Sex-specific vulnerabilities in early human neurodevelopment following SARS-CoV-2-induced maternal immune activation.

Abstract

This study examines the effects of SARS-CoV-2-induced maternal immune activation (MIA) on early neurodevelopment, focusing on sex-specific vulnerabilities related to early behavioral and regulatory functions, which may be precursors to later developmental or cognitive challenges. A total of 107 mother-infant dyads from the COGESTCOV-19 study were analyzed to assess neurodevelopmental outcomes in male and female infants at six weeks using the Neonatal Behavioral Assessment Scale (NBAS). Maternal and newborn cytokine levels-specifically interleukin-6 (IL-6), interleukin-10 (IL-10), and the IL-6/IL-10 ratio-were measured at the first prenatal visit at the time of study enrolment and at birth to evaluate inflammatory responses and homeostatic balance. Neither maternal nor newborn cytokine levels differed significantly between cases and controls. Significant sex-specific differences were observed in neurodevelopmental outcomes related to maternal SARS-CoV-2 exposure. Female infants exposed in utero showed significantly reduced performance in orientation and state regulation measures compared to exposed male infants and unexposed male and female controls. The findings suggest that SARS-CoV-2-induced MIA - not limited to IL-6/IL-10 balance - may have a differential impact on early neurodevelopment based on sex, underscoring the necessity for targeted interventions to mitigate these effects. Future studies should explore the mechanisms underlying these sex-specific differences and their long-term implications for neurodevelopment.