Alcohol Clin Exp Res (Hoboken). 2026 Oct;50(10):e70394. doi: 10.1111/acer.70394.
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.
PMID:42862085 | DOI:10.1111/acer.70394
