Schwartz J
Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115.
Neurotoxicology. 1993 Summer-Fall;14(2-3):237-46.
Determining the shape of dose-response relationships, including the possible existence of thresholds, is a central concern in the epidemiology of neurotoxins. Assessing the strengths of associations within a paper, and for the literature as a whole, are also critical concerns. Modern statistical and epidemiologic methods have considerable advantages for answering these questions. This is illustrated by using non-parametric smoothing to look for the existence of thresholds or non-linearities in the neurotoxic effects of lead, the use of multiple analyses and robust methods to test the stability of the association between dentine lead and children's IQ in the study of Needleman et al., 1979, and the examination of the stability of the association between full scale IQ and blood lead across studies. Non-parametric smoothing shows the dose response relationship between McCarthy score and blood lead reported by Bellinger et al., (1991) has no threshold down to blood lead levels of 1 microgram/dl. The association between blood lead and hearing threshold reported by Schwartz and Otto (1991) also has no threshold down to the lowest concentrations seen in that study. The association between dentine lead and IQ in the Needleman et al. (1979) data holds in the full data set with no exclusions and with control for age, is insensitive to exclusions of subjects or inclusions of other covariates, and to the use of robust estimation techniques. Nonparametric smoothing shows the association is supported across the entire range of lead exposure and is not driven by a few outliers. Examination of effect size estimates from the IQ-blood lead studies shows moderately good concordance. This suggests a causal relationship. A meta-analysis of those studies indicates that an increase in blood lead from 10 micrograms/dl to 20 micrograms/dl is associated with a reduction of 2.5 points in full scale IQ. The effect was highly significant.
确定剂量反应关系的形状，包括阈值的可能存在，是神经毒素流行病学的核心关注点。评估一篇论文内以及整个文献中关联的强度，也是至关重要的关注点。现代统计和流行病学方法在回答这些问题方面具有相当大的优势。这通过以下方式得以说明：使用非参数平滑来寻找铅的神经毒性作用中的阈值或非线性；在1979年尼德曼等人的研究中，使用多种分析和稳健方法来检验牙本质铅与儿童智商之间关联的稳定性；以及在各项研究中检验全量表智商与血铅之间关联的稳定性。非参数平滑显示，贝林格等人（1991年）报告的麦卡锡分数与血铅之间的剂量反应关系在血铅水平低至1微克/分升时没有阈值。施瓦茨和奥托（1991年）报告的血铅与听力阈值之间的关联在该研究中所见的最低浓度下也没有阈值。尼德曼等人（1979年）数据中牙本质铅与智商之间的关联在完整数据集中成立，无排除情况且对年龄进行了控制，对排除受试者或纳入其他协变量以及使用稳健估计技术不敏感。非参数平滑显示，该关联在铅暴露的整个范围内都得到支持，并非由少数异常值驱动。对智商 - 血铅研究的效应大小估计值的检查显示出适度良好的一致性。这表明存在因果关系。对这些研究的荟萃分析表明，血铅从10微克/分升增加到20微克/分升与全量表智商降低2.5分相关。该效应非常显著。
