Department of Epidemiology and Population Health, Stanford School of Medicine, Stanford, CA, USA.
Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Environ Int. 2024 Aug;190:108909. doi: 10.1016/j.envint.2024.108909. Epub 2024 Jul 25.
Hypertensive disorders of pregnancy (HDP) such as preeclampsia and gestational hypertension are major contributors to maternal and child morbidity and mortality. Previous studies have reported associations with selected metals and vitamins but are limited in sample size and non-prospective study designs. We evaluated prospective associations of metal mixtures with HDP and tested interactions by vitamins.
We measured first trimester (median = 10.1 weeks) concentrations of essential (copper, magnesium, manganese, selenium, zinc) and nonessential (arsenic, barium, cadmium, cesium, mercury, lead) metals in red blood cells (n = 1,386) and vitamins (B and folate) in plasma (n = 924) in Project Viva, a pre-birth US cohort. We collected diagnosis of HDP by reviewing medical records. We used multinomial logistic regression and Bayesian Kernel Machine Regression to estimate individual and joint associations of metals with HDP and interactions by vitamins, after adjusting for key covariates.
The majority of participants were non-Hispanic white (72.5 %), never smokers (68.5 %) with a mean (SD) age of 32.3 (4.6) years. Fifty-two (3.8 %) developed preeclampsia and 94 (6.8 %) gestational hypertension. A doubling in first trimester erythrocyte copper was associated with 78 % lower odds of preeclampsia (OR=0.22, 95 % confidence interval: 0.08, 0.60). We also observed significant associations between higher erythrocyte total arsenic and lower odds of preeclampsia (OR=0.80, 95 % CI: 0.66, 0.97) and higher vitamin B and increased odds of gestational hypertension (OR=1.79, 95 % CI: 1.09, 2.96), but associations were attenuated after adjustment for dietary factors. Lower levels of the overall metal mixture and essential metal mixture were associated with higher odds of preeclampsia. We found no evidence of interactions by prenatal vitamins or between metals.
Lower levels of a first-trimester essential metal mixture were associated with an increased risk of preeclampsia, primarily driven by copper. No associations were observed between other metals and HDP after adjustment for confounders and diet.
妊娠高血压疾病（HDP），如子痫前期和妊娠期高血压，是母婴发病率和死亡率的主要原因。先前的研究报告了与某些金属和维生素的关联，但样本量有限且为非前瞻性研究设计。我们评估了金属混合物与 HDP 的前瞻性关联，并通过维生素测试了相互作用。
我们在 Viva 项目中测量了 1386 名参与者在妊娠早期（中位数=10.1 周）的红细胞中必需（铜、镁、锰、硒、锌）和非必需（砷、钡、镉、铯、汞、铅）金属的浓度，以及 924 名参与者血浆中的维生素 B 和叶酸。我们通过查阅病历记录来收集 HDP 的诊断。我们使用多项逻辑回归和贝叶斯核机器回归来估计个体和联合金属与 HDP 的关联，以及维生素的相互作用，调整了关键协变量。
大多数参与者为非西班牙裔白人（72.5%），从不吸烟（68.5%），平均（SD）年龄为 32.3（4.6）岁。52 人（3.8%）患有子痫前期，94 人（6.8%）患有妊娠期高血压。妊娠早期红细胞铜的两倍增加与子痫前期的几率降低 78%相关（OR=0.22，95%置信区间：0.08，0.60）。我们还观察到红细胞总砷与子痫前期几率降低（OR=0.80，95%CI：0.66，0.97）和维生素 B 较高与妊娠期高血压几率增加（OR=1.79，95%CI：1.09，2.96）之间存在显著关联，但在调整饮食因素后，这些关联减弱。整体金属混合物和必需金属混合物水平较低与子痫前期的几率较高相关。我们没有发现产前维生素或金属之间存在相互作用的证据。
妊娠早期必需金属混合物水平较低与子痫前期风险增加有关，主要与铜有关。在调整混杂因素和饮食后，没有观察到其他金属与 HDP 之间存在关联。
