A meta-analysis of observational studies of the association between chronic occupational exposure to lead and amyotrophic lateral sclerosis

Abstract

Objective: The association between occupational exposure to lead and amyotrophic lateral sclerosis (ALS) was examined through systematic review and meta-analyses of relevant epidemiological studies and reported according to PRISMA guidelines.

Methods: Relevant studies were searched in multiple bibliographic databases through September 2013; additional articles were tracked through PubMed until submission. All records were screened in DistillerSR, and the data extracted from included articles were synthesized with meta-analysis.

Results: The risk of developing ALS among individuals with a history of exposure to lead was almost doubled (odds ratio, 1.81; 95% confidence interval, 1.39 to 2.36) on the basis of nine included case-control studies with specific lead exposure information, with no apparent heterogeneity across included studies (I = 14%). The attributable risk of ALS because of exposure to lead was estimated to be 5%.

Conclusions: Previous exposure to lead may be a risk factor for ALS.

FIGURE 1.

Literature search, screen, evaluation, data extraction, and data analysis flow chart for the meta-analysis of observational studies of the association between previous exposure and ALS.

FIGURE 2.

Previous exposure to lead/heavy metals is associated with increased risk of developing ALS. Exposure data were extracted from 13 case-control studies in which exposure to lead (9 studies) or heavy metals (4 studies) and the risk of ALS was assessed. No evidence of heterogeneity across the included studies was observed in a meta-analysis using a random-effects model. Nor was their evidence of significant publication bias (data not shown).

FIGURE 3.

Article quality among included studies does not affect the risk estimate. Included studies were assessed and divided into two groups (one comprising seven articles and the other six) on the basis of quality scores. If two articles with an identical quality score need to allocate into two groups, then we arbitrarily allocated the newer article to the high-quality group, to balance the group sizes. The meta-analysis of articles (random-effects model) with higher quality scores is shown in the upper panel, and the meta-analysis of articles with lower scores is presented in the lower panel.

FIGURE 4.

Meta-analysis using adjusted relative risk estimates provided by included articles. Seven articles were included in this analysis, including 5 case-control studies and 2 cohort studies. Two case-control studies presented risk estimates specifically for exposure to lead,, with the remaining case-control studies focusing on exposure to heavy metals, including lead. The two cohort studies gave estimates for exposure to heavy metals, including lead., The relative risk (OR or RR) from 7 included articles were first transformed to the log value, then estimated the confidence error on the basis of confidence interval log (95% upper CL − 95% lower CL). The meta-analysis was conducted with RevMan 5.1.