OBJECTIVES: The potential of micronutrients to ameliorate the impact of prenatal alcohol exposure was explored in a clinical trial conducted in Ukraine. Cardiac orienting responses during a habituation/dishabituation learning paradigm were obtained from 6–12-month-olds to assess neurophysiological encoding and memory of environmental events. MATERIALS AND METHODS: Women who differed in prenatal alcohol use were recruited during pregnancy and assigned to a group (no study-provided supplements, multivitamin/mineral supplement, or multivitamin/mineral supplement plus choline supplement). An infant habituation/dishabituation paradigm was used to assess outcomes in the offspring. Ten trials were used for the habituation and five for the dishabituation condition. Heart rate was collected for 30 sec prior to stimulus onset and then 12 sec post-stimulus onset. Difference values (ΔHR) were computed for the first three trials of each condition and aggregated for analysis. Gestational blood samples were collected to assess maternal nutritional status and changes as a function of the intervention. RESULTS: Choline supplementation resulted in a greater ΔHR on the visual habituation (Wald Chi-Square (1, 149) = 10.9, p < .001, eta-squared = .043) trials for all infants and for the infants with no prenatal alcohol exposure on the dishabituation (Wald Chi-Square (1, 139) = 6.1, p < .013, eta-squared = .065) trials. The latency of the response was reduced in both conditions (Habituation: Wald Chi-Square (1, 150) = 9.0, p < .003, eta-squared = .056; Dishabituation: Wald Chi-Square (1, 137) = 4.9, p < .027, eta-squared = .032) for all infants whose mothers received choline supplementation. Change in gestational choline level was positively related (r = .19) to ΔHR during habituation trials, and levels of one choline metabolite, dimethylglycine (DMG), predicted ΔHR during habituation trials (r = .23) and latency of responses (r = −.20). A trend was found between DMG and ΔHR on the dishabituation trials (r = .19) and latency of the response (r = −.18). Multivitamin/mineral or multivitamin/mineral plus choline supplementation did not significantly affect cardiac orienting responses to the auditory stimuli. CONCLUSION: Choline supplementation when administered together with routinely recommended multivitamin/mineral prenatal supplements during pregnancy may provide a beneficial impact to basic learning mechanisms involved in encoding and memory of environmental events in alcohol-exposed pregnancies as well as non- or low alcohol-exposed pregnancies. Changes in nutrient status of the mother suggested that this process may be mediated by the breakdown of choline to betaine and then to DMG. One mechanism by which choline supplementation may positively affect brain development is through prevention of fetal alcohol-related depletion of DMG, a metabolic nutrient that can protect against overproduction of glycine, during critical periods of neurogenesis
