Long-Term Neurodevelopmental Outcome Following Three Randomized Controlled Trials of Choline in Fetal Alcohol Spectrum Disorder (FASD)
In brief
Choline-treated children with FASD scored higher on IQ and working memory five years later
In a follow-up of 58 children from three randomized trials, those assigned choline scored 9.1% higher on non-verbal IQ and 11.3% higher on working memory than those assigned placebo, about five years after treatment ended. Mental health diagnoses did not differ significantly; the small follow-up sample leaves the durability and clinical impact of these cognitive advantages uncertain.
- Journal
- Alcohol, clinical & experimental research (Q1)
- Published
- 1 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Jeffrey R Wozniak, Judith K Eckerle, Blake A Gimbel, Abigail M Ernst, Mary E Anthony, Kent A Tuominen, et al.
- PMID
- 42862085
- DOI
- 10.1111/acer.70394
Why clinicians should know about it
- Picked for Pediatrics and Child Health (top studies of the week, 25 October 2026): Long‑term neurodevelopmental outcome of choline RCTs in FASD
Abstract
BACKGROUND: Fetal alcohol spectrum disorder (FASD) represents a range of neurodevelopmental outcomes from prenatal alcohol exposure for which there are few interventions. Preclinical studies have identified choline as a potential treatment for cognitive deficits in FASD. We previously conducted three randomized controlled trials (RCTs) in children under age 6 and reported on memory benefits following all three trials. Two RCTs compared a fixed 500 mg daily dose to placebo, and the third RCT tested a weight-adjusted choline dose. Here, we report on a longitudinal follow-up 5 years post-study completion. METHODS: The RCTs included 2.5- to 5.9-year-old children with FASD who received choline (n = 53) or placebo (n = 51). Participants described here (n = 28 choline; n = 30 placebo) were 9.1 years old on average at follow-up. Of these, 9% had fetal alcohol syndrome (FAS), 43% partial FAS (PFAS), and 48% alcohol-related neurodevelopmental disorder (ARND). Parents completed a diagnostic interview and behavior checklists while participants completed assessments of general cognitive ability, executive functioning, and memory. RESULTS: Participants who received choline in the initial RCT showed a medium effect size performance advantage (9.1% better) for non-verbal IQ and a medium effect size advantage (11.3% better) for working memory over placebo. Age at enrollment did not explain significant variance in outcome but choline dose was significantly associated with non-verbal IQ and working memory (higher dose contributed to better performance at follow-up). High rates of anxiety disorders and impulse-control disorders were observed. While there were no statistically significant differences in mental health diagnoses for choline versus placebo, there were some differences that neared significance. CONCLUSIONS: Very few RCTs have been conducted in FASD, and interventions targeting cognitive functioning are needed. The data reported here suggest that choline supplementation has long-lasting neurodevelopmental benefits, especially in non-verbal IQ and working memory for individuals with FASD.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.