Sex differences in early brain development in a multi-site ASD likelihood cohort

Biological sex is increasingly recognized as a fundamental dimension of brain organization, yet how it influences early neurodevelopment, particularly autism spectrum disorder (ASD), remains understudied. Using data from the International Infant EEG Data Integration Platform (EEG-IP), a multi-site longitudinal cohort of 179 infants (91 males, 88 females) at elevated (ELA) and typical (TLA) likelihood of ASD, we conducted a series of re-analyses of previously published EEG studies to examine whether key EEG metrics differ by biological sex and whether biological sex can moderate the relationship between early brain profiles and language development from 6 to 36 months. Across all EEG metrics, we found that females displayed significantly higher left-hemisphere functional connectivity within speech-related regions at 6 months of age compared to males. Females also demonstrated increased posterior theta consistency during face processing as well as steeper expressive language trajectories from 6 to 36 months. Speech connectivity at 6 months also moderated receptive language growth, but not expressive language growth in females, suggesting sex-specific relationships between brain dynamics and language. These findings show the importance of including biological sex as a primary variable in infant developmental studies and provide support for the study of sex-differentiated biomarkers in prospective ASD studies.