Amyotrophic Lateral Sclerosis and Occupational Exposures: A Systematic Literature Review and Meta-Analyses

Abstract

Objectives: We conducted a systematic literature review to identify studies fulfilling good scientific epidemiological standards for use in meta-analyses of occupational risk factors for amyotrophic lateral sclerosis (ALS). Methods: We identified 79 original publications on associations between work and ALS. The MOOSE (Meta-analysis Of Observational Studies in Epidemiology) and GRADE (Grading of Recommendations, Assessment, Development and Evaluations) guidelines were used to ensure high scientific quality, and reliable protocols were applied to classify the articles. Thirty-seven articles fulfilled good scientific standards, while 42 were methodologically deficient and thus were excluded from our meta-analyses. Results: The weighted relative risks for the various occupational exposures were respectively; 1.29 (95% confidence interval (CI): 0.97⁻1.72; six articles) for heavy physical work, 3.98 (95% CI: 2.04⁻7.77; three articles) for professional sports, 1.45 (95% CI: 1.07⁻1.96; six articles) for metals, 1.19 (95% CI: 1.07⁻1.33; 10 articles) for chemicals, 1.18 (95% CI: 1.07⁻1.31; 16 articles) for electromagnetic fields or working with electricity, and 1.18 (95% CI: 1.05⁻1.34; four articles) for working as a nurse or physician. Conclusions: Meta-analyses based only on epidemiologic publications of good scientific quality show that the risk of ALS is statistically significantly elevated for occupational exposures to excessive physical work, chemicals (especially pesticides), metals (especially lead), and possibly also to electromagnetic fields and health care work. These results are not explained by publication bias.

Keywords: chemicals; electromagnetic fields; epidemiology; metals; physical activity.

Figure 1

Forest plot for studies assessing the association between ALS (amyotrophic lateral sclerosis) and occupational exposure to heavy physical work. Results for men only are indicated by M; otherwise the results concern both sexes. Random effect models were used, with stratification of activities. Heterogeneity was tested by the I² statistic, with p < 0.05 indicating rejection of homogeneity. RR = relative risk.

Figure 2

Forest plot for studies assessing the association between ALS (amyotrophic lateral sclerosis) and occupational exposure to chemicals. Results for men only are indicated by M, results for women only are indicated by W; otherwise the results concern both sexes. Random effect models were used, with stratification of exposure related to chemical exposure related to agricultural work or other chemical exposures. Heterogeneity was tested by the I² statistic, with p < 0.05 indicating rejection of homogeneity.

Figure 3

Funnel plot for the 16 RR (relative risk) estimates of the association between ALS (amyotrophic lateral sclerosis) and occupational exposure to chemicals in Figure 2.

Figure 4

Forest plot for studies assessing the association between ALS (amyotrophic lateral sclerosis) and occupational exposure to metals. Results for men only are indicated by M; otherwise the results concern both sexes. Random effect models were used, with stratification of exposure to lead or other metals. Heterogeneity was tested by the I² statistic, with p < 0.05 indicating rejection of homogeneity.

Figure 5

Forest plot for studies assessing the association between ALS (amyotrophic lateral sclerosis) and occupational exposure to welding. Results for men only are indicated by M; otherwise the results concern both sexes. Random effect models were used. Heterogeneity was tested by the I² statistic, with p < 0.05 indicating rejection of homogeneity.

Figure 6

Forest plot for studies assessing the association between ALS (amyotrophic lateral sclerosis) and occupational exposure to work with electricity and electromagnetic fields (EMF). Results for men only are indicated by M, results for women only are indicated by W; otherwise the results concern both sexes. Random effect models were used, with stratification of exposure to work with electricity or EMF. Heterogeneity was tested by the I² statistic, with p < 0.05 indicating rejection of homogeneity.

Figure 7

Cumulative meta-analyses on the association between ALS (amyotrophic lateral sclerosis) and occupational exposure to EMF or work with electricity with the pooled estimate (Cum RR) updated for every new study, year by year.