The plasma metabolome of women in early pregnancy differs from that of non-pregnant women

Autoři: Samuel K. Handelman aff001;  Roberto Romero aff001;  Adi L. Tarca aff001;  Percy Pacora aff001;  Brian Ingram aff009;  Eli Maymon aff001;  Tinnakorn Chaiworapongsa aff001;  Sonia S. Hassan aff001;  Offer Erez aff001
Působiště autorů: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICH aff001;  Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, United States of America aff002;  Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, United States of America aff003;  Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan, United States of America aff004;  Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan, United States of America aff005;  Detroit Medical Center, Detroit, Michigan, United States of America aff006;  Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, United States of America aff007;  Department of Computer Science, Wayne State University College of Engineering, Detroit, Michigan, United States of America aff008;  Metabolon Inc., Raleigh-Durham, North Carolina, United States of America aff009;  Department of Obstetrics and Gynecology, Soroka University Medical Center, School of Medicine, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel aff010;  Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan, United States of America aff011;  Maternity Department "D," Division of Obstetrics and Gynecology, Soroka University Medical Center, School of Medicine, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel aff012
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224682



In comparison to the non-pregnant state, the first trimester of pregnancy is characterized by systemic adaptation of the mother. The extent to which these adaptive processes are reflected in the maternal blood metabolome is not well characterized.


To determine the differences between the plasma metabolome of non-pregnant and pregnant women before 16 weeks gestation.

Study design

This study included plasma samples from 21 non-pregnant women and 50 women with a normal pregnancy (8–16 weeks of gestation). Combined measurements by ultrahigh performance liquid chromatography/tandem mass spectrometry and by gas chromatography/mass spectrometry generated molecular abundance measurements for each sample. Molecular species detected in at least 10 samples were included in the analysis. Differential abundance was inferred based on false discovery adjusted p-values (FDR) from Mann-Whitney-Wilcoxon U tests <0.1 and a minimum median abundance ratio (fold change) of 1.5. Alternatively, metabolic data were quantile normalized to remove sample-to-sample differences in the overall metabolite abundance (adjusted analysis).


Overall, 637 small molecules met the inclusion criteria and were tested for association with pregnancy; 44% (281/637) of small molecules had significantly different abundance, of which 81% (229/281) were less abundant in pregnant than in non-pregnant women. Eight percent (14/169) of the metabolites that remained significant in the adjusted analysis also changed as a function of gestational age. A pathway analysis revealed enrichment in steroid metabolites related to sex hormones, caffeine metabolites, lysolipids, dipeptides, and polypeptide bradykinin derivatives (all, FDR < 0.1).


This high-throughput mass spectrometry study identified: 1) differences between pregnant vs. non-pregnant women in the abundance of 44% of the profiled plasma metabolites, including known and novel molecules and pathways; and 2) specific metabolites that changed with gestational age.

Klíčová slova:

Metabolic networks – Metabolic pathways – Metabolites – Metabolomics – Pregnancy – Small molecules – Steroid hormones – Steroids


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