The authors have declared that no competing interests exist.
Conceived and designed the experiments: HZ ZX. Performed the experiments: HZ CC YY. Analyzed the data: GC YY. Contributed reagents/materials/analysis tools: HZ ZX. Wrote the paper: HZ GC.
To estimate the relationship between exposure to extremely low-frequency electromagnetic fields (ELF-EMF) and the risk of amyotrophic lateral sclerosis (ALS) by a meta-analysis.
Through searching PubMed databases (or manual searching) up to April 2012 using the following keywords: “occupational exposure”, “electromagnetic fields” and “amyotrophic lateral sclerosis” or “motor neuron disease”, seventeen studies were identified as eligible for this meta-analysis. The associations between ELF-EMF exposure and the ALS risk were estimated based on study design (case-control or cohort study), and ELF-EMF exposure level assessment (job title or job-exposure matrix). The heterogeneity across the studies was tested, as was publication bias.
Occupational exposure to ELF-EMF was significantly associated with increased risk of ALS in pooled studies (RR = 1.29, 95%CI = 1.02–1.62), and case-control studies (OR = 1.39, 95%CI = 1.05–1.84), but not cohort studies (RR = 1.16, 95% CI = 0.80–1.69). In sub-analyses, similar significant associations were found when the exposure level was defined by the job title, but not the job-exposure matrix. In addition, significant associations between occupational exposure to ELF-EMF and increased risk of ALS were found in studies of subjects who were clinically diagnosed but not those based on the death certificate. Moderate heterogeneity was observed in all analyses.
Our data suggest a slight but significant ALS risk increase among those with job titles related to relatively high levels of ELF-EMF exposure. Since the magnitude of estimated RR was relatively small, we cannot deny the possibility of potential biases at work. Electrical shocks or other unidentified variables associated with electrical occupations, rather than magnetic-field exposure, may be responsible for the observed associations with ALS.
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder that results in the loss of motor neurons, and a rapidly progressive and fatal muscle paralysis. Although some ALS cases are familial, about 90% are sporadic
Studies over the past two decades have shown that occupational exposure to extremely low-frequency EMF (ELF-EMF) may be a causal factor of ALS
The inconsistent results across the studies may be due to the small sample size in each study, different study design and measurement of ELF-EMF exposure level. To fully evaluate the association between occupational ELF-EMF exposure and ALS risk, we systemically reviewed all published papers and performed a meta-analysis by pooled analyses of all studies and sub-analyses based on study design, exposure assessment method and criteria for ALS diagnosis.
This systematic review focuses on the association between occupational exposure to ELF-EMF and ALS risk among the exposed population. We conducted a literature search in the PubMed database up to April 2012 using the following keywords: “occupational exposure”, “electromagnetic fields” and “amyotrophic lateral sclerosis” or “motor neuron disease”. Additional studies were identified by manual search from the references of original studies or review articles on this topic. Full texts or abstracts of all related reports were then reviewed. The literature retrieval was performed by three independent reviewers (H Zhou, G Chen and C Chen).
The selected studies were required to meet all the following criteria: (1) each included study must be an unrelated case-control or cohort study and only the one with a larger sample size was selected if studies had partly overlapping subjects; (2) the studies should refer to the association between occupational ELF-EMF exposure and ALS risk; and (3) the outcome should be defined as a medical diagnosis of ALS or registered as ALS on the death certificate.
Occupational exposure to ELF-EMF is defined as workers exposed to ELF-EMF during the working period, such as electric power installers and repairers, power plant operators, electricians, electrical fitters, electrical and electronic equipment repairers, train drivers, telephone installers and repairers, and workers operating electrical equipment such as welders, carpenters, or machinists. In this meta-analysis, the exposure level of ELF-EMF was classified by job title or job-exposure matrix. The exposure level was assessed according to job title, then workers were divided into two categories: “electrical occupations” (exposure group) and “non-electrical occupations” (no-exposure group). Exposure level to ELF-EMF was measured by the job-exposure matrix, and then the exposure level was expressed as quantitative data. We extracted the relative risk (RR)/odds ratio (OR) and 95% confidence interval (95%CI) of risk of ALS and ELF-EMF exposure from the literature. However, if ELF-EMF exposure was estimated by the job-exposure matrix, only the OR/RR and 95%CI of the highest exposure group was extracted for final analyses.
ALS classification was based on clinical diagnosis or the death certificate. The criteria for ALS diagnosis followed the International Classification of Disease (ICD-8 348, ICD-9 335.2 and ICD-10 G12.2) and the World Federation of Neurology El Escorial.
The following information was extracted from the selected publications: first author, year of publication, study population, study design, duration of case retrieval or cohort establishment, method of case ascertainment, exposure assessment criteria, confounding variables, main results, and quality assessment of studies.
All analyses were conducted with Stata Software, version 11.0
Twenty abstracts were retrieved, and ten studies were identified as eligible. Out of the twenty, one study was excluded since it was an animal study
First author, year | Study population (country) | Design | Time period | Method of case ascertainment | Confounding variables | Exposure assessment, criteria | Main results |
Deapen, 1986 |
518 cases and 518 controls (USA) | Case-control | 1977–1979 | Clinical examination | Age, sex | Questionnaire survey by mailJob title | OR = 3.8 (1.4–13.0) |
Gunnarsson, 1991 |
1,961 cases and 2,245 controls (Sweden) | Case-control | 1970–1983 | Death certificates | Age, sex | 1960 national censusJob title | OR = 1.5 (0.9–2.6) |
Gunnarsson, 1992 |
92 cases and 372 controls (Sweden) | Case-control | 1960–1990 | Clinical examination | Age, sex | Questionnaire survey by mailJob title | OR = 6.7 (1.0–32.1) |
Strickland, 1996 |
25 cases and 50 controls (USA) | Case-control | 1982–1992 | Clinical examination | Age, sex, residence, physical capacities | InterviewJob title | OR = 8.0 (0.9–72.0) |
Davanipour, 1997 |
28 cases and 32 controls (USA) | Case-control | Not mentioned | Clinical examination | Age, sex, education, socioeconomic status | Questionnaire by interview Job-exposure matrix | OR = 2.3 (0.8–6.6) |
Savitz, 1998a |
114 cases and 228 controls (USA) nested in occupational cohorts | Case-control | 1985–1991 | Death certificates | Age, calendar year, social class, men only | From death certificateJob title | OR = 1.3 (1.1–1.6) |
Savitz, 1998b |
Cohort of 139,905 men and 33 cases (USA) | Cohort | 1950–1986 | Death certificates | Age, calendar year, race, social class, work status, PCB exposure, solvent exposure | Occupational recordsJob titleJob-exposure matrix(>1.1 µT) | RR = 2.4 (0.8–6.7)RR = 1.2 (0.5–3.0) |
Johansen, 2000 |
Cohort of 30,631 persons and 20 cases (Denmark) | Cohort | 1978–1993 | Clinical examination | Age, calendar period, duration of employment | Job-exposure matrix(>1.0 µT) | RR = 1.56 (0.29-8.53) |
Noonan, 2002 |
312 cases and 1,248 controls (USA) | Case-control | 1987–1996 | Death certificates | Age, race, social class, men only | Death certificatesJob titleJob-exposure matrix(>0.3 µT) | OR = 2.3 (1.29–4.09)OR = 0.77 (0.37–1.59) |
Feychting, 2003 |
Cohort of 4,812,646 persons and 1965 cases (Sweden) | Cohort | 1981–1995 | Death certificates | Age, sex, social class | 1970 and 1980 censusesJob titleJob-exposure matrix(>0.5 µT) | RR = 1.4 (1.0–1.8)RR = 0.7 (0.6–1.0) |
Hakansson, 2003 |
Cohort of 537,692 men and 180,529 women and 97 cases (Sweden) | Cohort | 1985–1996 | Death certificates | Age, sex, social class | Job-exposure matrix(>0.5 µT) | RR = 2.16 (1.01–4.66) |
Weisskopf, 2005 |
Cohort of 1,184,561 persons and 937 cases (USA) | Cohort | 1989–2002 | Death certificates | Age, sex | Questionnaire by interviewJob title | RR = 0.99 (0.49–1.99) |
Park, 2005 |
6347 cases (USA) | Case-control | 1992–1998; | Death certificates | Age, sex, race, region, socioeconomic status | Job-exposure matrix(0.9–0.99 µT) | OR = 0.94 (0.73–1.20) |
Roosli, 2007 |
Cohort of 20,141 persons and 15 cases (Switzerland) | Cohort | 1972–2002 | Death certificates | Age, time period, men only | death certificatesJob titleJob-exposure matrixCumulative lifetime Exposure >median | RR = 1.31 (0.31–5.59)RR = 2.32 (0.70–7.73) |
Sorahan, 2007 |
Cohort of 79,972 persons and 68 cases (England) | Cohort | 1973–2004 | Death certificates | Age, sex, socioeconomic status | Occupational recordsJob titleEstimated cumulative exposure to magnetic fieldsCumulative year >20 µT | RR = 0.87 (0.67–1.10)RR = 1.45 (0.60–3.55) |
Fang, 2009 |
109 cases and 253 controls (England) | Case-control | 1993–1996 | Clinical examination | sex, age | InterviewJob title | OR = 1.4 (0.9–2.3) |
Parlett, 2011 |
Cohort of 307,012 persons and 40 cases (USA) | Cohort | 1979–2011 | Death certificates | age, sex, and education | Job-exposure matrix>0.27 µT | RR = 0.98 (0.39–2.50) |
The main results of this meta-analysis and the heterogeneity test are shown in
Subgroup analysis | Case-control studies | Cohort studies | Pooled studies | ||||||
No. |
OR(95% CI) | I2 ( |
No. |
RR(95% CI) | I2 ( |
No. |
RR(95% CI) | I2 ( |
|
|
9 | 1.39(1.05–1.84) | 57.9% (0.015) | 8 | 1.16 (0.80–1.69) | 46.8% (0.069) | 17 | 1.29(1.02–1.62) | 58.9% (0.001) |
|
|||||||||
Job title | 7 | 1.76 (1.27–2.44) | 50.0% (0.062) | 5 | 1.16 (0.83–1.61) | 51.3% (0.084) | 12 | 1.45 (1.15–1.84) | 57.5% (0.007) |
quantitative data | 3 | 1.01 (0.67–1.52) | 33.6% (0.222) | 7 | 1.23(0.79–1.93) | 54.3% (0.041) | 10 | 1.09(0.82–1.43) | 45.2% (0.059) |
|
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Clinical diagnosis | 5 | 2.58 (1.35–4.92) | 42.2% (0.140) | 1 | 1.56 (0.29–8.53) | – | 6 | 2.31 (1.34–3.99) | 28.3% (0.223) |
Death certificate | 4 | 1.13 (0.88–1.45) | 52.3% (0.098) | 7 | 1.15 (0.78–1.72) | 52.8% (0.048) | 11 | 1.11 (0.88–1.39) | 57.5% (0.009) |
Number of studies.
Percentage of total variation across studies attributable to statistical heterogeneity rather than to chance (25%, low; 50%, moderate; 75%, high);
In addition, the studies were divided into two types by ALS ascertainment based on the clinical diagnosis or death certificate. The analyses revealed that exposure level was associated with an increased risk of ALS in the studies using clinical diagnosis (RR = 2.31, 95% CI = 1.34–3.99 for all studies, and OR = 2.58, 95% CI = 1.35–4.92 for case-control studies), but not in studies using the death certificate (RR = 1.11, 95% CI = 0.88–1.39). Meanwhile, moderate heterogeneity was present in all analyses.
Funnel plots were constructed, and Egger's test was performed to assess the publication bias of the selected studies. The shape of Begg's funnel plots revealed marked asymmetry for all effects (
Each point represents a separate study for the indicated association.
We conducted a meta-analysis of seventeen epidemiological studies on the association between occupational exposure to ELF-EMF and the risk of ALS. The results revealed a slight but significant increase in the risk of ALS among ELF-EMF-related occupations in pooled studies, job-title analysis and clinically diagnosed ALS studies, but not in job-exposure matrix studies and studies of ALS based on the death certificate. Moderate statistical heterogeneity across studies was found in all analyses.
Studies based on job-title showed that electrical occupations increased the risk of ALS, but the result from studies estimating exposure levels of ELF-EMF by the job-exposure matrix suggested that ELF-EMF was not significantly associated with ALS risk. Persons in electrical occupations may have a greater potential for electrical shocks. Electrical shocks or other unidentified variables associated with electrical occupations, rather than magnetic-field exposure, may distort real association between ELF-EMF and ALS risk
A significant association was found in the studies of clinically diagnosed ALS, but not in those based on the death certificate. Actually, the analyses of clinically diagnosed ALS studies included four job-title studies
However, epidemiological studies have several weaknesses, mostly in relation to case ascertainment and controls selection in case-control studies, exposure assessment, and control of confounders. Incomplete ascertainment of cases decrease the statistical power of case-control studies. In this meta-analysis, we found a higher pooled risk by pooling the studies based on clinical examination when compared to that based on death certificates, and observed substantial heterogeneity when the results from both approaches were compared (
Twelve studies used “job title” to characterize exposure, whereas ten assessed the levels of exposure to ELF-EMF by the job-exposure matrix. In studies using job title, occupations were grouped into “electrical” and “non-electrical” categories, but the criteria for defining “electrical occupation” varied across studies
Although potential confounders such as age and sex were controlled in most of these studies, other confounders might have derived from unknown and unmeasured variables. One potential confounding factor could be ELF-EMF exposure from non-occupational sources. ELF-EMF are generated by many sources, including power lines, electric transportation systems, and electrical appliances. These non-occupational sources could result in the same level of exposure as occupational sources
In addition to occupational ELF-EMF exposure, public exposure to environmental ELF-EMF has increased rapidly in the last a few decades. Future studies should examine the association between public ELF-EMF exposure level and ALS incidence to clarify the relation between ELF-EMF exposure and ALS risk.
Biological mechanisms have been explored to clarify the association between ELF-EMF exposure and ALS risk. Some laboratory studies indicated that
This meta-analysis included seventeen studies of the association between ALS risk and ELF-EMF exposure. Although there are potential limitations from study selection bias, exposure misclassification, and the confounding effect of individual studies in this meta-analysis, our data suggest a slight but significant ALS risk increase among those with job titles related to relatively high levels of ELF-EMF exposure. Since the magnitude of estimated RR was relatively small, we cannot deny the possibility of potential biases at work. Electrical shocks or other unidentified variables associated with electrical occupations, rather than magnetic-field exposure, may be responsible for the observed associations with ALS.
(DOC)
We thank Dr. Iain C Bruce from Zhejiang University School of Medicine for critical reading of the manuscript.