Longitudinal Plasma Metabolomics Profile in Pregnancy-A Study in an Ethnically Diverse U.S. Pregnancy Cohort.

Susanna D Mitro,Liwei Chen,Yiqing Song,Bizu Gelaye,Mengying Li,Yeyi Zhu,Michael Y Tsai,Katherine L Grantz,Cuilin Zhang,Stefanie N Hinkle,Yaqi Cao,Natalie L Weir,Jing Wu,Andrew A Bremer,Zhen Chen,Mohammad L Rahman

doi:10.3390/nu13093080

Abstract

Amino acids, fatty acids, and acylcarnitine metabolites play a pivotal role in maternal and fetal health, but profiles of these metabolites over pregnancy are not completely established. We described longitudinal trajectories of targeted amino acids, fatty acids, and acylcarnitines in pregnancy. We quantified 102 metabolites and combinations (37 fatty acids, 37 amino acids, and 28 acylcarnitines) in plasma samples from pregnant women in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies—Singletons cohort (n = 214 women at 10–14 and 15–26 weeks, 107 at 26–31 weeks, and 103 at 33–39 weeks). We used linear mixed models to estimate metabolite trajectories and examined variation by body mass index (BMI), race/ethnicity, and fetal sex. After excluding largely undetected metabolites, we analyzed 77 metabolites and combinations. Levels of 13 of 15 acylcarnitines, 7 of 25 amino acids, and 18 of 37 fatty acids significantly declined over gestation, while 8 of 25 amino acids and 10 of 37 fatty acids significantly increased. Several trajectories appeared to differ by BMI, race/ethnicity, and fetal sex although no tests for interactions remained significant after multiple testing correction. Future studies merit longitudinal measurements to capture metabolite changes in pregnancy, and larger samples to examine modifying effects of maternal and fetal characteristics.

Highlights

Metabolomics, the study of small molecules in plasma or other biological compartments, can describe a person’s complex metabolic state at the time of measurement
About half of the women (52%) had pre-pregnancy body mass index (BMI)
We observed suggestive evidence that trajectories of two saturated fatty acids and two acylcarnitines differed by fetal sex; five fatty acids and proline differed by maternal race/ethnicity; and five fatty acids, dodecenoylcarnitine, and alanine differed by pre-pregnancy BMI, though interactions were not significant after FDR

Summary

Introduction

Metabolomics, the study of small molecules in plasma or other biological compartments, can describe a person’s complex metabolic state at the time of measurement. Alterations in amino acids, fatty acids, and acylcarnitines have been significantly associated with gestational diabetes [2,3,4,5,6], and concentrations of acylcarnitines and amino acids have been linked to small for gestational age [7] Because of these links between metabolites and maternal and fetal outcomes, describing longitudinal plasma concentrations of these metabolites across pregnancy is critical. Three recent studies described longitudinal changes in targeted maternal plasma metabolomics (including amino acids, fatty acids, and acylcarnitines) over healthy pregnancy, but each collected samples at the same fixed times in all participants, leaving gaps in the remaining weeks of pregnancy and precluding description of continuous changes over time [8,9,10]. A few additional preliminary studies have measured metabolites (amino acids, fatty acids, and others) in maternal plasma at multiple points in pregnancy, but were all limited by methodological challenges including a small sample size (30 or fewer participants at each time point) and lack of repeated measurements on the same women [11,12,13,14]

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