Prenatal SARS‐CoV‐2 infection, COVID‐19 vaccination, and preschool neurodevelopment: A confounder‐adjusted cohort study

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Abstract Background The impact of maternal SARS‐CoV‐2 infection and COVID‐19 vaccination during pregnancy on child neurodevelopment remains unclear, with most studies limited by small samples and short follow‐up periods. This prospective cohort study assesses internalizing, externalizing, total problem behaviors, and social responsiveness in children prenatally exposed or unexposed to maternal SARS‐CoV‐2 infection or COVID‐19 vaccination. Methods The study leveraged a large NYC pregnancy cohort with detailed information on maternal infection and vaccination during pregnancy. Outcomes included parent‐reported CBCL and SRS. Analyses were adjusted for key sociodemographic and clinical factors, including race/ethnicity, maternal mental health condition, and child age at assessment. Results The study included 675 children (mean age = 3.2 years, SD = 0.8, 50.7% male), comprising 118 children prenatally exposed to SARS‐CoV‐2 and 557 unexposed. Regression analyses showed no significant associations between prenatal SARS‐CoV‐2 exposure and CBCL Internalizing ( β = 0.04 [95% CI: −0.85, 0.88]), CBCL Externalizing ( β = −0.31 [95% CI: −1.41, 0.87]), CBCL Total Problems ( β = −0.50 [95% CI: −3.46, 2.51]), and SRS ( β = −0.60 [95% CI: −4.09, 3.17]) scores. Comparing children prenatally exposed ( n = 68) and unexposed ( n = 607) to COVID‐19 vaccination revealed no significant associations with CBCL Internalizing ( β = 0.41 [95% CI: −0.52, 1.44]), CBCL Externalizing ( β = 1.42 [95% CI: −0.32, 2.95]), CBCL Total Problems ( β = 2.13 [95% CI: −1.22, 6.15]), and SRS ( β = −3.65 [95% CI: −7.93, 0.32]) scores. Sociodemographic covariates, such as race/ethnicity and educational attainment, were significantly associated with all neurodevelopmental outcomes. Conclusion Prenatal exposure to SARS‐CoV‐2 infection or COVID‐19 vaccination was not associated with adverse neurodevelopmental outcomes in preschool children. Sociodemographic factors showed stronger associations than infection or vaccination, underscoring the importance of confounder adjustment. Findings provide reassurance to pregnant individuals regarding potential long‐term neurodevelopmental outcomes in offspring following SARS‐CoV‐2 infection or COVID‐19 vaccination during pregnancy.