SARS-CoV-2 mRNA Vaccination in Pregnancy and Child Neurodevelopment at 18 to 30 Months

Importance Little is known about neurodevelopmental outcomes of children exposed to SARS-CoV-2 messenger RNA (mRNA) vaccine during pregnancy. Evidence on long-term offspring outcomes after in utero exposure to SARS-CoV-2 mRNA vaccination is needed to inform vaccine recommendations in pregnancy. Objective To evaluate whether there is an association between SARS-CoV-2 vaccination during or shortly before pregnancy and offspring neurodevelopmental measures. Design, Setting, and Participants This multicenter, prospective, cohort study of 18- to 30-month-old children was conducted at 14 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network from 2024 through 2025. Women who received a SARS-CoV-2 mRNA vaccine during or within 30 days prior to pregnancy (exposed) were matched with women who did not (unexposed) by delivery site, delivery date, insurance status, and race and ethnicity. These data were analyzed from June 2025 to May 2026. Exposures Maternal receipt of at least 1 dose of an mRNA SARS-CoV-2 vaccine during, or within 30 days prior to, the index pregnancy vs no SARS-CoV-2 vaccination during pregnancy or within 30 days prior. Main Outcomes and Measures The primary outcome was Ages and Stages Questionnaire version 3 (ASQ-3) total score, which was deemed to be equivalent between the exposed and unexposed groups if the 90% CI of the median difference was between −10 and 10. Secondary outcomes included domain-specific ASQ-3 scores, the Child Behavior Checklist, Modified Checklist for Autism in Toddlers, and Early Childhood Behavior Questionnaire scores. Results Of 3956 screened, 271 exposed and 240 unexposed children were enrolled. Matching on all characteristics was possible in 217 pairs. Of the 434 children enrolled, 258 (59.4%) were Non-Hispanic White, 96 (22.1%) Non-Hispanic Black, 52 (12.0%) Hispanic, and 28 (6.5%) were not represented by any of the above racial or ethnic groups. Median age at assessment was 25.8 [24.6 to 28.3] months, 221 were female (50.9%), and 213 were male (49.1%). Exposed mothers were more likely to be nulliparous; their children were slightly younger at assessment and more likely to have been vaccinated against SARS-CoV-2. The primary outcome of ASQ-3 score was equivalent between the exposed and unexposed groups (255 vs 260, adjusted median difference, −3.4; 90% CI, −9.8 to 3.0). There were no significant differences in secondary outcomes. Conclusions and Relevance In this multicenter cohort study, ASQ-3 scores were equivalent between 18- to 30-month-old children whose mothers did or did not receive mRNA SARS-CoV-2 vaccination during or immediately prior to pregnancy. These findings support continued recommendations for SARS-CoV-2 mRNA vaccination during pregnancy.