White matter alterations in young children with prenatal alcohol exposure

Abstract

Prenatal alcohol exposure (PAE) can lead to cognitive, behavioural, and socialemotional challenges. Previous neuroimaging research has identified structural brain alterations in newborns, older children, adolescents, and adults with PAE; however, little is known about brain structure in young children. Extensive brain development occurs during early childhood; therefore, understanding the neurological profiles of young children with PAE is critical for early identification and effective intervention.We studied 54 children (5.21 ± 1.11 years; 27 males) with confirmed PAE (94% also had other prenatal exposures, 74% had adverse postnatal experiences) compared with 54 age-and sex-matched children without PAE. Children underwent diffusion tensor imaging between 2 and 7 years of age. Mean fractional anisotropy (FA) and mean diffusivity (MD) were obtained for 10 major white matter tracts. Univariate analyses of covariance were used to test group differences (PAE vs. control) controlling for age and sex. The PAE group had higher FA in the genu of the corpus callosum and lower MD in the bilateral uncinate fasciculus. The PAE group also had lower tract volume in the corpus callosum, the bilateral inferior fronto-occipital fasciculi, and the right superior longitudinal fasciculus. Our findings align with studies of newborns with PAE reporting lower diffusivity, but contrast those in older populations with PAE, which consistently report lower FA and higher MD. Further research is needed to understand trajectories of white matter development and how our results of higher FA/lower MD in young children connect with lower FA/higher MD observed at older ages. K E Y W O R D Sdiffusion tensor imaging, fetal alcohol spectrum disorder, prenatal alcohol exposure, preschool children, white matter | 401

Trajectories of brain white matter development in young children with prenatal alcohol exposure

“…Detailed information about each child's prenatal and/or postnatal adverse experiences were obtained using their child welfare file (containing information from birth families, social workers, police records, and medical files) and/or from a semi‐structured interview with current caregivers, caseworkers, and/or birth families. A previously reported framework was used to comprehensively evaluate their prenatal and postnatal exposures (Lebel et al, 2019 ) and profiles are described in a previous study in this sample (Kar et al, 2021 ). All participants had confirmed PAE.…”

“…Here, we investigated the association between PAE and developmental trajectories of white matter microstructure between 2 and 8 years of age for the first time. Based on previous research in younger (Kar et al, 2021 ; Roos et al, 2021 ; Taylor et al, 2016 ) and older children (Treit et al, 2013 ), we hypothesized that young children with PAE would demonstrate slower increases in FA and slower decreases in MD compared to unexposed controls.…”

“…Newborns with PAE show lower diffusivity in the superior longitudinal fasciculus (SLF) compared to unexposed newborns (Donald, Roos, et al, 2015 ) and alterations throughout the brain (Taylor et al, 2016 ). Similarly, young children (2–7 years) generally show higher fractional anisotropy (FA) and/or lower mean diffusivity (MD) in brain white matter compared to unexposed children (Kar et al, 2021 ; Roos et al, 2021 ). In contrast, a broad range of literature in school‐aged children, adolescents, and adults (~5–32 years) has consistently reported the opposite—lower FA and/or higher MD compared to unexposed controls—across white matter (Fan et al, 2016 ; Lebel et al, 2008 ; Paolozza et al, 2017 ; Sowell et al, 2008 ; Wozniak et al, 2006 ; Wozniak et al, 2009 ) with only a few exceptions (Fryer et al, 2009 ; Lebel et al, 2008 ; Uban et al, 2017 ).…”

Prenatal and Postnatal Choline Supplementation in Fetal Alcohol Spectrum Disorder

“…The corpus callosum has been shown to be particularly susceptible to PAE-induced damage, with many studies reporting reduced volume and shape abnormalities, particularly in posterior regions [ 49 , 88 , 89 ]. Using diffusion tensor imaging (DTI) methodology, reduced white matter microstructural integrity has been consistently found in the corpus callosum, cingulum, cerebellar peduncles, and longitudinal fasciculi, as indicated by lower fractional anisotropy (FA) and higher mean diffusivity (MD) and radial diffusivity (RD; [ 49 ]), although some inconsistencies have been found in younger age groups [ 90 ]. Both volumetric and microstructural abnormalities in white matter pathways have been shown to correlate with neurocognitive performance in domains such as processing speed [ 91 ], working memory [ 92 ], language and reading [ 42 ], and mathematics [ 93 ] in individuals with PAE.…”

Premature white matter microstructure in female children with a history of concussion

“…Comparable profiles of atypical development of brain connectivity have been observed following pre- and post-natal adversity in other studies. 88,89 The current study is the first, to our knowledge, to show sex specific differences in diffusion measures between children with and without concussion. Previous studies which investigated post-acute diffusion in white matter microstructure following concussion did not detect significant interaction effects between sex and concussion, 43,45 suggesting that sex specific effects of concussion on white matter microstructure may only emerge once the physiological changes induced by concussion have had time to interact with neurodevelopmental processes.…”