Zhang, YuMustieles, VicenteWilliams, Paige L.Wylie, Blair J.Souter, IreneCalafat, Antonia M.Demokritou, MelinaLee, AlexandriaVagios, StylianosHauser, RussMesserlian, Carmen2023-01-202023-01-202021-02-25Zhang Y, Mustieles V, Williams PL, Wylie BJ, Souter I, Calafat AM, et al. Parental preconception exposure to phenol and phthalate mixtures and the risk of preterm birth. Environ Int. 2021 Jun;151:1064400160-4120http://hdl.handle.net/10668/4603Background: Parental preconception exposure to select phenols and phthalates was previously associated with increased risk of preterm birth in single chemical analyses. However, the joint effect of phenol and phthalate mixtures on preterm birth is unknown. Methods: We included 384 female and 211 male (203 couples) participants seeking infertility treatment in the Environment and Reproductive Health (EARTH) Study who gave birth to 384 singleton infants between 2005 and 2018. Mean preconception urinary concentrations of bisphenol A (BPA), parabens, and eleven phthalate bio markers, including di(2-ethylhexyl) phthalate (DEHP) metabolites, were examined. We used principal compo nent analysis (PCA) with log-Poisson regression and Probit Bayesian Kernel Machine Regression (BKMR) with hierarchical variable selection to examine maternal and paternal phenol and phthalate mixtures in relation to preterm birth. Couple-based BKMR model was fit to assess couples’ joint mixtures in relation to preterm birth. Results: PCA identified the same four factors for maternal and paternal preconception mixtures. Each unit in crease in PCA scores of maternal (adjusted Risk Ratio (aRR): 1.36, 95%CI: 1.00, 1.84) and paternal (aRR: 1.47, 95%CI: 0.90, 2.42) preconception DEHP-BPA factor was positively associated with preterm birth. Maternal and paternal BKMR models consistently presented the DEHP-BPA factor with the highest group Posterior Inclusion Probability (PIP). BKMR models further showed that maternal preconception BPA and mono(2-ethyl-5- hydroxyhexyl) phthalate, and paternal preconception mono(2-ethylhexyl) phthalate were positively associated with preterm birth when the remaining mixture components were held at their median concentrations. Couple based BKMR models showed a similar relative contribution of paternal (PIP: 61%) and maternal (PIP: 77%) preconception mixtures on preterm birth. We found a positive joint effect on preterm birth across increasing quantiles of couples’ total mixture concentrations. Conclusion: In this prospective cohort of subfertile couples, maternal BPA and DEHP, and paternal DEHP expo sure before conception were positively associated with preterm birth. Both parental windows jointly contributed to the outcome. These results suggest that preterm birth may be a couple-based pregnancy outcome.enAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/DEHPBPAPretermSingletonSubfertileCoupleDietilhexil ftalatoFenolesNacimiento prematuroMatrimonioFertilidadAtención preconceptivaMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Bayes TheoremMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Benzhydryl CompoundsMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Persons::Persons::Age Groups::Infant::Infant, NewbornMedical Subject Headings::Health Care::Environment and Public Health::Public Health::Environmental Pollution::Environmental Exposure::Paternal ExposureMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::PhenolsMedical Subject Headings::Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::PregnancyMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective StudiesMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Carbocyclic::Phthalic Acids::Diethylhexyl PhthalateMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Carbocyclic::Phthalic AcidsMedical Subject Headings::Diseases::Female Urogenital Diseases and Pregnancy Complications::Pregnancy Complications::Obstetric Labor Complications::Obstetric Labor, Premature::Premature BirthMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factorsresearch article33640694Acceso abierto10.1016/j.envint.2021.1064401873-6750PMC8488320