Neurodevelopmental outcomes of infants after in utero exposure to SARS-CoV-2 or mRNA-COVID-19 vaccine compared with unexposed infants: a COVI-PREG prospective cohort study

OBJECTIVES: Data are lacking regarding the long-term consequences of SARS-CoV-2 and COVID-19 mRNA vaccine on infants exposed in utero. We aimed to evaluate the neurodevelopment of infants exposed prenatally to SARS-CoV-2 or mRNA-COVID-19 vaccine during pregnancy at 12 months after birth. METHODS: Infants born to mothers exposed to SARS-CoV-2 or mRNA-COVID-19 vaccine during pregnancy, or unexposed to either the virus or the vaccine were enrolled from 2021 to 2023. Infants with prenatal exposure to the virus or vaccine were compared with infants without prenatal exposure to the virus and/or vaccine. Parents received a neurodevelopmental questionnaire (ages and stages questionnaire third edition) at 12 months after birth assessing five subdomains: communication, gross motor, fine motor, problem-solving, and personal social development. A low score was defined as <2 standard deviations below the normative mean in at least one of the subdomains. RESULTS: A total of 330 infants were included (76 in the SARS-CoV-2 group, 153 in the mRNA-COVID-19 vaccine group, and 101 in the reference group). In utero exposure to the SARS-CoV-2 or mRNA-COVID-19 vaccine was not associated with an increased risk of a low score for at least one subdomain compared with the reference group. The crude ORs were 1.16 (95% CI, 0.59-2.28) and 1.04 (95% CI, 0.58-1.86), respectively. Results remained consistent in the multivariate analysis, showing no increased risk of a low score for at least one subdomain for infants exposed to the SARS-CoV-2 or mRNA-COVID-19 vaccine, compared with the reference group. The adjusted ORs were 1.74 (95% CI, 0.76-3.99) and 0.76 (95% CI, 0.39-1.49), respectively. DISCUSSION: In utero exposure to SARS-CoV-2 or mRNA-COVID-19 vaccine was not associated with an increased risk of a low score for at least one ages and stages questionnaire third edition subdomain at 12 months after birth. Additional studies are needed to confirm our results, especially longer-term evaluation of infant development.