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

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2021 · $596,257

## 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. Few treatments have been investigated despite FASD’s
tremendous public health burden. Cognitive deficits are a core feature of FASD, and cognition is a
natural target for intervention. One potential intervention for cognition in FASD is the essential
nutrient choline - known to have effects on brain development and cognition. 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 long-term benefits for choline vs. placebo in non-verbal processing,
working memory, long-term verbal memory, and ADHD behavior. 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, it will be a two-arm block-randomized study with cumulative choline exposure
durations of 3 or 6 months. Results will directly inform future clinical implementation of choline as a
neurodevelopmental intervention. The proposed studies will also capitalize on three existing cohorts
for additional longitudinal studies that will determine durability of effects from 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 advanced 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 (CBCL) and a structured diagnostic interview (KSADS).
Select hippocampal sub-fields will be examined for volumetric improvements following choline or
placebo. Functional connectivity will be examined and is expected to reflect changes from early
choline supplementation. We will also use cortical myelin mapping to evaluate choline’s effect on
long-term myelin development. In addition, we will apply diffusion-weighted imaging to determine
choline’s effect on white matter microstructure – which is known to be disrupted in FASD.

## Key facts

- **NIH application ID:** 10295935
- **Project number:** 2R01AA024123-06A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Michael K. Georgieff
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $596,257
- **Award type:** 2
- **Project period:** 2015-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10295935

## Citation

> US National Institutes of Health, RePORTER application 10295935, Choline Supplementation as a Neurodevelopmental Intervention in Fetal Alcohol Spectrum Disorders (2R01AA024123-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10295935. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*