Choline During Pregnancy and Child Neurodevelopment: A Systematic Review of Randomized Controlled Trials and Observational Studies

Background: Most pregnant women have choline intakes below recommendations. Animal studies suggest that choline supplementation during pregnancy improves cognitive outcomes in the offspring. This review aims to determine whether higher choline levels during pregnancy are associated with improved child brain development. Methods: We systematically reviewed the evidence for the role of choline in pregnancy for human neurodevelopment in clinical trials and observational studies. Results: We identified four randomized trials of choline supplementation in pregnancy and five observational studies of prenatal choline. Neurodevelopmental assessments of these studies were reported across 20 eligible publications. Within both the trials and observational studies, most neurodevelopmental outcomes assessed did not support the hypothesis that higher prenatal choline benefits neurodevelopment. Among identified clinical trials, there were some instances where children whose mothers received choline supplementation had a better score on a neurodevelopmental measure. Still, each trial included multiple outcomes, and most were null. Observational studies were mixed as to whether an association between prenatal choline and an aspect of child neurodevelopment was identified. Critical limitations were present across clinical trials and observational studies, preventing confidence in the results and evidence base. Conclusions: Current evidence is insufficient to support or refute the hypothesis that increasing choline intake in pregnancy improves the neurodevelopmental outcomes of the child.