Euan Wallace

BackgroundIn July 2017, the State of Victoria’s largest maternity service implemented a new clinical guideline to reduce the rates of stillbirth at term for South Asian women.ObjectiveThis study aimed to evaluate the impact of offering fetal surveillance from 39 weeks to South Asian-born women on rates of stillbirth and neonatal and obstetrical interventions.Study DesignThis was a cohort study of all women receiving antenatal care at 3 large metropolitan university-affiliated teaching hospitals in Victoria, who gave birth in the term period between January 2016 and December 2020. Differences in rates of stillbirth, neonatal deaths, perinatal morbidities, and interventions after July 2017 were determined. Multigroup interrupted time-series analysis was used to assess changes in rates of stillbirth and induction of labor.ResultsA total of 3506 South Asian-born women gave birth before, and 8532 after the change in practice …

Objective To evaluate whether induction of labor (IOL) is associated with cesarean birth (CB) and perinatal mortality in uncomplicated first births at term compared with expectant management outside the confines of a randomized controlled trial. Methods Population‐based retrospective cohort study of all births in Victoria, Australia, from 2010 to 2018 (n = 640,191). Preliminary analysis compared IOL at 37 weeks with expectant management at that gestational age and beyond for uncomplicated pregnancies. Similar comparisons were made for IOL at 38, 39, 40, and 41 weeks of gestation and expectant management. The primary analysis repeated these comparisons, limiting the population to nulliparous women with uncomplicated pregnancies and excluding those with a medical indication for IOL. We compared perinatal mortality between groups using Chi‐square tests and multivariable logistic regression for …

BackgroundPolicy responses to COVID-19 in Victoria, Australia over 2020–2021 have been supported by evidence generated through mathematical modelling. This study describes the design, key findings, and process for policy translation of a series of modelling studies conducted for the Victorian Department of Health COVID-19 response team during this period.MethodsAn agent-based model, Covasim, was used to simulate the impact of policy interventions on COVID-19 outbreaks and epidemic waves. The model was continually adapted to enable scenario analysis of settings or policies being considered at the time (e.g. elimination of community transmission versus disease control). Model scenarios were co-designed with government, to fill evidence gaps prior to key decisions.ResultsUnderstanding outbreak risk following incursions was critical to eliminating community COVID-19 transmission. Analyses …

Background We proposed a Phase I dose escalation trial to assess the safety of allogeneic human amniotic epithelial cells (hAECs) in stroke patients with a view to informing the design for a Phase II trial. Methods The design is based on 3 + 3 dose escalation design with additional components for measuring MR signal of efficacy as well as the effect of hAECs (2–8 × 106/kg, i.v.) on preventing immunosuppression after stroke. Results Eight patients (six males) were recruited within 24 h of ischemic stroke onset and were infused with hAECs. We were able to increase the dose of hAECs to 8 × 106 cells/kg (2 × 106/kg, n = 3; 4 × 106/kg, n = 3; 8 × 106/kg, n = 2). The mean age is 68.0 ± 10.9 (mean ± SD). The frequencies of hypertension and hyperlipidemia were 87.5%, diabetes was 37.5%, atrial fibrillation was 50%, ischemic heart disease was 37.5% and ever-smoker was 25%. Overall, baseline NIHSS was 7.5 ± 3.1, 7.8 ± 7.2 at 24 h, and 4.9 ± 5.4 at 1 week (n = 8). The modified Rankin scale at 90 days was 2.1 ± 1.2. Supplemental oxygen was given in five patients during hAEC infusion. Using pre-defined criteria, two serious adverse events occurred. One patient developed recurrent stroke and another developed pulmonary embolism whilst in rehabilitation. For the last four patients, infusion of hAECs was split across separate infusions on subsequent days to reduce the risk for fluid overload. Conclusion Our Phase I trial demonstrates that a maximal dose of 2 × 106/kg hAECs given intravenously each day over 2 days (a total of 4 × 106/kg) is safe and optimal for use in a Phase II trial. Clinical trial registration ClinicalTrials.gov, identifier …

Activin A is a two-subunit protein belonging to the transforming growth factor β superfamily. First discovered almost three decades ago, it has since been implicated in diverse physiological roles, ranging from wound repair to reproduction. After 30 years of research, altered activin A levels are now understood to be associated with the development of various diseases, making activin A potential therapeutic target. In pregnancy, the placenta and fetal membranes are major producers of activin A, with significantly enhanced serum concentrations now recognised as a contributor to numerous gestational disorders. Evidence now suggests that circulating levels of activin A may be clinically relevant in the early detection of pregnancy complications, including miscarriage and preeclampsia. This review aims to summarise our current understanding of activin A as a potential diagnostic marker in common pregnancy pathologies.

Aim To explore the association between induction of labour at full‐term gestations in low‐risk nulliparous women and childhood school outcomes. Methods A retrospective whole‐of‐population cohort study linking perinatal data to educational test scores at grades 3, 5 and 7 in Victoria, Australia. Low‐risk nulliparous women with singleton pregnancies induced at 39 and 40 weeks without a medical indication were compared to those expectantly managed from that week of gestation. Multivariable logistic regressions were used as well as generalised estimating equations on longitudinal data. Results At 39 weeks, there were 3687 and 103 164 infants in the induction and expectant arms, respectively. At 40 weeks' gestation, there were 7914 and 70 280 infants, respectively. Infants born to nulliparous women induced at 39 weeks' gestation had significantly poorer educational outcomes at grade 3 (adjusted …

In the published article, there was an error in the author list, and author “Mirja Krause” was erroneously excluded. The corrected author list and author contributions section are appears below.

Background Following the development of the Royal Australian College of Obstetricians and Gynaecologists Intrapartum Fetal Surveillance Guideline in 2003, an education program was developed to support guideline implementation and clinical practice. It was intended that improved clinician knowledge, particularly of cardiotocography, would reduce rates of intrapartum fetal morbidity and mortality. The program contains a multiple-choice assessment, designed to assess fetal surveillance knowledge and the application of that knowledge. We used the results of this assessment over time to evaluate the impact of the education program on clinicians’ fetal surveillance knowledge and interpretive skills, in the immediate and longer-term. Methods We undertook a retrospective analysis of the assessment results for all participants in the Fetal Surveillance Education Program, between 2004 and 2018. Classical Test Theory and Rasch Item Response Theory analysis were used to evaluate the statistical reliability and quality of the assessment, and the measurement invariance or stability of the assessments over time. Clinicians’ assessment scores were then reviewed by craft group and previous exposure to the program. Results The results from 64,430, broadly similar assessments, showed that participation in the education program was associated with an immediate improvement in clinician performance in the assessment. Performance improvement was sustained for up to 18 months following participation in the program and recurrent participation was associated with progressive improvements. These trends were observed for all craft groups …

ObjectivesTo evaluate how medical comorbidities – chronic hypertension, pre-gestational or gestational diabetes and obesity – influence maternal and neonatal complications from preeclampsia.Study design: We undertook a retrospective cohort study of women delivering in Victoria, Australia, between 2009 and 2017. We compared the likelihood of having a maternal complication before delivery or neonatal complication after birth between women with and without comorbidities. We used causal mediation analysis for neonatal outcomes to separate the effects of comorbidities and of prematurity on morbidity.Main outcome measures: Pregnancy complications (eclampsia; haemolysis, elevated liver enzymes, low platelets syndrome; placental abruption; stillbirth) and neonatal complications (respiratory distress syndrome; neonatal sepsis; a 5-minute APGAR < 5; neonatal intensive care unit admission).ResultsWomen …

Objective To assess pregnancy outcomes following first trimester combined screening for preterm preeclampsia in Australia. Methods We compared pregnancy outcomes of women with singleton pregnancies who underwent first trimester combined preeclampsia screening with the Fetal Medicine Foundation algorithm between 2014 and 2017 in Melbourne and Sydney, Australia, with those from women who received standard care. The primary outcomes were preterm preeclampsia and screening performance. Effect estimates were presented as risk ratios with 95% confidence intervals. Results A total of 29 618 women underwent combined screening and 301 566 women received standard care. Women who had combined screening were less likely to have preeclampsia, preterm birth, small neonates, and low Apgar scores than the general population. Women with high‐risk results (≥1 in 100) were more likely …

Nuclear factor erythroid 2-related factor-2 (Nrf2), and the less well characterised proteins Nrf1 and Nrf3, are member of the cap ‘n’ collar family of transcription factors. Nrf proteins regulate the expression of endogenous antioxidant enzymes and have recently become the targets for various therapeutic treatments. Recently, Nrf proteins have been of particular interest as a target in placental-derived oxidative stress induced pregnancy disorders. Here, we report the presence of Nrf1, Nrf2 and Nrf3 proteins in both human primary trophoblast and human trophoblast choriocarcinoma cell line (BeWo). We also detail the steps taken to successfully silence all Nrf proteins in both human primary trophoblast cells and BeWo via detection of mRNA and protein using quantitative PCR, and SDS-PAGE and Western Blotting respectively.

Research indicates that soluble fms-like tyrosine kinase 1 (sFLT-1) and placental growth factor (PLGF) have diagnostic and prognostic significance for women with preeclampsia. However, sparse research has studied these biomarkers in women with preexisting comorbidities such as chronic hypertension, diabetes mellitus, systemic lupus erythematosus and chronic kidney disease. We undertook a prospective longitudinal cohort study to compare the sFLT-1: PlGF ratio between women with and without comorbidities who did and did not go on to develop preeclampsia. We found that women with comorbidities may develop preeclampsia with a milder elevation in sFLT-1: PlGF than do women without comorbidities. This has clinical and research implications.

Background Preterm birth is the greatest cause of death up to five years of age and an important contributor to lifelong disability. There is increasing evidence that a meaningful proportion of early births may be prevented, but widespread introduction of effective preventive strategies will require financial support. Aims This study estimated the economic cost to the Australian government of preterm birth, up to 18 years of age. Materials and Methods A decision‐analytic model was developed to estimate the costs of preterm birth in Australia for a hypothetical cohort of 314 814 children, the number of live births in 2016. Costs to Australia’s eight jurisdictions included medical expenditures and additional costs to educational services. Results The total cost of preterm birth to the Australian government associated with the annual cohort was estimated at $1.413 billion (95% CI 1047‒1781). Two‐thirds of the costs were …

Background and rationaleExtracellular vesicles (EVs) are a potential cell-free regenerative medicine. Human amniotic epithelial cells (hAECs) are a viable source of cell therapy for diseases like bronchopulmonary dysplasia (BPD). However, little is known about the impact of gestational age of the donor on the quality of hAEC-derived EVs. AimsTo determine the impact of gestational age on hAEC-derived EVs in experimental BPD. ResultsTerm hAEC-derived EVs displayed a significantly higher density of surface epitopes (CD142 and CD133) and induced greater macrophage phagocytosis compared to preterm hAEC-EVs. However, T cell proliferation was more significantly suppressed by preterm hAEC-EVs. Using a model of experimental BPD, we observed that term but not preterm hAEC-EVs improved tissue-to-airspace ratio and septal crest density. While both term and preterm hAEC-EVs reduced the levels of …

ProblemCurrently <1% of Australian women give birth at home.BackgroundIn Australia there are very few options for women to access public funded homebirth.AimWe aimed to use geo-mapping to identify the number of women eligible for homebirth in Victoria, based on the criteria of uncomplicated pregnancies and residing within 15–25 kms of suitable maternity services, to plan future maternity care options.MethodsRetrospective study of births between 2015 and 2017 in Victoria, Australia. All women who were identified as having a low risk pregnancy at the beginning of pregnancy were included. The number of women within 15 and 25 km of a suitable Victorian public maternity hospital and catchment boundaries around each hospital were determined.FindingsBetween 2015 and 2017, 126,830 low risk women gave birth in Victoria, of whom half live within 25 km of seven Victorian hospitals. Currently, 2% of …

BackgroundTo investigate the childhood school outcomes for infants born to women with hypertensive disorders during pregnancy.Study designA retrospective population-based cohort study linking perinatal data from 2003 to 2013 to developmental scores at preparatory school and educational scores at school grades 3, 5, and 7 in Victoria, Australia. Exposures of interest were the presence of hypertensive disorders during pregnancy and iatrogenic delivery for preeclampsia. Multivariable logistic regression and generalised estimating equation models were employed.ResultsIn total, 682,386 births ≥32 weeks’ gestation were linked to 175,665 child developmental results and 412,834 with at least one educational result. Compared to infants born to women without a hypertensive disorder, infants born to women with a hypertensive disorder had no increased risk of poorer developmental outcomes at school entry …

Objective To assess the performance of placental, fetal and maternal cardiovascular markers in the prediction of adverse perinatal and maternal outcomes in women with suspected or confirmed pre‐eclampsia. Methods This was a prospective prognostic accuracy study of women with suspected or confirmed pre‐eclampsia who underwent a series of investigations to measure maternal hemodynamic indices, mean arterial pressure, augmentation index, ophthalmic artery peak systolic velocity (PSV) ratio, uterine artery pulsatility index (UtA‐PI), fetal biometric and Doppler parameters, soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and placental growth factor (PlGF). The performance of these markers, individually or in combination, in predicting adverse perinatal and maternal outcomes was then assessed using receiver‐operating‐characteristics (ROC)‐curve analysis. Adverse maternal outcome was defined as one or …

The present disclosure relates to the control of fungal infection of horn-like envelopes covering dorsal and terminal phalanges in humans and animals and related cerebral protrusions in animals as well as keratin comprising material on surfaces of humans and animals. Agents and natural and synthetic formulations and extracts useful for the control of fungal infection of these envelopes and related protrusions and keratin comprising material are also encompassed by the subject disclosure. In an embodiment, the present disclosure teaches the treatment of fungal infection of nails and in particular onychomycosis in humans.

Aim To examine the association between Apgar score at 5 min and childhood developmental and educational outcome. Methods A population‐based data linkage study of births ≥37 weeks' gestation linked to developmental outcomes at preparatory school and educational outcomes at school grades 3, 5 and 7 in Victoria, Australia. Multivariable logistic regressions and generalised estimating equations were used. Results There were 167,126 singleton infants with developmental results and 392,933 singleton infants with at least one educational result. There was an inverse relationship between Apgar score at 5 min and poor developmental and educational outcomes, with the worst outcomes among Apgar scores of 0–3. Apgar scores of 7, 8 and 9 were all associated with poorer developmental outcomes (aOR = 1.31, 95% CI: 1.12–1.54; aOR = 1.17, 95% CI: 1.05–1.29; aOR = 1.08, 95% CI: 1.02–1.13 …

Preeclampsia is a multisystem hypertensive disorder of pregnancy that remains one of the leading causes of maternal and perinatal morbidity and mortality worldwide. The widespread maternal endothelial dysfunction that underlies preeclampsia is thought to arise from excessive placental production of various factors combined with enhanced oxidative stress. While previous studies have reported elevated activin A in women diagnosed with preeclampsia, whether activin A can cause vascular dysfunction has not yet been thoroughly investigated. Here, we demonstrated that different subtypes of activin A receptors were localised to the endothelial and smooth muscle cells of mouse and human aortae. Then, the aorta of healthy female C57Bl6J mice (n=8) were incubated for 24 hours in various concentrations of recombinant activin A to mimic early pregnancy (5ng/mL), late pregnancy (20ng/mL) and preeclampsia …