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.

Setting

Case-control and cohort studies from any location published after 1st January 2020, including pre-print articles.

Participants

Neonates born to pregnant women diagnosed with a SARS-CoV-2 infection at any stage during pregnancy, including asymptomatic women.

Primary and secondary outcome measures

Neonatal mortality and morbidity, including 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 outcomes were selected according to a Core Outcome Set developed between health professionals, researchers and parents.

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 is limited data on neonatal morbidity and mortality following maternal SARS-CoV-2 infection in pregnancy, particularly from low-income countries and following early pregnancy infections. Large, representative studies addressing these outcomes are needed to better understand the consequences for babies born to women with SARS-CoV-2 in pregnancy.

Trial registration

PROSPERO ID: CRD42021249818

Strengths and limitations

• Inclusion of studies of both asymptomatic and symptomatic SARS-CoV-2 infections at any point in pregnancy to maximise generalisability of findings

• Focus on neonatal outcomes, as opposed to purely obstetric outcomes, to accurately quantify neonatal morbidity

• Study is limited by available data; important data gap in low-income settings