Longitudinal Metabolomic Profile Trajectories in Healthy Pregnancy and Variation by BMI and Fetal Sex
Abstract Objectives Maternal plasma metabolites have been linked with pregnancy outcomes, and two studies reported that metabolite levels differ by trimester. However, dynamic metabolite trajectories in normal pregnancy have not been characterized. We examined metabolite trajectories and tested whether trajectories differed by maternal body mass index (BMI) or fetal sex. Methods We quantified 3 panels of targeted metabolites—37 amino acids, 37 phospholipid fatty acids and 28 acylcarnitines—in blood samples collected longitudinally from 214 pregnant women (at 10–14, 15–26, 26–31, and 33–39 weeks, staggered to sample most weeks of pregnancy). Participants were healthy controls in a nested case-control study in the Fetal Growth Studies—Singletons. We used linear mixed models to estimate metabolite trajectories and evaluate if trajectories varied by maternal BMI (<25, 25–29.9, 30) or fetal sex. We used novel methods such as hierarchical clustering to group metabolite trajectories. Results Concentrations of most carnitines, 57% of fatty acids, and 24% of amino acids (e.g., branched chain amino acids) significantly decreased over pregnancy; 22% of fatty acids and 24% of amino acids (e.g., threonine, histidine) significantly increased. Trajectories of 2 carnitines (propionylcarnitine and stearoylcarnitine) and 3 fatty acids (15:0, 17:0, 22:0) significantly differed by sex. Trajectories of dodecenoylcarnitine, 2 fatty acids and 2 fatty acid ratios (17:0, 20:3n6, AA/DHA, AA/(DHA + EPA)) significantly differed by BMI: specifically, 17:0, AA/DHA, and AA/(DHA + EPA) decreased less over pregnancy for women with high BMI. Conclusions Concentrations of most metabolites significantly changed during pregnancy, and trajectories of some carnitines and fatty acids differed significantly by maternal BMI and fetal sex. Future pregnancy metabolomics studies should consider BMI, fetal sex, and multiple samples across pregnancy. Funding Sources Eunice Kennedy Shriver National Institute of Child Health and Human Development.