The Effect of Maternal Choline Intake on Offspring Cognition in Adolescence: Protocol for a 14-year Follow-Up of a Randomized Controlled Feeding Trial.

Abstract

Background: Choline is an essential micronutrient crucial for fetal neurodevelopment. Numerous rodent studies reveal that compared to maternal consumption of standard chow, maternal prenatal choline deficiency produces lifelong offspring cognitive deficits, and maternal choline supplementation produces lifelong improvements in offspring cognition. Few studies have evaluated this question in humans, with mixed results. Nonetheless, the available data raise concerns about the low choline intakes of pregnant women and highlight the need for knowledge of the functional consequences of various choline intakes during pregnancy.

Objective: This study will evaluate the cognitive and affective functioning of adolescents born to women who participated in a randomized controlled trial (RCT) of 2 levels of choline intake during pregnancy, with the primary aim of assessing offspring attention and spatial memory.

Methods: In a double-blind, randomized controlled choline feeding trial 26 women beginning their third trimester of pregnancy were randomly assigned to 2 groups: daily choline consumption at 480 or 930 mg/day. In this 14-year follow-up, the offspring (n=21) of these women will complete cognitive tests proctored over videoconferencing software. Cognitive function domains will be assessed using web-based software from the Cambridge Neuropsychological Test Automated Battery (CANTAB Connect). We will also assess facets of mental health using the Achenbach System of Empirically Based Assessment (ASEBA). These assessments will test the hypothesis that third-trimester maternal choline intake exerts lasting effects on offspring attention, memory, executive function, and mental health.

Results: Between January 2009 and October 2010, 26 women beginning their third trimester of pregnancy from the Ithaca area were enrolled in the original controlled feeding study. We successfully re-recruited 21 (80%) of the original 26 offspring to this 14-year remote follow-up study. Recruitment started in August 2023 and was concluded in October 2023. Analysis is ongoing, and the first results are expected to be submitted for publication in the fall of 2025. We hypothesize that adolescent offspring born to women in the 930 mg/day group will perform better in domains of attention, memory, executive function, and mental health than offspring of women in the 480 mg/day group. This study is unique because the 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 prenatal intervention.

Conclusions: 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 registration: ClinicalTrials.gov: NCT05859126; https://clinicaltrials.gov/study/NCT05859126.

International registered report identifier (irrid): DERR1-10.2196/73508.