State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China; Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Environ Int. 2021 Nov;156:106731. doi: 10.1016/j.envint.2021.106731. Epub 2021 Jun 28.
Maternal exposure to some individual rare earth elements and trace elements is associated with preterm birth, but few elements have been studied and little is known about the potential effect of simultaneous exposure to multiple elements. We examined individual and mixture effects of elements on preterm birth among 745 pregnant women in a prospective birth cohort in Bangladesh (2008-2011). We measured 56 elements in umbilical cord blood collected during delivery using inductively coupled plasma-mass spectrometry. Using elastic net (ENET) regularization and multivariate logistic regression, we examined independent associations between element concentrations and preterm birth. Bayesian kernel machine regression identified mixture effects of elements most critical to preterm birth, accounting for correlated exposure and interaction. ENET identified titanium (Ti), arsenic (As), and barium (Ba) as the most important predictors of shortened gestational age and preterm birth. In adjusted models, cord blood Ti (OR = 2.52; 95% CI: 1.08-5.93; P = 0.033), As (odds ratio (OR) = 1.34; 95% CI: 1.04-1.73; P = 0.023), and Ba (OR = 1.18; 95% CI: 1.02-1.38; P = 0.029) were significantly associated with preterm birth. Bayesian kernel machine regression suggested an interaction effect between As and Ba. Further, we constructed an element risk score (ERS) using estimated weights from a multivariate regression model for Ti, As, and Ba and regressed preterm birth by this score (OR = 2.72, 95% CI: 1.57-4.69; P = 3.35 × 10). Additionally, we observed a significant modification effect of child marriage on ERS, which means marriage before the age of 18 (P = 0.0438). This study identified element exposures profiles in cord blood and constructed metal risk score that are jointly associated with the risk of preterm birth. Ti, As, and Ba exposure may adversely affect birth outcomes as well as child marriage may be a modifiable factor potentially affecting environmental element exposure and preterm birth.
母体暴露于某些个体稀土元素和微量元素与早产有关，但研究的元素很少，对同时暴露于多种元素的潜在影响知之甚少。我们在孟加拉国的一个前瞻性出生队列中（2008-2011 年），对 745 名孕妇的脐带血样本进行了 56 种元素的测量，使用电感耦合等离子体质谱法进行检测。使用弹性网络（ENET）正则化和多元逻辑回归，我们检查了元素浓度与早产之间的独立关联。贝叶斯核机器回归确定了对早产最重要的元素混合物效应，同时考虑了相关暴露和相互作用。ENET 确定钛（Ti）、砷（As）和钡（Ba）是缩短胎龄和早产的最重要预测因子。在调整后的模型中，脐带血 Ti（比值比（OR）=2.52；95%CI：1.08-5.93；P=0.033）、As（OR=1.34；95%CI：1.04-1.73；P=0.023）和 Ba（OR=1.18；95%CI：1.02-1.38；P=0.029）与早产显著相关。贝叶斯核机器回归表明 As 和 Ba 之间存在相互作用效应。此外，我们使用 Ti、As 和 Ba 的多元回归模型的估计权重构建了一个元素风险评分（ERS），并通过该评分回归早产（OR=2.72，95%CI：1.57-4.69；P=3.35×10）。此外，我们观察到儿童婚姻对 ERS 的显著修饰效应，这意味着 18 岁以下结婚（P=0.0438）。本研究确定了脐带血中的元素暴露特征，并构建了与早产风险相关的金属风险评分。Ti、As 和 Ba 的暴露可能会对出生结局产生不利影响，而儿童婚姻可能是一个可改变的因素，可能会影响环境元素暴露和早产。
