Choline enhances elicited imitation memory performance in preschool children with prenatal alcohol exposure: a cumulative report of 3 randomized controlled trials

Jeffrey R Wozniak; Judith K Eckerle; Blake A Gimbel; Abigail M Ernst; Mary E Anthony; Kent A Tuominen; Erik de Water; Steven H Zeisel; Michael K Georgieff

doi:10.1016/j.ajcnut.2025.02.009

Choline enhances elicited imitation memory performance in preschool children with prenatal alcohol exposure: a cumulative report of 3 randomized controlled trials

Am J Clin Nutr. 2025 Feb 14:S0002-9165(25)00077-2. doi: 10.1016/j.ajcnut.2025.02.009. Online ahead of print.

Authors

Jeffrey R Wozniak¹, Judith K Eckerle², Blake A Gimbel³, Abigail M Ernst⁴, Mary E Anthony⁴, Kent A Tuominen⁴, Erik de Water⁵, Steven H Zeisel⁶, Michael K Georgieff²

Affiliations

¹ Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, United States. Electronic address: jwozniak@umn.edu.
² Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States.
³ Department of Pediatric Psychology and Neuropsychology, Nationwide Children's Hospital, Columbus, OH, United States; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States.
⁴ Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, United States.
⁵ Great Lakes Neurobehavioral Center, Eagan, MN, United States.
⁶ University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.

PMID: 39956364
DOI: 10.1016/j.ajcnut.2025.02.009

Abstract

Background: Fetal alcohol spectrum disorders (FASDs) are associated with neurocognitive deficits for which there are no biological treatments. Choline supplementation may attenuate these deficits.

Objectives: This study was aimed to evaluate choline as a neurodevelopmental intervention for preschool-aged children with FASD.

Methods: We present combined data from 104 participants with FASD (aged 2.5-5.9 y) from 3 placebo randomized controlled trials (RCTs). Participants in RCT1 and RCT2 were randomly assigned to 9 mo choline (500 mg daily) or placebo. Participants in RCT3 were randomly assigned to 9 mo choline (19 mg/kg daily) or placebo. The primary outcome measure was an elicited imitation (EI) memory task.

Results: Adherence was high (78% doses received). Adverse effects were similar across groups except fishy body odor: choline group, 36%; placebo group, 8%. We observed a trend-level choline advantage; participants receiving choline performed 25% better on EI short-delay adjacent pairs (sequential memory) than those on placebo, with a steeper increase in scores between 6 and 9 mo (ŷ = -10.06; P = 0.03; 95% CI: -19.13, -0.99). No sex difference in response was seen, nor did we observe a dose-response relationship. Age-moderated response to choline between baseline and 9 mo (ŷ = 10.02; P = 0.01; 95% CI: 2.47, 17.57), with greater response in younger (≤4.2 y) than that in older (>4.2 y) participants. Overall, choline showed a beneficial effect on memory but no impact on executive functioning or intelligent quotient.

Conclusions: The results support choline as a neurodevelopmental intervention for improvement of memory in young children exposed to alcohol prenatally. Specifically, the use of choline bitartrate as a supplement in the range of 260-500 mg/d in children between 2.5 and 5.9 y of age is supported. Future studies are needed to further define appropriate dosage as well as optimal lengths and developmental windows for supplementation. This trial was registered at clinicaltrials.gov as NCT01149538 and NCT02735473.

Keywords: alcohol-related neurodevelopmental disorder; children; choline; cognition; fetal alcohol spectrum disorders; fetal alcohol syndrome; memory; partial fetal alcohol syndrome; randomized controlled trial.

Associated data

ClinicalTrials.gov/NCT02735473
ClinicalTrials.gov/NCT01149538

Abstract

Associated data

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