Four-year follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder

Michael K Georgieff,Christopher Lindgren,Birgit A Fink,Kristin E Sandness,Judith K Eckerle,Ann M Brearley,Jeffrey R Wozniak,Anita J Fuglestad,Christopher J Boys,Steven H Zeisel,Neely C Miller,Joshua P Radke

doi:10.1186/s11689-020-09312-7

Abstract

BackgroundDespite the high prevalence of fetal alcohol spectrum disorder (FASD), there are few interventions targeting its core neurocognitive and behavioral deficits. FASD is often conceptualized as static and permanent, but interventions that capitalize on brain plasticity and critical developmental windows are emerging. We present a long-term follow-up study evaluating the neurodevelopmental effects of choline supplementation in children with FASD 4 years after an initial efficacy trial.MethodsThe initial study was a randomized, double-blind, placebo-controlled trial of choline vs. placebo in 2–5-year-olds with FASD. Participants include 31 children (16 placebo; 15 choline) seen 4 years after trial completion. The mean age at follow-up was 8.6 years. Diagnoses were 12.9% fetal alcohol syndrome (FAS), 41.9% partial FAS, and 45.1% alcohol-related neurodevelopmental disorder. The follow-up included measures of intelligence, memory, executive functioning, and behavior.ResultsChildren who received choline had higher non-verbal intelligence, higher visual-spatial skill, higher working memory ability, better verbal memory, and fewer behavioral symptoms of attention deficit hyperactivity disorder than the placebo group. No differences were seen for verbal intelligence, visual memory, or other executive functions.ConclusionsThese data support choline as a potential neurodevelopmental intervention for FASD and highlight the need for long-term follow-up to capture treatment effects on neurodevelopmental trajectories.Trial registrationClinicalTrials.Gov #NCT01149538; Registered: June 23, 2010; first enrollment July 2, 2010

Highlights

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 [1]
Cognition is a natural target for intervention in FASD because cognitive deficits contribute to problems with adaptive functioning, social skills, and capacity for independent living [11]
General cognitive functioning Scores from the SB-5 at follow-up were compared across groups with a univariate General Linear Model (GLM) analysis for Full-Scale IQ and a separate multivariate GLM for the index-scores: Verbal

Summary

Introduction

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 [1]. Despite being more common than autism spectrum disorder, which has a prevalence of 0.6% [6], FASD remains under-recognized [7]. Cognitive deficits are a core feature of FASD, ranging from serious intellectual impairment to more select deficits in attention, executive functioning, memory, visualperceptual/motor skills, and academics [10]. Cognition is a natural target for intervention in FASD because cognitive deficits contribute to problems with adaptive functioning, social skills, and capacity for independent living [11]. Despite the high prevalence of fetal alcohol spectrum disorder (FASD), there are few interventions targeting its core neurocognitive and behavioral deficits. We present a long-term follow-up study evaluating the neurodevelopmental effects of choline supplementation in children with FASD 4 years after an initial efficacy trial

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Discussion

Conclusion