Written by Joyce Smith, BS. A high dose of choline administered early in pregnancy can mitigate adverse effects of heavy prenatal alcohol exposure in offspring.

Infant and Children's HealthCholine, found in large quantities in meat, dairy products, eggs, and some vegetables, is an essential nutrient that is a precursor to the neurotransmitter acetylcholine. It readily crosses the placenta and accumulates in the fetal brain, where it plays an important role in cell membrane integrity, trans-membrane signaling, and lipid and cholesterol transport and metabolism. 1 Choline is also an important precursor to acetylcholine, as well as a methyl-group donor for homocysteine metabolism and DNA methylation, and thus influences downstream alterations in gene expression as seen in alcohol teratogenesis 2.

In a previous study, Jacobson et al demonstrated that choline was both a feasible and acceptable supplementation for women who drank heavily during pregnancy. In this study 3, they report the effectiveness of that intervention. The study’s objective 4 was to assess the ability of prenatal choline supplementation to mitigate the adverse effects of parental alcohol exposure (PAE) on infant growth and cognitive function. The primary outcome, eyeblink conditioning (EBC), was assessed at 6.5 months. The mitigating effect of choline supplementation was measured at 6.5 and 12 months as three secondary outcomes: pre- and postnatal growth restriction, recognition memory, and information processing speed. In addition, they hoped to determine the effects of choline on Fetal Alcohol Spectrum Disorders (FASD) diagnosis and the degree to which choline supplementation is particularly effective in women with choline deficient diets and in women who carry the rs12325817 variant of the enzyme phosphatidylethanolamine-N-methyltransferase (PEMT), which limits endogenous choline synthesis of choline to phosphatidylcholine 4.

The 69 women in the study were recruited in mid-pregnancy, having started prenatal care by the 23rd week of gestation. They were randomly assigned to receive a daily oral dose of either 2 grams of choline (1.25 g of bitartrate containing 1 gram of  bioavailable choline cation) or placebo. Interviews were done from the time of study enrollment until women gave birth to determine average alcohol consumption. Heavy drinking during pregnancy was defined as an average of at least 2 standard drinks (1.0 oz absolute alcohol) /day or 2 or more incidents of binge drinking (4 or more drinks /occasion).

Children born to study participants were tested at ages 6 months and 12 months on a variety of measures, including physical growth as well as cognitive, learning, and memory performance. The researchers reported that, although infants in both groups were small at birth, choline-exposed infants showed considerable catchup growth in weight and head circumference at 6 and 12 months, when compared with infants in the placebo group. Also, at 12 months, infants in the choline intervention group scored higher than infants in the placebo group on tests of visual recognition memory.

This exploratory study provides evidence that a high dose of choline supplementation early in pregnancy may have the potential to protect against a range of alcohol-related cognitive deficits that do not become evident until childhood; therefore, follow-up of this cohort will be important to determine whether the positive effects of choline supplementation persist into childhood.

Source: Jacobson, Sandra W., R. Colin Carter, Christopher D. Molteno, Mark E. Stanton, Jane S. Herbert, Nadine M. Lindinger, Catherine E. Lewis et al. “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.” Alcoholism: Clinical and Experimental Research 42, no. 7 (2018): 1327-1341.

Posted March 30, 2020.

Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from  the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.

References:

  1. Zeisel SH, Niculescu MD. Perinatal choline influences brain structure and function. Nutrition reviews. 2006;64(4):197-203.
  2. Zeisel SH. What choline metabolism can tell us about the underlying mechanisms of fetal alcohol spectrum disorders. Molecular neurobiology. 2011;44(2):185-191.
  3. Resseguie M, Song J, Niculescu MD, da Costa K-A, Randall TA, Zeisel SH. Phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is induced by estrogen in human and mouse primary hepatocytes. The FASEB Journal. 2007;21(10):2622-2632.
  4. Jacobson, Sandra W., R. Colin Carter, Christopher D. Molteno, Mark E. Stanton, Jane S. Herbert, Nadine M. Lindinger, Catherine E. Lewis et al. “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.” Alcoholism: Clinical and Experimental Research 42, no. 7 (2018): 1327-1341.4.