Health Effects of Dental Amalgams in Children

银汞合金作为牙科修复材料的安全性自150年前问世以来一直存在争议，但直到最近，人们还普遍认为银汞合金对汞的暴露仅限于急性种植阶段。最近的一些研究(主要是观察性的，主要是成年人)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。这项名为儿童汞齐试验(CAT)的随机试验旨在全面评估银汞合金与替代的无汞材料的相对安全性，证明认知和肾脏结果相同。从新英格兰的两个社区(马萨诸塞州波士顿/坎布里奇的乡村主城区和市中心)招募了6-10岁的儿童，在可行的范围内，代表了美国儿童可能受到的影响。选择儿童参加这项试验是因为他们在随机试验中最有可能是不含汞齐的，而且考虑到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)。这5年的竞争延续将使试验对象的6年观察/从1997年8月至1999年9月随机进行)。目前的资助截止到2001年7月，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，主要终点测量是韦克斯勒儿童智力量表第三版(WISC III)的全程智商得分，主要结果是根据基线智商得分调整后的基线和随机化后6年之间得分的估计变化。次要结果包括将每年监测的更直接测量的安全终点，其中包括：尿汞水平；尿蛋白试纸筛查试验(由白蛋白水平确认)；和伽马-谷氨酰转肽酶(伽马-GTP)。其他终点包括广泛的神经心理测试组合的认知功能的其他方面，而关键的协变量包括饮食汞(头发水平)的测量和汞齐剂量在暴露的“表面年”总结。到目前为止，534名受试者已经被随机分组(107%)，通过12个月的随访，尽管还没有完成，但表明最初(12个月)的应答率应该至少是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组之间智商得分的等价性，类似的建模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.