Magnetic Resonance Imaging Outcomes From a Comprehensive Magnetic Resonance Study of Children With Fetal Alcohol Spectrum Disorders

Abstract

Background Magnetic resonance (MR) technology offers non-invasive methods for in vivo assessment of neuroabnormalities. Methods A comprehensive neuropsychological/psychiatric battery, coupled with MR imaging, (MRI), MR spectroscopy (MRS), and functional MRI (fMRI) assessments, were administered to children with fetal alcohol spectrum disorders (FASD) to determine if global and/or focal abnormalities could be identified, and distinguish diagnostic subclassifications across the spectrum. The four study groups included: 1. FAS/Partial FAS; 2. Static Encephalopathy/Alcohol Exposed (SE/AE); 3. Neurobehavioral Disorder/Alcohol Exposed (ND/AE) as diagnosed with the FASD 4-Digit Code; and 4. healthy peers with no prenatal alcohol exposure. Presented here are the MRI assessments used to compare the sizes of brain regions between the four groups. The neuropsychological/behavioral, MRS, and fMRI outcomes are reported separately. Results Progressing across the four study groups from Controls to ND/AE to SE/AE to FAS/PFAS, the mean absolute size of the total brain, frontal lobe, caudate, putamen, hippocampus, cerebellar vermis, and corpus callosum length decreased incrementally and significantly. The FAS/PFAS group (the only group with the 4-Digit FAS facial phenotype) had disproportionately smaller frontal lobes relative to all other groups. The FAS/PFAS and SE/AE groups (the two groups with the most severe CNS dysfunction) had disproportionately smaller caudate regions relative to the ND/AE and Control groups. The prevalence of subjects in the FAS/PFAS, SE/AE, and ND/AE groups that had one or more brain regions, two or more standard deviations below the mean size observed in the Control group was78%, 58%, and 43%, respectively . Significant correlations were observed between size of brain regions and level of prenatal alcohol exposure, magnitude of FAS facial phenotype, and level of CNS dysfunction. Conclusions MRI provided further validation that ND/AE, SE/AE, and FAS/PFAS, as defined by the FASD 4-Digit Code, are three clinically distinct and increasingly more affected diagnostic subclassifications under the umbrella of FASD. Neurostructural abnormalities are present across the spectrum. MRI could importantly augment diagnosis of conditions under the umbrella of FASD, once population-based norms for structural development of the human brain are established.

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

“…Of note, the largest group difference was observed in the caudate (18% reduction in FASD), in agreement with two recent studies showing ϳ20% reductions of caudate volume (Astley et al, 2009b;Fryer et al, 2012); though these studies also demonstrate correlations with neurocognitive scores (Fryer et al, 2012) and diagnosis severity (Astley et al, 2009b). Reductions in cortical gray matter, white matter, thalamus, globus pallidus, and putamen volumes in this study remained significant after controlling for total brain volume, and have been reported as disproportionately reduced in other samples (Archibald et al, 2001;Roussotte et al, 2011).…”

“…We found no difference between groups on annual household income or primary caregiver education, suggesting approximately matched socioeconomic status at the time of MRI study participation; however, we cannot rule out the influence of numerous other possible disparities, including adverse early life experience, polysubstance exposures, and unknown genetic factors that could influence sensitivity to alcohol-induced brain injury (Warren and Li, 2005). Ethnicity was not balanced between groups in this study, which may also confer systematic genetic differences, though brain volume reductions of our sample are on par with those of larger more ethnically diverse samples (Astley et al, 2009a). Finally, the relatively small sample size of this study required that we approximate a linear fit to the data despite converging evidence that development is nonlinear (Giedd et al, 1999;Lebel et al, 2008a), and combining left and right tracts may have masked hemispheric asymmetries.…”

“…A similar trend was observed in the SFO, SLF, and UF (data not shown) despite comparable cognitive profiles (at the time of study participation) between more versus less severe subgroups (scan 1: reading 92 Ϯ 13 versus 94 Ϯ 8, math 91 Ϯ 16 versus 89 Ϯ 17, scan 2: reading 97 Ϯ 6 versus 88 Ϯ 22, math 90 Ϯ 7 versus 89 Ϯ 13, IQ 99 Ϯ 15 versus 98 Ϯ 15). Of note, a diagnosis of FAS or pFAS requires the presence of characteristic facial dysmorphology, which is associated with alcohol exposure during a critical period in the first trimester (Sulik et al, 1981) and has been correlated with structural brain abnormalities (Astley et al, 2009a;Lebel et al, 2012;Roussotte et al, 2012). Children with more severe diagnoses in this study appear to undergo the largest diffusion changes across this age range, which may relate to timing of gestational exposure or degree of initial injury, among other variables.…”

“…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).…”

Review of Current Neuroimaging Studies of the Effects of Prenatal Drug Exposure: Brain Structure and Function

“…Among pregnant women, the rate of any illicit drug use is 5.4% and has not changed significantly since 2010-2011 [12]. Use remains higher in younger women (14.6%, ages 18-25) compared to older women (3.2%, ages [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44]. A high proportion of women are using marijuana illegally and fail to disclose their use to their providers.…”