At present, the literature on interventions for individuals with Fetal Alcohol Spectrum Disorders (FASD) is very limited, with only two published randomized controlled trials, yet there are promising new treatment options that have not been applied in humans. Recent pre-clinical studies have dramatically demonstrated that dietary choline supplementation pre-natally and even post-natally, as late as days 21-30 in the rodent (equivalent to human childhood), attenuates the memory and behavioral deficits associated with prenatal alcohol exposure (Thomas et al., 2007;Thomas et al., 2000). We propose a two-year project to evaluate the feasibility and tolerability of post-natal choline supplementation in young children with pre-natal alcohol exposure followed by a three-year double-blind, placebo-controlled pilot study examining the efficacy of choline supplementation in improving the cognitive and behavioral functioning of these children. In the R21 feasibility phase, 20 children between the ages of 12 months and 54 months will be randomized to nine months of choline supplementation or placebo. Follow-up visits at 6 months and 9 months will include parent ratings of behavior, cognitive measures including the Mullen Scales of Early Learning and an elicited imitation (EI) hippocampal paradigm, and electrophysiological measures including a VEP measure of myelination-associated processing speed. Based on data collected in the R21 phase, the study design will be modified and implemented on a larger scale in the R33 phase. During the R33 phase, 40 children will be randomized to choline supplementation or placebo. Follow-up measures will be the same or slightly modified based on the R21 study. Results of the studies will be used to design a larger, full-scale clinical trial to test the efficacy of post-natal choline supplementation in young children with pre-natal alcohol exposure. Given the potential effects on hippocampal development, myelination, and other basic aspects of brain development, this treatment may have significant applicability to a host of other neurodevelopmental disorders.
Alcohol consumption during pregnancy is known to contribute to permanent brain damage in the child, yet there are no established treatments. Recently, animal studies have demonstrated that postnatal supplementation with choline, an essential nutrient found in many foods, can attenuate the cognitive and behavioral deficits typically seen in alcohol-exposed animals. A human study of choline supplementation in children has not yet been done. The proposed study will evaluate if choline supplementation during a specific developmental window when the child's brain remains somewhat plastic is able to attenuate the deficits in thinking, memory, processing speed, and behavior that are common in children with Fetal Alcohol Spectrum Disorders (FASD). We expect that this study will provide important information about the practicality of choline supplementation in children 1-5 years of age and will provide initial estimates of its effectiveness.
