Tracy A Manuck1, Yunjia Lai2, Hongyu Ru2, Angelica V Glover3, Julia E Rager4, Rebecca C Fry4, Kun Lu4. 1. Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine and University of North Carolina Health, Chapel Hill, NC (Drs Manuck and Glover); Institute for Environmental Health Solutions, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC (Drs Manuck, Rager, Fry, and Lu). Electronic address: tmanuck@med.unc.edu. 2. Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC (Ms Lai and Drs Ru, Rager, Fry, and Lu). 3. Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine and University of North Carolina Health, Chapel Hill, NC (Drs Manuck and Glover). 4. Institute for Environmental Health Solutions, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC (Drs Manuck, Rager, Fry, and Lu); Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC (Ms Lai and Drs Ru, Rager, Fry, and Lu).
Abstract
BACKGROUND: There is an increased awareness regarding the association between exposure to environmental contaminants and adverse pregnancy outcomes including preterm birth. Whether an individual's metabolic profile can be utilized during pregnancy to differentiate the subset of patients who are ultimately destined to delivered preterm remains uncertain but could have MEANINGFUL clinical implications. OBJECTIVE: We sought to objectively quantify metabolomic profiles of patients at high risk of preterm birth by evaluating midtrimester maternal plasma and to measure whether endogenous metabolites and exogenous environmental substances differ among those who ultimately deliver preterm compared with those who deliver at term. STUDY DESIGN: This was a case-control analysis from a prospective cohort of patients carrying a singleton, nonanomalous gestation who were at high risk of spontaneous preterm birth. Subjects with a plasma blood sample drawn at <28 weeks' gestation and no evidence of preterm labor at the time of enrollment were included. Metabolites were extracted from frozen samples, and metabolomic analysis was performed using liquid chromatography/mass spectrometry. The primary outcome was preterm birth at 16.0 to 36.9 weeks' gestation. RESULTS: A total of 42 patients met the inclusion criteria. Of these, 25 (59.5%) delivered preterm at <37 weeks' gestation, at a median of 30.14 weeks' gestation (interquartile range, 28.14-34.14). A total of 812 molecular features differed between preterm birth cases and term controls with a minimum fold change of 1.2 and P<.05. Of these, 570 of 812 (70.1%) were found in higher abundances in preterm birth cases; the other 242 of 812 (29.9%) were in higher abundance in term birth controls. The identity of the small molecule/compound represented by the molecular features differing statistically between preterm birth cases and term controls was identified as ranging from those involved with endogenous metabolic pathways (including lipid catabolism, steroids, and steroid-related molecules) to exogenous exposures (including avocadyne, diosgenin, polycyclic aromatic hydrocarbons, acetaminophen metabolites, aspartame, and caffeine). Random forest analyses evaluating the relative contribution of each of the top 30 compounds in differentiating preterm birth and term controls accurately classified 21 of 25 preterm birth cases (84%). CONCLUSION: Both endogenous metabolites and exogenous exposures differ in maternal plasma in the midtrimester among patients who ultimately delivered preterm compared with those who deliver at term.
BACKGROUND: There is an increased awareness regarding the association between exposure to environmental contaminants and adverse pregnancy outcomes including preterm birth. Whether an individual's metabolic profile can be utilized during pregnancy to differentiate the subset of patients who are ultimately destined to delivered preterm remains uncertain but could have MEANINGFUL clinical implications. OBJECTIVE: We sought to objectively quantify metabolomic profiles of patients at high risk of preterm birth by evaluating midtrimester maternal plasma and to measure whether endogenous metabolites and exogenous environmental substances differ among those who ultimately deliver preterm compared with those who deliver at term. STUDY DESIGN: This was a case-control analysis from a prospective cohort of patients carrying a singleton, nonanomalous gestation who were at high risk of spontaneous preterm birth. Subjects with a plasma blood sample drawn at <28 weeks' gestation and no evidence of preterm labor at the time of enrollment were included. Metabolites were extracted from frozen samples, and metabolomic analysis was performed using liquid chromatography/mass spectrometry. The primary outcome was preterm birth at 16.0 to 36.9 weeks' gestation. RESULTS: A total of 42 patients met the inclusion criteria. Of these, 25 (59.5%) delivered preterm at <37 weeks' gestation, at a median of 30.14 weeks' gestation (interquartile range, 28.14-34.14). A total of 812 molecular features differed between preterm birth cases and term controls with a minimum fold change of 1.2 and P<.05. Of these, 570 of 812 (70.1%) were found in higher abundances in preterm birth cases; the other 242 of 812 (29.9%) were in higher abundance in term birth controls. The identity of the small molecule/compound represented by the molecular features differing statistically between preterm birth cases and term controls was identified as ranging from those involved with endogenous metabolic pathways (including lipid catabolism, steroids, and steroid-related molecules) to exogenous exposures (including avocadyne, diosgenin, polycyclic aromatic hydrocarbons, acetaminophen metabolites, aspartame, and caffeine). Random forest analyses evaluating the relative contribution of each of the top 30 compounds in differentiating preterm birth and term controls accurately classified 21 of 25 preterm birth cases (84%). CONCLUSION: Both endogenous metabolites and exogenous exposures differ in maternal plasma in the midtrimester among patients who ultimately delivered preterm compared with those who deliver at term.
Authors: Michael S Kramer; Aris Papageorghiou; Jennifer Culhane; Zulfiqar Bhutta; Robert L Goldenberg; Michael Gravett; Jay D Iams; Agustin Conde-Agudelo; Sarah Waller; Fernando Barros; Hannah Knight; Jose Villar Journal: Am J Obstet Gynecol Date: 2011-10-25 Impact factor: 8.661
Authors: Paul A Harris; Robert Taylor; Robert Thielke; Jonathon Payne; Nathaniel Gonzalez; Jose G Conde Journal: J Biomed Inform Date: 2008-09-30 Impact factor: 6.317
Authors: Christina Virgiliou; Helen G Gika; Michael Witting; Anna A Bletsou; Apostolos Athanasiadis; Menelaos Zafrakas; Nikolaos S Thomaidis; Nikolaos Raikos; Georgios Makrydimas; Georgios A Theodoridis Journal: J Proteome Res Date: 2017-01-23 Impact factor: 4.466
Authors: Sharon K Sagiv; Sheryl L Rifas-Shiman; Abby F Fleisch; Thomas F Webster; Antonia M Calafat; Xiaoyun Ye; Matthew W Gillman; Emily Oken Journal: Am J Epidemiol Date: 2018-04-01 Impact factor: 4.897
Authors: Laura L Jelliffe-Pawlowski; Mary E Norton; Rebecca J Baer; Nicole Santos; George W Rutherford Journal: Am J Obstet Gynecol Date: 2015-12-11 Impact factor: 8.661
Authors: Eugenio Baraldi; Giuseppe Giordano; Matteo Stocchero; Laura Moschino; Patrizia Zaramella; Maria Rosa Tran; Silvia Carraro; Roberto Romero; Maria Teresa Gervasi Journal: PLoS One Date: 2016-10-18 Impact factor: 3.240
Authors: Kyle Roell; Lauren E Koval; Rebecca Boyles; Grace Patlewicz; Caroline Ring; Cynthia V Rider; Cavin Ward-Caviness; David M Reif; Ilona Jaspers; Rebecca C Fry; Julia E Rager Journal: Front Toxicol Date: 2022-06-22
Authors: Christy L Avery; Annie Green Howard; Anna F Ballou; Victoria L Buchanan; Jason M Collins; Carolina G Downie; Stephanie M Engel; Mariaelisa Graff; Heather M Highland; Moa P Lee; Adam G Lilly; Kun Lu; Julia E Rager; Brooke S Staley; Kari E North; Penny Gordon-Larsen Journal: Environ Health Perspect Date: 2022-05-09 Impact factor: 11.035