies in growth restricted animal models demonstrate increased neuroinflammation. This review describes the role of neuroinflammation in the progression of brain injury in growth restricted neonates. Identifying the mediators responsible for alterations in brain development in the IUGR infant is key to prevention and treatment of brain injury in these infants.
Cerebral blood flow is not affected during perfluorocarbon dosing with volume‐controlled ventilation
Publisher: Wiley
Date: 19-06-2013
DOI: 10.1111/JPC.12297
Abstract: Perfluorocarbon administration increases cerebral blood flow. This can be mitigated by preventing a rise in carbon dioxide by adjusting pressure-controlled ventilation. Volume-controlled ventilation should prevent increases in arterial carbon dioxide and cerebral blood flow. This study aims to determine if cerebral blood flow is increased during administration of 10 mL/kg of perfluorocarbon while using volume-controlled ventilation. Two New Zealand white rabbits, ventilated with volume-control, were each allocated to six dosing events where each dosing event was randomly allocated to one of two dosing strategies: a control group - given a sham dose of air (10 mL/kg) over 20 min or a partial liquid ventilation group - given 10 mL/kg FC-77 slowly over 20 min. Data were recorded for 1 min before and 30 min after the start of each dosing event. No adjustment of ventilation (except fraction of inspired oxygen) was allowed during each dosing event. There were no significant changes over time and no differences between groups for carotid blood flow (P = 0.48 at the end of the dose). There were slight increases in cortical cerebral blood flow in both groups there was no statistically significant difference between groups (P = 0.56 at end dose and P = 0.49 at time of maximum difference). There was no difference between groups for the variability in carotid blood flow or cortical cerebral blood flow. Cerebral blood flow was not significantly increased during administration of a dose of 10 mL/kg of perfluorocarbon during commencement of partial liquid ventilation when using volume-controlled ventilation.
Generalised phase synchrony within multivariate signals: An emerging concept in time-frequency analysis
Publisher: IEEE
Date: 03-2012
A cost-effectiveness analysis of the intrapartum fetal pulse oximetry multicentre randomised controlled trial (the FOREMOST trial)
Publisher: Wiley
Date: 25-08-2006
DOI: 10.1111/J.1471-0528.2006.01044.X
Abstract: To report an economic analysis of the Australian intrapartum fetal pulse oximetry (FPO) multicentre randomised controlled trial (the FOREMOST trial), which examined whether adding FPO to conventional cardiotocographic (CTG) monitoring (intervention group) was cost-effective in reducing operative delivery rates for non-reassuring fetal status compared with the use of CTG alone (control group). Cost-effectiveness analysis of the FOREMOST trial. Four Australian maternity hospitals, each with more than 4000 births/year. Women in labour at > or =36 weeks of gestation, with a non-reassuring CTG. Costs were for treatment-related expenses, incorporating diagnosis-related grouping costs and direct costs (including fetal monitoring). Incremental cost-effectiveness ratio (ICER) and cost-effectiveness plane were calculated, and sensitivity analysis was conducted. The primary outcome was that of the clinical trial: operative delivery for non-reassuring fetal status avoided in the intervention group relative to that in the control group. The ICER. The ICER demonstrated a saving of $A813 for each operative birth for non-reassuring fetal status averted by the addition of FPO to CTG monitoring compared with the use of CTG monitoring alone. The addition of FPO to CTG monitoring represented a less costly and more effective use of resources to reduce operative delivery rates for non-reassuring fetal status than the use of conventional CTG monitoring alone.
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