Temporal trends and determinants of COVID-19 vaccine series initiation after recent pregnancy.

During the rapid deployment of COVID-19 vaccines in 2021, safety concerns may have led some pregnant individuals to postpone vaccination until after giving birth. This study aimed to describe temporal patterns and factors associated with COVID-19 vaccine series initiation after recent pregnancy in Ontario, Canada. Using the provincial birth registry linked with the COVID-19 vaccine database, we identified all individuals who gave birth between January 1 and December 31, 2021, and had not yet been vaccinated by the end of pregnancy, and followed them to June 30, 2022 (follow-up ranged from 6 to 18 months). We used cumulative incidence curves to describe COVID-19 vaccine initiation after pregnancy and assessed associations with sociodemographic, pregnancy-related, and health behavioral factors using Cox proportional hazards regression to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Among 137,198 individuals who gave birth in 2021, 87,376 (63.7%) remained unvaccinated at the end of pregnancy; of these, 65.0% initiated COVID-19 vaccination by June 30, 2022. Lower maternal age (<25 vs. 30-34 y aHR: 0.73, 95%CI: 0.70-0.77), smoking during pregnancy (vs. nonsmoking aHR: 0.68, 95%CI: 0.65-0.72), lower neighborhood income (lowest quintile vs. highest aHR: 0.79, 95%CI: 0.76-0.83), higher material deprivation (highest quintile vs. lowest aHR: 0.74, 95%CI: 0.70-0.79), and exclusive breastfeeding (vs. other feeding aHR: 0.81, 95%CI: 0.79-0.84) were associated with lower likelihood of vaccine initiation. Among unvaccinated individuals who gave birth in 2021, COVID-19 vaccine initiation after pregnancy reached 65% by June 30, 2022, suggesting persistent issues with vaccine hesitancy and/or access to vaccination in this population.

SARS-CoV-2 Exposure from Health Care Workers to Infants: Effects and Outcomes.

OBJECTIVE: This study aimed to evaluate the risk and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission from positive health care workers (HCW) to infants in the neonatal intensive care unit (NICU) and the postnatal ward. STUDY DESIGN: We conducted a retrospective analysis of infants in NICU and the postnatal ward postexposure to a COVID-19 positive HCW between May 1 and July 31, 2020. HCW had the detection of SARS-CoV-2 after being symptomatic. Infants exposed to these HCW were tested for SARS-CoV-2 and were classified as confirmed positive when test was positive 24 hours after exposure; confirmed negative when test was negative with no escalation of respiratory support provided; and probable if test was negative. However, infant required escalation of respiratory support. Infants were followed at 14 days postexposure then at the end of the study period for admitted infants. RESULTS: A total of 31 infants were exposed to SARS-CoV-2 positive HCWs (42 exposure incidences). The median age at exposure was 21 days. None of the infants was confirmed positive. Nine infants were classified as probable cases of whom five infants with underlying chronic illnesses died, two were discharged home, and two were still admitted. Of the 22 confirmed negative cases, 15 were discharged and were well on follow-up, and 7 were still admitted. CONCLUSION: No active transmission of infection from infected HCW to admitted infants was identified. Although some infants had respiratory escalation postexposure none were confirmed positive. Adhering to personal protective equipment by HCW or low susceptibility of infants to SARS-CoV-2 infection may explain the lack of transmission. KEY POINTS: · There are no reported cases of transmission of SARS-CoV-2 infection from infected HCW to infants admitted to the NICU in our study.. · Adherence to personnel protective equipment is important to prevent transmission of SARS-CoV-2. · When an infant is exposed to a HCW who is positive for SARS-CoV-2 and has escalation of respiratory support, SARS-CoV-2 as a cause should be investigated.

Multisystemic Inflammatory Syndrome in Neonates: A Systematic Review.

INTRODUCTION: Multisystem inflammatory syndrome in neonates (MIS-N) related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has increasingly been reported worldwide amid the spread of the SARS-CoV-2 pandemic. METHODS: We searched PubMed, EMBASE, and CINAHL and preprint servers (BioRxiv.org and MedRxiv.org) using a specified strategy integrating Medical Subject Headings terms and keywords until October 20, 2021. Our aim was to systematically review demographic profiles, clinical features, laboratory parameters, complications, treatments, and outcomes of neonates with MIS-N. Studies were selected when fulfilling the inclusion criteria. Articles were included if they fulfilled the World Health Organization (WHO), Centers for Disease Control (CDC) definitions of MIS-C, or our proposed definition. RESULTS: Sixteen reports of MIS-N including 47 neonates meeting MIS-N criteria were identified. Presentation included cardiovascular compromise (77%), respiratory involvement (55%), and fever in (36%). Eighty-three percent of patients received steroids, and 76% received immunoglobulin. Respiratory support was provided to 60% of patients and inotropes to 45% of patients. Five (11%) neonates died. CONCLUSION: The common presentation of MIS-N included cardiorespiratory compromise with the possibility of high mortality. Neonates with MIS-N related to SARS-CoV-2 may be at higher risk of adverse outcomes.

Temporal trends and determinants of COVID-19 vaccine coverage and series initiation during pregnancy in Ontario, Canada, December 2020 to December 2021: A population-based retrospective cohort study.

BACKGROUND: Population-based COVID-19 vaccine coverage estimates among pregnant individuals are limited. We assessed temporal patterns in vaccine coverage (≥1 dose before or during pregnancy) and evaluated factors associated with vaccine series initiation (receiving dose 1 during pregnancy) in Ontario, Canada. METHODS: We linked the provincial birth registry with COVID-19 vaccination records from December 14, 2020 to December 31, 2021 and assessed coverage rates among all pregnant individuals by month, age, and neighborhood sociodemographic characteristics. Among individuals who gave birth since April 2021-when pregnant people were prioritized for vaccination-we assessed associations between sociodemographic, behavioral, and pregnancy-related factors with vaccine series initiation using multivariable regression to estimate adjusted risk ratios (aRR) and risk differences (aRD) with 95% confidence intervals (CI). RESULTS: Among 221,190 pregnant individuals, vaccine coverage increased to 71.2% by December 2021. Gaps in coverage across categories of age and sociodemographic characteristics decreased over time, but did not disappear. Lower vaccine series initiation was associated with lower age (<25 vs. 30-34 years: aRR 0.53, 95%CI 0.51-0.56), smoking (vs. non-smoking: 0.64, 0.61-0.67), no first trimester prenatal care visit (vs. visit: 0.80, 0.77-0.84), and residing in neighborhoods with the lowest income (vs. highest: 0.69, 0.67-0.71). Vaccine series initiation was marginally higher among individuals with pre-existing medical conditions (vs. no conditions: 1.07, 1.04-1.10). CONCLUSIONS: COVID-19 vaccine coverage among pregnant individuals remained lower than in the general population, and there was lower vaccine initiation by multiple characteristics.

Infants Born to Mothers Who Were SARS-CoV-2 Positive during Pregnancy and Admitted to Neonatal Intensive Care Unit.

INTRODUCTION: Our objective was to compare neonatal outcomes and resource use of neonates born to mothers with SARS-CoV-2 positivity during pregnancy with neonates born to mothers without SARS-CoV-2 positivity. METHODS: We conducted a two-country cohort study of neonates admitted between January 1, 2020, and September 15, 2021, to tertiary neonatal intensive care unit (NICU) in Canada and Sweden. Neonates from mothers who were SARS-CoV-2 positive during pregnancy were compared with three randomly selected NICU neonates of mothers who were not test-positive, matched on gestational age, sex, and birth weight (±0.25 SD). Subgroup analyses were conducted for neonates born <33 weeks' gestation and mothers who were SARS-CoV-2 positive ≤10 days prior to birth. Primary outcome was duration of respiratory support. Secondary outcomes were in-hospital mortality, neonatal morbidity, late-onset sepsis, receipt of breast milk at discharge, and length of stay. RESULTS: There were 163 exposed and 468 matched neonates in Canada, and 303 exposed and 903 matched neonates in Sweden. There was no statistically significant difference in invasive or noninvasive respiratory support durations, mortality, respiratory and other neonatal morbidities, or resource utilizations between two groups in both countries in entire cohort and in subgroup analyses. Receipt of breast milk at discharge was lower in the Canadian neonates of mothers who were SARS-CoV-2 positive ≤10 days before birth (risk ratio 0.68, 95% CI: 0.57-0.82). CONCLUSION: Maternal SARS-CoV-2 positivity was not associated with increased durations of respiratory support, morbidities, mortality, or length of hospital stay in Canada and Sweden among neonates admitted to tertiary NICU.

Risk of preterm birth, small for gestational age at birth, and stillbirth after covid-19 vaccination during pregnancy: population based retrospective cohort study.

OBJECTIVE: To assess the risk of preterm birth, small for gestational age at birth, and stillbirth after covid-19 vaccination during pregnancy. DESIGN: Population based retrospective cohort study. SETTING: Ontario, Canada, 1 May to 31 December 2021. PARTICIPANTS: All liveborn and stillborn infants from pregnancies conceived at least 42 weeks before the end of the study period and with gestational age ≥20 weeks or birth weight ≥500 g. MAIN OUTCOME MEASURES: Using Cox regression, hazard ratios and 95% confidence intervals were estimated for preterm birth before 37 weeks (overall and spontaneous preterm birth), very preterm birth (<32 weeks), small for gestational age at birth (<10th centile), and stillbirth. Vaccination against covid-19 was treated as a time varying exposure in the outcome specific risk window, and propensity score weighting was used to adjust hazard ratios for potential confounding. RESULTS: Among 85 162 births, 43 099 (50.6%) occurred in individuals who received one dose or more of a covid-19 vaccine during pregnancy-42 979 (99.7%) received an mRNA vaccine. Vaccination during pregnancy was not associated with any increased risk of overall preterm birth (6.5% among vaccinated v 6.9% among unvaccinated; adjusted hazard ratio 1.02, 95% confidence interval 0.96 to 1.08), spontaneous preterm birth (3.7% v 4.4%; 0.96, 0.90 to 1.03), or very preterm birth (0.59% v 0.89%; 0.80, 0.67 to 0.95). No increase was found in risk of small for gestational age at birth (9.1% v 9.2%; 0.98, 0.93 to 1.03) or stillbirth (0.25% v 0.44%; 0.65, 0.51 to 0.84). Findings were similar by trimester of vaccination, mRNA vaccine product, and number of doses received during pregnancy. CONCLUSION: The findings suggest that vaccination against covid-19 during pregnancy is not associated with a higher risk of preterm birth, small for gestational age at birth, or stillbirth.

Adapting obstetric and neonatal services during the COVID-19 pandemic: a scoping review.

BACKGROUND: The provision of care to pregnant persons and neonates must continue through pandemics. To maintain quality of care, while minimizing physical contact during the Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV2) pandemic, hospitals and international organizations issued recommendations on maternity and neonatal care delivery and restructuring of clinical and academic services. Early in the pandemic, recommendations relied on expert opinion, and offered a one-size-fits-all set of guidelines. Our aim was to examine these recommendations and provide the rationale and context to guide clinicians, administrators, educators, and researchers, on how to adapt maternity and neonatal services during the pandemic, regardless of jurisdiction. METHOD: Our initial database search used Medical subject headings and free-text search terms related to coronavirus infections, pregnancy and neonatology, and summarized relevant recommendations from international society guidelines. Subsequent targeted searches to December 30, 2020, included relevant publications in general medical and obstetric journals, and updated society recommendations. RESULTS: We identified 846 titles and abstracts, of which 105 English-language publications fulfilled eligibility criteria and were included in our study. A multidisciplinary team representing clinicians from various disciplines, academics, administrators and training program directors critically appraised the literature to collate recommendations by multiple jurisdictions, including a quaternary care Canadian hospital, to provide context and rationale for viable options. INTERPRETATION: There are different schools of thought regarding effective practices in obstetric and neonatal services. Our critical review presents the rationale to effectively modify services, based on the phase of the pandemic, the prevalence of infection in the population, and resource availability.

SARS-CoV-2 Positivity in Early Infancy: A National Cohort From Saudi Arabia.

Background: Data on SARS-CoV-2 in infants ≤ 90 days are limited with conflicting reports regarding its presentation and outcomes. Methods: We conducted an ambispective cohort study using prospectively collected Health Electronic Surveillance Network Database by the Ministry of Health, Saudi Arabia. Infants of ≤ 90 days of age who had a positive RT-PCR test for SARS-CoV-2 virus were included. Patients were divided in Early neonatal (0-6 days), late neonatal (7-27 days), and post- neonatal (28-90 days) groups and were compared for clinical characteristics and outcomes by contacting parents and collecting information retrospectively. Results: Of 1,793 infants, 898 infants were included for analysis. Most infants in the early neonatal group had no features of infection (tested based on maternal positivity), whereas most infants in the late and post- neonatal groups were tested because of clinical features of infection. Fever and respiratory signs were the most common presenting feature in the late and post-neonatal groups. Hospitalization was higher in the early neonatal group (80%), compared to the two other groups. The overall mortality in the cohort was 1.6%. Conclusion: SARS-CoV-2 infection in infants ≤ 90 days might not be as rare as previously reported. The clinical presentation varies based on age at positive RT-PCR result.

Outcomes of infants with hypoxic-ischemic encephalopathy during COVID-19 pandemic lockdown in Canada: a cohort study.

PURPOSE: To evaluate change in the severity of hypoxic-ischemic encephalopathy (HIE) and associated morbidities between pre- and during COVID-19 pandemic periods in Canada. METHODS: We conducted a retrospective cohort study extracting the data from level-3 NICUs participating in Canadian Neonatal Network (CNN). The primary outcome was a composite of death in the first week after birth and/or stage 3 HIE (Sarnat and Sarnat). Secondary outcomes included rate and severity of HIE among admitted neonates, overall mortality, brain injury on magnetic resonance imaging (MRI), neonates requiring resuscitation, organ dysfunction, and therapeutic hypothermia (TH) usage. We included 1591 neonates with gestational age ≥ 36 weeks with HIE during the specified periods: pandemic cohort from April 1st to December 31st of 2020; pre-pandemic cohort between April 1st and December 31st of 2017, 2018, and 2019. We calculated the odds ratio (OR) and confidence intervals (CI). RESULTS: We observed no significant difference in the primary outcome (15% vs. 16%; OR 1.08; 95%CI 0.78-1.48), mortality in the first week after birth (6% vs. 6%; OR 1.10, 95%CI 0.69-1.75), neonates requiring resuscitation, organ dysfunction, TH usage, or rate of brain injury. In the ad hoc analysis, per 1000 live births, there was an increase in the rate of infants with HIE and TH use. CONCLUSIONS: Severity of HIE, associated morbidities, and mortality were not significantly different during the pandemic lockdown compared to a pre-pandemic period in Canada. Anticipated risks and difficulties in accessing healthcare have not increased the mortality and morbidities in neonates with HIE in Canada.

Association of SARS-CoV-2 Infection During Pregnancy With Maternal and Perinatal Outcomes.

Importance: There are limited high-quality, population-level data about the effect of SARS-CoV-2 infection on pregnancy using contemporaneous comparator cohorts. Objectives: To describe maternal and perinatal outcomes associated with SARS-CoV-2 infection in pregnancy and to assess variables associated with severe disease in the pregnant population. Design, Setting, and Participants: CANCOVID-Preg is an observational surveillance program for SARS-CoV-2-affected pregnancies in Canada. This analysis presents exploratory, population-level data from 6 Canadian provinces for the period of March 1, 2020, to October 31, 2021. A total of 6012 pregnant persons with a positive SARS-CoV-2 polymerase chain reaction test result at any time in pregnancy (primarily due to symptomatic presentation) were included and compared with 2 contemporaneous groups including age-matched female individuals with SARS-CoV-2 and unaffected pregnant persons from the pandemic time period. Exposure: SARS-CoV-2 infection during pregnancy. Incident infections in pregnancy were reported to CANCOVID-Preg by participating provinces/territories. Main Outcomes and Measures: Maternal and perinatal outcomes associated with SARS-CoV-2 infection as well as risk factors for severe disease (ie, disease requiring hospitalization, admission to an intensive care unit/critical care unit, and/or oxygen therapy). Results: Among 6012 pregnant individuals with SARS-CoV-2 in Canada (median age, 31 [IQR, 28-35] years), the greatest proportion of cases were diagnosed at 28 to 37 weeks' gestation (35.7%). Non-White individuals were disproportionately represented. Being pregnant was associated with a significantly increased risk of SARS-CoV-2-related hospitalization compared with SARS-CoV-2 cases among all women aged 20 to 49 years in the general population of Canada (7.75% vs 2.93%; relative risk, 2.65 [95% CI, 2.41-2.88]) as well as an increased risk of intensive care unit/critical care unit admission (2.01% vs 0.37%; relative risk, 5.46 [95% CI, 4.50-6.53]). Increasing age, preexisting hypertension, and greater gestational age at diagnosis were significantly associated with worse maternal outcomes. The risk of preterm birth was significantly elevated among SARS-CoV-2-affected pregnancies (11.05% vs 6.76%; relative risk, 1.63 [95% CI, 1.52-1.76]), even in cases of milder disease not requiring hospitalization, compared with unaffected pregnancies during the same time period. Conclusions and Relevance: In this exploratory surveillance study conducted in Canada from March 2020 to October 2021, SARS-CoV-2 infection during pregnancy was significantly associated with increased risk of adverse maternal outcomes and preterm birth.

Probable congenital SARS-CoV-2 infection in a neonate born to a woman with active SARS-CoV-2 infection: CMAJ

Kirtsman et al discuss the probable congenital SARS-CoV-2 infection in a neonate born to a woman with active SARS-CoV-2 infection. They present a case study of a 40-year-old woman who was admitted to a tertiary hospital in Toronto, Ontario. She had familial neutropenia, gestational diabetes and a history of frequent bacterial infections during pregnancy, which resolved with antibiotic treatment. Details of the maternal course and outcome have been published separately because of her hematologic condition. A nasopharyngeal swab was positive for suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gene targets via reverse transcription polymerase chain reaction (RT-PCR) testing. There were no fetal concerns during the pregnancy or following admission. A semiurgent cesarean delivery was done under regional anesthesia, with airborne, droplet and contact precautions, owing to worsening coagulopathy and reducing platelet count at 35 weeks. Artificial rupture of membranes was performed at operation. The male neonate was vigorous and did not require resuscitation. His Apgar scores were 9 at 1 minute and 9 at 5 minutes, but all 3 of the neonate's nasopharyngeal swabs were positive for SARS-CoV-2 gene targets via RT-PCR testing.

SARS-CoV-2 Positivity in Early Infancy: A National Cohort From Saudi Arabia

Background Data on SARS-CoV-2 in infants ≤ 90 days are limited with conflicting reports regarding its presentation and outcomes. Methods We conducted an ambispective cohort study using prospectively collected Health Electronic Surveillance Network Database by the Ministry of Health, Saudi Arabia. Infants of ≤ 90 days of age who had a positive RT-PCR test for SARS-CoV-2 virus were included. Patients were divided in Early neonatal (0–6 days), late neonatal (7–27 days), and post- neonatal (28–90 days) groups and were compared for clinical characteristics and outcomes by contacting parents and collecting information retrospectively. Results Of 1,793 infants, 898 infants were included for analysis. Most infants in the early neonatal group had no features of infection (tested based on maternal positivity), whereas most infants in the late and post- neonatal groups were tested because of clinical features of infection. Fever and respiratory signs were the most common presenting feature in the late and post-neonatal groups. Hospitalization was higher in the early neonatal group (80%), compared to the two other groups. The overall mortality in the cohort was 1.6%. Conclusion SARS-CoV-2 infection in infants ≤ 90 days might not be as rare as previously reported. The clinical presentation varies based on age at positive RT-PCR result.

Feasibility of establishing a Canadian Obstetric Survey System (CanOSS) for severe maternal morbidity: a study protocol.

INTRODUCTION: Severe maternal morbidity (SMM)-an unexpected pregnancy-associated maternal outcome resulting in severe illness, prolonged hospitalisation or long-term disability-is recognised by many, as the preferred indicator of the quality of maternity care, especially in high-income countries. Obtaining comprehensive details on events and circumstances leading to SMM, obtained through maternity units, could complement data from large epidemiological studies and enable targeted interventions to improve maternal health. The aim of this study is to assess the feasibility of gathering such data from maternity units across Canadian provinces and territories, with the goal of establishing a national obstetric survey system for SMM in Canada. METHODS AND ANALYSIS: We propose a sequential explanatory mixed-methods study. We will first distribute a cross-sectional survey to leads of all maternity units across Canada to gather information on (1) Whether the unit has a system for reviewing SMM and the nature and format of this system, (2) Willingness to share anonymised data on SMM by direct entry using a web-based platform and (3) Respondents' perception on the definition and leading causes of SMM at a local level. This will be followed by semistructured interviews with respondent groups defined a priori, to identify barriers and facilitators for data sharing. We will perform an integrated analysis to determine feasibility outcomes, a narrative description of barriers and facilitators for data-sharing and resource implications for data acquisition on an annual basis, and variations in top-5 causes of SMM. ETHICS AND DISSEMINATION: The study has been approved by the Mount Sinai and Hamilton Integrated Research Ethics Boards. The study findings will be presented at annual scientific meetings of the Society of Obstetricians and Gynaecologists of Canada, North American Society of Obstetric Medicine, and International Network of Obstetric Survey Systems and published in an open-access peer-reviewed Obstetrics and Gynaecology or General Internal Medicine journal.

Association of COVID-19 Vaccination in Pregnancy With Adverse Peripartum Outcomes.

Importance: There is limited comparative epidemiological evidence on outcomes associated with COVID-19 vaccination during pregnancy; monitoring pregnancy outcomes in large populations is required. Objective: To evaluate peripartum outcomes following COVID-19 vaccination during pregnancy. Design, Setting, and Participants: Population-based retrospective cohort study in Ontario, Canada, using a birth registry linked with the provincial COVID-19 immunization database. All births between December 14, 2020, and September 30, 2021, were included. Exposures: COVID-19 vaccination during pregnancy, COVID-19 vaccination after pregnancy, and no vaccination. Main Outcomes and Measures: Postpartum hemorrhage, chorioamnionitis, cesarean delivery (overall and emergency cesarean delivery), admission to neonatal intensive care unit (NICU), and low newborn 5-minute Apgar score (<7). Linear and robust Poisson regression was used to generate adjusted risk differences (aRDs) and risk ratios (aRRs), respectively, comparing cumulative incidence of outcomes in those who received COVID-19 vaccination during pregnancy with those vaccinated after pregnancy and those with no record of COVID-19 vaccination at any point. Inverse probability of treatment weights were used to adjust for confounding. Results: Among 97 590 individuals (mean [SD] age, 31.9 [4.9] years), 22 660 (23%) received at least 1 dose of COVID-19 vaccine during pregnancy (63.6% received dose 1 in the third trimester; 99.8% received an mRNA vaccine). Comparing those vaccinated during vs after pregnancy (n = 44 815), there were no significantly increased risks of postpartum hemorrhage (incidence: 3.0% vs 3.0%; aRD, -0.28 per 100 individuals [95% CI, -0.59 to 0.03]; aRR, 0.91 [95% CI, 0.82-1.02]), chorioamnionitis (0.5% vs 0.5%; aRD, -0.04 per 100 individuals [95% CI, -0.17 to 0.09]; aRR, 0.92 [95% CI, 0.70-1.21]), cesarean delivery (30.8% vs 32.2%; aRD, -2.73 per 100 individuals [95% CI, -3.59 to -1.88]; aRR, 0.92 [95% CI, 0.89-0.95]), NICU admission (11.0% vs 13.3%; aRD, -1.89 per 100 newborns [95% CI, -2.49 to -1.30]; aRR, 0.85 [95% CI, 0.80-0.90]), or low Apgar score (1.8% vs 2.0%; aRD, -0.31 per 100 newborns [95% CI, -0.56 to -0.06]; aRR, 0.84 [95% CI, 0.73-0.97]). Findings were qualitatively similar when compared with individuals who did not receive COVID-19 vaccination at any point (n = 30 115). Conclusions and Relevance: In this population-based cohort study in Ontario, Canada, COVID-19 vaccination during pregnancy, compared with vaccination after pregnancy and with no vaccination, was not significantly associated with increased risk of adverse peripartum outcomes. Study interpretation should consider that the vaccinations received during pregnancy were primarily mRNA vaccines administered in the second and third trimester.

Coronavirus disease 2019 pandemic and pregnancy and neonatal outcomes in general population: A living systematic review and meta-analysis (updated Aug 14, 2021).

INTRODUCTION: Conflicting reports of increases and decreases in rates of preterm birth (PTB) and stillbirth in the general population during the coronavirus disease 2019 (COVID-19) pandemic have surfaced. The objective of our study was to conduct a living systematic review and meta-analyses of studies reporting pregnancy and neonatal outcomes by comparing the pandemic and pre-pandemic periods. MATERIAL AND METHODS: We searched PubMed and Embase databases, reference lists of articles published up until August 14, 2021 and included English language studies that compared outcomes between the COVID-19 pandemic time period and the pre-pandemic time periods. Risk of bias was assessed using the Newcastle-Ottawa scale. We conducted random-effects meta-analysis using the inverse variance method. RESULTS: Forty-five studies with low-to-moderate risk of bias, reporting on 1 843 665 pregnancies during the pandemic period and 23 564 552 pregnancies during the pre-pandemic period, were included. There was significant reduction in unadjusted estimates of PTB (35 studies, unadjusted odds ratio [uaOR] 0.95, 95% CI 0.92-0.98), but not in adjusted estimates (six studies, adjusted OR [aOR] 0.95, 95% CI 0.80-1.13). This reduction was noted in studies from single centers/health areas (25 studies, uaOR 0.90, 95% CI 0.86-0.96) but not in regional/national studies (10 studies, uaOR 0.99, 95% CI 0.95-1.02). There was reduction in spontaneous PTB (six studies, uaOR 0.89, 95% CI 0.81-0.96) and induced PTB (five studies, uaOR 0.89, 95% CI 0.81-0.97). There was no difference in the odds of stillbirth between the pandemic and pre-pandemic time periods (24 studies, uaOR 1.11, 95% CI 0.97-1.26 and four studies, aOR 1.06, 95% CI 0.81-1.38). There was an increase in mean birthweight during the pandemic period compared with the pre-pandemic period (six studies, mean difference 17 g, 95% CI 7-28 g). The odds of maternal mortality were increased (four studies, uaOR 1.15, 95% CI 1.05-1.26); however, only unadjusted estimates were available and the result was mostly influenced by one study from Mexico. There was significant publication bias for the outcome of PTB. CONCLUSIONS: The COVID-19 pandemic may be associated with a reduction in PTB; however, referral bias cannot be excluded. There was no statistically significant difference in stillbirth between pandemic and pre-pandemic periods.

Preterm birth and stillbirth rates during the COVID-19 pandemic: a population-based cohort study.

BACKGROUND: Conflicting reports have emerged for rates of preterm births and stillbirths during the COVID-19 pandemic. Most of these reports did not account for natural variation in these rates. We aimed to evaluate variations in preterm birth and stillbirth rates before and during the COVID-19 pandemic in Ontario, Canada. METHODS: We conducted a retrospective cohort study using linked population health administrative databases of pregnant people giving birth in any hospital in Ontario between July 2002 and December 2020. We calculated preterm birth and stillbirth rates. We assessed preterm birth at 22-28, 29-32 and 33-36 weeks' gestation, and stillbirths at term and preterm gestation. We used Laney control P' charts for the 18-year study period (6-mo observation periods) and interrupted time-series analyses for monthly rates for the most recent 4 years. RESULTS: We evaluated 2 465 387 pregnancies, including 13 781 that resulted in stillbirth. The mean preterm birth rate for our cohort was 7.96% (range 7.32%-8.59%). From January to December 2020, we determined that the preterm birth rate in Ontario was 7.87%, with no special cause variation. The mean stillbirth rate for the cohort was 0.56% (range 0.48%-0.70%). From January to December 2020, the stillbirth rate was 0.53%, with no special cause variation. We did not find any special cause variation for preterm birth or stillbirth subgroups. We found no changes in slope or gap between prepandemic and pandemic periods using interrupted time-series analyses. INTERPRETATION: In Ontario, Canada, we found no special cause variation (unusual change) in preterm birth or stillbirth rates, overall or by subgroups, during the first 12 months of the COVID-19 pandemic compared with the previous 17.5 years.