Prenatal choline lowered social withdrawal, improved IQ in children

Clinical takeaway: Counsel interested patients that many prenatal supplements contain little or no choline, so separate supplementation may be required. In this trial, maternal supplementation with 6300 mg/day of phosphatidylcholine (approximately 900 mg/day of choline) was associated with improved behavioral and cognitive outcomes in children through age 4.

Clinicians counseling pregnant women on supplements have had little human evidence to draw on for choline. The nutrient helps the fetal brain build its connections, and many women don’t get enough of it from food. 

Animal studies and a small earlier trial pointed toward benefit for early behavior, while another trial of the same form found no effect on cognition. This randomized trial of phosphatidylcholine, the form of choline found in food, extends that work to a larger group of women and their children. 

Parents reported multiple or pervasive social withdrawal problems in 24% of children in the placebo group compared with 4% of children whose mothers received phosphatidylcholine, an absolute difference of 20 percentage points. The groups did not differ in attention problems, the study's other primary outcome.

Full-scale IQ, a secondary outcome, averaged 106.0 at age 4 in the phosphatidylcholine group versus 98.2 in the placebo group. The estimated between-group difference was 7.78 points, with a plausible range from approximately 2 to 14 points. Improvements were concentrated in the working memory and visual-spatial domains.

This double-blind trial randomized 206 pregnant women at 16 weeks' gestation to phosphatidylcholine 9,000 mg/day or placebo until delivery. Behavioral assessments were completed for 142 children and IQ testing for 103. In a sensitivity analysis that excluded 20 women who received open-label phosphatidylcholine during the COVID-19 pandemic, the reduction in social withdrawal remained significant, whereas the confidence interval for the IQ difference widened to include no effect.

Three similarly sized prenatal choline trials are currently recruiting, but follow-up data through age 4 are not expected for another 5 to 7 years. Until then, support for the 900-mg daily dose comes largely from consistency with an earlier trial that used 6,300 mg of phosphatidylcholine and produced similar findings. The dose exceeds current choline intake recommendations from the American College of Obstetricians and Gynecologists.

“Choline in the baby’s circulation comes from the choline eaten by the mother which activates this receptor,” said Robert Freedman, MD, professor of psychiatry at the University of Colorado School of Medicine, referring to the alpha-7 nicotinic receptor, which helps developing nerve cells form connections. “But many mothers don’t get enough choline in their diets to fully give the baby all that it needs to complete the activation of its neurons. Unfortunately, once the opportunity to do so before birth passes there is no way to go back and correct the problem in brain development.” 

Source: Hunter SK, et al. (2026 Oct 19) Am J Obstet Gynecol. Prenatal Maternal Phosphatidylcholine and Children’s Behavior and Cognition through 4 Years of Age: Randomized Clinical Trial