Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill (UNC-Chapel Hill), Chapel Hill, North Carolina, USA.
Institute for Environmental Health Solutions, Gillings School of Global Public Health, UNC-Chapel Hill, Chapel Hill, North Carolina, USA.
Environ Health Perspect. 2023 Aug;131(8):86002. doi: 10.1289/EHP11872. Epub 2023 Aug 30.
Neural tube defects (NTDs) affect pregnancies worldwide annually. Few nongenetic factors, other than folate deficiency, have been identified that may provide intervenable solutions to reduce the burden of NTDs. Prenatal exposure to toxic metals [arsenic (As), cadmium (Cd), mercury (Hg), manganese (Mn) and lead (Pb)] may increase the risk of NTDs. Although a growing epidemiologic literature has examined associations, to our knowledge no systematic review has been conducted to date.
Through adaptation of the Navigation Guide systematic review methodology, we aimed to answer the question "does exposure to As, Cd, Hg, Mn, or Pb during gestation increase the risk of NTDs?" and to assess challenges to evaluating this question given the current evidence.
We selected available evidence on prenatal As, Cd, Hg, Mn, or Pb exposure and risk of specific NTDs (e.g., spina bifida, anencephaly) or all NTDs via a comprehensive search across MEDLINE, Embase, Web of Science, and TOXLINE databases and applied inclusion/exclusion criteria. We rated the quality and strength of the evidence for each metal. We applied a customized risk of bias protocol and evaluated the sufficiency of evidence of an effect of each metal on NTDs.
We identified 30 studies that met our criteria. Risk of bias for confounding and selection was high in most studies, but low for missing data. We determined that, although the evidence was limited, the literature supported an association between prenatal exposure to Hg or Mn and increased risk of NTDs. For the remaining metals, the evidence was inadequate to establish or rule out an effect.
The role of gestational As, Cd, or Pb exposure in the etiology of NTDs remains unclear and warrants further investigation in high-quality studies, with a particular focus on controlling confounding, mitigating selection bias, and improving exposure assessment. https://doi.org/10.1289/EHP11872.
神经管缺陷（NTDs）每年影响全球范围内的妊娠。除叶酸缺乏外，很少有其他非遗传因素被确定可以提供可行的解决方案来降低 NTD 的负担。产前暴露于有毒金属（砷[As]、镉[Cd]、汞[Hg]、锰[Mn]和铅[Pb]）可能会增加 NTD 的风险。尽管越来越多的流行病学文献研究了相关性，但据我们所知，迄今为止尚未进行系统评价。
通过采用导航指南系统评价方法，我们旨在回答“怀孕期间暴露于 As、Cd、Hg、Mn 或 Pb 是否会增加 NTD 的风险？”这一问题，并评估鉴于当前证据评估这一问题所面临的挑战。
我们通过全面搜索 MEDLINE、Embase、Web of Science 和 TOXLINE 数据库，选择了关于产前 As、Cd、Hg、Mn 或 Pb 暴露与特定 NTD（例如脊柱裂、无脑畸形）或所有 NTD 风险的现有证据，并应用了纳入/排除标准。我们对每种金属的证据质量和强度进行了评级。我们应用了定制的偏倚风险协议，并评估了每种金属对 NTD 影响的证据充分性。
我们确定了符合我们标准的 30 项研究。大多数研究中混杂和选择偏倚的风险较高，但缺失数据的风险较低。我们确定，尽管证据有限，但文献支持产前暴露于 Hg 或 Mn 与 NTD 风险增加之间存在关联。对于其余金属，证据不足以确定或排除其影响。
妊娠期 As、Cd 或 Pb 暴露在 NTD 发病机制中的作用仍不清楚，需要在高质量研究中进一步调查，特别关注控制混杂、减轻选择偏倚和改善暴露评估。https://doi.org/10.1289/EHP11872.
