Systematic Review and Meta-Analysis: The Associations of Prenatal Exposure to SARS-CoV-2 Infection and COVID-19 Vaccination With Child Neurodevelopment

Objective: To systematically review and meta-analyze evidence on the associations between prenatal exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection or COVID-19 vaccination and child neurodevelopmental outcomes. Method(s): MEDLINE, EMBASE, PsycINFO, Web of Science, Scopus, and Cochrane CENTRAL databases were searched for original research on neurodevelopmental outcomes in children prenatally exposed to SARS-CoV-2 infection and COVID-19 vaccination published in any language before November 8, 2024. Meta-analyses were performed on any outcome reported in >=3 controlled studies. Result(s): A total of 70 studies were identified on neurological (7), neuroimaging (12), motor (3), audiological (29), and neurodevelopmental (35) assessments and neurodevelopmental disorders (2) with median sample sizes of 117 (interquartile range: 44-340) and follow-up <=36 months. Meta-analyses of neonatal auditory screenings (10), Ages and Stages Questionnaire, 3rd Edition (9), and Ages and Stages Questionnaire: Social-Emotional (3) data suggested a higher risk of transient hearing impairment (risk ratio 2.01, 95% CI 1.39-2.91) and delays in fine motor (risk ratio 1.55, 95% CI 1.14-2.10) and problem-solving (risk ratio 1.32, 95% CI 1.01-1.74) skills in children prenatally exposed to SARS-CoV-2 compared with unexposed children. Conclusion(s): Prenatal SARS-CoV-2 exposure was associated with early impairments in hearing, fine motor skills, and problem-solving skills, which appear to resolve with time. No associations were identified with atypical neurological or neuroimaging outcomes. No adverse neurodevelopmental effects were reported in 2 studies that examined prenatal COVID-19 vaccination. Study quality was generally moderate, with small sample sizes, inappropriate control groups, and unmeasured confounding. Taken together, the current body of research does not support a causal relation between prenatal exposure to SARS-CoV-2 infection or COVID-19 vaccination and adverse neurodevelopmental outcomes. Study registration information: The Association of Intrauterine Exposure to SARS-CoV-2 and the COVID-19 Vaccine With Child Neurodevelopment: A Systematic Review; Copyright © 2025 American Academy of Child and Adolescent Psychiatry