COVID-19 pandemic and population-level pregnancy and neonatal outcomes in general population: A living systematic review and meta-analysis (Update#2: November 20, 2021)

Abstract

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 the PubMed and Embase databases and reference lists of articles published up until November 20, 2021, and included English language studies that compared outcomes between the COVID-19 pandemic time period with 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: Fifty-two studies with low-to-moderate risk of bias, reporting on 2 372 521 pregnancies during the pandemic period and 28 518 300 pregnancies during the pre-pandemic period, were included. There was significant reduction in unadjusted estimates of PTB (43 studies, unadjusted odds ratio [uaOR] 0.95, 95% CI 0.93-0.98), but not in adjusted estimates (five studies, adjusted OR [aOR] 0.94, 95% CI 0.74-1.19). This reduction was noted in studies from single centers/health areas (29 studies, uaOR 0.90, 95% CI 0.85-0.94) but not in regional/national studies (14 studies, uaOR 0.99, 95% CI 0.99-1.01). There was reduction in spontaneous PTB (nine studies, uaOR 0.91, 95% CI 0.88-0.94) but not in induced PTB (eight studies, uaOR 0.90, 95% CI 0.79-1.01). There was no difference in the odds of stillbirth between the pandemic and pre-pandemic time periods (32 studies, uaOR 1.07, 95% CI 0.97-1.18 and three studies, aOR 1.18, 95% CI 0.86-1.63). There was an increase in mean birthweight during the pandemic period compared with the pre-pandemic period (nine studies, mean difference 21 g, 95% CI 13-30 g). The odds of maternal mortality were increased (five 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 stillbirths between pandemic and pre-pandemic periods.

Keywords: birthweight; epidemic; maternal mortality; neonatal mortality; preterm birth; severe acute respiratory syndrome coronavirus 2; stillbirth; stress.