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.

There is a tacit assumption that the majority of nutritional anemia is caused by iron deficiency. However, several other key micronutrients are involved in iron and/or erythrocyte metabolism and thus play a role in the development of nutritional anemia. This consensus paper provides an updated review that synthesizes current evidence on the role of individual micronutrients, beyond iron, in the development of nutritional anemia and identifies emerging hypotheses and potential mechanistic links to erythropoiesis and iron metabolism involving nutrients of both established and growing interest. To achieve this, we convened leading experts in micronutrients and nutritional anemia to categorize 10 key micronutrients of interest into a hierarchy based on the scope and strength of evidence for their roles in the development of anemia, erythropoiesis, and iron metabolism. Folate, vitamin B12, and vitamin A were ranked as having strong evidence, meaning data are consistent in describing a causal association between nutrient status and anemia development, and the evidence for the proposed mechanism(s) is well-established. Riboflavin, zinc, vitamin B6, vitamin C, and vitamin E were ranked as having moderate evidence, and vitamin D and copper were ranked as having potential and/or emerging evidence. We also identify critical gaps in the current evidence and propose priority areas for future research for each micronutrient. This perspective paper aims to serve as a comprehensive reference to inform future research priorities and guide global nutrition policy, strategy, and programming related to anemia prevention and control.