Amniotic fluid metabolomic analysis in spontaneous preterm birth

Ramkumar Menon, Janice Jones, Phillip R. Gunst, Marian Kacerovsky, Stephen J. Fortunato, George Saade, Sanmaan Basraon

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Objective: To identify metabolic changes associated with early spontaneous preterm birth (PTB; <34 weeks) and term births, using high-throughput metabolomics of amniotic fluid (AF) in African American population. Method: In this study, AF samples retrieved from spontaneous PTB (<34 weeks [n = 25]) and normal term birth (n = 25) by transvaginal amniocentesis at the time of labor prior to delivery were subjected to metabolomics analysis. Equal volumes of samples were subjected to a standard solvent extraction method and analyzed using gas chromatography/mass spectrometry (MS) and liquid chromatography/MS/MS. Bio-chemicals were identified through matching of ion features to a library of biochemical standards. After log transformation and imputation of minimum observed values for each compound, t test, correlation tests, and false discovery rate corrections were used to identify differentially regulated metabolites. Data were controlled for clinical/demographic variables and medication during pregnancy. Results: Of 348 metabolites measured in AF samples, 121 metabolites had a gestational age effect and 116 differed significantly between PTB and term births. A majority of significantly altered metabolites could be classified into 3 categories, namely, (I) liver function, (2) fatty acid and coenzyme A (CoA) metabolism, and (3) histidine metabolism. The signature of altered liver function was apparent in many cytochrome P450-related pathways including bile acids, steroids, xanthines, heme, and phase II detoxification of xenobiotics with the largest fold change seen with pantothenol, a CoA synthesis inhibitor that was 8-fold more abundant in PTB. Conclusion: Global metabolic profiling of AF revealed alteration in hepatic metabolites involving xenobiotic detoxification and CoA metabolism in PTB. Maternal and/or fetal hepatic function differences may be devel-opmentally related and its contribution PTB as a cause or effect of PTB is still unclear.

Original languageEnglish (US)
Pages (from-to)791-803
Number of pages13
JournalReproductive Sciences
Volume21
Issue number6
DOIs
StatePublished - 2014

Fingerprint

Metabolomics
Premature Birth
Amniotic Fluid
Term Birth
Coenzyme A
Liver
Xenobiotics
Phase II Metabolic Detoxication
Xanthines
Amniocentesis
Tandem Mass Spectrometry
Bile Acids and Salts
Heme
Histidine
Liquid Chromatography
African Americans
Gas Chromatography-Mass Spectrometry
Cytochrome P-450 Enzyme System
Gestational Age
Libraries

Keywords

  • African Americans
  • liver functions
  • OMICs
  • pregnancy
  • prematurity

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Medicine(all)

Cite this

Menon, R., Jones, J., Gunst, P. R., Kacerovsky, M., Fortunato, S. J., Saade, G., & Basraon, S. (2014). Amniotic fluid metabolomic analysis in spontaneous preterm birth. Reproductive Sciences, 21(6), 791-803. https://doi.org/10.1177/1933719113518987

Amniotic fluid metabolomic analysis in spontaneous preterm birth. / Menon, Ramkumar; Jones, Janice; Gunst, Phillip R.; Kacerovsky, Marian; Fortunato, Stephen J.; Saade, George; Basraon, Sanmaan.

In: Reproductive Sciences, Vol. 21, No. 6, 2014, p. 791-803.

Research output: Contribution to journalArticle

Menon, R, Jones, J, Gunst, PR, Kacerovsky, M, Fortunato, SJ, Saade, G & Basraon, S 2014, 'Amniotic fluid metabolomic analysis in spontaneous preterm birth', Reproductive Sciences, vol. 21, no. 6, pp. 791-803. https://doi.org/10.1177/1933719113518987
Menon, Ramkumar ; Jones, Janice ; Gunst, Phillip R. ; Kacerovsky, Marian ; Fortunato, Stephen J. ; Saade, George ; Basraon, Sanmaan. / Amniotic fluid metabolomic analysis in spontaneous preterm birth. In: Reproductive Sciences. 2014 ; Vol. 21, No. 6. pp. 791-803.
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abstract = "Objective: To identify metabolic changes associated with early spontaneous preterm birth (PTB; <34 weeks) and term births, using high-throughput metabolomics of amniotic fluid (AF) in African American population. Method: In this study, AF samples retrieved from spontaneous PTB (<34 weeks [n = 25]) and normal term birth (n = 25) by transvaginal amniocentesis at the time of labor prior to delivery were subjected to metabolomics analysis. Equal volumes of samples were subjected to a standard solvent extraction method and analyzed using gas chromatography/mass spectrometry (MS) and liquid chromatography/MS/MS. Bio-chemicals were identified through matching of ion features to a library of biochemical standards. After log transformation and imputation of minimum observed values for each compound, t test, correlation tests, and false discovery rate corrections were used to identify differentially regulated metabolites. Data were controlled for clinical/demographic variables and medication during pregnancy. Results: Of 348 metabolites measured in AF samples, 121 metabolites had a gestational age effect and 116 differed significantly between PTB and term births. A majority of significantly altered metabolites could be classified into 3 categories, namely, (I) liver function, (2) fatty acid and coenzyme A (CoA) metabolism, and (3) histidine metabolism. The signature of altered liver function was apparent in many cytochrome P450-related pathways including bile acids, steroids, xanthines, heme, and phase II detoxification of xenobiotics with the largest fold change seen with pantothenol, a CoA synthesis inhibitor that was 8-fold more abundant in PTB. Conclusion: Global metabolic profiling of AF revealed alteration in hepatic metabolites involving xenobiotic detoxification and CoA metabolism in PTB. Maternal and/or fetal hepatic function differences may be devel-opmentally related and its contribution PTB as a cause or effect of PTB is still unclear.",
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