Health Effects of Dental Amalgams in Children

银合金作为牙科修复材料的安全性自150年前引入以来一直存在争议，但直到最近，人们普遍认为牙科汞合金的汞暴露仅限于急性放置阶段。最近的一些研究（大多是观察性的，主要针对成年人）表明，在咀嚼和刷牙过程中，汞合金填充物会长期释放汞蒸气，这引发了新的安全问题。随机试验，儿童汞合金试验（CAT）旨在全面评估银汞合金与替代无汞材料相比的相对安全性，证明认知和肾脏结局的等效性。从两个新英格兰社区（马萨诸塞州的主要农村和内城波士顿/剑桥）招募了最后一个生日时未进行牙齿修复（以尽量减少既往汞暴露）和混合（乳牙和恒牙）牙列的6-10岁儿童，以尽可能代表美国儿童的可能影响。选择儿童进行本试验是因为他们在随机分组时最有可能不含汞，并且鉴于他们较小的体重和发育阶段，更有可能表现出身体汞负荷增加的不良影响（如果有的话）。该5年竞争性继续研究将使试验受试者/随机化（1997年8月至1999年9月）完成6年观察。到2001年7月为止的现有资金只包括两年的观察。鉴于汞对认知功能的潜在长期影响具有明显的公共卫生意义，主要终点指标是韦氏儿童智力量表：第三版（WISC III）的全量表IQ评分，主要结局是基线与随机化后6年之间评分的估计变化，根据基线IQ评分进行调整。次要结局包括每年监测的更直接测量的安全性终点，包括：尿汞水平;尿蛋白试纸筛查试验（通过白蛋白水平证实）;和γ-谷氨酰转肽酶（γ-GTP）。其他终点包括来自广泛的神经心理测试组合的认知功能的其他方面，而关键协变量包括饮食汞（头发水平）的测量和以“表面年”暴露总结的汞合金剂量。迄今为止，534例受试者已接受随机化（107%），随访至12个月访视，尽管尚未完成，但表明初始（12个月）缓解率应至少为92%。预计后续损失可以忽略不计（每年约2%）。非正交协方差分析将检验治疗组之间IQ评分的等效性，相似模型将用于解决次要目的。

The safety of silver amalgam as a dental restorative material has been controversial since its introduction 150 years ago, but-until recently it has been generally assumed that the exposure to mercury from dental amalgam is limited to the acute placement phase. Some recent studies (mostly observational and primarily of adults) have demonstrated chronic release of mercury vapor from amalgam fillings during chewing and brushing, raising new safety concerns. The randomized trial, Children's Amalgam Trial (CAT) is designed as a comprehensive assessment of the relative safety of silver amalgam, compared to the alternate, mercury-free materials, demonstrating equivalence of cognitive and renal outcomes. Children aged 6-10 at last birthday with no prior dental restoration (to minimize prior mercury exposure) and mixed (primary and permanent) dentition were recruited from two New England communities (rural Main and inner city Boston/Cambridge, Massachusetts) to represent, to the extent feasible, the likely effects in children in the US. Children were chosen for this trial as they are most likely to be amalgam-free at randomization and, given their smaller body mass and developmental stage, more likely to demonstrate adverse effects (if any) of increased body mercury burden. This 5-year competing continuation will enable completion of 6 years of observation of the trial subjects/randomized from August 1997 to September 1999). Current funding, through July 2001, will include two years of observation only. Given the obvious public health significance of the potential long range impact of mercury on cognitive function, the primary endpoint measure is the full scale IQ score of the Wechsler Intelligence Scale for Children: Third Edition (WISC III) and the primary outcome is the estimated change in the score between Baseline and 6 years post randomization, adjusted for the baseline IQ score. Secondary outcomes include more immediately measured safety endpoints that will be monitored annually, including: urine mercury levels; a dip-stick screening test for urinary protein (confirmed by albumin level); and gamma-glutamyl transpeptidase (gamma-GTP). Other endpoints include other aspects of cognitive function from an extensive neuropsychological test battery, while key covariates include a measure of dietary mercury (hair levels) and the dose of amalgam summarized in "surface-years" of exposure. To date, 534 subjects have been randomized (107%) and follow-up through the 12 month visit, although not yet complete, indicates that the initial (12 month) response rate should be at least 92%. Subsequent losses are expected to be negligible (about 2% per year). A non- orthogonal analysis of covariance will test for equivalence on IQ scores between treatments arms similar modeling will be used to address secondary aims.