Women with Symptomatic Preterm Birth Have a Distinct Cervicovaginal Metabolome

Abstract

Objective The objective was to determine if women with symptoms of preterm labor who ultimately have a spontaneous preterm birth (sPTB) have a distinct cervicovaginal (CV) metabolome compared with women who deliver at term.

Study Design A nested case–control study of women presenting with symptoms of preterm labor was performed. CV fluid was collected from women between 22 and 33^6/7 weeks' gestation. The CV metabolome was compared between women with sPTB (n = 20) and women who delivered at term (n = 30). Global biochemical profiles were determined using ultraperformance liquid chromatography/tandem mass spectrometry. Welch's two-sample t-test was used to identify metabolites that differed significantly. Level of significance was defined as p ≤ 0.05.

Results Eighty-eight percent of women were African-American and none had a prior history of sPTB. A total of 301 metabolites were identified in CV fluid. Thirty metabolites were significantly different in women with preterm birth compared with term birth. Two metabolites (mannitol and methyl phosphate) were significantly upregulated, and the remaining 28 metabolites were significantly downregulated and consisted of medium chain-fatty acids and collagen degradation markers.

Conclusion The CV metabolome is significantly altered among women who present with preterm labor symptoms and ultimately have a sPTB.

Keywords

spontaneous preterm birth - cervicovaginal metabolome - vaginal microbiota - metabolomics

Note

This research was presented as a poster presentation at the 37th Annual Meeting for the Society for Maternal-Fetal Medicine in Las Vegas, NV, January 23 to 28, 2017.

Funding

The funding was provided by Maternal and Child Health Research Fund.

• References

• 1 Martin JA, Hamilton BE, Osterman MJ, Driscoll AK, Mathews TJ. Births: final data for 2015. Natl Vital Stat Rep 2017; 66 (01) 1
• 2 Practice Bulletin No. 171: Management of Preterm Labor. Obstet Gynecol 2016; 128 (04) ee155-64
• 3 Meis PJ, Klebanoff M, Thom E. , et al; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med 2003; 348 (24) 2379-2385
• 4 Owen J, Hankins G, Iams JD. , et al. Multicenter randomized trial of cerclage for preterm birth prevention in high-risk women with shortened midtrimester cervical length. Am J Obstet Gynecol 2009; 201 (04) 375.e1-375.e8
• 5 Ghartey J, Bastek JA, Brown AG, Anglim L, Elovitz MA. Women with preterm birth have a distinct cervicovaginal metabolome. Am J Obstet Gynecol 2015; 212 (06) 776.e1-776.e12
• 6 Russell WR, Hoyles L, Flint HJ, Dumas ME. Colonic bacterial metabolites and human health. Curr Opin Microbiol 2013; 16 (03) 246-254
• 7 Ishikawa S, Sugimoto M, Kitabatake K. , et al. Effect of timing of collection of salivary metabolomic biomarkers on oral cancer detection. Amino Acids 2017; 49 (04) 761-770
• 8 Nishiumi S, Kobayashi T, Kawana S. , et al. Investigations in the possibility of early detection of colorectal cancer by gas chromatography/triple-quadrupole mass spectrometry. Oncotarget 2017; 8 (10) 17115-17126
• 9 Graça G, Goodfellow BJ, Barros AS. , et al. UPLC-MS metabolic profiling of second trimester amniotic fluid and maternal urine and comparison with NMR spectral profiling for the identification of pregnancy disorder biomarkers. Mol Biosyst 2012; 8 (04) 1243-1254
• 10 Horgan RP, Broadhurst DI, Dunn WB. , et al. Changes in the metabolic footprint of placental explant-conditioned medium cultured in different oxygen tensions from placentas of small for gestational age and normal pregnancies. Placenta 2010; 31 (10) 893-901
• 11 Ivorra C, García-Vicent C, Chaves FJ, Monleón D, Morales JM, Lurbe E. Metabolomic profiling in blood from umbilical cords of low birth weight newborns. J Transl Med 2012; 10 (142) 142 . Doi: 10.1186/1479-5876-10-142
• 12 Fanos V, Atzori L, Makarenko K, Melis GB, Ferrazzi E. Metabolomics application in maternal-fetal medicine. BioMed Res Int 2013; 2013 (10) 720514 . Doi: 10.1155/2013/720514
• 13 Menon R, Jones J, Gunst PR. , et al. Amniotic fluid metabolomic analysis in spontaneous preterm birth. Reprod Sci 2014; 21 (06) 791-803
• 14 Auray-Blais C, Gagnon R, Berthiaume M, Pasquier JC. Metabolomics and preterm birth: what biomarkers in cervicovaginal secretions are predictive of high-risk pregnant women. Int J Mass Spectrom 2011; 307: 33-38
• 15 Thomas MM, Sulek K, McKenzie EJ. , et al. Metabolite profile of cervicovaginal fluids from early pregnancy is not predictive of spontaneous preterm birth. Int J Mol Sci 2015; 16 (11) 27741-27748
• 16 Evans AM, DeHaven CD, Barrett T, Mitchell M, Milgram E. Integrated, nontargeted ultrahigh performance liquid chromatography/electrospray ionization tandem mass spectrometry platform for the identification and relative quantification of the small-molecule complement of biological systems. Anal Chem 2009; 81 (16) 6656-6667
• 17 Nieman DC, Shanely RA, Gillitt ND, Pappan KL, Lila MA. Serum metabolic signatures induced by a three-day intensified exercise period persist after 14 h of recovery in runners. J Proteome Res 2013; 12 (10) 4577-4584
• 18 Benjamini Y, Yosef H. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B 1995; 57 (01) 289-300
• 19 Bobiński R, Mikulska M, Mojska H, Ulman-Włodarz I. The dietary composition of women who delivered healthy full-term infants, preterm infants, and full-term infants who were small for gestational age. Biol Res Nurs 2015; 17 (05) 495-502
• 20 Kamarajan P, Rajendiran TM, Kinchen J, Bermúdez M, Danciu T, Kapila YL. Head and neck squamous cell carcinoma metabolism draws on glutaminolysis, and stemness is specifically regulated by glutaminolysis via aldehyde dehydrogenase. J Proteome Res 2017; 16 (03) 1315-1326