Prenatal Maternal Phosphatidylcholine and Children's Behavior and Cognition through 4 Years of Age: Randomized Clinical Trial.

Abstract

Background: Increasing popularity of choline supplements may prompt patients to seek advice on safe, effective doses during prenatal visits. Rationale for prenatal phosphatidylcholine supplements stems from the fetal developmental role of α7-nicotinic cholinergic receptor gene CHRNA7, associated with Schizophrenia, Attention Deficit Disorder, and Autism Spectrum Disorder. Fetal brain developmental problems, including those linked to CHRNA7, convey risk for these mental illnesses. Choline derived from maternal phosphatidylcholine intake activates fetal α7-nicotinic receptors, which facilitate brain neurosynaptic development, observed after birth as robust inhibition of cerebral neurophysiological responses to repeated stimuli. A previous study found that maternal prenatal phosphatidylcholine compared to placebo significantly improved newborns' neurophysiology and thereby decreased the children's attention and social withdrawal problems at 40 months of age.

Objective: To assess whether maternal prenatal phosphatidylcholine compared to placebo in a larger randomized clinical trial supports fetal brain development to decrease childhood attention and social behavioral problems and increase cognitive performance.

Study design: A clinical trial at University of Colorado Hospital Prenatal Clinics and affiliated community hospitals randomized 206 women to 9000 mg phosphatidylcholine (the form of choline occurring naturally in food) or placebo from 16 weeks' gestation through delivery. From 18 months to 4 years of age, 142 children were assessed by parents on the Child Behavior Check List 1.5-5-year version (CBCL_1.5-5yr). The 2 primary outcomes were Withdrawn and Attention Problems. A secondary outcome was the Wechsler Preschool and Primary Scale of Intelligence-IV Full Scale Intelligence Quotient (Full Scale-IQ). Cerebral neurophysiological inhibition, assessed soon after birth, confirmed phosphatidylcholine's fetal developmental effects.

Results: Prenatal phosphatidylcholine supplements compared to placebo produced fewer children with multiple or pervasive Withdrawn problems and increased WPPSI-IV Full-Scale IQ (mean difference 7.78, 95% CI 1.88, 13.7; p = .010). Attention problems did not decrease significantly. In exploratory analyses, 11 children had CBCL_1.5-5yr Autism Spectrum T-scores in the clinical referral range and language deficits typical of Autism Spectrum Disorder, 10 of 71 from women who had placebo and 1 of 71 who had phosphatidylcholine, Risk Ratio 10.0; 95% CI 1.31, 76.1; p = .026. Twelve children had Full-Scale IQ > 120 (>90 %ile), 10 of 54 from women who had phosphatidylcholine and 2 of 49 who had placebo, Risk Ratio 4.54; 95% CI 1.05, 19.7; p = .044. Positive effects were observed regardless of presence or absence of maternal mental disorders. Phosphatidylcholine produced no significant adverse effects or safety problems for women or children. Nausea, vomiting, dizziness, and hypertension were not increased. The children had normal physical parameters at birth and through childhood. Several limitations temper the study's findings: effects on Attention problems did not reach significance, parents rated social behavior, and one-third of women were lost between prenatal enrollment and 4-year assessments.

Conclusion: Prenatal phosphatidylcholine supplements provide safe, effective support of fetal brain development. Comparison of doses from this and previous trials suggests 6300 mg phosphatidylcholine or 900 mg choline, beginning as early as possible in gestation. Outcomes for the children include fewer social withdrawal problems and increased cognitive test performance.