Choline supplementation in children with fetal alcohol spectrum disorders has high feasibility and tolerability

Abstract

There are no biological treatments for fetal alcohol spectrum disorders (FASD), lifelong conditions associated with physical anomalies, brain damage, and neurocognitive abnormalities. In pre-clinical studies, choline partially ameliorates memory and learning deficits from prenatal alcohol exposure. This Phase I pilot study evaluated the feasibility, tolerability, and potential adverse effects of choline supplementation in children with FASD. We hypothesized that choline would be well-tolerated with minimal adverse events. The study design was a double-blind, randomized, placebo-controlled trial. Participants included 20 children, ages 2.5–4.9y, with prenatal alcohol exposure and FASD diagnoses. Participants were randomly assigned to 500 mg. choline or placebo daily for nine months (10 active; 10 placebo). Primary outcome measures included feasibility, tolerability, adverse effects, and serum choline levels. Seventeen participants completed the study. Compliance was 82–87% as evidenced by parent-completed logsheets and dose counts. Periodic 24-hour dietary recalls showed no evidence of dietary confounding. Adverse events were minimal and were equivalent in the active and placebo arms with the exception of fishy body odor, which occurred only in the active group. There were no serious adverse events to research participants. This Phase I pilot study demonstrates that choline supplementation at 500 mg per day for nine months in children ages 2–5 is feasible and has high tolerability. Further examination of the efficacy of choline supplementation in FASD is currently underway.

Randomized, double-blind, placebo-controlled clinical trial of choline supplementation in school-aged children with fetal alcohol spectrum disorders

“…Ninety-five percent of participants completed treatment with a compliance rate of 96%. These rates are consistent with those of previous studies (14,16) and further support that choline supplementation is feasible and tolerable in children with FASDs.…”

“…On the basis of expected medium effect sizes (Cohen's d = 0.29-0.42) that were observed in early phase I analyses by Wozniak et al (16), we calculated that a total sample size of w50 subjects would be needed for 80% power to detect significant differences between treatment groups with an a level of P , 0.05. Individuals were recruited through the following 2 primary sites: the Center for Behavioral Teratology at San Diego State University and Double ARC, which is a nonprofit organization providing services to families of children with FASDs in Toledo, Ohio.…”

Maternal choline supplementation in a sheep model of first trimester binge alcohol fails to protect against brain volume reductions in peripubertal lambs

“…If doses of choline (as a nutraceutical, rather than just to correct a deficiency) need to be high (as used in the rodent studies), this may limit the feasibility in clinical settings due to tolerability. Currently, there is one study in children (aged 2–5 years old) with FASD that assessed tolerability and potential adverse effects associated with choline supplementation (Wozniak et al, 2013), but this information is not known for pregnant women.…”

“…The choline group was given a daily dose of 750 mg (~10 mg/kg per day), thus helping to guide the decision for the dose of choline used in the sheep model (Coles et al, 2015). Higher daily doses of choline (on a mg/kg basis) may be given postnatally in humans (Wozniak et al, 2013), but this sheep model was developed to test choline supplementation during pregnancy with binge-like alcohol exposure during the first-trimester equivalent. Consequently, the dosing regimen used in this sheep model is both relevant and highly translational in respect to dose of choline and timing outcome of the children postnatally.…”

The impact of sensory integration therapy on gross motor function in children after prenatal exposure to alcohol

“…In children whose mothers drank alcohol there are functional difficulties that are difficult to diagnose and classify, and often sensory integration dysfunction. For these children SI therapy is necessary and effective [10][11][12][13][14][15][16][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. This work, because of the breadth of statistical analysis, only shows the effects of SI therapy on gross motor function.…”