Association of preconception mixtures of phenol and phthalate metabolites with birthweight among subfertile couples

Yu Zhang; Vicente Mustieles; Paige L Williams; Irene Souter; Antonia M Calafat; Melina Demokritou; Alexandria Lee; Stylianos Vagios; Russ Hauser; Carmen Messerlian

doi:10.1097/EE9.0000000000000222

Association of preconception mixtures of phenol and phthalate metabolites with birthweight among subfertile couples

Environ Epidemiol. 2022 Aug 31;6(5):e222. doi: 10.1097/EE9.0000000000000222. eCollection 2022 Oct.

Authors

Yu Zhang¹, Vicente Mustieles², Paige L Williams^{3

4}, Irene Souter⁵, Antonia M Calafat⁶, Melina Demokritou¹, Alexandria Lee³, Stylianos Vagios⁵, Russ Hauser^{1

3}, Carmen Messerlian^{1

3}

Affiliations

¹ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
² University of Granada, Center for Biomedical Research (CIBM), Instituto de Investigación Biosanitaria Ibs GRANADA, Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Granada, Spain.
³ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
⁴ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
⁵ Massachusetts General Hospital Fertility Center, Boston, Massachusetts.
⁶ National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia.

Abstract

Although parental preconception exposure to some phenols and phthalates have been associated with reduced birthweight, few studies have examined these chemicals as complex mixtures.

Methods: We included 384 mothers and 211 fathers (203 couples) who gave birth to 384 singletons from a prospective cohort of couples seeking fertility evaluation. Urinary concentrations of bisphenol A (BPA), parabens, and 11 phthalate metabolites including those of di(2-ethylhexyl) phthalate (DEHP) were examined. Birthweight was abstracted from delivery records. We used principal component analysis and Bayesian Kernel Machine Regression (BKMR) to examine maternal and paternal preconception mixtures in relation to singleton birthweight. We also fit couple-based BKMR with hierarchical variable selection to assess couples' joint mixtures in relation to birthweight.

Results: PC scores of maternal and paternal preconception low molecular weight phthalates factor, and paternal preconception DEHP-BPA factor were associated with reduced birthweight. In BKMR models, we found that maternal preconception monoethyl phthalate and BPA concentrations, and paternal preconception mono-n-butyl phthalate concentrations were inversely associated with birthweight when the remaining mixture components were held at their median concentrations. In couple-based BKMR models, paternal preconception biomarkers contributed more to couples' joint effect on birthweight compared with maternal preconception biomarkers. A decreasing trend of birthweight was observed across quantiles of maternal, paternal, and couples' total preconception mixture concentrations, respectively.

Conclusions: Results from this preconception cohort of subfertile couples suggest a complex interplay between paternal and maternal preconception exposure to mixtures of nonpersistent chemicals, with both parental windows of exposure jointly contributing to reduced birthweight.

Keywords: birthweight; paternal; phenol; phthalate; preconception; singleton.