Assessing Exposome Effects on Pregnancy through Urine Metabolomics of a Portuguese (Estarreja) Cohort


This nuclear magnetic resonance metabolomics study compared the influence of two different central Portugal exposomes, one of which comprised an important source of pollutants (the Estarreja Chemical Complex, ECC), on the urinary metabolic trajectory of a cohort of healthy pregnant women (total n = 107). An exposome-independent description of pregnancy metabolism was found to comprise a set of 18 metabolites reflecting expected changes in branched-chain amino acid catabolism and hormone and lipid metabolisms. In addition, a set of small changes in some metabolites was suggested to be exposome-dependent and characteristic of pregnant subjects from the Estarreja region. These results suggested that the Estarreja exposome may impact to a very low extent pregnancy metabolism, inducing slight changes in amino acid metabolism (alanine, glycine, and 3-hydroxyisobutyrate, possibly involved in valine metabolism), tricarboxylic acid (TCA) cycle (cis-aconitate), diet, or gut microflora (furoylglycine) as well as allantoin, 2-hydroxyisobutyrate, and an unassigned resonance at delta 8.45. Furthermore, the urine of Estarreja subjects was found to generally contain higher levels of 4-hydroxyphenylacetate and lower levels of citrate. However, out of the above metabolites, only glycine and citrate seemed to correlate with the proximity to the ECC, with slightly relative higher levels of these compounds found for subjects living closer to the ECC. This suggested possible small effects of local pollutants on energy metabolism, with the remaining exposome-dependent metabolite changes most probably originating from other aspects of the local exposome such as diet and lifestyle. Despite the limitation of this study regarding the unavailability of objective environmental parameters for the period under study, our results confirm the usefulness of metabolomics of human urine to gauge exposome effects on human health and, particularly, during pregnancy.




Biochemistry & Molecular Biology


Gil, AM; Duarte, D; Pinto, J; Barros, AS

nossos autores


This project was funded by the Observatoire hommes-milieux (OHM) Estarreja and CNRS, France (project OHM-E/2014/Proj.1) and developed within the scope of the project CICECO-Aveiro Institute of Materials, POCI-01-0145- FEDER-007679 (FCT ref. UID/CTM/50011/2013), financed by national funds through the FCT/MEC and when appropriate cofinanced by FEDER under the PT2020 Partnership Agreement. We also acknowledge the Portuguese National NMR Network (RNRMN), supported by FCT funds, and D.D. acknowledges FCT grant SFRH/BD/119509/2016. We are also grateful to all of the doctors and nurses who have aided in the logistics of sample and information collection at the different health centers in the Estarreja region: Manuel Sebe (Agrupamento de centros de saucle-Baixo Vouga), Andreia Ferreira, Andreia Azevedo, Paula Silva, Romana Si, Joana Pinho, Sandra Borges (Health Center of Salreu, Unidade de Safide Familiar Terras de Antua), Ofelia Almeida, Barbara Pinto, Joao Lopes, Rodrigo Reis (Health Center of Estarreja, Unidade de Cuidados de Saucle Personalizados Estarreja I), and Luisa Machado (Health Center of Avanca, Extensa de Saude de Avanca).

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