Neonatal outcomes and indirect consequences following maternal SARS-CoV-2 infection in pregnancy: A systematic review

Objectives: Identify the association between maternal SARS-CoV-2 infection in pregnancy and individual neonatal morbidities and outcomes, particularly longer-term outcomes such as neurodevelopment. Design: Systematic review of outcomes of neonates born to pregnant women diagnosed with a SARS-CoV-2 infection at any stage during pregnancy, including asymptomatic women. Data sources: MEDLINE, Embase, Global Health, WHOLIS and LILACS databases, last searched 28th July 2021. Eligibility criteria: Case-control and cohort studies published after 1st January 2020, including pre-print articles were included. Study outcomes included neonatal mortality and morbidity, preterm birth, Caesarean delivery, small for gestational age, admission to neonatal intensive care unit, level of respiratory support required, diagnosis of culture-positive sepsis, evidence of brain injury, necrotising enterocolitis, visual or hearing impairment, neurodevelopmental outcomes, and feeding method. These were selected according to a Core Outcome Set. Data extraction and synthesis: Data were extracted into Microsoft Excel by 2 researchers, with statistical analysis completed using IBM SPSS. Risk of bias was assessed using a modified Newcastle-Ottawa scale. Results: The search returned 3234 papers, from which 204 were included with a total of 45,646 infants born to mothers with SARS-CoV-2 infection during pregnancy across 36 countries. We found limited evidence of an increased risk of some neonatal morbidities, including respiratory disease. There was minimal evidence from low-income settings (1 study) and for neonatal outcomes following first trimester infection (17 studies). Neonatal mortality was very rare. Preterm birth, neonatal unit admission and small for gestational age status were more common in infants born following maternal SARS-CoV-2 infection in pregnancy in most larger studies. Conclusions: There are limited data on neonatal morbidity and mortality following maternal SARS-CoV-2 infection, particularly from low-income countries and following early pregnancy infections. Large, representative studies addressing these outcomes are needed to understand the consequences for babies born to women with SARS-CoV-2. Trial registration: PROSPERO ID: CRD4202124981