Linking Pre- and Perinatal Risk Factors to a Multivariate Fusion of Child Cortical Structure

Abstract

Pre- and perinatal factors such as maternal pregnancy and child birth complications affect child 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 pre- and perinatal variables into four overarching dimensions; maternal pregnancy complications, maternal substance use, compromised fetal growth, 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 compromised fetal growth, including low birth weight, being born preterm, or as a twin, were associated with smaller global surface area. Additionally, compromised fetal growth was associated with two regional patterns reflecting a complex combination of 1) smaller occipital, inferior frontal and insular cortex, larger fronto-temporal cortex, thinner pre- and post-central cortex, and thicker inferior frontal and insular cortex, and 2) smaller and thicker occipital and temporal lobe cortex, and larger and thinner insular cortex. In contrast, maternal substance use and newborn birth complications showed no associations with child cortical structure. By employing a multifactorial and multivariate morphometric fusion approach, we connected complications during pregnancy and fetal growth to global surface area and specific regional signatures across child cortical MRI features.