Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, NH, USA; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Department of Environmental Health, Boston University School of Public Health, Boston, MA, USA.
Environ Res. 2021 May;196:110388. doi: 10.1016/j.envres.2020.110388. Epub 2020 Oct 28.
Fetal growth is predictive of health later in life. Both toxic and essential metals influence fetal growth, but most studies have focused on these elements individually and used birth weight as an indicator of fetal growth. The objective of the current study was to investigate the impact of a mixture of metals on fetal size in mid-pregnancy in a predominately lower income Hispanic pregnancy cohort in Los Angeles.
For our primary analysis, we focused on six elements that have previously been associated individually with fetal size, including arsenic (As), barium (Ba), cadmium (Cd), mercury (Hg), molybdenum (Mo), and tin (Sn), measured in maternal urine samples collected in early pregnancy (median: 12.4 weeks gestation). In an exploratory analysis, we additionally included cobalt (Co), nickel (Ni), antimony (Sb), and thallium (Tl). Using covariate-adjusted Bayesian Kernel Machine Regression (BKMR) as our main mixture modeling approach, we examined the impact of these metals on fetal biometry measures obtained between 18 and 22 weeks gestation, with a focus on estimated fetal weight (EFW).
BKMR identified Mo and Ba as the mixture components that contributed most to associations with EFW. Linear associations were observed for both metals. An increase in Mo from the 25th to 75th percentile was associated with a 0.114 (95% credible interval (CI): 0.019, 0.247) SD higher EFW, equivalent to a 7.4 g difference. Similar associations were observed between Mo and the other fetal measures evaluated. In contrast, an increase in Ba from the 25th to 75th percentile was associated with a -0.076 (95% CI: 0.217, 0.066) SD lower EFW, equivalent to a 4.9 g difference. Similar inverse associations were observed for Ba in relation to abdominal circumference and biparietal diameter. BKMR also identified a possible interaction between Ba and Mo in relation to head circumference, suggesting that the positive associations between Mo and this outcome may be attenuated at high levels of Ba, which was consistent with findings from linear regression (P = 0.03). In an exploratory analysis accounting for a larger mixture of metals, Mo and Ba consistently contributed most to associations with EFW. An inverse association was also identified between Sb and EFW.
Our results suggest that Mo may promote fetal growth, while Ba and Sb may reduce fetal growth, in this population.
胎儿的生长情况可以预测其日后的健康状况。有毒金属和必需金属都会影响胎儿的生长，但大多数研究都集中在这些元素个体上，且使用出生体重作为胎儿生长的指标。本研究的目的是调查在洛杉矶以西班牙裔为主的低收入妊娠人群中，混合金属在妊娠中期对胎儿大小的影响。
在我们的主要分析中，我们重点研究了六种元素，这些元素之前曾被单独研究与胎儿大小有关，包括在妊娠早期（中位数：12.4 周妊娠）收集的孕妇尿液样本中测量的砷（As）、钡（Ba）、镉（Cd）、汞（Hg）、钼（Mo）和锡（Sn）。在一项探索性分析中，我们还额外纳入了钴（Co）、镍（Ni）、锑（Sb）和铊（Tl）。我们使用协变量调整的贝叶斯核机器回归（BKMR）作为主要的混合物建模方法，研究了这些金属对 18 至 22 周妊娠期间胎儿生物测量值的影响，重点是估计胎儿体重（EFW）。
BKMR 确定 Mo 和 Ba 是与 EFW 关联最大的混合物成分。两种金属均呈线性关联。Mo 从第 25 百分位到第 75 百分位的增加与 EFW 高出 0.114（95%可信区间（CI）：0.019，0.247）SD 相关，相当于 7.4g 的差异。Mo 与评估的其他胎儿指标之间也观察到类似的关联。相比之下，Ba 从第 25 百分位到第 75 百分位的增加与 EFW 低 0.076（95%CI：0.217，0.066）SD 相关，相当于 4.9g 的差异。Ba 与腹围和双顶径的关系也观察到类似的反比关联。BKMR 还确定了 Ba 和 Mo 之间与头围相关的可能相互作用，表明 Mo 与该结局之间的正相关可能在高水平 Ba 时减弱，这与线性回归的结果一致（P=0.03）。在一项考虑更大混合金属的探索性分析中，Mo 和 Ba 始终对 EFW 的关联贡献最大。Sb 与 EFW 之间也存在反比关联。
本研究结果表明，在该人群中，Mo 可能促进胎儿生长，而 Ba 和 Sb 可能会抑制胎儿生长。
