# Choline Supplementation as a Neurodevelopmental Intervention in Fetal Alcohol Spectrum Disorders

> **NIH NIH R56** · UNIVERSITY OF MINNESOTA · 2020 · $154,167

## Abstract

PROJECT SUMMARY / ABSTRACT
Fetal alcohol spectrum disorders (FASDs) comprise a range of effects resulting from prenatal alcohol exposure
(PAE) including neurological abnormalities, cognitive and behavioral impairments, growth retardation, and
craniofacial anomalies. Very few treatments have been investigated despite FASD’s tremendous public health
burden. Neurocognitive deficits are a core feature of FASD, and cognition is a natural target for intervention
because deficits contribute to problems with adaptive functioning, social skills, and independent living. One
potential intervention for the cognitive impairments in FASD is the essential nutrient choline - which is known to
have numerous direct effects on brain development and emerging cognition. Choline impacts
neurodevelopment broadly, but especially in the hippocampus; choline contributes to increased dendritic
arborization, larger cells, and functional changes. Choline affects the cholinergic system and alters brain
structure and function in regions essential for memory functioning, including methylation in the hippocampus
and prefrontal cortex. Only a handful of human choline studies for FASD have been undertaken and our group
has conducted most of them. Our early double-blind, randomized, controlled trial established safety and
tolerability. Our subsequent trial revealed beneficial effects for sequential delayed memory in participants with
FASD (greater in younger [ages 2-3] rather than older [ages 3-5] children). Our third (ongoing) study included
a long-term follow-up that demonstrated permanent benefits for choline vs. placebo in non-verbal processing,
working memory, long-term verbal memory, and ADHD behavior. The proposed studies will capitalize on
three existing cohorts for additional longitudinal studies that have the potential to show permanency of the
effects of early treatment. A 4-year and 8-year follow-up study will each examine cognitive effects as well as
structural and functional brain effects using advance MRI methods. Cognitive measures will include the
Stanford-Binet Intelligence Scale, the Elicited Imitation memory test, the NIH Toolbox Flanker test and Picture
Sequence Memory Test, and the Minnesota Executive Function Scale. We will examine choline effects on
behavior using parent-report (Child Behavior Checklist). Hippocampus in particular will be examined for
volumetric alterations following choline, including alterations at the level of sub-structures. Hippocampal
connectivity will be examined and is expected to reflect changes from early choline supplementation. Lastly,
the proposed studies will include a new clinical trial with a new cohort of 2-5 year old children with FASD.
Rather than a placebo-controlled trial, this will be a 3-arm dose finding study in which participants will receive
choline for one of three durations (3, 6, or 9 months). Results of the trial will directly inform future clinical
implementation of choline as a neurodevelopmental intervention.

## Key facts

- **NIH application ID:** 10250653
- **Project number:** 2R56AA024123-06
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Michael K. Georgieff
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $154,167
- **Award type:** 2
- **Project period:** 2015-08-15 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10250653

## Citation

> US National Institutes of Health, RePORTER application 10250653, Choline Supplementation as a Neurodevelopmental Intervention in Fetal Alcohol Spectrum Disorders (2R56AA024123-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10250653. Licensed CC0.

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