Linking Pregnancy- and Birth-Related Risk Factors to a Multivariate Fusion of Child Cortical Structure

Pregnancy- and birth-related factors affect offspring brain development, emphasizing the importance of early life exposures. While most previous studies have focused on a few variables in isolation, here we investigated associations between a broad range of pregnancy- and birth-related variables and multivariate cortical brain MRI features. Our sample consisted of 8,396 children aged 8.9 to 11.1 years from the ABCD Study. Through multiple correspondence analysis and factor analysis of mixed data, we distilled numerous pregnancy and birth variables into four overarching dimensions; maternal pregnancy complications, maternal substance use, low birth weight and prematurity, and newborn birth complications. Vertex-wise measures of cortical thickness, surface area, and curvature were fused using linked independent component analysis. Linear mixed effects models showed that maternal pregnancy complications and low birth weight and prematurity were associated with smaller global surface area. Additionally, low birth weight and prematurity was associated with complex regional cortical patterns reflecting bidirectional variations in both surface area and cortical thickness. Newborn birth complications showed multivariate patterns reflecting smaller occipital- and larger temporal area, bi-directional frontal area variations, and reduced cortical thickness across the cortex. Maternal substance use showed no associations with child cortical structure. By employing a multifactorial and multivariate morphometric fusion approach, we connected complications during pregnancy and fetal size and prematurity to global surface area and specific regional signatures across child cortical MRI features. Significance Statement Early life stages, including pregnancy and birth circumstances, are critically important for a wide range of real-life outcomes for the child. In this study, we linked maternal complications during pregnancy and low birth weight and prematurity to globally reduced cortical surface area, and low birth weight and prematurity, in addition to pregnancy and birth complications, to complex cortical structural patterns later in late childhood. Our findings underscore the importance of providing support to mothers and children during these crucial phases, helping to ensure optimal conditions for healthy child development.