Parental Preconception Phenol and Phthalate Mixtures in Relation to Birth Weight

Abstract

Background: Although maternal and paternal preconception exposures to some phenols and phthalates have been associated with reduced birthweight in single-chemical analyses, their effect in the context of complex mixtures is unknown. Methods: We used principal component analysis (PCA) with multivariable linear regression and Bayesian Kernel Machine Regression (BKMR) to examine maternal and paternal preconception mixtures of urinary concentrations of phenol and phthalate biomarkers in relation to birthweight among 384 singletons (384 mothers, 211 fathers, 203 couples) from the Environment and Reproductive Health (EARTH) Study, a prospective cohort of couples seeking fertility evaluation. We also fit couple-based BKMR with hierarchical variable selection to assess couples’ joint mixtures in relation to birthweight. Natural log-concentrations of bisphenol A (BPA), parabens, and eleven phthalate metabolites including those of di(2-ethylhexyl) phthalate (DEHP) were examined. Birthweight was abstracted from medical records. Results: The PCA identified the same four main factors for maternal and paternal preconception mixtures. Each 1-unit increase in PCA scores of maternal (-51g; 95%: -105, 2) and paternal (-73g; 95%CI: -141, -4) preconception low molecular weight phthalates factors, and paternal preconception DEHP-BPA factor (-63g; 95%CI: -134, 7) were associated with reduced birthweight. In BKMR models of individual biomarkers, we found that maternal preconception monoethyl phthalate and BPA, and paternal preconception mono-n-butyl phthalate were inversely associated with birthweight when the remaining mixture components were held at their median concentration. In couple-based BKMR models, we observed a negative joint effect on birthweight across increasing quantiles of couples’ total phenol and phthalate mixture concentration. Paternal preconception biomarkers contributed more to couples’ joint effect on birthweight (Posterior Inclusion Probability (PIP)=70%) compared with maternal preconception biomarkers (PIP=18%). Conclusions: Our analysis suggests a complex interplay between paternal and maternal preconception exposure to mixtures of non-persistent chemicals, with both parental windows of exposure independently and jointly contributing to reduced birthweight.