A Longitudinal Study of the Long-Term Consequences of Drinking during Pregnancy: HeavyIn UteroAlcohol Exposure Disrupts the Normal Processes of Brain Development

Abstract

Exposure to alcohol in utero can cause birth defects including face and brain abnormalities, and is the most common preventable cause of intellectual disabilities. Here we use structural magnetic resonance imaging (MRI) to measure cortical volume change longitudinally in a cohort of human children and youth with prenatal alcohol exposure (PAE) and a group of unexposed control subjects, demonstrating that the normal processes of brain maturation are disrupted in individuals whose mothers drank heavily during pregnancy. Trajectories of cortical volume change within children and youth with PAE differed from those of unexposed control subjects in posterior brain regions, particularly in the parietal cortex. In these areas, control children appear to show a particularly plastic cortex with a prolonged pattern of cortical volume increases followed by equally vigorous volume loss during adolescence, while the alcohol-exposed participants showed primarily volume loss, demonstrating decreased plasticity. Furthermore, smaller volume changes between scans were associated with lower intelligence and worse facial morphology in both groups, and were related to the amount of PAE during each trimester of pregnancy in the exposed group. This demonstrates that measures of IQ and facial dysmorphology predict, to some degree, the structural brain development that occurs in subsequent years. These results are encouraging in that interventions aimed at altering “experience” over time may improve brain trajectories in individuals with heavy PAE, and possibly other neurodevelopmental disorders.

Longitudinal MRI Reveals Altered Trajectory of Brain Development during Childhood and Adolescence in Fetal Alcohol Spectrum Disorders

“…1; Table 1). Fourteen of 17 FASD scan 1 data were included in our cross-sectional DTI study (Lebel et al, 2008b), 9 of these 14 were also included in our cross-sectional deep gray matter volumetric study (Nardelli et al, 2011), and all control participant scans were a subset from our previous longitudinal study of healthy brain development . A total of 92 scans were collected: 15 subjects with FASD and 25 controls with two scans each; two subjects with FASD and two controls with three scans each.…”

“…Tractography. A previously described semiautomated tractography method (Lebel et al, 2008a) was used to delineate 11 major white matter tracts for each scan. Subject images were normalized to a template using a nonaffine transformation, saving warping parameters for each subject.…”

“…White matter tracts included the genu (gCC), body (bCC), and splenium (sCC) of the corpus callosum, the anterior limb of the internal capsule (ALIC), corticospinal tracts (CST), superior and inferior longitudinal fasciculus (SLF; ILF), superior and inferior fronto-occipital fasciculus (SFO; IFO), cingulum, and uncinate fasciculus (UF). Tractography was performed in native space for each subject, using a deterministic streamline method in ExploreDTI (Leemans et al, 2009), and fibers in the left and right hemisphere were measured separately at this stage for all tracts except the corpus callosum. A minimum FA threshold of 0.25 was used to initiate and continue tracking, and an angle threshold of 60°was set for the UF and SLF and 30°f or all other tracts.…”

“…One of the most robust findings is reduced brain volume, with many studies reporting reduced total brain, gray and white matter, as well as numerous deep gray matter volumes, with some reductions persisting after controlling for total brain volume (Astley et al, 2009a;. Diffusion tensor imaging (DTI) studies of children with FASD have revealed microstructural abnormalities in the corpus callosum, cingulum, cortico-spinal tracts, cerebellar peduncles, and a number of association fibers (Wozniak et al, 2006(Wozniak et al, , 2009Lebel et al, 2008b;Sowell et al, 2008;Fryer et al, 2009;Spottiswoode et al, 2011). Brain volume (Coles et al, 2011) and DTI abnormalities Li et al, 2009) also persist in adult subjects with FASD.…”

“…Likewise, increases of fractional anisotropy (FA) and reductions of mean diffusivity (MD) of white matter have been observed in longitudinal DTI studies of healthy children and adolescents (Bava et al, 2010;Giorgio et al, 2010;, and are presumed to reflect reduced water content, increased myelination and/or increased coherence/packing of axons within white matter tracts. One recent longitudinal volume study has shown altered trajectories of cortical volume growth in FASD, but did not include DTI (Lebel et al, 2012). To better understand how brain abnormalities evolve during these key developmental periods of behavioral and cognitive progression, this study aims to examine for the first time within-subject longitudinal changes in white matter DTI parameters in FASD during childhood and adolescence.…”