Which prenatal biomarker is most appropriate for methylmercury dose-response for neurodevelopmental effects?

Developmental neurotoxicity (DNT) is a well-established hazard attributed to methylmercury (MeHg) exposure. This evidence is based primarily upon includes studies that measured biomarkers of MeHg exposure in samples of maternal hair and blood, and cord blood. The aim of this review was to investigate which of these prenatal biomarkers is most appropriate for quantifying the DNT effects attributed to MeHg. A comprehensive literature search covered MeHg dose-response literature published 1998–2022. Studies were evaluated for risk of bias and study sensitivity using IRIS approach. Quantitative results of investigations were extracted and statistically compared. Seven studies were identified that measured both maternal hair and cord blood Hg levels. In these investigations, several DNT umbrella tests and their sub-tests results were modeled. Cord blood MeHg was more sensitive, producing larger estimates of MeHg potency, in most of the comparisons (91%) with maternal hair MeHg estimates for the same sub-tests in the same study. When comparing results from cord blood Hg to maternal hair Hg there was a 75% increase in sensitivity (range: 4–583%). In the two domains where results for maternal hair Hg were more sensitive, the rise was only 18% (Range: 7–29%). There were limited data (two studies) that compared maternal blood and maternal hair biomarkers (maternal blood Hg was more sensitive (mean 320% and range 43–855%) and cord blood biomarkers (maternal blood Hg was more sensitive by approximately 30%). Maternal hair Hg remains an appropriate biomarker for exposure monitoring in many populations, but these data suggest that cord blood Hg is more appropriate for dose-response modeling of MeHg DNT effects.

发育性神经毒性（Developmental neurotoxicity, DNT）是甲基汞（methylmercury, MeHg）暴露所公认的有害效应。此类证据主要基于一系列检测母发、母血及脐带血中甲基汞暴露生物标志物的研究。本综述旨在探究上述产前生物标志物中，哪一种最适用于量化甲基汞暴露所致的发育性神经毒性效应。研究团队通过全面的文献检索，覆盖了1998年至2022年间发表的甲基汞剂量-反应关系相关文献。采用综合风险信息系统（Integrated Risk Information System, IRIS）方法对纳入研究的偏倚风险及研究敏感性进行评估，提取各项研究的定量结果并开展统计学比较。最终纳入7项同时检测母发与脐带血汞水平的研究，对其中多项发育性神经毒性伞形检验及其子检验的结果进行了建模分析。在多数对照分析中（91%），针对同一研究的相同子检验，脐带血甲基汞的检测敏感性更高，所得甲基汞效应强度估计值也更大。将脐带血汞与母发汞的检测结果进行对比时，前者的敏感性提升了75%（波动范围为4%至583%）。在母发汞检测敏感性更高的两个领域中，敏感性提升幅度仅为18%（波动范围为7%至29%）。现有对比母血与母发生物标志物、以及母血与脐带血生物标志物的研究数据十分有限，仅纳入2项相关研究：对比母血与母发汞时，母血汞的检测敏感性更高，平均提升320%（波动范围为43%至855%）；对比母血与脐带血生物标志物时，母血汞的敏感性约提升30%。母发汞仍是多数人群暴露监测的适宜生物标志物，但本研究数据表明，脐带血汞更适用于甲基汞暴露所致发育性神经毒性效应的剂量-反应关系建模。