Maternal, perinatal, neonatal, and postpartum outcomes following SARS-CoV-2 infection in pregnancy: A WHO multi-country prospective cohort study

Background Our aim was to determine if SARS-CoV-2 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 across 43 health facilities, in 10 predominantly primarily low- and middle-income countries, comprising mainly maternity, public and private hospitals in rural and urban areas. A total of 16,007 pregnant women were consecutively recruited between January 2021 and October 2023 (75% in pre-Omicron period and 25% in Omicron period), followed from enrollment through delivery and to six weeks postpartum. The main outcomes are: miscarriage, haemorrhage, preeclampsia/eclampsia, hypertensive disorders of pregnancy, thromboembolic disease, preterm labour, placental abruption, near-miss at delivery, Cesarean delivery, maternal death, modified maternal morbidity and mortality index (MMMI); stillbirth, preterm birth, low birth weight, congenital anomalies, NICU admission, perinatal death, severe perinatal morbidity and mortality index (SPMMI); haemorrhage, infection, or readmission to hospital during postpartum period. Results Based on RT-PCR or antigen testing at enrolment and serial serologic testing, 2,189 participants had confirmed SARS-CoV-2 infection during pregnancy, 116 were classified as probable infection, 7,332 as possible infection, 402 participants were considered probably uninfected, 1,053 had no evidence of infection, and 4,915 had unknown infection status. During the pre-Omicron era, the risk of several outcomes was significantly higher among the infected group compared to those uninfected: emergency Cesarean delivery (RR 1.26, CI 1.03–1.53); MMMI (RR 1.27, CI 1.12–1.44), preterm birth < 37 weeks (RR 1.73, CI 1.32–2.28), < 34 weeks (RR 3.69, CI 1.92–7.09), < 32 weeks (RR 7.58, CI 2.19–26.19), NICU admission (RR 1.90, CI 1.28–2.82) and SPMMI (RR 1.76, CI 1.01–3.05). During the Omicron era, the only outcome with a significantly elevated risk was preterm birth < 34 weeks (RR 1.88, CI 1.04–3.39). Conclusions SARS-CoV-2 infection during pregnancy was associated with an increased risk of several adverse maternal, perinatal, and neonatal outcomes, particularly in the pre-Omicron era. These risks were largely attenuated during the Omicron period; however, the persistent elevated risk for preterm birth < 34 weeks gestation underscores the need for updated evidence on SARS-CoV-2 infection and pregnancy outcomes, especially in relation to emerging Omicron sub-variants.