Prenatal choline trial links supplement to fewer social withdrawal problems in children

A randomised trial found fewer reported social withdrawal problems and higher cognitive scores among four-year-olds exposed to phosphatidylcholine before birth, though researchers say larger studies are needed.

A new randomised clinical trial suggests that a form of choline taken during pregnancy may have lasting benefits for children’s brain development, with researchers reporting fewer social withdrawal problems and stronger scores on cognitive tests among children whose mothers received the supplement. The study, published last week in the American Journal of Obstetrics and Gynaecology, followed children from infancy to the age of four and adds to a growing, but still unsettled, body of evidence on prenatal choline intake.

Choline is an essential nutrient involved in early brain development, and the study’s authors set out to test whether boosting maternal intake during pregnancy could improve outcomes for children later on. They enrolled 206 pregnant women and randomly assigned them at 16 weeks’ gestation to receive either 9,000 milligrams of phosphatidylcholine each day or a placebo until delivery. The children were then assessed for behaviour between 18 months and four years of age, and their cognitive performance was measured at ages three and four.

Among children whose parents completed the behavioural questionnaires, 4% in the supplement group showed increased social withdrawal, compared with 24% in the placebo group. That category can include limited interest in other people, reduced eye contact and pulling away from social activities. The researchers also reported higher cognitive scores in the children exposed to the supplement in the womb, although they cautioned that the findings should be interpreted carefully because around a third of participants did not complete the four-year follow-up and some of the behaviour data came from parental reports.

The lead author, Friedman, said the findings strengthen the argument that choline supplementation in pregnancy can influence children’s brain development over the long term. He explained that choline appears to act by stimulating a receptor linked to the CHRNA7 gene in developing nerve cells, helping them mature before birth. Friedman also argued that it is difficult to obtain enough choline from an ordinary diet alone to fully activate that pathway, although he suggested the dose used in the trial may have been higher than necessary and proposed a lower amount for future use. The researchers reported no major safety concerns, but they said larger studies with longer follow-up are still needed to determine whether the effects persist as children grow.

The new findings sit alongside earlier research that has pointed in different directions. A 2012 trial found no measurable cognitive benefit from phosphatidylcholine in infancy, while a 2017 study reported faster reaction times in babies whose mothers received higher choline intake in late pregnancy. A 2025 review in the journal Nutrients concluded that the overall evidence remains mixed and insufficient to confirm or rule out a benefit from increasing choline during pregnancy. That makes the latest study notable, but not definitive, as scientists continue to work out whether prenatal choline should play a larger role in guidance for expectant mothers.