Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Box 630, Rochester, NY 14642, United States; Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, United States.
Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, United States; Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, United States; Department of Neurology, University of Rochester Medical Center, Rochester, NY, United States.
Neurotoxicology. 2022 Jul;91:234-244. doi: 10.1016/j.neuro.2022.05.016. Epub 2022 May 25.
Methylmercury (MeHg) is a known neurodevelopmental toxicant in sufficient dosage and is universally found in fish. Current fish advisories for children are based on epidemiology studies examining prenatal exposure with a premise that MeHg exposure resulting from children eating fish could also be neurotoxic and have long-term consequences. However, the evidence that this assumption is true is limited. We investigated postnatal MeHg exposure from regular fish consumption using time weighted Hg measurements to determine if there are neurotoxic consequences.
We examined 85 neurodevelopmental outcomes measured from ages 9-24 years in the Seychelles Child Development Study Main Cohort (n = 312-550) and examined their association with time-weighted measures of postnatal MeHg exposure in childhood and early adulthood. Postnatal MeHg exposure measured in the first cm of participants' hair samples collected at seven evaluations were used to create two time-weighted (TW) average MeHg exposure metrics, one for childhood (TW-C) and the other for early adulthood (TW-A). TW-C was based on Hg measures at three ages between 6 months and 5.5 years, and TW-A was based on Hg measured at up to four ages between 17 and 24 years. We examined the association between each of these exposure metrics and the neurodevelopmental outcomes using linear regression with adjustment for covariates known to influence neurodevelopmental outcomes.
There were 14 statistically significant associations between a postnatal metric and an endpoint. Six were associated with the TW-C and eight with the TW-A. Thirteen were adverse. Only the TW-C association at 9 years with the Bender Gestalt error score showed improvement. TW-C was adversely associated at 9 years with the Continuous Performance Task risk score, at 22 years with the Boston Naming Test (BNT) total and no cues scores, and at 24 years with the Test of Variables of Attention (TOVA) auditory response time variability and visual response time mean on the logarithmic scale. TW-A was adversely associated at 17 years with the Wisconsin Card Sorting Test % total errors, the Woodcock-Johnson passage comprehension, and the CANTAB rapid visual information processing false alarms, and at 22 years with the BNT total and no cue scores, the CANTAB rapid visual information processing false alarms and the intra-extra dimensional shift total errors and trials.
These findings suggest that postnatal MeHg exposure may be adversely associated with neurodevelopmental outcomes in early adulthood. However, the associations are statistical and of unknown, if any, clinical significance. The results need confirmation in other cohorts.
甲基汞(MeHg)在足够剂量下是一种已知的神经发育毒物,普遍存在于鱼类中。目前针对儿童的鱼类食用建议是基于流行病学研究,这些研究检查了产前暴露情况,并假设儿童吃鱼导致的 MeHg 暴露也可能具有神经毒性,并产生长期影响。然而,这一假设成立的证据有限。我们通过时间加权汞测量来研究儿童期经常吃鱼导致的后天 MeHg 暴露,以确定是否存在神经毒性后果。
我们检查了塞舌尔儿童发展研究主要队列中 85 项神经发育结果,这些结果来自 9-24 岁的年龄(n=312-550),并检查了它们与儿童期和成年早期的后天 MeHg 暴露时间加权测量值之间的关联。在 7 次评估中,参与者头发样本的前 1 厘米处采集的后天 MeHg 暴露测量值被用来创建两个后天时间加权(TW)平均 MeHg 暴露指标,一个用于儿童期(TW-C),另一个用于成年早期(TW-A)。TW-C 基于 6 个月至 5.5 岁之间三个年龄的 Hg 测量值,TW-A 基于 17 至 24 岁之间最多四个年龄的 Hg 测量值。我们使用线性回归,根据已知影响神经发育结果的协变量进行调整,检查了这些暴露指标中的每一个与神经发育结果之间的关联。
在一个后天指标和一个终点之间有 14 个具有统计学意义的关联。其中 6 个与 TW-C 有关,8 个与 TW-A 有关。其中 13 个是不利的。只有在 9 岁时 TW-C 与 Bender Gestalt 错误评分之间的关联显示出改善。在 9 岁时,TW-C 与连续动作任务风险评分、22 岁时与波士顿命名测试(BNT)总评分和无线索评分、24 岁时与注意力变量测试(TOVA)听觉反应时变异性和视觉反应时对数评分均呈负相关。在 17 岁时,TW-A 与威斯康星卡片分类测试%总错误、伍德考克-约翰逊篇章理解、CANTAB 快速视觉信息处理假警报有关,在 22 岁时与 BNT 总评分和无线索评分、CANTAB 快速视觉信息处理假警报和内外维度转换总错误和试验有关。
这些发现表明,后天 MeHg 暴露可能与成年早期的神经发育结果呈负相关。然而,这些关联是统计学上的,其临床意义未知。结果需要在其他队列中得到证实。