Health Effects of Dental Amalgams in Children

银汞合金作为牙齿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安置阶段。最近的一些研究（主要是观察性的，主要针对成年人）表明，在咀嚼和刷牙时，汞合金填充物会长期释放汞蒸气，这引起了新的安全问题。儿童汞合金试验（CAT）是一项随机试验，旨在全面评估银汞合金与替代无汞材料的相对安全性，证明认知和肾脏结果等效。从两个新英格兰社区（缅因州农村和马萨诸塞州波士顿/剑桥内城）招募了年龄在6-10岁的儿童，他们没有事先进行牙齿修复（以尽量减少先前的汞暴露）和混合（原牙和恒牙），以在可行的范围内代表美国儿童的可能影响。本试验选择儿童是因为他们在随机分配时最有可能不含汞，而且考虑到他们的体重和发育阶段较小，更有可能表现出身体汞负担增加的不利影响（如果有的话）。这个5年的竞争延续将使试验对象完成6年的观察（从1997年8月到1999年9月随机分配）。到2001年7月为止的现有经费将只包括两年的观察。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，主要终点测量是韦氏儿童智力量表：第三版（WISC III）的全量表智商得分，主要终点是随机化后基线和6年之间的估计得分变化，并根据基线智商得分进行调整。次要结局包括更直接测量的安全终点，将每年监测，包括：尿汞水平；尿蛋白蘸棒筛查试验（白蛋白水平证实）；-谷氨酰转肽酶（- gtp）。其他终点包括从广泛的神经心理学测试中获得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）的测量和汞合金暴露“表面年”的剂量。迄今为止，534名受试者（107%）已被随机分配，随访12个月，虽然尚未完成，但表明初始（12个月）缓解率应至少为92%。随后的损失预计可以忽略不计（每年约2%）。协方差的非正交分析将检验治疗之间的智商分数是否相等，类似的模型将用于解决次要目标。

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.