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

J Neurodev Disord. 2022 Dec 16;14(1):59. doi: 10.1186/s11689-022-09470-w.

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.

Keywords: Choline; Cognition; Diffusion MRI; Fetal alcohol spectrum disorders; Longitudinal studies; Neurite orientation dispersion and density imaging.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Child
  • Child, Preschool
  • Choline / therapeutic use
  • Corpus Callosum / diagnostic imaging
  • Female
  • Fetal Alcohol Spectrum Disorders* / drug therapy
  • Follow-Up Studies
  • Humans
  • Pregnancy
  • White Matter* / diagnostic imaging

Substances

  • Choline

Associated data

  • ClinicalTrials.gov/NCT01149538