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

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.

Novel Interventions on Comorbidities in Patients with Fetal Alcohol Spectrum Disorder (FASD): An Integrative Review

“…As reported in Table 2 , most of the clinical studies carried out in the last ten years concerned both perinatally [ 67 , 68 , 69 , 70 ] and postnatally [ 71 , 72 , 73 , 74 , 75 , 76 ] the use of choline and/or vitamins as nutritional interventions for ND due to alcohol exposure. After the promising results obtained in animal studies, tolerability, adherence and side effects of choline were evaluated in humans, when perinatally and postnatally administered for approximately 6 and 9 months to pregnant alcohol users and 2–5 year-old children, respectively.…”

Atypical developmental trajectories of white matter microstructure in prenatal alcohol exposure: Preliminary evidence from neurite orientation dispersion and density imaging

“…As such, our preliminary findings may reflect biologically-meaningful relationships between CC microstructure development and dysmorphic facial features, warranting further study with advanced biophysical modeling of diffusion data (e.g., with NODDI) that may be sensitive to subtle developmental disruptions in white matter microstructure in individuals with PAE. Indeed, preliminary data from our recent study examining long-term outcomes following early choline supplementation in young children with PAE suggested a significant correlation between splenium ODI and the degree of facial dysmorphology ( Gimbel et al, 2022 ), highlighting the need for further investigation.…”

Advocacy for Equity Around Evidence-Based Treatments: Overview and Proceedings of the AMERSA 2023 Conference

“…The presentation reinforced the importance to critically assess, diagnose, and provide evidence-based care for persons across the lifespan who are affected by alcohol use during pregnancy as there are many effective interventions to improve the lives of our patients and families affected by FASD. [13][14][15][16][17][18][19]…”