Long-term follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder: corpus callosum white matter microstructure and neurocognitive outcomes

胆碱治疗胎儿酒精谱系障碍神经发育的随机对照试验的长期随访:胼胝体白质微结构和神经认知结果

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Abstract

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is a lifelong condition. Early interventions targeting core neurocognitive deficits have the potential to confer long-term neurodevelopmental benefits. Time-targeted choline supplementation is one such intervention that has been shown to provide neurodevelopmental benefits that emerge with age during childhood. We present a long-term follow-up study evaluating the neurodevelopmental effects of early choline supplementation in children with FASD approximately 7 years on average after an initial efficacy trial. METHODS: The initial study was a randomized, double-blind, placebo-controlled trial of choline vs. placebo in 2.5 to 5 year olds with FASD. Participants in this long-term follow-up study include 18 children (9 placebo; 9 choline) seen 7 years on average following initial trial completion. The mean age at follow-up was 11.0 years old. Diagnoses were 28% fetal alcohol syndrome (FAS), 28% partial FAS, and 44% alcohol-related neurodevelopmental disorder. The follow-up included measures of executive functioning and an MRI scan. RESULTS: Children who received choline had better performance on several tasks of lower-order executive function (e.g., processing speed) and showed higher white matter microstructure organization (i.e., greater axon coherence) in the splenium of the corpus callosum compared to the placebo group. CONCLUSIONS: These preliminary findings, although exploratory at this stage, highlight potential long-term benefits of choline as a neurodevelopmental intervention for FASD and suggest that choline may affect white matter development, representing a potential target of choline in this population. TRIAL REGISTRATION: Prior to enrollment, this trial was registered with clinicaltrials.gov ( NCT01149538 ) on June 23, 2010.

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