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.

Magnetic resonance (MR) technology offers noninvasive methods for in vivo assessment of neuroabnormalities. A comprehensive neuropsychological/behavioral, MR imaging (MRI), MR spectroscopy (MRS) and functional MRI (fMRI) assessment was administered to children with fetal alcohol spectrum disorders (FASD) to determine whether global and/or focal abnormalities could be identified and to 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. Results are presented in four separate reports: MRS (reported here) and neuropsychological/behavioral, MRI and fMRI outcomes (reported separately). MRS was used to compare neurometabolite concentrations [choline (Cho), n-acetyl-aspartate (NAA) and creatine (Cre)] in a white matter region and a hippocampal region between the four study groups. Choline concentration in the frontal/parietal white matter region, lateral to the midsection of the corpus callosum, was significantly lower in FAS/PFAS relative to all other study groups. Choline decreased significantly with decreasing frontal white matter volume and corpus callosum length. These outcomes suggest low choline concentrations may reflect white matter deficits among FAS/PFAS. Choline also decreased significantly with increasing severity of the 4-Digit FAS facial phenotype, increasing impairment in psychological performance and increasing alcohol exposure. NAA and Cre concentrations did not vary significantly. This study provides further evidence of the vulnerability of the cholinergic system in FASD.

A comprehensive neuropsychological/psychiatric, MR imaging, (MRI), MR spectroscopy (MRS), and functional MRI (fMRI) assessment was 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); and 4. healthy peers with no prenatal alcohol exposure. fMRI outcomes are reported here. The neuropsychological/psychiatric, MRI, and MRS outcomes are reported separately. fMRI was used to assess activation in seven brain regions during performance of N-back working memory tasks. Children across the full spectrum of FASD exhibited significant working memory deficits and altered activation patterns in brain regions that are known to be involved in working memory. These results demonstrate the potential research and diagnostic value of this non-invasive MR tool in the field of FASD.

Background: As clinicians strive to achieve consensus worldwide on how best to diagnose fetal alcohol spectrum disorders (FASD), the most recent FASD diagnostic systems show convergence and divergence. Applying these systems to a single clinical population illustrates the contrasts between them, but validation studies are ultimately required to identify the best system. Methods: The 4-Digit-Code, Hoyme 2016, Canadian 2015 and Australian 2016 FASD diagnostic systems were applied to 1,392 patient records evaluated for FASD at the University of Washington. The diagnostic criteria and tools, the prevalence and concordance of diagnostic outcomes, and validity measures were compared between the systems. Results: The proportion diagnosed with fetal alcohol syndrome (FAS) and FASD varied significantly (4-Digit-Code 2.1%, ≤79%; Hoyme 6.4%, 44%, Australian 1.8%, 29%; Canadian 1.8%, 16%). Eighty-two percent were diagnosed FASD by at least one system; only 11% by all four systems. Key factors contributing to discordance include: requiring high alcohol exposure; excluding growth deficiency; relaxing the facial criteria; requiring brain criteria that prevent diagnosis of infants/toddlers; and excluding moderate dysfunction from the spectrum. Primate research confirms moderate dysfunction (1–2 domains ≤-2 standard deviations) is the most prevalent outcome caused by PAE (FAS 5%, severe dysfunction 31%, moderate dysfunction 59%). Only the 4-Digit-Code replicated this diagnostic pattern. Conclusion: The needs of individuals with FASD are best met when diagnostic systems provide accurate, validated diagnoses across the lifespan, the full spectrum of outcome, the full continuum of alcohol exposure; and utilize diagnostic nomenclature that accurately reflects the association between outcome and alcohol exposure.