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COVID-19 pandemic and population-level pregnancy and neonatal outcomes: a living systematic review and meta-analysis.

ABSTRACT:

Introduction

Conflicting reports of increases and decreases in rates of preterm birth (PTB) and stillbirth in the general population during the 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 14 May 2021 and included English language studies that compared outcomes between the COVID-19 pandemic time period and 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

Thirty-seven studies with low-to-moderate risk of bias, reporting on 1 677 858 pregnancies during the pandemic period and 21 028 650 pregnancies during the pre-pandemic period, were included. There was a significant reduction in unadjusted estimates of PTB (28 studies, unadjusted odds ratio [uaOR] 0.94, 95% confidence [CI] 0.91-0.98) but not in adjusted estimates (six studies, adjusted OR [aOR] 0.95, 95% CI 0.80-1.13). The reduction was noted in studies from single centers/health areas (uaOR 0.90, 95% CI 0.86-0.94) but not in regional/national studies (uaOR 0.99, 95% CI 0.95-1.03). There was reduction in spontaneous PTB (five studies, uaOR 0.89, 95% CI 0.82-0.98) and induced PTB (four studies, uaOR 0.90, 95% CI 0.81-1.00). There was no reduction in PTB when stratified by gestational age <34, <32 or <28 weeks. There was no difference in stillbirths between the pandemic and pre-pandemic time periods (21 studies, uaOR 1.08, 95% CI 0.94-1.23; four studies, aOR 1.06, 95% CI 0.81-1.38). There was an increase in birthweight (six studies, mean difference 17 g, 95% CI 7-28 g) during the pandemic period. There was an increase in maternal mortality (four studies, uaOR 1.15, 95% CI 1.05-1.26), which was mostly influenced by one study from Mexico. There was significant publication bias for the outcome of PTB.

Conclusions

The COVID-19 pandemic time period may be associated with a reduction in PTB; however, referral bias cannot be excluded. There was no difference in stillbirth between the pandemic and pre-pandemic period.

SUBMITTER: Yang J

PROVIDER: S-EPMC8222877 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionConflicting 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 methodsWe 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.ResultsForty-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.ConclusionsThe 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.

Project description:ObjectivesThe low COVID-19 vaccine uptake rate among pregnant women is mainly due to safety concerns about COVID-19 vaccines due to limited safety evidence. Our goal was to evaluate the safety of COVID-19 vaccination during pregnancy with up-to-date evidence.MethodsA comprehensive search of MEDLINE, EMBASE, the Cochrane Library, and clinicaltrials.gov was performed on April 5th, 2022, and updated on May 25th, 2022. Studies evaluating the association of COVID-19 vaccination during pregnancy with adverse maternal and neonatal outcomes were included. Two reviewers independently performed the risk of bias assessment and data extraction. Inverse variance random effect meta-analyses were performed to pool outcome data.ResultsForty-three observational studies were included. COVID-19 vaccination [96,384 (73.9%) BNT162b2, 30,889 (23.7%) mRNA-1273, and 3,172 (2.4%) other types] during pregnancy [23,721 (18.3%) in the first trimester, 52,778 (40.5%) in the second trimester, and 53,886 (41.2%) in the third trimester].was associated with reduced risks of stillbirth or neonatal death (OR, 0.74; 95% CI, 0.60-0.92). Sensitivity analysis restricted to studies in participants without COVID-19 showed that the pooled effect was not robust. COVID-19 vaccination during pregnancy was not associated with congenital anomalies (OR, 0.83; 95% CI, 0.63-1.08), preterm birth (OR, 0.98; 95% CI, 0.90-1.06), NICU admission or hospitalization (OR, 0.94; 95% CI, 0.84-1.04), an Apgar score at 5 min <7 (OR, 0.93; 95% CI, 0.86-1.01), low birth weight (OR, 1.00; 95% CI, 0.88-1.14), miscarriage (OR, 0.99; 95% CI, 0.88-1.11), cesarean delivery (OR, 1.07; 95% CI, 0.96-1.19), or postpartum hemorrhage (OR, 0.91; 95% CI, 0.81-1.01).ConclusionsCOVID-19 vaccination during pregnancy was not associated with any of the adverse neonatal or maternal outcomes studied. Interpretation of study findings is limited by the types and timing of vaccination. The vaccinations in our study received during pregnancy were primarily mRNA vaccines administered in the second and third trimester. Future RCTs and meta-analysis are warranted to evaluate the efficacy and long-term effects of the COVID-19 vaccines.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022322525, identifier: PROSPERO, CRD42022322525.

Project description:ObjectiveCOVID-19 is a rapidly changing and developing emergency that requires constant re-evaluation of available data. We report a systematic review and meta-analysis based on all published high-quality data up to and including June 3, 2021 on the maternal and neonatal outcomes in pregnant women infected with COVID-19.Data sourcesPubMed, SCOPUS, MEDLINE, ClinicalTrials.gov, and Web of Science databases were queried from inception up to June 3, 2021.Study eligibility criteriaWe included all clinical studies (prospective and retrospective cohort studies, case-control studies, case series, and rapid communications) that reported data on any maternal and neonatal outcomes of pregnant women with COVID-19.MethodsThe data were analyzed as pooled proportions or odds ratios and 95% confidence intervals in meta-analysis models.ResultsWe included 111 studies enrolling 42,754 COVID-19-positive pregnant women. From COVID-19-positive pregnant women, the incidence rates were 53.2% (95% confidence interval, 48-58.4) for cesarean delivery, 41.5% (95% confidence interval, 36.3-46.8) for spontaneous vaginal delivery, and 6.4% (95% confidence interval, 4.5-9.2) for operative delivery. The rates of some adverse neonatal events, including premature delivery (16.7%; 95% confidence interval, 12.8-21.5) and low birthweight (16.7%; 95% confidence interval, 12.8-21.5) were relatively high in mothers infected with COVID-19. Vertical transmission (3.5%; 95% confidence interval, 2.7-4.7), neonatal death (3%; 95% confidence interval, 2-4), stillbirth (1.9%; 95% confidence interval, 1.5-2.4), and maternal mortality (0.012%; 95% confidence interval, 0.010-0.014) were rare adverse events. The mean birthweight was 3069.7 g (95% confidence interval, 3009.7-3129.8 g). In the comparative analysis, COVID-19 significantly increased the risk of premature delivery (odds ratio, 1. 48 [95% confidence interval, 1.22-1.8]), preeclampsia (odds ratio, 1.6 [95% confidence interval, 1.2-2.1]), stillbirth (odds ratio, 2.36 [95% confidence interval, 1.24-4.462]), neonatal mortality (odds ratio, 3.35 [95% confidence interval, 1.07-10.5]), and maternal mortality (odds ratio, 3.08 [95% confidence interval, 1.5-6.3]). The pooled analyses were homogenous, with mild heterogeneity in premature delivery and preeclampsia outcomes.ConclusionThe data must be interpreted with caution as limited data are available, and no complete assessment of bias is possible at this time. Our data suggest that pregnant women who test positive for COVID-19 seem to be at a higher risk of lower birth weights and premature delivery. There is no evidence at this time of the sharply increased maternal mortality that was seen previously with both the 2003 SARS and 2012 MERS pandemics.

Project description:ObjectiveTo assess perinatal outcomes for pregnancies affected by suspected or confirmed SARS-CoV-2 infection.MethodsProspective, web-based registry. Pregnant women were invited to participate if they had suspected or confirmed SARS-CoV-2 infection between 1st January 2020 and 31st March 2021 to assess the impact of infection on maternal and perinatal outcomes including miscarriage, stillbirth, fetal growth restriction, pre-term birth and transmission to the infant.ResultsBetween April 2020 and March 2021, the study recruited 8239 participants who had suspected or confirmed SARs-CoV-2 infection episodes in pregnancy between January 2020 and March 2021. Maternal death affected 14/8197 (0.2%) participants, 176/8187 (2.2%) of participants required ventilatory support. Pre-eclampsia affected 389/8189 (4.8%) participants, eclampsia was reported in 40/ 8024 (0.5%) of all participants. Stillbirth affected 35/8187 (0.4 %) participants. In participants delivering within 2 weeks of delivery 21/2686 (0.8 %) were affected by stillbirth compared with 8/4596 (0.2 %) delivering ≥ 2 weeks after infection (95 % CI 0.3-1.0). SGA affected 744/7696 (9.3 %) of livebirths, FGR affected 360/8175 (4.4 %) of all pregnancies. Pre-term birth occurred in 922/8066 (11.5%), the majority of these were indicated pre-term births, 220/7987 (2.8%) participants experienced spontaneous pre-term births. Early neonatal deaths affected 11/8050 livebirths. Of all neonates, 80/7993 (1.0%) tested positive for SARS-CoV-2.ConclusionsInfection was associated with indicated pre-term birth, most commonly for fetal compromise. The overall proportions of women affected by SGA and FGR were not higher than expected, however there was the proportion affected by stillbirth in participants delivering within 2 weeks of infection was significantly higher than those delivering ≥ 2 weeks after infection. We suggest that clinicians' threshold for delivery should be low if there are concerns with fetal movements or fetal heart rate monitoring in the time around infection. The proportion affected by pre-eclampsia amongst participants was not higher than would be expected, although we report a higher than expected proportion affected by eclampsia. There appears to be no effect on birthweight or congenital malformations in women affected by SARS-CoV-2 infection in pregnancy and neonatal infection is uncommon. This study reflects a population with a range of infection severity for SARS-COV-2 in pregnancy, generalisable to whole obstetric populations.

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Project description:Vitamin D has well-defined classical functions related to calcium metabolism and bone health but also has non-classical effects that may influence other aspects of health. There has been considerable recent interest in the role of vitamin D on outcomes related to pregnancy and young child health but few efforts have been made to systematically consolidate this evidence to inform the research and policy agenda for low-income countries. A systematic review was undertaken to identify intervention and observational studies of vitamin D supplementation, intake or status (25-hydroxy-vitamin D) during pregnancy on perinatal and infant health outcomes. Data from trials and observational studies isolating the effect of vitamin D supplementation and intake were extracted and study quality was evaluated. Meta-analysis was used to pool effect estimates. We identified five randomised trials with outcomes of relevance to our review. All had small sample size and dosage amount, duration and frequency varied as did the ability to correct deficiency. Pooled analysis of trials using fixed-effects models suggested protective effects of supplementation on low birthweight (three trials, risk ratio (RR) = 0.40 [95% confidence interval (CI) 0.23, 0.71]) and non-significant but suggestive effects of daily supplementation on small-for-gestational age (two trials, RR = 0.67 [0.40, 1.11]). No effect on preterm delivery (<37 weeks) was evident (two trials, RR = 0.77 [0.35, 1.66]). Little evidence from trials exists to evaluate the effect of vitamin D supplementation during pregnancy on maternal, perinatal or infant health outcomes. Based on both trials and observational studies, we recommend that future research explore small-for-gestational age, preterm delivery, pre-eclampsia, and maternal and childhood infections, as outcomes of interest. Trials should focus on populations with a high prevalence of vitamin D deficiency, explore the relevance of timing of supplementation, and the dosage used in such trials should be sufficient to correct deficiency.

Project description:AimsThe aim of this study was to continually evaluate the association between cardiovascular drug exposure and COVID-19 clinical outcomes (susceptibility to infection, disease severity, hospitalization, hospitalization length, and all-cause mortality) in patients at risk of/with confirmed COVID-19.MethodsEligible publications were identified from more than 500 databases on 1 November 2020. One reviewer extracted data with 20% of the records independently extracted/evaluated by a second reviewer.ResultsOf 52 735 screened records, 429 and 390 studies were included in the qualitative and quantitative syntheses, respectively. The most-reported drugs were angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) with ACEI/ARB exposure having borderline association with confirmed COVID-19 infection (OR 1.14, 95% CI 1.00-1.31). Among COVID-19 patients, unadjusted estimates showed that ACEI/ARB exposure was associated with hospitalization (OR 1.76, 95% CI 1.34-2.32), disease severity (OR 1.40, 95% CI 1.26-1.55) and all-cause mortality (OR 1.22, 95% CI 1.12-1.33) but not hospitalization length (mean difference -0.27, 95% CI -1.36-0.82 days). After adjustment, ACEI/ARB exposure was not associated with confirmed COVID-19 infection (OR 0.92, 95% CI 0.71-1.19), hospitalization (OR 0.93, 95% CI 0.70-1.24), disease severity (OR 1.05, 95% CI 0.81-1.38) or all-cause mortality (OR 0.84, 95% CI 0.70-1.00). Similarly, subgroup analyses involving only hypertensive patients revealed that ACEI/ARB exposure was not associated with confirmed COVID-19 infection (OR 0.93, 95% CI 0.79-1.09), hospitalization (OR 0.84, 95% CI 0.58-1.22), hospitalization length (mean difference -0.14, 95% CI -1.65-1.36 days), disease severity (OR 0.92, 95% CI 0.76-1.11) while it decreased the odds of dying (OR 0.76, 95% CI 0.65-0.88). A similar trend was observed for other cardiovascular drugs. However, the validity of these findings is limited by a high level of heterogeneity and serious risk of bias.ConclusionCardiovascular drugs are not associated with poor COVID-19 outcomes in adjusted analyses. Patients should continue taking these drugs as prescribed.