Maternal, perinatal, neonatal, and postpartum outcomes following Severe Acute Respiratory Syndrome - Coronavirus-2 infection in pregnancy: a World Health Organization multi-country prospective cohort study.

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has raised global concerns regarding its impact on pregnant women and their infants, particularly across evolving variants. This study aimed to determine if infection during pregnancy increased the risk of adverse maternal, perinatal, neonatal, or postpartum outcomes during pre-Omicron and Omicron periods.

Methods: We conducted a prospective cohort study in 10 primarily low- and middle-income countries, comprising public and private maternity hospitals in rural and urban areas. Maternal age and comorbidity adjusted mixed-effects models with country-specific random intercepts were used to estimate relative risks (RRs) comparing participants with and without infection during pregnancy and assess differences by variant period (pre-Omicron vs. Omicron). A total of 16,005 pregnant women were consecutively recruited (all eligible women were enrolled in sequence as they presented at the study facilities) between January 2021 and October 2023 and followed from enrollment through delivery and to six weeks postpartum. Main outcomes included maternal outcomes (haemorrhage, hypertensive disorders of pregnancy, emergency caesarean delivery, maternal death, and modified maternal morbidity and mortality index (MMMI)), and perinatal and neonatal outcomes (preterm birth, congenital anomalies, neonatal intensive care unit (NICU) admission, and severe perinatal morbidity and mortality index (SPMMI)).

Results: Based on reverse transcription polymerase chain reaction (RT-PCR) or antigen (Ag) testing and serial serology, 2,187 participants had confirmed SARS-CoV-2 infection during pregnancy, 116 were classified as probable infection, 7,332 as possible infection, 402 participants were probably uninfected, 1,053 had no evidence of infection, and 4,915 had unknown infection status. During the pre-Omicron era, infected women had higher risks of emergency caesarean delivery (RR 1.26, CI 1.03-1.55); MMMI (RR 1.28, CI 1.13-1.45), preterm birth < 37 weeks (RR 1.73, CI 1.31-2.28), < 34 weeks (RR 3.67, CI 1.92-7.04), < 32 weeks (RR 7.62, CI 2.16-26.85), NICU admission (RR 1.90, CI 1.28-2.83) and SPMMI (RR 1.76, CI 1.01-3.06). During the Omicron era, only preterm birth < 34 weeks remained at significantly elevated risk (RR 1.88, CI 1.04-3.05).

Conclusions: SARS-CoV-2 infection during pregnancy was associated with an increased risk of adverse maternal, perinatal, and neonatal outcomes in the pre-Omicron era, with attenuation during the Omicron period. Persistent elevated risk for preterm birth < 34 weeks underscores the need for ongoing evaluation with emerging variants.