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Trace biomarkers associated with spontaneous preterm birth from the maternal serum metabolome of asymptomatic nulliparous women - parallel case-control studies from the SCOPE cohort.

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posted on 14.10.2019, 08:34 by RT Souza, EJ McKenzie, B Jones, JV de Seymour, MM Thomas, E Zarate, TL Han, L McCowan, K Sulek, S Villas-Boas, LC Kenny, JG Cecatti, PN Baker
Prediction of spontaneous preterm birth (sPTB) in asymptomatic women remains a great challenge; accurate and reproducible screening tools are still not available in clinical practice. We aimed to investigate whether the maternal serum metabolome together with clinical factors could be used to identify asymptomatic women at risk of sPTB. We conducted two case-control studies using gas chromatography-mass spectrometry to analyse maternal serum samples collected at 15- and 20-weeks' gestation from 164 nulliparous women from Cork, and 157 from Auckland. Smoking and vaginal bleeding before 15 weeks were the only significant clinical predictors of sPTB for Auckland and Cork subsets, respectively. Decane, undecane, and dodecane were significantly associated with sPTB (FDR < 0.05) in the Cork subset. An odds ratio of 1.9 was associated with a one standard deviation increase in log (undecane) in a multiple logistic regression which also included vaginal bleeding as a predictor. In summary, elevated serum levels of the alkanes decane, undecane, and dodecane were associated with sPTB in asymptomatic nulliparous women from Cork, but not in the Auckland cohort. The association is not strong enough to be a useful clinical predictor, but suggests that further investigation of the association between oxidative stress processes and sPTB risk is warranted.
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We would like to acknowledge Rennae Taylor for assistance accessing the Auckland SCOPE biobank, and Emma Snapes, Ali Khashan and the SCOPE team at University College Cork for assistance with shipping samples. Thanks also to the staff at the Centre for Genomics, Proteomics & Metabolomics (University of Auckland), and at the Liggins Institute. We acknowledge that this manuscript is part of the RTS’s PhD thesis – Post-Graduation Programme in Obstetrics and Gynaecology of Unicamp, Brazil63. This study was jointly supported by the Brazilian National Research Council (CNPq) (Award 401636/2013-5), and the Bill and Melinda Gates Foundation (Award OPP1107597- Grand Challenges Brazil: Reducing the burden of preterm birth). The SCOPE database is provided and maintained by MedSciNet AB (http://medscinet.com). The New Zealand SCOPE study was funded by the New Enterprise Research Fund, Foundation for Research Science and Technology; Health Research Council (04/198); Evelyn Bond Fund, Auckland District Health Board Charitable Trust. The Australian SCOPE study was funded by the Premier’s Science and Research Fund, South Australian Government (http://www.dfeest.sa.gov.au/science- research/premiers-research-and-industry-fund). The Irish SCOPE study was funded by the Health Research Board of Ireland (CSA/2007/2; http://www.hrb.ie). The UK SCOPE study was funded by National Health Service NEAT Grant (Neat Grant FSD025), Biotechnology and Biological Sciences Research council (www. bbsrc.ac.uk/funding; GT084) and University of Manchester Proof of Concept Funding (University of Manchester); Guy’s and St. Thomas’ Charity (King’s College London) and Tommy’s charity (http://www.tommys.org/; King’s College London and University of Manchester); and Cerebra UK (www.cerebra.org.uk; University of Leeds). The current analyses were designed, sponsored and developed as part of the Preterm SAMBA study, a collaborative study group on Preterm Birth Research jointly issued by the Brazili



Scientific Reports, 2019, volume 9, Article number: 13701

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Te analysis in this study used the information from two centres from the SCOPE Consortium that has the ownership of data. Any requirement regarding this data can be directed to Prof. Philip N Baker. Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-019-50252-7.





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