Long-Term Neurodevelopmental Outcome Following Three Randomized Controlled Trials of Choline in Fetal Alcohol Spectrum Disorder (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.