White Matter Microstructure and Externalizing Symptoms in Young Children with Prenatal Alcohol Exposure

Introduction: Prenatal alcohol exposure (PAE) can result in widespread brain alterations and behavioral problems, including externalizing behaviors such as aggression, inattention, and hyperactivity (Ghazi Sherbaf et al., 2019; Pei et al., 2011). These behaviours typically emerge in early childhood and have been associated with poor mental health outcomes, but little is known about these behaviors or their brain correlates in young children with PAE (Ghazi Sherbaf et al., 2019; Pei et al., 2011). We aimed to investigate how white matter microstructure relates to externalizing behaviors in young children with PAE. Methods: 51 children (5.26±1.11 years; 26 males) with confirmed PAE and 53 unexposed typically-developing children (4.60±0.86 years; 26 males) underwent diffusion tensor imaging between 2 and 7 years; some children returned multiple times, providing a total of 96 PAE datasets and 93 control datasets. The Behavioral Assessment System for Children parent-rating scale (BASC-2, BASC-3) was completed at each visit to measure externalizing behaviors. Linear mixed effects were used to investigate group differences (PAE vs. control) in externalizing behavior scores and fractional anisotropy (FA, measure sensitive to myelination/axonal packing/fibre coherence) in the uncinate fasciculus and cingulum. Results: Results show that the children with PAE had worse externalizing behaviors (higher scores) than controls (PAE: 66.47±12.47; Controls: 49.95±8.73; p<0.001). Children with PAE showed higher FA in the bilateral uncinate fasciculus than controls (Left: PAE = 0.40±0.02; Controls = 0.39±0.02; p=0.008) (Right: PAE = 0.40±0.02; Controls: = 0.39±0.02; p=0.025). There were no significant associations between externalizing behaviors and FA.  Conclusion: Children with PAE show more externalizing behaviors than controls, consistent with previous research. Higher FA in the uncinate fasciculus in children with PAE contrasts research in older PAE populations reporting lower FA; this may suggest premature development of this white matter tract in response to PAE teratogenesis that then plateaus too early later in childhood. The lack of white matter and behavior associations suggests that future research in a larger sample may be needed.