Prenatal DHA & Neurofunctional Development

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 DESCRIPTION (provided by applicant): Docosahexaenoic acid (DHA) is essential for neurodevelopment. If maternal DHA reserves are adequate during pregnancy, at parturition RBC-DHA of the mother would be ≥ the infant, i.e., DHA equilibrium. Previously, we randomized pregnant women to placebo oil or DHA (600 mg/day). We discovered that the majority of subjects did not achieve DHA equilibrium (5% placebo, 35% DHA), indicating DHA insufficiency, which has been reported to limit infant neurodevelopment. To test whether DHA insufficiency limited fetal neurodevelopment in our sample, we applied an innovative analysis method to estimate fetal brain maturation. Results confirmed that maternal DHA insufficiency significantly constrained fetal autonomic brain age scores (fABAS). Our hypothesis is that many pregnant women fail to get adequate DHA in their diet and that DHA insufficiency constrains fetal and infant neurodevelopment. The long-term goal is to provide the neuroscience to inform public health recommendations related to the use and dose of prenatal DHA supplementation, the influence of dietary fatty acids and the effect on offspring neurodevelopment. This is aligned with the strategic and scientific vision of NICHD and the mission of national and international health organizations that recognize that prenatal exposures set the stage for future health and disease. We propose a randomized Phase III clinical trial of 200 or 800 mg/day DHA during the last two trimesters of pregnancy to achieve these aims: Aim 1) Increase the incidence of DHA equilibrium with 800 mg/day maternal DHA supplementation. Hypothesis: The dosing strategy will result in significant group differences with a higher incidence of DHA equilibrium in the grou receiving 800 mg/day DHA supplementation. Aim 2) Establish whether failure to achieve DHA equilibrium constrains fetal neurodevelopment. Hypothesis: DHA insufficiency will constrain fetal neurodevelopment as evidenced by lower fetal cardiac and brain autonomic indices (HRV, fABAS) at 32 and 36 weeks GA. Aim 3) Determine if fetal neurodevelopmental scores predict infant neurodevelopment. Hypothesis: DHA insufficiency associated with lower fetal HRV and fABAS scores will have a programming effect evidenced by 1) lower band-limited EEG power at 1 month of age to infrequent auditory stimuli, 2) decreased habituation to familiar visual stimuli at 6 and 12 months, evidenced by a larger ERP negative central (NC) component and 3) reduced maintenance of sustained attention and longer overall ocular latency between 4-6 months. Relevance to Public Health: Currently, there are no FDA recommendations for DHA supplementation during pregnancy. If the aims of this proposal are achieved, it could lead to informed recommendations with respect to the appropriate use and effective dose of supplemental DHA and dietary recommendations during pregnancy, especially in populations where the nutritional status of the diet is suboptimal.