Reduction in Spontaneous and Iatrogenic Preterm Births in Twin Pregnancies During COVID-19 Lockdown in Melbourne, Australia: A Multicenter Cohort Study (preprint)

Background: 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. Objective: To compare the rates of adverse perinatal outcomes in twin pregnancies exposed and unexposed to lockdown restrictions in Melbourne. Study Design: 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<37 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. Results: We included 2267 women birthing twins. Total preterm births<37 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 driven by both fewer iatrogenic preterm births (44.1% vs 48.1%; aRR 0.97 95% CI 0.92-1.03, p=0.39) and fewer spontaneous preterm births (18.9% vs 20.3%; aRR 0.95 95% CI 0.90-0.99, p=0.04). There were also significantly lower rates of preterm birth<34 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<0.001). 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), adjusted stillbirths, birthweight<3rd 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<37 or <34 weeks (p>0.05). However, during exposure 2 the rate of preterm birth<28 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<0.0001) compared with the pre-pandemic period. Conclusions: Melbourne's first lockdown-exposure period was associated with fewer twin preterm births<34 and <37 weeks without significant differences in stillbirths or adverse newborn outcomes. These lower rates were not sustained into 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.

Reductions in stillbirths and preterm birth in COVID-19 vaccinated women: a multi-center cohort study of vaccination uptake and perinatal outcomes (preprint)

Background: 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. Objective: 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. Study design: 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 1st 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 <= 3rd 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. Results: 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 <= 3rd 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). Conclusions 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.

Indirect impact of the COVID-19 pandemic on emergency department presentations and hospital admissions for urgent early pregnancy conditions: a population-based retrospective cohort study (preprint)

Objective: To compare emergency department (ED) presentations and hospital admissions for urgent early pregnancy conditions in Victoria before and after the onset of COVID-19 lockdown on 31 March 2020. Design: Population-based retrospective cohort study Setting: Australian state of Victoria Population: Pregnant women presenting to emergency departments or admitted to hospital Methods: We obtained state-wide hospital separation data from the Victorian Emergency Minimum Dataset and the Victorian Admitted Episodes Dataset from January 1, 2018, to October 31, 2020. A linear prediction model based on the pre-COVID period was used to identify the impact of COVID restrictions. Main outcome measures: Monthly ED presentations for miscarriage and ectopic pregnancy, hospital admissions for termination of pregnancy, with subgroup analysis by region, socioeconomic status, disease acuity, hospital type. Results: There was an overall decline in monthly ED presentations and hospital admissions for early pregnancy conditions in metropolitan areas where lockdown restrictions were most stringent. Monthly ED presentations for miscarriage during the COVID period were consistently below predicted, with the nadir in April 2020 (790 observed vs 985 predicted, 95% CI 835-1135). Monthly admissions for termination of pregnancy were also below predicted throughout lockdown, with the nadir in August 2020 (893 observed vs 1116 predicted, 95% CI 905-1326). There was no increase in ED presentations for complications following abortion, ectopic or molar pregnancy during the COVID period. Conclusions: Fewer women in metropolitan Victoria utilized hospital-based care for early pregnancy conditions during the first seven months of the pandemic, without any observable increase in maternal morbidity.

Increase 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 (preprint)

ObjectivesThe 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. DesignRetrospective multi-centre cohort study of perinatal outcomes before and during COVID-19 lockdown SettingBirth outcomes from all 12 public maternity hospitals in metropolitan Melbourne Inclusion criteriaSingleton 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 measuresOdds of stillbirth, preterm birth (PTB), birth weight < 3rd centile, and iatrogenic PTB for fetal compromise, adjusting for multiple covariates. ResultsThere 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). ConclusionsLockdown 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 registrationThis study was registered as an observational study with the Australian and New Zealand Clinical Trials Registry (ACTRN12620000878976).

A collaborative maternity dashboard (CoMaND) for the COVID-19 pandemic: a protocol for timely, adaptive monitoring of perinatal outcomes in Melbourne, Australia (preprint)

Background: 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. Methods: 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. Ethics and Dissemination: This study has been registered as an observational study with the Australian and New Zealand Clinical Trials Registry (ACTRN12620000878976).