Maternal SARS-CoV-2 infection during pregnancy and child neurodevelopmental outcomes: A systematic review and meta-analysis of observational studies.

OBJECTIVE

To assess: (a) associations between prenatal SARS-CoV-2 exposure and early childhood neurodevelopmental outcomes, and (b) whether these varied by infection trimester.

METHODS

We conducted a systematic review and meta-analysis of observational studies modelling the neurodevelopmental outcomes of children prenatally exposed to SARS-CoV-2 compared to unexposed children. PubMed and PsychInfo were systematically searched from inception to March 2025. Primary analysis was random-effects modelling of overall associations. Secondary analysis assessed variation by trimester via standardised mean differences (SMD).

RESULTS

11 observational studies were included. Overall, there was no statistically significant association between prenatal SARS-CoV-2 exposure and early childhood neurodevelopmental outcomes, both before (odds ratio: 1.08; 95% confidence intervals: 0.82, 1.42) and after (odds ratio: 0.98; 95% CI: 0.81, 1.17) excluding high variance studies. First trimester prenatal SARS-CoV-2 exposure was associated with poorer neurodevelopmental scores (3.87; 95% CI: 3.19, 4.55) than prenatal exposure in the second trimester (6.07; 95% CI: 5.11, 7.03) or third trimester (6.31; 95% CI: 5.54, 7.09). However, this analysis was limited to three studies only, with high heterogeneity between studies.

CONCLUSIONS

Prenatal SARS-CoV-2 exposure is not associated with early childhood neurodevelopmental outcomes. Future research should keep monitoring associations as more data becomes available. More robust research is required on trimester-specific associations.