Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
Graduate School of Public Health, University of Puerto Rico, San Juan, Puerto Rico, USA.
Environ Health Perspect. 2022 Mar;130(3):37009. doi: 10.1289/EHP8990. Epub 2022 Mar 25.
Humans are exposed to complex mixtures of phthalate chemicals from a range of consumer products. Previous studies have reported significant associations between individual phthalate metabolites and pregnancy outcomes, but mixtures research is limited.
We used the Puerto Rico Testsite for Exploring Contamination Threats longitudinal pregnancy cohort to investigate associations between phthalate metabolite mixtures and pregnancy outcomes.
Women ( carrying females, carrying males) provided up to three urine samples throughout gestation (median 18, 22, and 26 wk), which were analyzed for 13 phthalate metabolites. Pregnancy outcomes including preterm birth (PTB), spontaneous PTB, small and large for gestational age (SGA, LGA), birth weight -score, and gestational age at delivery were abstracted from medical records. Environmental risk scores (ERS) were calculated as a weighted linear combination of the phthalates from ridge regression and adaptive elastic net, which are variable selection methods to handle correlated predictors. Birth outcomes were regressed on continuous ERS. We assessed gestational average and visit-specific ERS and stratified all analyses by fetal sex. Finally, we used Bayesian kernel machine regression (BKMR) to explore nonlinear associations and interactions between metabolites.
Differences in metabolite weights from ridge and elastic net were apparent between birth outcomes and between fetal sexes. An interquartile range increase in gestational average phthalate ERS was associated with increased odds of PTB [male ; 95% confidence interval (CI): 1.08, 2.27; female ; 95% CI: 1.23, 2.98], spontaneous PTB (male ; 95% CI: 1.46, 3.68; female ; 95% CI: 1.04, 3.82), and reduced gestational age at birth (male wk, 95% CI: , ; female wk, 95% CI: , ). Analyses by study visit suggested that exposure at wk (range 20-24 wk) was driving those associations. Bivariate plots from BKMR analysis revealed some nonlinear associations and metabolite interactions that were different between fetal sexes.
These results suggest that exposure to phthalate mixtures was associated with increased risk of early delivery and highlight the need to study mixtures by fetal sex. We also identified various metabolites displaying nonlinear relationships with measures of birth weight. https://doi.org/10.1289/EHP8990.
人类会从各种消费产品中接触到多种邻苯二甲酸酯化学物质的混合物。先前的研究报告称，个别邻苯二甲酸酯代谢物与妊娠结局之间存在显著关联，但混合物研究仍有限。
我们使用波多黎各探索污染威胁的测试地点进行了纵向妊娠队列研究，以调查邻苯二甲酸酯代谢物混合物与妊娠结局之间的关联。
女性（怀有女性，怀有男性）在整个孕期（中位数为 18、22 和 26 周）中提供了多达三个尿液样本，这些样本分析了 13 种邻苯二甲酸酯代谢物。从医疗记录中提取了早产（PTB）、自发性早产、小胎龄儿和大胎龄儿（SGA、LGA）、出生体重评分和分娩时的孕龄等妊娠结局。环境风险评分（ERS）是通过脊回归和自适应弹性网计算的，这是两种处理相关预测因素的变量选择方法。将出生结局回归到连续 ERS 上。我们评估了妊娠中期平均和各次就诊的 ERS，并按胎儿性别对所有分析进行分层。最后，我们使用贝叶斯核机器回归（BKMR）来探索代谢物之间的非线性关联和相互作用。
脊回归和弹性网之间的代谢物权重差异在出生结局和胎儿性别之间是明显的。妊娠中期邻苯二甲酸酯 ERS 的一个四分位距增加与 PTB 的几率增加有关[男性；95%置信区间（CI）：1.08，2.27；女性；95%CI：1.23，2.98]、自发性早产（男性；95%CI：1.46，3.68；女性；95%CI：1.04，3.82）和出生时孕龄降低（男性 周，95%CI： ， ；女性 周，95%CI： ， ）。各次就诊的分析表明，20-24 周的暴露（范围）推动了这些关联。BKMR 分析的双变量图显示了一些不同胎儿性别之间存在的非线性关联和代谢物相互作用。
这些结果表明，接触邻苯二甲酸酯混合物与早产风险增加有关，并强调需要按胎儿性别研究混合物。我们还发现了各种与出生体重测量值呈非线性关系的代谢物。https://doi.org/10.1289/EHP8990。
