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Urine Metabolic Signatures of Multiple Environmental Pollutants in Pregnant Women: An Exposome Approach.

Authors
  • Maitre, Léa1, 2, 3
  • Robinson, Oliver1, 2, 3, 4
  • Martinez, David1, 2, 3
  • Toledano, Mireille B4
  • Ibarluzea, Jesús3, 5, 6, 7
  • Marina, Loreto Santa3, 6, 7
  • Sunyer, Jordi1, 2, 3, 8
  • Villanueva, Cristina M1, 2, 3, 8
  • Keun, Hector C9
  • Vrijheid, Martine1, 2, 3
  • Coen, Muireann10, 11
  • 1 ISGlobal, Institute for Global Health , Barcelona , Spain. , (Spain)
  • 2 Universitat Pompeu Fabra (UPF) , Barcelona , Spain. , (Spain)
  • 3 CIBER Epidemiología y Salud Pública (CIBERESP) , Madrid , Spain. , (Spain)
  • 4 Medical Research Council-Public Health England (MRC-PHE) Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health , Imperial College London , London , U.K.
  • 5 School of Psychology , University of the Basque Country UPV/EHU , San Sebastian , Basque Country Spain. , (Spain)
  • 6 Biodonostia Health Research Institute , San Sebastian , Basque Country Spain. , (Spain)
  • 7 Sub-Directorate for Public Health of Gipuzkoa, Department of Health , Government of the Basque Country , San Sebastian , Basque Country Spain. , (Spain)
  • 8 Municipal Institute of Medical Research (IMIM-Hospital del Mar) , Barcelona , Spain. , (Spain)
  • 9 Division of Cancer, Department of Surgery & Cancer, Faculty of Medicine , Imperial College London , U.K.
  • 10 Integrative Systems Medicine & Digestive Disease, Department of Surgery & Cancer, Faculty of Medicine , Imperial College London , U.K.
  • 11 Oncology Safety, Drug Safety and Metabolism , IMED Biotech Unit, AstraZeneca, 1 Francis Crick Avenue , Cambridge CB2 0RE , U.K.
Type
Published Article
Journal
Environmental Science & Technology
Publisher
American Chemical Society
Publication Date
Nov 20, 2018
Volume
52
Issue
22
Pages
13469–13480
Identifiers
DOI: 10.1021/acs.est.8b02215
PMID: 30285427
Source
Medline
Language
English
License
Unknown

Abstract

Exposure to environmental pollutants, particularly during pregnancy, can have adverse consequences on child development but little is known about the effects of pollutant mixtures on endogenous metabolism in pregnant women. We aimed to identify urinary metabolic signatures associated with low level exposure to multiple environmental pollutants in pregnant women from the INMA (INfancia y Medio Ambiente) birth cohort (Spain, N = 750). 35 chemical exposures were quantified in first trimester blood samples (organochlorine pesticides, PCBs, PFAS), in cord blood (mercury), and twice in urine at 12 and 32 weeks of pregnancy (metals, phthalates, bisphenol A). 1H nuclear magnetic resonance (NMR) metabolic profiles of urine were acquired in the same samples as pollutants. We explored associations between exposures and metabolism through an exposome-metabolome wide association scan and multivariate O2PLS modeling. Novel and reproducible associations were found across two periods of pregnancy for three nonpersistent pollutants and across two subcohorts for four of the persistent pollutants. We found novel metabolic signatures associated with arsenic exposure: TMAO and dimethylamine possibly related to gut microbial methylamine metabolism and homarine related to fish intake. Tobacco smoke exposure was related to coffee metabolism and PCBs with 3-hydroxyvaleric acid, usually released under ketoacidosis. These findings will have implications for further understanding of maternal-fetal health, and health across the life-course.

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