ORCID Profile
0000-0001-8267-1630
Current Organisations
Brown University
,
University of Alabama
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Publisher: Wiley
Date: 29-10-2020
DOI: 10.1111/AJO.13270
Publisher: F1000 Research Ltd
Date: 02-02-2021
DOI: 10.12688/WELLCOMEOPENRES.16507.1
Abstract: 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.
Publisher: Cold Spring Harbor Laboratory
Date: 06-07-2022
DOI: 10.1101/2022.07.04.22277193
Abstract: COVID-19 infection in pregnancy is associated with a higher risk of progression to severe disease, but vaccine uptake by pregnant women is hindered by persistent safety concerns. COVID-19 vaccination in pregnancy has been shown to reduce stillbirth, but its relationship with preterm birth is uncertain. The aim of this study was to investigate the sociodemographic characteristics associated with vaccine uptake in Melbourne, Australia, and to compare perinatal outcomes by vaccination status. Retrospective multicenter cohort study in Melbourne following the national recommendations for mRNA COVID-19 vaccination during pregnancy in June 2021. Routinely collected data from all 12 public maternity hospitals in Melbourne were extracted on births ≥ 20 weeks’ gestation from 1 st July 2021 to 31 March 2022. Maternal sociodemographic characteristics were analyzed from the total birth cohort. Perinatal outcomes were compared between vaccinated and unvaccinated women for whom weeks 20-43 of gestation fell entirely within the 9-month data collection period. The primary outcome was the rate of congenital anomaly in singleton infants ≥ 20 weeks’ gestation among women vaccinated during pregnancy. Secondary perinatal outcomes including stillbirth, preterm birth (spontaneous and iatrogenic), birthweight ≤ 3 rd centile, and newborn intensive care unit admissions were examined for singleton infants ≥ 24 weeks’ gestation without congenital anomalies. We calculated the adjusted odds ratio of congenital anomalies and perinatal outcomes among vaccinated versus unvaccinated women using inverse propensity score weighting regression adjustment with multiple covariates p 0.05 was considered statistically significant. Births from 32,536 women were analyzed: 17,365 (53.4%) were vaccinated and 15,171 (47.6%) were unvaccinated. Vaccinated women were significantly more likely to be older, nulliparous, non-smoking, not requiring an interpreter, of higher socioeconomic status, and vaccinated against pertussis and influenza. Vaccination status also varied by region of birth: compared with women born in Australia, women born in South and Eastern Europe, the Middle East, Africa and Oceania had lower adjusted odds of vaccination. There was no significant increase in the rate of congenital anomalies or birth weight ≤ 3 rd centile in vaccinated women. Vaccinated women were significantly less like to have an infant with a major congenital anomaly compared with the unvaccinated group (2.4% vs 3.0%, aOR 0.72, 95%CI 0.56-0.94, p=0.02). This finding remained significant even when the analysis was restricted to women vaccinated before 20 weeks’ gestation. Vaccinated women had a significantly lower rate of stillbirth (0.2% vs 0.8%, aOR 0.18, 95%CI 0.09-0.37, P 0.001. Vaccination was associated with a significant reduction in total preterm births 37 weeks (5.1% vs 9.2%, aOR 0.60, 95% CI 0.51-0.71, p 0.001), spontaneous preterm birth (2.4% vs 4.0%, aOR 0.73 95% CI 0.56-0.96, p=0.02) and iatrogenic preterm birth (2.7% vs 5.2%, aOR 0.52, 95%CI 0.41-0.65, p 0.001). COVID-19 Vaccine coverage was significantly influenced by known social determinants of health, which is likely to influence the strong association between COVID-19 vaccination and lower risks of stillbirth and preterm birth. We did not observe any adverse impacts of vaccination on fetal growth or development. ⍰ COVID-19 infection in pregnancy is associated with a higher risk of progression to severe disease, but vaccine uptake by pregnant women is hindered by persistent safety concerns. COVID-19 vaccination in pregnancy has been shown to reduce stillbirth, but its relationship with preterm birth is uncertain. ⍰ Most of the published literature on COVID-19 vaccination in pregnancy have methodological limitations including fixed cohort bias and time-varying exposure. ⍰ We conducted this multicenter study to provide robust evidence on mRNA COVID-19 vaccination and perinatal outcomes including congenital anomalies, stillbirth, and preterm birth. ⍰ The adjusted odds of stillbirth, preterm birth, and neonatal intensive care admission were significantly reduced among infants born to COVID-19 vaccinated women compared with unvaccinated women. COVID-19 vaccination during pregnancy was not associated with an increase in congenital anomalies. ⍰ Our results conclusively demonstrate a significant reduction in both spontaneous and iatrogenic preterm birth for vaccinated women ⍰ Vaccinated women were significantly more likely to be older, nulliparous, non-smoking, not requiring an interpreter, residing in a higher socioeconomic postcode, and vaccinated against pertussis and influenza. There were also significant differences in vaccination rates by region of birth. ⍰ Our analysis confirmed a strong relationship between the COVID-19 mRNA vaccine and lower preterm births and stillbirths ⍰ In addition to its impact on reducing severe COVID-19 illness, vaccination may be a proxy for other biological and social determinants of health among our pregnant population.
Publisher: Public Library of Science (PLoS)
Date: 12-07-2021
DOI: 10.1371/JOURNAL.PNTD.0009516
Abstract: Zika virus (ZIKV) has generated global interest in the last five years mostly due to its resurgence in the Americas between 2015 and 2016. It was previously thought to be a self-limiting infection causing febrile illness in less than one quarter of those infected. However, a rise in birth defects amongst children born to infected pregnant women, as well as increases in neurological manifestations in adults has been demonstrated. We systemically reviewed the literature to understand clinical manifestations and health outcomes in adults globally. This review was registered prospectively with PROPSERO (CRD 42018096558). We systematically searched for studies in six databases from inception to the end of September 2020. There were no language restrictions. Critical appraisal was completed using the Joanna Briggs Institute Critical Appraisal Tools. We identified 73 studies globally that reported clinical outcomes in ZIKV-infected adults, of which 55 studies were from the Americas. For further analysis, we considered studies that met 70% of critical appraisal criteria and described subjects with confirmed ZIKV. The most common symptoms included: exanthema (5,456/6,129 89%), arthralgia (3,809/6,093 63%), fever (3,787/6,124 62%), conjunctivitis (2,738/3,283 45%), myalgia (2,498/5,192 48%), headache (2,165/4,722 46%), and diarrhea (337/2,622 13%). 36/14,335 (0.3%) of infected cases developed neurologic sequelae, of which 75% were Guillain-Barré Syndrome (GBS). Several subjects reported recovery from peak of neurological complications, though some endured chronic disability. Mortality was rare (0.1%) and hospitalization (11%) was often associated with co-morbidities or GBS. The ZIKV literature in adults was predominantly from the Americas. The most common systemic symptoms were exanthema, fever, arthralgia, and conjunctivitis GBS was the most prevalent neurological complication. Future ZIKV studies are warranted with standardization of testing and case definitions, consistent co-infection testing, reporting of laboratory abnormalities, separation of adult and pediatric outcomes, and assessing for causation between ZIKV and neurological sequelae.
Publisher: Cold Spring Harbor Laboratory
Date: 18-05-2023
DOI: 10.1101/2023.05.16.23289144
Abstract: Melbourne, Australia, recorded one of the longest and most stringent pandemic lockdowns in 2020, which was associated with an increase in preterm stillbirths among singleton pregnancies. Twin pregnancies may be particularly susceptible to the impacts of pandemic disruptions to maternity care due to their higher background risk of adverse perinatal outcomes. To compare the rates of adverse perinatal outcomes in twin pregnancies exposed and unexposed to lockdown restrictions in Melbourne. Multicenter retrospective cohort study of all twin pregnancies birthing in public maternity hospitals in Melbourne. We compared perinatal outcomes between a pre- pandemic group (‘unexposed’) and two lockdown-exposed groups: exposure 1 from 22 March 2020 to 21 March 2021 and exposure 2 from 22 March 2021 to 27 March 2022. We analyzed routinely-collected maternity data on all twin births ≥ 20 weeks where outcomes were available for both infants. The primary outcomes were rates of preterm birth weeks and all-cause stillbirth. Multivariable log-binomial regression models were used to compare perinatal outcomes between the pre-pandemic group and women in whom weeks 20 +0 to 40 +0 of their pregnancy occurred entirely during each lockdown-exposure period. Perinatal outcomes were calculated per infant maternal outcomes were calculated per pregnancy. We included 2267 women birthing twins. Total preterm births weeks were significantly lower in the exposure 1 group compared with the pre-pandemic group (63.1% vs 68.3% respectively adjusted risk ratio, aRR 0.92 95% CI 0.87-0.98, p=0.01). This was mainly driven by fewer spontaneous preterm births (18.9% vs 20.3% aRR 0.95 95%CI 0.90- 0.99, p=0.04) and a trend to fewer iatrogenic preterm births (44.1% vs 48.1% aRR 0.97 95%CI 0.92-1.03, p=0.39). There were also significantly lower rates of preterm birth weeks in the exposure 1 group compared with the pre-pandemic group (19.9% vs 23.0%, aRR 0.93 95%CI 0.89-0.98 p=0.01). Total iatrogenic births for fetal compromise were significantly lower (13.4% vs 20.4% aRR 0.94 95%CI 0.89–0.98, p=0.01). There were fewer special care nursery admissions (38.5% vs 43.4% aRR 0.91 95%CI 0.87-0.95, p .001). There was no associated difference in all-cause stillbirths (1.5% vs 1.6% aRR 1.00 95%CI 0.99-1.01, p=0.82), birthweight rd centile (5.7% vs 6.0% aRR 1.00, 95%CI 0.98-1.02 p=0.74) or neonatal intensive care unit admissions in the exposure 1 group compared to the pre-pandemic group. In contrast, when comparing the pre-pandemic group with exposure 2 group, there was no significant difference in the rates of preterm birth or weeks. However, during exposure 2 the rate of preterm birth weeks was significantly higher (7.2% vs 4.8% aRR 1.03 95%CI 1.01-1.05, p=0.04) and infants were more likely to be admitted to a neonatal intensive care unit (25.0% vs 19.6% aRR 1.06 95%CI 1.03-1.10, p .0001) compared with the pre-pandemic period. Melbourne’s first lockdown-exposure period was associated with fewer twin preterm births and weeks without significant differences in stillbirths or adverse newborn outcomes. These lower rates were not sustained in the second exposure period. Pandemic conditions may provide important lessons for future antenatal care of twin pregnancies, including prevention of preterm birth and optimal timing of birth.
Publisher: Informa UK Limited
Date: 27-03-2019
Publisher: Springer Science and Business Media LLC
Date: 08-2020
Abstract: The combination of measurements of the W boson polarization in top quark decays performed by the ATLAS and CMS collaborations is presented. The measurements are based on proton-proton collision data produced at the LHC at a centre-of-mass energy of 8 TeV, and corresponding to an integrated luminosity of about 20 fb − 1 for each experiment. The measurements used events containing one lepton and having different jet multiplicities in the final state. The results are quoted as fractions of W bosons with longitudinal ( F 0 ), left-handed ( F L ), or right-handed ( F R ) polarizations. The resulting combined measurements of the polarization fractions are F 0 = 0 . 693 ± 0 . 014 and F L = 0 . 315 ± 0 . 011. The fraction F R is calculated from the unitarity constraint to be F R = − 0 . 008 ± 0 . 007. These results are in agreement with the standard model predictions at next-to-next-to-leading order in perturbative quantum chromodynamics and represent an improvement in precision of 25 (29)% for F 0 ( F L ) with respect to the most precise single measurement. A limit on anomalous right-handed vector ( V R ), and left- and right-handed tensor ( g L , g R ) tWb couplings is set while fixing all others to their standard model values. The allowed regions are [ − 0 . 11 , 0 . 16] for V R , [ − 0 . 08 , 0 . 05] for g L , and [ − 0 . 04 , 0 . 02] for g R , at 95% confidence level. Limits on the corresponding Wilson coefficients are also derived.
Publisher: Informa UK Limited
Date: 22-02-2020
DOI: 10.1080/14767058.2019.1582027
Abstract: Many studies have reported on the association of reduced fetal movements and stillbirth, but little is known about excessive fetal movements and adverse pregnancy outcome. First described in 1977, sudden excessive fetal movement was noted to reflect acute fetal distress and subsequent fetal demise. Subsequently, little was reported regarding this phenomenon until 2012. However, emerging data suggest that 10-30% of the women that subsequently suffer a stillbirth describe a single episode of excessive fetal movement prior to fetal demise. These episodes are poorly understood but may reflect fetal seizure activity secondary to fetal asphyxia, cord entanglement or an adverse intrauterine environment. At present, the challenge in managing women with excessive fetal movements is a timely assessment of the fetus to identify those women at risk of adverse fetal outcomes who may benefit from intervention.
Publisher: Research Square Platform LLC
Date: 21-01-2020
Abstract: Background: Open spina bifida (OSB) is one of the most common congenital central nervous system defects and leads to long-term physical and cognitive disabilities. Open fetal surgery for OSB improves neurological outcomes and reduces the need for ventriculoperitoneal shunting, compared to postnatal surgery, at the expense of increased prematurity. It however confers significant morbidity to the mother in the index pregnancy and potential risks to future pregnancies. Fetoscopic surgery may prevent maternal morbidity yet the question remains whether the procedure is neuroprotective and reduces prematurity. Comparison of outcomes between different treatment options is challenging due to inconsistent outcome reporting. We aim to develop and disseminate a core outcome set (COS) for fetal OSB, to ensure that outcomes relevant to all stakeholders are collected and reported in a standardised fashion in future studies. Methods: The COS will be developed using a validated Delphi methodology. A systematic literature review will be performed to identify previously reported outcomes focused on prenatally diagnosed OSB. Outcomes assessed will include maternal (primary and subsequent pregnancies), fetal, neonatal and childhood to adolescence. In a second phase, semi-structured interviews with stakeholders will be performed to ensure representation of additional relevant outcomes that may not have been reported in the literature. We will include patients and parents, as well as health professionals involved in the care of these pregnancies and children (fetal medicine specialists, fetal surgeons, neonatologists aediatricians, and allied health). Subsequently, an international group of key stakeholders will rate the importance of the identified outcomes using three sequential, online, rounds of a modified Delphi Survey. Final agreement on outcomes to be included in the COS, their definition and measurement will be achieved through a final face-to-face consensus meeting with all stakeholder groups represented. Dissemination of the final COS will be ensured through different media and relevant societies. Discussion: Development and implementation of a COS for fetal OSB will ensure consistent outcome reporting in future clinical trials, systematic reviews, and clinical practice guidelines. This will lead to higher quality research, better evidence-based clinical practice and ultimately improved maternal, fetal and long term childhood outcomes. Trial registration: Core Outcome Measures in Effectiveness Trials (COMET): 1187. International Prospective Register of Systematic Reviews (PROSPERO): CRD42018104880.
Publisher: Research Square Platform LLC
Date: 10-08-2020
Abstract: Background: Open spina bifida (OSB) is one of the most common congenital central nervous system defects and leads to long-term physical and cognitive disabilities. Open fetal surgery for OSB improves neurological outcomes and reduces the need for ventriculoperitoneal shunting, compared to postnatal surgery, but is associated with a significant risk of prematurity and maternal morbidity. Fetoscopic surgery comes with less maternal morbidity yet the question remains whether the procedure is neuroprotective and reduces prematurity. Comparison of outcomes between different treatment options is challenging due to inconsistent outcome reporting. We aim to develop and disseminate a core outcome set (COS) for fetal OSB, to ensure that outcomes relevant to all stakeholders are collected and reported in a standardised fashion in future studies. Methods: The COS will be developed using a validated Delphi methodology. A systematic literature review will be performed to identify outcomes previously reported for prenatally diagnosed OSB. We will assess will maternal (primary and subsequent pregnancies), fetal, neonatal and childhood outcomes until adolescence. In a second phase, we will conduct semi-structured interviews with stakeholders, to ensure representation of additional relevant outcomes that may not have been reported in the literature. We will include patients and parents, as well as health professionals involved in the care of these pregnancies and children (fetal medicine specialists, fetal surgeons, neonatologists aediatricians, and allied health). Subsequently, an international group of key stakeholders will rate the importance of the identified outcomes using three sequential online rounds of a modified Delphi Survey. Final agreement on outcomes to be included in the COS, their definition and measurement will be achieved through a face-to-face consensus meeting with all stakeholder groups. Dissemination of the final COS will be ensured through different media and relevant societies. Discussion: Development and implementation of a COS for fetal OSB will ensure consistent outcome reporting in future clinical trials, systematic reviews, and clinical practice guidelines. This will lead to higher quality research, better evidence-based clinical practice and ultimately improved maternal, fetal and long term childhood outcomes. Trial registration: Core Outcome Measures in Effectiveness Trials (COMET): 1187. International Prospective Register of Systematic Reviews (PROSPERO): CRD42018104880.
Publisher: Wiley
Date: 31-07-2023
DOI: 10.1002/UOG.26206
Abstract: To examine the relationship between umbilical cord insertion site, placental pathology and adverse pregnancy outcome in a cohort of normal and complicated pregnancies. Sonographic measurement of the cord insertion and detailed placental pathology were performed in 309 participants. Associations between cord insertion site, placental pathology and adverse pregnancy outcome (pre‐ecl sia, preterm birth, small‐for‐gestational age) were examined. A total of 93 (30%) participants were identified by pathological examination to have a peripheral cord insertion site. Only 41 of the 93 (44%) peripheral cords were detected by prenatal ultrasound. Peripherally inserted cords were associated significantly ( P 0.0001) with diagnostic placental pathology (most commonly with maternal vascular malperfusion (MVM)) of which 85% had an adverse pregnancy outcome. In cases of isolated peripheral cords, without placental pathology, the incidence of adverse outcome was not statistically different when compared to those with central cord insertion and no placental pathology (31% vs 18% P = 0.3). A peripheral cord with an abnormal umbilical artery (UA) pulsatility index (PI) corresponded to an adverse outcome in 96% of cases compared to 29% when the UA‐PI was normal. This study demonstrates that peripheral cord insertion is often part of the spectrum of findings of MVM disease and is associated with adverse pregnancy outcome. However, adverse outcome was uncommon when there was an isolated peripheral cord insertion and no placental pathology. Therefore, additional sonographic and biochemical features of MVM should be sought when a peripheral cord is observed. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.
Publisher: Cold Spring Harbor Laboratory
Date: 23-07-2021
DOI: 10.1101/2021.07.22.21261008
Abstract: The COVID-19 pandemic has resulted in a range of unprecedented disruptions to the delivery of maternity care globally and has been associated with regional changes in perinatal outcomes such as stillbirth and preterm birth. Metropolitan Melbourne endured one of the longest and most stringent lockdowns in 2020. This paper presents the protocol for a collaborative maternity dashboard project to monitor perinatal outcomes in Melbourne, Australia, during the COVID-19 pandemic. De-identified maternal and newborn outcomes will be collected monthly from all public maternity services in Melbourne, allowing rapid analysis of a multitude of perinatal indicators. Weekly outcomes will be displayed as run charts according to established methods for detecting non-random ‘signals’ in health care. A pre-pandemic median for all indicators will be calculated for the period of January 2018 to March 2020. A significant shift is defined as ≤ six consecutive weeks, all above or below the pre-pandemic 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. This study has been registered as an observational study with the Australian and New Zealand Clinical Trials Registry (ACTRN12620000878976). ⍰ This project is the first clinician-led, multi-centre perinatal data collection system for metropolitan Melbourne. ⍰ It complements the state government data collection, with the significant benefits of more timely and flexible reporting of outcomes, and granular detail on emerging areas of concern. ⍰ The study relies on primary source coding of exposure and outcomes from each hospital that have not been internally validated during the study period. ⍰ Data from private maternity hospitals, containing 25% of Melbourne births, are not available. ⍰ This resource will support data-informed hospital pandemic responses through to the end of 2022.
Publisher: Cold Spring Harbor Laboratory
Date: 05-10-2021
DOI: 10.1101/2021.10.04.21264500
Abstract: 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. Retrospective multi-centre cohort study of perinatal outcomes before and during COVID-19 lockdown Birth outcomes from all 12 public maternity hospitals in metropolitan Melbourne 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. Odds of stillbirth, preterm birth (PTB), birth weight 3 rd centile, and iatrogenic PTB for fetal compromise, adjusting for multiple covariates. 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). 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. This study was registered as an observational study with the Australian and New Zealand Clinical Trials Registry (ACTRN12620000878976).
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Clare Whitehead.