The effect of maternal choline Intake on offspring cognition in adolescence: protocol for a 14-year follow-up of a controlled feeding trial

BackgroundCholine is an essential micronutrient crucial for fetal neurodevelopment. Numerous rodent studies reveal that maternal prenatal choline deficiency produces lifelong offspring cognitive deficits and that maternal choline supplementation produces lifelong improvements to offspring cognition. Few studies have evaluated this question in humans, and with mixed results. Nonetheless, the available data raise concerns about the low choline intakes of pregnant women and highlight the need for knowledge on the functional consequences of various choline intakes during pregnancy. To address this, the present study evaluates the cognitive and affective functioning of adolescents born to women who participated in a randomized controlled trial of two levels of choline intake during pregnancy. MethodsIn a double-blind controlled choline feeding trial, (N = 26) third-trimester pregnant women were randomly assigned to daily choline consumption at 480 mg/d or 930 mg/d. In this 14-year follow-up, the offspring (n = 21) of these women will complete cognitive tests proctored over conferencing software. We will also assess facets of mental health using the Achenbach System of Empirically Based Assessment. These assessments will test the hypothesis that third trimester maternal choline intake exerts lasting effects on offspring attention, memory, executive function, and mental health. Significance and ImpactWe hypothesize that adolescent offspring born to women in the 930 mg/d group will perform better in domains of memory, attention, executive function, and mental health than offspring of the 480 mg/d group. This study is unique because total maternal choline intake is precisely known, and the offspring are followed into adolescence, a time when group differences are indicative of lifelong effects of the prenatal intervention. The findings will provide important new information concerning the lasting functional consequences of maternal choline intake during pregnancy for offspring neurobehavioral health, thereby informing dietary recommendations and supplementation policies for pregnant women. Trial registrationClinicalTrials.gov: NCT05859126