Prenatal phosphatidylcholine: higher child IQ at four, but attention did not improve

Design

Randomised, placebo-controlled trial, single centre with affiliated sites

Population

206 pregnant women from 16 weeks; 142 children assessed to age 4

Primary outcome

Parent-rated withdrawn behaviour and attention problems (CBCL 1.5-5)

Effect

Fewer withdrawn problems; attention not significant; Full Scale IQ +7.78 (95% CI 1.88 to 13.7)

A placebo-controlled trial at one US university hospital and its affiliated community sites randomised 206 pregnant women to phosphatidylcholine 9,000 mg daily, the form of choline found in food, or placebo, from 16 weeks to delivery. Of these, 142 children were assessed between 18 months and 4 years. The two primary outcomes were parent-rated withdrawn behaviour and attention problems; Full Scale IQ was secondary.

Children in the supplement group had fewer multiple or pervasive withdrawn-behaviour problems and a higher Full Scale IQ, by a mean of 7.8 points. Attention problems, the other primary outcome, did not differ significantly. In exploratory analyses, autism-range scores with language deficits were seen in 1 of 71 children in the supplement group against 10 of 71 with placebo. No safety problems were reported in mothers or children.

The authors propose a dose from comparison with an earlier trial. That proposal goes beyond what a single trial with one-third attrition, one negative primary outcome and parent-rated behaviour can carry. The autism signal rests on 11 children and was not a planned outcome.

When a patient asks about choline supplements, the honest answer is that this is promising but unconfirmed. Dietary choline from eggs, dairy, legumes and meat is reasonable advice; a high-dose supplement is not yet a routine recommendation.

• Expect questions about choline supplements in antenatal clinic; this trial will be cited.
• Tell patients the IQ result is from one trial with substantial loss to follow-up and needs repeating.
• Food sources of choline include eggs, dairy, legumes and meat; dietary advice carries no new risk.
• Do not quote the autism finding as a benefit: it was exploratory and based on 11 children.
• No maternal or child safety problems were reported at 9 g a day, but this is one trial.

Why it matters

Choline is already sold as a pregnancy supplement, and this trial will be used to justify it before anyone has replicated it.

Don't overread it

One of the two primary outcomes was negative, and the autism finding was exploratory; this does not show the supplement prevents autism.

The statistics, in plain English

The IQ difference of 7.8 points has a 95% confidence interval of 1.9 to 13.7, so the true effect could be small or large. The autism risk ratio of 10.0 has an interval of 1.3 to 76, which shows how few events it rests on. Losing a third of participants between pregnancy and age 4 can bias results if those who left differed between groups.

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