The plasma metabolome of women in early pregnancy differs from that of non-pregnant women.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
08
05
2019
accepted:
18
10
2019
entrez:
15
11
2019
pubmed:
15
11
2019
medline:
18
3
2020
Statut:
epublish
Résumé
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. 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.
Sections du résumé
BACKGROUND
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.
OBJECTIVE
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).
RESULTS
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).
CONCLUSIONS
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.
Identifiants
pubmed: 31726468
doi: 10.1371/journal.pone.0224682
pii: PONE-D-19-13033
pmc: PMC6855901
doi:
Types de publication
Clinical Trial
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0224682Subventions
Organisme : NICHD NIH HHS
ID : HHSN275201300006C
Pays : United States
Déclaration de conflit d'intérêts
BI is employed by Metabolon Inc., who provided the metabolomics profiling on a pay for service basis. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
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