Obstetrics and Gynaecology - Research Publications
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ItemNo Preview AvailableState-Wide Utilization and Performance of Traditional and Cell-Free DNA-Based Prenatal Testing Pathways: The Victorian Perinatal Record Linkage (PeRL) Study(LIPPINCOTT WILLIAMS & WILKINS, 2021-01)(Abstracted from Ultrasound Obstet Gynecol 2020;56:215–224) In recent years, the use of combined first-trimester screening (CFTS) and cell-free DNA (cfDNA) screening has increased. With the rise of CFTS and cfDNA prenatal testing, there has been a dramatic decrease in the number of invasive diagnostic tests performed during pregnancy.
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ItemIncrease in preterm stillbirths and reduction in iatrogenic preterm births for fetal compromise: a multi-centre cohort study of COVID-19 lockdown effects in Melbourne, Australia( 2021)
ABSTRACT
Objectives
The COVID-19 pandemic has been associated with a worsening of perinatal outcomes in many settings due to the combined impacts of maternal COVID-19 disease, disruptions to maternity care, and overloaded health systems. In 2020, Melbourne endured a unique natural experiment where strict lockdown conditions were accompanied by very low COVID-19 case numbers and the maintenance of health service capacity. The aim of this study was to compare stillbirth and preterm birth rates in women who were exposed or unexposed to lockdown restrictions during pregnancy.Design
Retrospective multi-centre cohort study of perinatal outcomes before and during COVID-19 lockdownSetting
Birth outcomes from all 12 public maternity hospitals in metropolitan MelbourneInclusion criteria
Singleton births without congenital anomalies from 24 weeks’ gestation. The lockdown-exposed cohort were those women for whom weeks 20- 40 of gestation would have occurred during the lockdown period of 23 March 2020 to 14 March 2021. The control cohort comprised all pregnancies in the corresponding periods one and two years prior to the exposed cohort.Main outcome measures
Odds of stillbirth, preterm birth (PTB), birth weight < 3 rd centile, and iatrogenic PTB for fetal compromise, adjusting for multiple covariates.Results
There were 24,017 births in the exposed and 50,017 births in the control group. There was a significantly higher risk of preterm, but not term, stillbirth in the exposed group compared with the control group (0.26% vs 0.18%, aOR 1.49, 95%CI 1.08 to 2.05, P = 0.015). There was also a significant reduction in preterm birth < 37 weeks (5.93% vs 6.23%, aOR 0.93, 95%CI 0.87 to 0.99, P=0.03), largely mediated by a reduction in iatrogenic PTB for live births (3.01% vs 3.27%, aOR 0.89, 95%CI 0.81 to 0.98, P = 0.015), including iatrogenic PTB for suspected fetal compromise (1.25% vs 1.51%, aOR 0.79, 95%CI 0.69 to 0.91, P= 0.001). There was no significant difference in the spontaneous PTB rate between the exposed and control groups (2.69% vs 2.82%, aOR 0.94, 95%CI 0.86 to 0.1.03, P=0.25).Conclusions
Lockdown restrictions in a high-income setting, in the absence of high rates of COVID-19 disease, were associated with a significant increase in preterm stillbirths, and a significant reduction in iatrogenic PTB for suspected fetal compromise.Trial registration
This study was registered as an observational study with the Australian and New Zealand Clinical Trials Registry (ACTRN12620000878976). -
ItemStudy protocol: childhood outcomes of fetal genomic variants: the PrenatAL Microarray (PALM) cohort study(BMC, 2021-10-11)BACKGROUND: The implementation of genomic testing in pregnancy means that couples have access to more information about their child's genetic make-up before birth than ever before. One of the resulting challenges is the management of genetic variations with unclear clinical significance. This population-based study will help to close this critical knowledge gap through a multidisciplinary cohort study of children with and without genomic copy number variants (CNVs) diagnosed before birth. By comparing children with prenatally-ascertained CNVs to children without a CNV, we aim to (1) examine their developmental, social-emotional and health status; (2) measure the impact of prenatal diagnosis of a CNV on maternal perceptions of child health, behavior and development; and (3) determine the proportion of prenatally-ascertained CNVs of unknown or uncertain significance that are reclassified as benign or pathogenic after 2 or more years. METHODS: This study will establish and follow up a cohort of mother-child pairs who have had a prenatal diagnosis with a chromosomal microarray from 2013-2019 in the Australian state of Victoria. Children aged 12 months to 7 years will be assessed using validated, age-appropriate measures. The primary outcome measures will be the Wechsler Preschool and Primary Scale of Intelligence IV (WPSSI-IV) IQ score (2.5 to 7 year old's), the Ages and Stages Questionnaire (12-30 months old), and the Brief Infant- Toddler Social and Emotional Assessment (BITSEA) score. Clinical assessment by a pediatrician will also be performed. Secondary outcomes will be scores obtained from the: Vineland Adaptive Behavior Scale, Maternal Postnatal Attachment Questionnaire, the Vulnerable Child Scale, Profile of Mood States, Parent Sense of Competence Scale. A descriptive analysis of the reclassification rates of CNVs after ≥2 years will be performed. DISCUSSION: This study protocol describes the first Australian cohort study following children after prenatal diagnostic testing with chromosomal microarray. It will provide long-term outcomes of fetal genomic variants to guide evidence-based pre-and postnatal care. This, in turn, will inform future efforts to mitigate the negative consequences of conveying genomic uncertainty during pregnancy. TRIAL REGISTRATION: ACTRN12620000446965p ; Registered on April 6, 2020.
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ItemAccelerated fetal growth velocity across the third trimester is associated with increased shoulder dystocia risk among fetuses who are not large-for-gestational-age: A prospective observational cohort study(PUBLIC LIBRARY SCIENCE, 2021-10-20)OBJECTIVE: To investigate whether fetuses with accelerated third trimester growth velocity are at increased risk of shoulder dystocia, even when they are not large-for-gestational-age (LGA; estimated fetal weight (EFW) >95th centile). METHODS: Fetal growth velocity and birth outcome data were prospectively collected from 347 nulliparous women. Each had blinded ultrasound biometry performed at 28 and 36 weeks' gestation. Change in EFW and abdominal circumference (AC) centiles between 28-36 weeks were calculated, standardised over exactly eight weeks. We examined the odds of shoulder dystocia with increasing EFW and AC growth velocities among women with 36-week EFW ≤95th centile (non-LGA), who went on to have a vaginal birth. We then examined the relative risk (RR) of shoulder dystocia in cases of accelerated EFW and AC growth velocities (>30 centiles gained). Finally, we compared the predictive performances of accelerated fetal growth velocities to 36-week EFW >95th centile for shoulder dystocia among the cohort planned for vaginal birth. RESULTS: Of the 226 participants who had EFW ≤95th centile at 36-week ultrasound and birthed vaginally, six (2.7%) had shoulder dystocia. For each one centile increase in EFW between 28-36 weeks, the odds of shoulder dystocia increased by 8% (odds ratio (OR [95% Confidence Interval (CI)]) = 1.08 [1.04-1.12], p<0.001). For each one centile increase in AC between 28-36 weeks, the odds of shoulder dystocia increased by 9% (OR[95%CI] = 1.09 [1.05-1.12], p<0.001). When compared to the rest of the cohort with normal growth velocity, accelerated EFW and AC velocities were associated with increased relative risks of shoulder dystocia (RR[95%CI] = 7.3 [1.9-20.6], p = 0.03 and 4.8 [1.7-9.4], p = 0.02 respectively). Accelerated EFW or AC velocities predicted shoulder dystocia with higher sensitivity and positive predictive value than 36-week EFW >95th centile. CONCLUSIONS: Accelerated fetal growth velocities between 28-36 weeks' gestation are associated with increased risk of shoulder dystocia, and may predict shoulder dystocia risk better than the commonly used threshold of 36-week EFW >95th centile.
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ItemCollaborative maternity and newborn dashboard (CoMaND) for the COVID-19 pandemic: a protocol for timely, adaptive monitoring of perinatal outcomes in Melbourne, Australia(BMJ PUBLISHING GROUP, 2021-11)BACKGROUND: The COVID-19 pandemic has resulted in a range of unprecedented disruptions to maternity care with documented impacts on perinatal outcomes such as stillbirth and preterm birth. Metropolitan Melbourne has endured one of the longest and most stringent lockdowns in globally. This paper presents the protocol for a multicentre study to monitor perinatal outcomes in Melbourne, Australia, during the COVID-19 pandemic. METHODS: Multicentre observational study analysing monthly deidentified maternal and newborn outcomes from births >20 weeks at all 12 public maternity services in Melbourne. Data will be merged centrally to analyse outcomes and create run charts according to established methods for detecting non-random 'signals' in healthcare. Perinatal outcomes will include weekly rates of total births, stillbirths, preterm births, neonatal intensive care admissions, low Apgar scores and fetal growth restriction. Maternal outcomes will include weekly rates of: induced labour, caesarean section, births before arrival to hospital, postpartum haemorrhage, length of stay, general anaesthesia for caesarean birth, influenza and COVID-19 vaccination status, and gestation at first antenatal visit. A prepandemic median for all outcomes will be calculated for the period of January 2018 to March 2020. A significant shift is defined as ≥6 consecutive weeks, all above or below the prepandemic median. Additional statistical analyses such as regression, time series and survival analyses will be performed for an in-depth examination of maternal and perinatal outcomes of interests. ETHICS AND DISSEMINATION: Ethics approval for the collaborative maternity and newborn dashboard project has been obtained from the Austin Health (HREC/64722/Austin-2020) and Mercy Health (ref. 2020-031). TRIAL REGISTRATION NUMBER: ACTRN12620000878976; Pre-results.
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ItemFetal fraction and noninvasive prenatal testing: What clinicians need to know(WILEY, 2020-01)The fetal fraction (FF) is a function of both biological factors and bioinformatics algorithms used to interpret DNA sequencing results. It is an essential quality control component of noninvasive prenatal testing (NIPT) results. Clinicians need to understand the biological influences on FF to be able to provide optimal post-test counseling and clinical management. There are many different technologies available for the measurement of FF. Clinicians do not need to know the details behind the bioinformatics algorithms of FF measurements, but they do need to appreciate the significant variations between the different sequencing technologies used by different laboratories. There is no universal FF threshold that is applicable across all platforms and there have not been any differences demonstrated in NIPT performance by sequencing platform or method of FF calculation. Importantly, while FF should be routinely measured, there is not yet a consensus as to whether it should be routinely reported to the clinician. The clinician should know what to expect from a standard test report and whether reasons for failed NIPT results are revealed. Emerging solutions to the challenges of samples with low FF should reduce rates of failed NIPT in the future. In the meantime, having a "plan B" prepared for those patients for whom NIPT is unsuccessful is essential in today's clinical practice.
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ItemMaternal and perinatal outcomes for women with body mass index ≥50 kg/m2 in a non-tertiary hospital setting(WILEY, 2020-06)BACKGROUND: Obesity is prevalent in the Australian antenatal population, but there are scarce data on the prevalence and associated outcomes of body mass index (BMI) ≥50 kg/m2 . AIMS: To examine the prevalence and outcomes for women with BMI ≥50 kg/m2 delivering in a non-tertiary hospital. MATERIALS AND METHODS: Retrospective cohort study of women delivering a singleton pregnancy in a non-tertiary Victorian hospital during 2011-2016. Women >180 kg were excluded as their care was managed in a tertiary centre. Maternal and perinatal outcomes were analysed by BMI group. Statistical analysis was performed using χ2 , Kruskal-Wallis and logistic regression with a significance level of 0.05. RESULTS: Of the 18 518 births between 2011 and 2016, 99.4% had a maternal BMI recorded. The prevalence of BMI ≥50 kg/m2 was 0.5%. Highest complication rates were observed among women with BMI ≥50 kg/m2 , including gestational diabetes (29%), hypertensive disorders of pregnancy (20%) and caesarean section (48%). Of infants born to women with BMI ≥50 kg/m2 , 12% were late-pre-term, 23% required special or intensive care and 20% had birth weight ≥4.0 kg. When compared with obese women with BMI 30-49 kg/m2 , women with BMI ≥50 kg/m2 were significantly more likely to develop a hypertensive disorder of pregnancy (preeclampsia adjusted odds ratio (aOR) 3.98 (1.93-8.18), pregnancy-induced hypertension aOR 3.55 (1.79-7.03)) and deliver a late pre-term infant (aOR 2.45 (1.31-4.58)). CONCLUSIONS: The prevalence of severe maternal obesity in our non-tertiary setting is higher than previous national estimates. Women with BMI ≥50 kg/m2 are an important subgroup of the obese obstetric population who experience high rates of complications and interventions. Health services need to respond to evolving needs of the antenatal population to achieve the best outcomes for mothers and babies.
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ItemThe international Perinatal Outcomes in the Pandemic (iPOP) study: protocol.(F1000 Research Ltd, 2021)Preterm birth is the leading cause of infant death worldwide, but the causes of preterm birth are largely unknown. During the early COVID-19 lockdowns, dramatic reductions in preterm birth were reported; however, these trends may be offset by increases in stillbirth rates. It is important to study these trends globally as the pandemic continues, and to understand the underlying cause(s). Lockdowns have dramatically impacted maternal workload, access to healthcare, hygiene practices, and air pollution - all of which could impact perinatal outcomes and might affect pregnant women differently in different regions of the world. In the international Perinatal Outcomes in the Pandemic (iPOP) Study, we will seize the unique opportunity offered by the COVID-19 pandemic to answer urgent questions about perinatal health. In the first two study phases, we will use population-based aggregate data and standardized outcome definitions to: 1) Determine rates of preterm birth, low birth weight, and stillbirth and describe changes during lockdowns; and assess if these changes are consistent globally, or differ by region and income setting, 2) Determine if the magnitude of changes in adverse perinatal outcomes during lockdown are modified by regional differences in COVID-19 infection rates, lockdown stringency, adherence to lockdown measures, air quality, or other social and economic markers, obtained from publicly available datasets. We will undertake an interrupted time series analysis covering births from January 2015 through July 2020. The iPOP Study will involve at least 121 researchers in 37 countries, including obstetricians, neonatologists, epidemiologists, public health researchers, environmental scientists, and policymakers. We will leverage the most disruptive and widespread "natural experiment" of our lifetime to make rapid discoveries about preterm birth. Whether the COVID-19 pandemic is worsening or unexpectedly improving perinatal outcomes, our research will provide critical new information to shape prenatal care strategies throughout (and well beyond) the pandemic.
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Item40 years of prenatal diagnosis in 2020(WILEY, 2020-12)
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