Prenatal alcohol exposure and white matter microstructural changes across the first 6-7 years of life: A longitudinal diffusion tensor imaging study of a South African birth cohort

ABSTRACT Prenatal alcohol exposure (PAE) can affect brain development in early life, but few studies have investigated the effects of PAE on trajectories of white matter tract maturation in young children. Here we used diffusion weighted imaging (DWI) repeated over three time points in a South African birth cohort, to measure the effects of PAE on patterns of white matter microstructural development during the pre-school years. A total of 342 scans acquired from 237 children as neonates (N=82 scans: 30 PAE; 52 controls) and at ages 2-3 (N=121 scans: 27 PAE; 94 controls) and 6-7 years (N=139 scans: 45 PAE; 94 controls) were included. Maternal alcohol use during pregnancy and other antenatal covariates were collected from 28-32 weeks’ gestation. Linear mixed effects models were implemented to investigate the effects of PAE on fractional anisotropy (FA) and mean diffusivity (MD) in specific white matter tracts over time, while adjusting for child sex and maternal education. We found significant PAE-by-time effects on trajectories of FA development in the left superior cerebellar peduncle (SCP-L: p=0.001; survived FDR correction) and right superior longitudinal fasciculus (SLF-R: p=0.046), suggesting altered white matter development among children with PAE. Compared with controls, children with PAE demonstrated a more rapid change in FA in these tracts from the neonatal period to 2-3 years of age, followed by a more tapered trajectory for the period from 2-3 to 6-7 years of age, with these trajectories differing from unexposed control children. Given their supporting roles in various aspects of neurocognitive functioning (i.e., motor regulation, learning, memory, language), altered patterns of maturation in the SCP and SLF may contribute to a spectrum of physical, social, emotional, and cognitive difficulties often experienced by children with PAE. This study highlights the value of repeated early imaging in longitudinal studies of PAE, and focus for early childhood as a critical window of potential susceptibility as well as an opportunity for early intervention.