Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2015 Nov;102(5):1113-25.
doi: 10.3945/ajcn.114.099168. Epub 2015 Oct 7.

Choline Supplementation in Children With Fetal Alcohol Spectrum Disorders: A Randomized, Double-Blind, Placebo-Controlled Trial

Affiliations
Free PMC article
Randomized Controlled Trial

Choline Supplementation in Children With Fetal Alcohol Spectrum Disorders: A Randomized, Double-Blind, Placebo-Controlled Trial

Jeffrey R Wozniak et al. Am J Clin Nutr. .
Free PMC article

Abstract

Background: Fetal alcohol spectrum disorders (FASDs) are conditions characterized by physical anomalies, neurodevelopmental abnormalities, and neurocognitive deficits, including intellectual, executive, and memory deficits. There are no specific biological treatments for FASDs, but rodent models have shown that prenatal or postnatal choline supplementation reduces cognitive and behavioral deficits. Potential mechanisms include phospholipid production for axonal growth and myelination, acetylcholine enhancement, and epigenetic effects.

Objective: Our primary goal was to determine whether postnatal choline supplementation has the potential to improve neurocognitive functioning, particularly hippocampal-dependent memory, in children with FASDs.

Design: The study was a double-blind, randomized, placebo-controlled pilot trial in children (aged 2.5-5 y at enrollment) with FASDs (n = 60) who received 500 mg choline or a placebo daily for 9 mo. Outcome measures were Mullen Scales of Early Learning (primary) and the elicited imitation (EI) memory paradigm (secondary).

Results: The administration proved feasible, and choline was well tolerated. Participants received a dose on 88% of enrolled days. The only adverse event linked to choline was a fishy body odor. Choline supplementation improved the secondary outcome (EI) only after immediate recall performance was controlled for, and the outcome was moderated by age. The treatment effect on EI items recalled was significant in the younger participants (2.5- to ≤4.0-y-olds); the young choline group showed an increase of 12-14 percentage points greater than that of the young placebo group on delayed recall measures during treatment. However, there was a marginal baseline difference in delayed item recall between the young choline and placebo groups as well as a potential ceiling effect for item recall, both of which likely contributed to the observed treatment effect. We also observed a trend toward a negative effect of choline supplementation on the immediate EI recall of ordered pairs; the young placebo group showed an increase of 8-17 percentage points greater than that of the choline group during treatment. There was an inverse relation between choline dose (in mg/kg) and memory improvement (P = 0.041); the data suggest that weight-adjusted doses may be a better alternative to a fixed dose in future studies. Limitations included trend-level baseline differences in performance, the post-hoc determination of age moderation, and potential ceiling effects for the memory measure.

Conclusions: This pilot study suggests that an additional evaluation of choline supplementation as an intervention for memory functioning in children with FASDs is warranted. The observed interaction between age and choline's effect on EI suggests that potential sensitive periods should be considered in future work. This trial was registered at clinicaltrials.gov as NCT01149538.

Keywords: children; fetal alcohol spectrum disorder; fetal alcohol syndrome; memory; randomized double-blind placebo-controlled trial.

Figures

FIGURE 1
FIGURE 1
Flowchart of the randomized clinical trial of postnatal choline supplementation.
FIGURE 2
FIGURE 2
Treatment effect on elicited imitation delayed performance was moderated by age for items [slope: γ = −14.75 (95% CI: −30.38, 0.88), t(84.9) = −1.88, P = 0.064] and ordered pairs [slope: γ = −13.68 (95% CI: −28.89), 1.52, t(89.1) = −1.79, P = 0.077]. The largest improvement in elicited imitation delayed performance occurred in the young choline group (2.5- to ≤4.0-y-olds). (A) Percentages of individual items recalled. (B) Percentages of ordered pairs recalled. Choline: n = 30 (young: n = 16; old: n = 14); placebo: n = 29 (young: n = 13; old: n = 16).
FIGURE 3
FIGURE 3
Treatment effect on elicited imitation immediate performance. Choline was not associated with the immediate score for items [intercept: γ = −11.06 (95% CI: −32.31, 10.19), t(105) = −1.03, P = 0.304; slope: γ = 3.94 (95% CI: −13.19, 21.08), t(86.6) = 0.46, P = 0.649]. A trend was seen for immediate ordered pairs [intercept: γ = −19.14 (95% CI: −40.43, 2.15), t(119) = −1.78, P = 0.078; slope: γ = 17.23 (95% CI: −0.97, 35.42), t(93.2) = 1.88, P = 0.063]. (A) Percentages of individual items recalled. (B) Percentages of ordered pairs recalled. Choline: n = 30 (young: n = 16; old: n = 14); placebo: n = 29 (young: n = 13; old: n = 16).
FIGURE 4
FIGURE 4
Lower daily dose of choline was associated with a greater treatment effect of choline for elicited imitation delayed items [slope: γ = −0.82 (95% CI: −1.60, −0.04), t(34.9) = −2.13, P = 0.041) (A) but not for ordered pairs [slope: γ = −0.30 (95% CI: −1.10, 0.49), t(36.6) = −0.77, P = 0.446] (B). The daily dose was not associated with the intercept for elicited imitation delayed items (P = 0.152) or for ordered pairs (P = 0.343). Choline group (n = 25)—10–19 mg/kg: n = 6; 20–26 mg/kg: n = 6; 27–33 mg/kg: n = 7; and 35–42 mg/kg: n = 6.
FIGURE 5
FIGURE 5
Prevalence of fishy body odor was greater in the highest quartile for the choline dose than in the lower 3 quartiles for the choline dose (P = 0.020; Fisher’s exact test). There were no differences in the presence of a fishy odor between the lowest 3 quartiles for the choline dose. Choline group (n = 25)—10–19 mg/kg: n = 6; 20–26 mg/kg: n = 6; 27–33 mg/kg: n = 7; and 35–42 mg/kg: n = 6.

Similar articles

See all similar articles

Cited by 24 articles

See all "Cited by" articles

Publication types

MeSH terms

Associated data

Feedback