Abnormalities of the Corpus Callosum in Children Prenatally Exposed to Alcohol

For 20 years, it has been known that fetal alcohol syndrome (FAS) is associated with abnormal brain development. Early autopsy studies point to the corpus callosum as one area affected by heavy alcohol exposure. Little is known, however, about the integrity of the brain in alcohol-exposed children who survive the perinatal period. This study was designed to assess the corpus callosum in living children exposed to high doses of alcohol prenatally. Thirteen children with histories of significant prenatal alcohol exposure and 12 normal control children were evaluated using magnetic resonance imaging. Using the midsagittal section, images were measured for the area of the corpus callosum using a computer-assisted measurement technique. In addition to the overall area, five equiangular regions were determined for each corpus callosum. Of the 13 alcohol-exposed children assessed, two had agenesis of the corpus callosum. The remaining alcohol-exposed children had significantly smaller overall callosal areas, as well as smaller regional areas of four of the five callosal regions, when compared with the normal control children. Importantly, when corrected for brain size, three of the five callosal regions were still smaller in the alcohol-exposed children, although overall area of the corpus callosum was no longer significantly different. These results suggest that prenatal exposure to high levels of alcohol is associated with abnormalities of the corpus callosum. They verify callosal agenesis in children with FAS, which previously had only been noted in autopsy reports. The current findings further document selective reductions in the area of certain regions of the corpus callosum after in utero alcohol exposure, extending our current understanding of alcohol's teratogenic effects on brain development. There is also some indication that the selective reduction in the area of the corpus callosum is similar to that reported in attention deficit disorder.     

Attention Deficits in Children Exposed to Alcohol Prenatally

Twenty children with fetal alcohol syndrome or fetal alcohol effect (FAS/FAE) were compared with 20 attention deficit disorder (ADD) children and 20 normal controls on three experimental tasks designed to isolate four different components of attention. Parents completed three questionnaires regarding their child's activity level and overall functioning, and the children completed a short form of an IQ test. The children in each group ranged from 5 to 12 years. Results indicate that although the children with FAS/FAE are significantly more impaired intellectually, their attentional deficits and behavioral problems are similar to those of children with ADD. These findings imply that the treatments known to facilitate learning in children with ADD may also benefit children with FAS/FAE.     

Abnormal Development of the Cerebellar Vermis in Children Prenatally Exposed to Alcohol: Size Reduction in Lobules I–V

Abnormalities of the cerebellar vermis have been well documented in animal models of fetal alcohol syndrome. At this point, it is not known if the same brain region is affected in humans prenatally exposed to alcohol. In this study, the area of the cerebellar vermis was measured from brain magnetic resonance images of 9 children and young adults with prenatal alcohol exposure and 24 control subjects in the same age range. Six of the exposed children met standard criteria for fetal alcohol syndrome. The remaining three subjects had significant histories of prenatal exposure to alcohol, but did not have enough of the classic facial features for the diagnosis. For each subject with a suitable midsagittal section, three vermal areas were circumscribed: anterior vermis (vermal lobules I–V), posterior vermis (vermal lobules VI and VII), and the remaining vermal area (including lobules VIII–X). Statistical analyses revealed that the anterior region of the vermis was significantly smaller in subjects with prenatal alcohol exposure, whereas the posterior region and the remaining vermal area did not differ between groups. Previous findings from an animal model of neonatal alcohol exposure have documented Purkinje cell loss in vermal lobules I–V and IX–X, with notable sparing in lobules VI–VII. Thus, the results of both studies indicate similar patterns of abnormal brain development in the anterior vermal region, with apparent sparing in the posterior vermal region. Our findings, for the first time, suggest that regionally specific Purkinje cell death may also occur in humans prenatally exposed to alcohol.     

Toward a Neurobehavioral Profile of Fetal Alcohol Spectrum Disorders

Background: A primary goal of recent research is the development of neurobehavioral profiles that specifically define fetal alcohol spectrum disorders (FASD), which may assist differential diagnosis or improve treatment. In the current study, we define a preliminary profile using neuropsychological data from a multisite study. Methods: Data were collected using a broad neurobehavioral protocol from 2 sites of a multisite study of FASD. Subjects were children with heavy prenatal alcohol exposure and unexposed controls. The alcohol‐exposed group included children with and without fetal alcohol syndrome (FAS). From 547 neuropsychological variables, 22 variables were selected for analysis based on their ability to distinguish children with heavy prenatal alcohol exposure from nonexposed controls. These data were analyzed using latent profile analysis (LPA). Results: The results indicated that a 2‐class model best fit the data. The resulting profile was successful at distinguishing subjects with FAS from nonexposed controls without FAS with 92% overall accuracy; 87.8% of FAS cases and 95.7% of controls were correctly classified. The same analysis was repeated with children with heavy prenatal alcohol exposure but without FAS and nonexposed controls with similar results. The overall accuracy was 84.7%; 68.4% of alcohol‐exposed cases and 95% of controls were correctly classified. In both analyses, the profile based on neuropsychological variables was more successful at distinguishing the groups than was IQ alone. Conclusions: We used data from 2 sites of a multisite study and a broad neuropsychological test battery to determine a profile that could be used to accurately identify children affected by prenatal alcohol exposure. Results indicated that measures of executive function and spatial processing are especially sensitive to prenatal alcohol exposure.     

Implicit strategy affects learning in children with heavy prenatal alcohol exposure

BACKGROUND: Learning and memory deficits are commonly reported in children with heavy prenatal alcohol exposure. Our recent work suggested that children with heavy prenatal alcohol exposure retained information as well as controls on a verbal learning test but not on a test of nonverbal learning and memory. To better understand the cause of this differential pattern of performance, the current study re-analyzed data from our previous study to determine if the presence of an implicit learning strategy may account, at least in part, for the finding of spared retention. METHODS: The current study examined verbal learning and memory abilities in 35 children with Fetal Alcohol Spectrum Disorders (FASD) and 34 nonexposed controls (CON) matched for age (9-16 years), sex, ethnicity, handedness, and socioeconomic status. Groups were compared on two measures of verbal learning, one with an implicit strategy (California Verbal Learning Test-Children's Version; CVLT-C) and one without (Verbal Learning subtest of the Wide Range Assessment of Memory and Learning; VL-WRAML). RESULTS: Children with FASD learned less information overall than children in the CON group. Both groups learned a greater percentage of information and reached a learning plateau earlier on the CVLT-C compared with the VL-WRAML. Groups also showed comparable rates of retention after a delay on the CVLT-C. In contrast, on the VL-WRAML, children with FASD showed poorer retention rates than children in the CON group. Interestingly, children with FASD did not differ from children in the CON group on CVLT-C semantic clustering scores for learning trials 1 through 3, and greater utilization of semantic clustering was correlated with better learning and memory performance in both groups. This overall pattern of results was not related to overall intellectual level. CONCLUSIONS: The finding of spared retention of verbal information on the CVLT-C in our earlier studies may be related to test characteristics of the CVLT-C rather than a finding of spared verbal retention per se, given that spared retention was not found on a separate test of verbal learning and memory without an implicit learning strategy. These results suggest that the use of an implicit strategy positively affected the ability of alcohol-exposed children to learn and retain new verbal information.