First-trimester metabolomic prediction of stillbirth.

Abstract

Background: Stillbirth remains a major problem in both developing and developed countries. Omics evaluation of stillbirth has been highlighted as a top research priority. Objective: To identify new putative first-trimester biomarkers in maternal serum for stillbirth prediction using metabolomics-based approach. Methods: Targeted, nuclear magnetic resonance (NMR) and mass spectrometry (MS), and untargeted liquid chromatography-MS (LC-MS) metabolomic analyses were performed on first-trimester maternal serum obtained from 60 cases that subsequently had a stillbirth and 120 matched controls. Metabolites by themselves or in combination with clinical factors were used to develop logistic regression models for stillbirth prediction. Prediction of stillbirths overall, early (<28 weeks and <32 weeks), those related to growth restriction/placental disorder, and unexplained stillbirths were evaluated. Results: Targeted metabolites including glycine, acetic acid, L-carnitine, creatine, lysoPCaC18:1, PCaeC34:3, and PCaeC44:4 predicted stillbirth overall with an area under the curve [AUC, 95% confidence interval (CI)] = 0.707 (0.628-0.785). When combined with clinical predictors the AUC value increased to 0.740 (0.667-0.812). First-trimester targeted metabolites also significantly predicted early, unexplained, and placental-related stillbirths. Untargeted LC-MS features combined with other clinical predictors achieved an AUC (95%CI) = 0.860 (0.793-0.927) for the prediction of stillbirths overall. We found novel preliminary evidence that, verruculotoxin, a toxin produced by common household molds, might be linked to stillbirth. Conclusions: We have identified novel biomarkers for stillbirth using metabolomics and demonstrated the feasibility of first-trimester prediction.

• Authors: Ray O Bahado-Singh, Argyro Syngelaki, Rupsari Mandal, BeomSoo Han, Liang Li, Trent C Bjorndahl, Nan Wang, Dev Maulik, Edison Dong, Onur Turkoglu, Chiao-Li Tseng, Amna Zeb, Mark Redman, David S Wishart, Kypros H Nicolaides
• Journal: The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians (J Matern Fetal Neonatal Med) Vol. 32 Issue 20 Pg. 3435-3441 (Oct 2019) ISSN: 1476-4954 [Electronic] England
• PMID: 29712497 (Publication Type: Evaluation Study, Journal Article)

Chemical References

• Biomarkers

Topics

• Adult
• Biomarkers (blood, metabolism)
• Case-Control Studies
• Chromatography, Liquid
• Feasibility Studies
• Female
• Humans
• Infant, Newborn
• Live Birth
• Magnetic Resonance Spectroscopy
• Male
• Mass Spectrometry
• Metabolome
• Metabolomics (methods)
• Pregnancy
• Pregnancy Trimester, First (blood, metabolism)
• Prenatal Diagnosis (methods)
• Prognosis
• Stillbirth
• Young Adult