title: 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 (FASDs), lifelong conditions associated with physical anomalies, brain damage, and neurocognitive abnormalities. In preclinical 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 aged 2.5 to 4.9 years with prenatal alcohol exposure and FASD diagnoses. Participants were randomly assigned to 500 mg choline or placebo daily for 9 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% to 87%, as evidenced by parent-completed log sheets 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/d for 9 months in children aged 2 to 5 years is feasible and has high tolerability. Further examination of the efficacy of choline supplementation in FASD is currently underway.
authors.affiliation: Department of Psychiatry, University of Minnesota, Minneapolis, MN 55454, USA. Electronic address: jwozniak@umn.edu.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Wozniak
authors.forename: Anita J
authors.initials: AJ
authors.lastname: Fuglestad
authors.forename: Judith K
authors.initials: JK
authors.lastname: Eckerle
authors.forename: Maria G
authors.initials: MG
authors.lastname: Kroupina
authors.forename: Neely C
authors.initials: NC
authors.lastname: Miller
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Boys
authors.forename: Ann M
authors.initials: AM
authors.lastname: Brearley
authors.forename: Birgit A
authors.initials: BA
authors.lastname: Fink
authors.forename: Heather L
authors.initials: HL
authors.lastname: Hoecker
authors.forename: Steven H
authors.initials: SH
authors.lastname: Zeisel
authors.forename: Michael K
authors.initials: MK
authors.lastname: Georgieff
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects*; D002675:Child, Preschool; D002794:Choline / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000188:drug therapy*; D006801:Humans; D008297:Male; D010349:Patient Compliance; D010865:Pilot Projects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D002794:Choline
keywords: AI; ARND; CNS; Children; Choline; Clinical trial; FAS; FASD; Fetal alcohol (FAS, FASD); Treatment; adequate intake; alcohol-related neurodevelopmental disorder; central nervous system; fetal alcohol spectrum disorders; fetal alcohol syndrome