Efficacy of Maternal Choline Supplementation During Pregnancy in Mitigating Adverse Effects of Prenatal Alcohol Exposure on Growth and Cognitive Function: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Abstract

Background: We recently demonstrated the acceptability and feasibility of a randomized, double-blind choline supplementation intervention for heavy drinking women during pregnancy. In this study, we report our results relating to the efficacy of this intervention in mitigating adverse effects of prenatal alcohol exposure (PAE) on infant growth and cognitive function.

Methods: Sixty-nine Cape Coloured (mixed ancestry) heavy drinkers in Cape Town, South Africa, recruited in mid-pregnancy, were randomly assigned to receive a daily oral dose of either 2 g of choline or placebo from time of enrollment until delivery. Each dose consisted of an individually wrapped packet of powder that, when mixed with water, produced a sweet tasting grape-flavored drink. The primary outcome, eyeblink conditioning (EBC), was assessed at 6.5 months. Somatic growth was measured at birth, 6.5, and 12 months, recognition memory and processing speed on the Fagan Test of Infant Intelligence, at 6.5 and 12 months.

Results: Infants born to choline-treated mothers were more likely to meet criterion for conditioning on EBC than the placebo group. Moreover, within the choline arm, degree of maternal adherence to the supplementation protocol strongly predicted EBC performance. Both groups were small at birth, but choline-treated infants showed considerable catch-up growth in weight and head circumference at 6.5 and 12 months. At 12 months, the infants in the choline treatment arm had higher novelty preference scores, indicating better visual recognition memory.

Conclusions: This exploratory study is the first to provide evidence that a high dose of choline administered early in pregnancy can mitigate adverse effects of heavy PAE on EBC, postnatal growth, and cognition in human infants. These findings are consistent with studies of alcohol-exposed animals that have demonstrated beneficial effects of choline supplementation on classical conditioning, learning, and memory.

Keywords: Choline Supplementation; Eyeblink Conditioning; Fetal Alcohol Spectrum Disorders; Fetal Alcohol Syndrome; Growth; Prenatal Alcohol Exposure.

Figure 1

Flow diagram of the progression of participants through the trial

Figure 2

Headband supporting tube that (1) delivers air puff to right eye and (2) photodiode that measures right eyelid closure, at a distance of ~2.5 cm.

Figure 3

CS and US onset and offset times (2000 milliseconds total) and data recording windows for CR and UR. CS, conditioned stimulus (tone); US, unconditioned stimulus (air puff); CR, conditioned response (blink to CS); UR, unconditioned response (blink to US); a, startle response.

Figure 4

Percent CRs across the three eyeblink conditioning sessions by treatment group.

Figure 5

Relation of protocol adherence (% packets used) in the choline-treated group to percent CRs during eyeblink conditioning session 3.