IMPACT OF PRENATAL NUTRITIONAL STATUS ON FETAL GROWTH AND BIRTH OUTCOMES

Abstract

Placental nutrient transporters are important in determining fetal growth, and maternal nutrition during pregnancy has a strong impact on placental function, but there are limited simple and cost-effective measures of placental function. We tested the hypothesis that the maternal nutritional sufficiency score (MNSS) is related to placental mechanistic target of rapamycin (mTOR) pathway and amino acid transporter activity, and that these are markers of fetal growth. We followed 287 women during pregnancy for three trimesters to measure dietary intake, blood nutrient concentrations (folate, iron, vitamin D, omega-3 fatty acids) and to create a composite MNSS. We collected placenta at birth and measured phosphorylation of mTOR (p-mTOR) to total mTOR (western blot) and System L amino acid transporter activity (³H-leucine uptake). Babies were born small-for-gestational age (SGA, 12.9%), appropriate-for-gestational age (AGA, 78.4%) or large-for-gestational age (LGA, 8.7%). Logistic regression, linear mixed models, mediation analysis, structural equation modeling and machine learning models were used. First trimester's MNSS was strongly correlated with placental mTOR activity  and System L activity. Mediation analysis showed that 61% of MNSS' effect on System L was via mTOR. MNSS had an AUC for SGA prediction, with MNSS+mTOR having an AUC 0.901. The ensemble machine learning model's accuracy  was 87.9% (classification 3 classes). E-value analysis demonstrated the model was unlikely to be confounded by unmeasured variables. Placental System L was the best individual predictor of birth weight . First trimester maternal nutritional sufficiency score is a low cost, easy to calculate measure of the placental mTOR-System L axis, and a reliable predictor of fetal growth. Our findings highlight the need for early pregnancy nutritional assessment to prevent adverse birth outcomes, and to prevent transgenerational programming.