Parental preconception exposure to phenol and phthalate mixtures and the risk of preterm birth,Environment International

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Parental preconception exposure to phenol and phthalate mixtures and the risk of preterm birth
Environment International ( IF 10.3 ) Pub Date : 2021-02-25 , DOI: 10.1016/j.envint.2021.106440
Yu Zhang ₁ , Vicente Mustieles ₂ , Paige L Williams ₃ , Blair J Wylie ₄ , Irene Souter ₅ , Antonia M Calafat ₆ , Melina Demokritou ₇ , Alexandria Lee ₈ , Stylianos Vagios ₅ , Russ Hauser ₁ , Carmen Messerlian ₉

Affiliation

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
University of Granada, Center for Biomedical Research (CIBM), Spain; Instituto de Investigación Biosanitaria Ibs GRANADA, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 18100, Spain.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Massachusetts General Hospital Fertility Center, Harvard Medical School, Boston, MA, USA; Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA.
National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Massachusetts General Hospital Fertility Center, Harvard Medical School, Boston, MA, USA; Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA.

Background

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 biomarkers, including di(2-ethylhexyl) phthalate (DEHP) metabolites, were examined. We used principal component 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 increase 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 exposure 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.

中文翻译：

父母对苯酚和邻苯二甲酸酯混合物的孕前暴露和早产风险

背景

先前在单一化学分析中，父母对选择的酚类和邻苯二甲酸盐的孕前暴露与早产风险增加有关。然而，苯酚和邻苯二甲酸酯混合物对早产的联合影响尚不清楚。

方法

我们纳入了在环境与生殖健康 (EARTH) 研究中寻求不孕症治疗的 384 名女性和 211 名男性（203 对夫妇）参与者，他们在 2005 年至 2018 年期间生下了 384 名单胎婴儿。双酚 A (BPA)、对羟基苯甲酸酯、苯甲酸酯的平均孕前尿浓度并检查了 11 种邻苯二甲酸酯生物标志物，包括邻苯二甲酸二（2-乙基己基）酯 (DEHP) 代谢物。我们使用带有 log-Poisson 回归的主成分分析 (PCA) 和带有分层变量选择的 Probit Bayesian Kernel Machine Regression (BKMR) 来检查与早产相关的母亲和父亲苯酚和邻苯二甲酸酯混合物。基于夫妻的 BKMR 模型适合评估与早产相关的夫妻关节混合物。

结果

PCA 确定了母亲和父亲孕前混合物的相同四个因素。孕前 DEHP-BPA 因子的母亲（调整后的风险比 (aRR)：1.36, 95%CI: 1.00, 1.84）和父亲（aRR: 1.47, 95%CI: 0.90, 2.42）的 PCA 评分每增加一个单位，与早产。母系和父系 BKMR 模型始终以最高的组后包含概率 (PIP) 呈现 DEHP-BPA 因子。BKMR 模型进一步表明，当剩余混合物组分保持在其中值浓度时，母亲孕前 BPA 和邻苯二甲酸单（2-乙基-5-羟基己基）酯，以及父亲孕前孕前邻苯二甲酸单（2-乙基己基）酯与早产呈正相关。基于夫妻的 BKMR 模型显示父亲（PIP：61%）和母亲（PIP：77%) 早产的孕前混合物。我们发现随着夫妻总混合物浓度的增加分位数对早产产生积极的联合影响。