International study of childhood leukemia in residences near electrical transformer rooms.

OBJECTIVES: New epidemiologic approaches are needed to reduce the scientific uncertainty surrounding the association between extremely low frequency magnetic fields (ELF-MF) and childhood leukemia. While most previous studies focused on power lines, the Transformer Exposure study sought to assess this association using a multi-country study of children who had lived in buildings with built-in electrical transformers. ELF-MF in apartments above built-in transformers can be 5 times higher than in other apartments in the same building. This novel study design aimed to maximize the inclusion of highly exposed children while minimising the potential for selection bias. METHODS: We assessed associations between residential proximity to transformers and risk of childhood leukemia using registry based matched case-control data collected in five countries. Exposure was based on the location of the subject's apartment relative to the transformer, coded as high (above or adjacent to transformer), intermediate (same floor as apartments in high category), or unexposed (other apartments). Relative risk (RR) for childhood leukemia was estimated using conditional logistic and mixed logistic regression with a random effect for case-control set. RESULTS: Data pooling across countries yielded 16 intermediate and 3 highly exposed cases. RRs were 1.0 (95% CI: 0.5, 1.9) for intermediate and 1.1 (95% CI: 0.3, 3.8) for high exposure in the conditional logistic model. In the mixed logistic model, RRs were 1.4 (95% CI: 0.8, 2.5) for intermediate and 1.3 (95% CI: 0.4, 4.4) for high. Data of the most influential country showed RRs of 1.1 (95% CI: 0.5, 2.4) and 1.7 (95% CI: 0.4, 7.2) for intermediate (8 cases) and high (2 cases) exposure. DISCUSSION: Overall, evidence for an elevated risk was weak. However, small numbers and wide confidence intervals preclude strong conclusions and a risk of the magnitude observed in power line studies cannot be excluded.

Pooled analysis of recent studies of magnetic fields and childhood leukemia.

BACKGROUND: Over forty epidemiologic studies have addressed an association between measured or calculated extremely-low-frequency magnetic fields (MF) and childhood leukemia. These studies have been aggregated in a series of pooled analyses, but it has been 10 years since the last such. METHODS: We present a pooled analysis combining individual-level data (24,994 cases, 30,769 controls) from four recent studies on MF and childhood leukemia. RESULTS: Unlike previous pooled analyses, we found no increased risk of leukemia among children exposed to greater MF: odds ratio (OR) = 1.01, for exposure ≥0.4 µT (µT) compared with exposures <0.1 µT. Similarly, no association was observed in the subset of acute lymphoblastic leukemia, birth homes, studies using calculated fields, or when geocoding accuracy was ignored. In these studies, there is a decline in risk over time, also evident when we compare three pooled analyses. A meta-analysis of the three pooled analyses overall presents an OR of 1.45 (95% CI: 0.95-2.20) for exposures ≥0.4 µT. CONCLUSIONS: Our results are not in line with previous pooled analysis and show a decrease in effect to no association between MF and childhood leukemia. This could be due to methodological issues, random chance, or a true finding of disappearing effect.

Receipt of Electroconvulsive Therapy and Subsequent Development of Amyotrophic Lateral Sclerosis: A Cohort Study.

We investigated the potential relationship between receipt of electroconvulsive therapy (ECT) and development of amyotrophic lateral sclerosis (ALS). We conducted a cohort study using a sample of more than one million beneficiaries enrolled in the U.S. Medicare health insurance program from 1997 to 2017. Using time-varying proportional hazard modeling, we compared ALS occurrence among patients diagnosed with psychiatric conditions who received ECT to ALS occurrence among patients diagnosed with psychiatric conditions but who did not receive ECT. We observed moderately increased, but imprecise, hazard ratios (HR) for ALS following ECT (HR = 1.39, 95% confidence interval [CI]: 0.69-2.80). A statistically significant increase in the HR of ALS was observed among those who received more than 10 ECT treatments (>10 treatments, HR = 2.24, 95% CI: 1.00-5.01), compared to those receiving no ECT, with an even stronger association observed among subjects older than 65 years (HR = 3.03, 95% CI: 1.13-8.10). No monotonic exposure-response relationship was detected in categorical analyses. Our results provide weak support for the hypothesis that receipt of ECT increases the risk of developing ALS. Additional studies in larger populations, or in populations where ECT is more common, will be needed to refute or confirm an association between receipt of ECT and subsequent development of ALS. Bioelectromagnetics. 43:81-89, 2022. © 2021 Bioelectromagnetics Society.

Residential proximity to plant nurseries and risk of childhood leukemia.

BACKGROUND: Pesticides are a potential risk factor for childhood leukemia. Studies evaluating the role of prenatal and/or early life exposure to pesticides in the development of childhood leukemia have produced a range of results. In addition to indoor use of pesticides, higher risks have been reported for children born near agricultural crops. No studies have looked at pesticide exposure based on proximity of birth residence to commercial plant nurseries, even though nurseries are located much closer to residences than agricultural crops and can potentially result in chronic year-round pesticide exposure. OBJECTIVES: To evaluate whether risk of childhood leukemia is associated with pesticide use as determined by distance of residence at birth to commercial, outdoor plant nurseries. METHODS: We conducted a large statewide, record-based case-control study of childhood leukemia in California, which included 5788 childhood leukemia cases and an equal number of controls. Pesticide exposure was based on a spatial proximity model, which combined geographic information system data with aerial satellite imagery. RESULTS: Overall, the results supported an increased childhood leukemia risk only for birth residences very close to nurseries. For birth residences less than 75 m from plant nurseries, we found an increased risk of childhood leukemia (odds ratio (OR) 2.40, 95% confidence interval (CI) 0.99-5.82) that was stronger for acute lymphocytic leukemia (OR 3.09, 95% CI 1.14-8.34). DISCUSSION: The association was robust to choices of reference group, cut points and data quality. Our findings suggest that close proximity to plant nurseries may be a risk factor for childhood leukemia and that this relationship should be further evaluated.

Associations of Maternal Cell-Phone Use During Pregnancy With Pregnancy Duration and Fetal Growth in 4 Birth Cohorts.

Results from studies evaluating potential effects of prenatal exposure to radio-frequency electromagnetic fields from cell phones on birth outcomes have been inconsistent. Using data on 55,507 pregnant women and their children from Denmark (1996-2002), the Netherlands (2003-2004), Spain (2003-2008), and South Korea (2006-2011), we explored whether maternal cell-phone use was associated with pregnancy duration and fetal growth. On the basis of self-reported number of cell-phone calls per day, exposure was grouped as none, low (referent), intermediate, or high. We examined pregnancy duration (gestational age at birth, preterm/postterm birth), fetal growth (birth weight ratio, small/large size for gestational age), and birth weight variables (birth weight, low/high birth weight) and meta-analyzed cohort-specific estimates. The intermediate exposure group had a higher risk of giving birth at a lower gestational age (hazard ratio = 1.04, 95% confidence interval: 1.01, 1.07), and exposure-response relationships were found for shorter pregnancy duration (P < 0.001) and preterm birth (P = 0.003). We observed no association with fetal growth or birth weight. Maternal cell-phone use during pregnancy may be associated with shorter pregnancy duration and increased risk of preterm birth, but these results should be interpreted with caution, since they may reflect stress during pregnancy or other residual confounding rather than a direct effect of cell-phone exposure.

The sensitivity of reported effects of EMF on childhood leukemia to uncontrolled confounding by residential mobility: a hybrid simulation study and an empirical analysis using CAPS data.

PURPOSE: Residential mobility is considered as a potential source of confounding in studies assessing environmental exposures, including in studies of electromagnetic field (EMF) exposures and childhood leukemia. METHODS: We present a hybrid simulation study where we simulate a synthetic dataset based on an existing study and use it to assess the sensitivity of EMF-leukemia associations to different scenarios of uncontrolled confounding by mobility under two major hypotheses of the infectious etiology of childhood leukemia. We then used the findings to conduct sensitivity analysis and empirically offset the potential bias due to unmeasured mobility in the California Power Line Study dataset. RESULTS: As expected, the stronger the assumed relationship between mobility and exposure and outcome, the greater the potential bias. However, no scenario created a bias strong enough to completely explain away previously observed associations. CONCLUSIONS: We conclude that uncontrolled confounding by residential mobility had some impact on the estimated effect of EMF exposures on childhood leukemia, but that it was unlikely to be the primary explanation behind previously observed largely consistent, but unexplained associations.

Childhood leukemia risk in the California Power Line Study: Magnetic fields versus distance from power lines.

Pooled analyses have suggested a small increased risk of childhood leukemia associated with distance and with exposure to high magnetic fields from power transmission lines. Because magnetic fields are correlated with distance from lines, the question of whether the risk is due to magnetic fields exposure or to some other factor associated with distance from lines is unresolved. We used data from a large records-based case-control study to examine several research questions formulated to disentangle the relationships among magnetic fields, distance from high voltage lines, and childhood leukemia risk. In models examining an interaction between distance and magnetic fields exposure, we found that neither close proximity to high voltage lines alone nor exposure to high calculated fields alone were associated with childhood leukemia risk. Rather, elevated risk was confined to the group that was both very close to high voltage lines (<50 m) and had high calculated fields (≥0.4 µT) (odds ratio 4.06, 95% CI 1.16, 14.3). Further, high calculated fields (≥0.4 µT) that were due solely to lower voltage lines (<200 kV) were not associated with elevated risk; rather, risk was confined to high fields attributable to high voltage lines. Whilst other explanations are possible, our findings argue against magnetic fields as a sole explanation for the association between distance and childhood leukemia and in favor of some other explanation linked to characteristics of power lines.

Proximity to overhead power lines and childhood leukaemia: an international pooled analysis.

BACKGROUND: Although studies have consistently found an association between childhood leukaemia risk and magnetic fields, the associations between childhood leukaemia and distance to overhead power lines have been inconsistent. We pooled data from multiple studies to assess the association with distance and evaluate whether it is due to magnetic fields or other factors associated with distance from lines. METHODS: We present a pooled analysis combining individual-level data (29,049 cases and 68,231 controls) from 11 record-based studies. RESULTS: There was no material association between childhood leukaemia and distance to nearest overhead power line of any voltage. Among children living < 50 m from 200 + kV power lines, the adjusted odds ratio for childhood leukaemia was 1.33 (95% CI: 0.92-1.93). The odds ratio was higher among children diagnosed before age 5 years. There was no association with calculated magnetic fields. Odds ratios remained unchanged with adjustment for potential confounders. CONCLUSIONS: In this first comprehensive pooled analysis of childhood leukaemia and distance to power lines, we found a small and imprecise risk for residences < 50 m of 200 + kV lines that was not explained by high magnetic fields. Reasons for the increased risk, found in this and many other studies, remains to be elucidated.

Residential magnetic fields exposure and childhood leukemia: a population-based case-control study in California.

PURPOSE: Studies have reported an increased risk of childhood leukemia associated with exposure to magnetic fields. We conducted a large records-based case-control study of childhood leukemia risk and exposure to magnetic fields from power lines in California. METHODS: The study included 5,788 childhood leukemia cases (born in and diagnosed in California 1986-2008) matched to population-based controls on age and sex. We calculated magnetic fields at birth addresses using geographic information systems, aerial imagery, historical information on load and phasing, and site visits. RESULTS: Based on unconditional logistic regression controlling for age, sex, race/ethnicity, and socioeconomic status using subjects geocoded to a basic standard of accuracy, we report a slight risk deficit in two intermediate exposure groups and a small excess risk in the highest exposure group (odds ratio of 1.50 (95% confidence interval [0.70, 3.23])). Subgroup and sensitivity analyses as well as matched analyses gave similar results. All estimates had wide confidence intervals. CONCLUSION: Our large, statewide, record-based case-control study of childhood leukemia in California does not in itself provide clear evidence of risk associated with greater exposure to magnetic fields from power lines, but could be viewed as consistent with previous findings of increased risk.

Comparative analyses of studies of childhood leukemia and magnetic fields, radon and gamma radiation.

In this paper we compare the findings of epidemiologic studies of childhood leukemia that examined at least two of ELF magnetic fields and/or distance to power lines, and exposure to radon and gamma radiation or distance to nuclear plants. Many of the methodologic aspects are common to studies of non-ionising (i.e. ELF-MF) and ionising radiation. A systematic search and review of studies with more than one exposure under study identified 33 key and 35 supplementary papers from ten countries that have been included in this review. Examining studies that have looked at several radiation exposures, and comparing similarities and differences for the different types of radiation, through the use of directed acyclic graphs, we evaluate to what extent bias, confounding and other methodological issues might be operating in these studies. We found some indication of bias, although results are not clear cut. There is little evidence that confounding has had a substantial influence on results. Influence of the residential mobility on the study conduct and interpretation is complex and can manifest as a selection bias, confounding, increased measurement error or could also be a potential risk factor. Other factors associated with distance to power lines and to nuclear power plants should be investigated. A more complete and consistent reporting of results in the future studies will allow for a more informative comparison across studies and integration of results.

Childhood leukaemia and distance from power lines in California: a population-based case-control study.

BACKGROUND: Studies have reported an increased risk of childhood leukaemia associated with living near high-voltage electric power transmission lines that extend to distances at which magnetic fields from lines are negligible. We conducted a large records-based case-control study of childhood leukaemia risk in the population living near power lines in California. METHODS: The study included 5788 childhood leukaemia and 3308 central nervous system (CNS) cancer cases (for comparison) born in and diagnosed in California (1986-2008), and matched to population-based controls by age and sex. We geocoded birth address and estimated the distance from residence to transmission lines using geographic information systems, aerial imagery, and, for some residences, site visits. RESULTS: For leukaemia, there was a slight excess of cases within 50 m of a transmission line over 200 kV (odds ratio 1.4, 95% confidence interval 0.7-2.7). There was no evidence of increased risk for distances beyond 50 m, for lower-voltage lines, or for CNS cancers. CONCLUSIONS: Our findings did not clearly support an increased childhood leukaemia risk associated with close proximity (<50 m) to higher voltage lines, but could be consistent with a small increased risk. Reports of increased risk for distances beyond 50 m were not replicated.

Reported associations between asthma and acute lymphoblastic leukemia: insights from a hybrid simulation study.

Numerous studies have reported a protective association between asthma and acute lymphoblastic leukemia (ALL), but the causal structure of this association remains unclear. We present a hybrid simulation to examine the compatibility of this association with uncontrolled confounding by infection or another unmeasured factor. We generated a synthetic cohort using inputs on the interrelations of asthma, ALL, infections, and other suggested risk factors from the literature and the Danish National Birth Cohort. We computed odds ratios (ORs) between asthma and ALL in the synthetic cohort with and without adjustment for infections and other (including unmeasured) confounders. Only if infection was an extremely strong risk factor for asthma (OR of 10) and an extremely strong protective factor against ALL (OR of 0.1) was the asthma-ALL association compatible with the literature (OR of 0.78). Similarly, strong uncontrolled confounding by an unmeasured factor could downwardly bias the asthma-ALL association, but not enough to replicate findings in the literature. This investigation illustrates that the reported protective association between asthma and ALL is unlikely to be entirely due to uncontrolled confounding by infections or an unmeasured confounder alone. Simulation can be used to advance our understanding of risk factors for rare outcomes as demonstrated by this study.

Health-Economics Analyses Applied to ELF Electric and Magnetic Fields.

Extremely low frequency electric and magnetic fields (ELF EMFs) are a common exposure for modern populations. The prevailing public-health protection paradigm is that quantitative exposure limits are based on the established acute effects, whereas the possible chronic effects are considered too uncertain for quantitative limits, but might justify precautionary measures. The choice of precautionary measures can be informed by a health-economics analysis (HEA). We consider four such analyses of precautionary measures that have been conducted at a national or state level in California, the Netherlands, the United Kingdom, and Israel. We describe the context of each analysis, examine how they deal with some of the more significant issues that arise, and present a comparison of the input parameters and assumptions used. The four HEAs are methodologically similar. The most significant qualitative choices that have to be made are what dose-response relationship to assume, what allowance if any to make for uncertainty, and, for a CBA only, what diseases to consider, and all four analyses made similar choices. These analyses suggest that, on the assumptions made, there are some low-cost measures, such as rephasing, that can be applied to transmission in some circumstances and that can be justifiable in cost-benefit terms, but that higher cost measures, such as undergrounding, become unjustifiable. Of the four HEAs, those in the United Kingdom and Israel were influential in determining the country's EMF policy. In California and Netherlands, the HEA may well have informed the debate, but the policy chosen did not stem directly from the HEA.

Methods to Explore Uncertainty and Bias Introduced by Job Exposure Matrices.

Job exposure matrices (JEMs) are used to measure exposures based on information about particular jobs and tasks. JEMs are especially useful when individual exposure data cannot be obtained. Nonetheless, there may be other workplace exposures associated with the study disease that are not measured in available JEMs. When these exposures are also associated with the exposures measured in the JEM, biases due to uncontrolled confounding will be introduced. Furthermore, individual exposures differ from JEM measurements due to differences in job conditions and worker practices. Uncertainty may also be present at the assessor level since exposure information for each job may be imprecise or incomplete. Assigning individuals a fixed exposure determined by the JEM ignores these uncertainty sources. We examine the uncertainty displayed by bias analyses in a study of occupational electric shocks, occupational magnetic fields, and amyotrophic lateral sclerosis.

Occupational Exposure to Electric Shocks and Magnetic Fields and Amyotrophic Lateral Sclerosis in Sweden.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) has been consistently related to "electric occupations," but associations with magnetic field levels were generally weaker than those with electrical occupations. Exposure to electric shock has been suggested as a possible explanation. Furthermore, studies were generally based on mortality or prevalence of ALS, and studies often had limited statistical power. METHODS: Using two electric shock and three magnetic field job-exposure matrices, we evaluated the relationship of occupational magnetic fields, electric shocks, electric occupations, and incident ALS in a large population-based nested case-control study in Sweden. Subanalyses, specified a priori, were performed for subjects by gender and by age (less than and more than 65 years). RESULTS: Overall, we did not observe any associations between occupational magnetic field or electric shock exposure and ALS. For individuals less than 65 years old, high electric shock exposure was associated with an odds ratio (OR) of 1.22 (95% confidence interval [CI] = 1.03, 1.43). The corresponding result for the age group 65 years or older was OR = 0.92 (95% CI = 0.81, 1.05). Results were similar regardless which job exposure matrices, exposure definitions, or cutpoints were used. For electric occupations, ORs were close to unity, regardless of age. For welders, no association was observed overall, although for welders <65 years the OR was 1.52 (95% CI = 1.05, 2.21). CONCLUSIONS: In this very large population-based study based on incident ALS case subjects, we did not confirm previous observations of higher risk of ALS in electrical occupations, and provided only weak support for associations between electric shocks and ALS.

Estimating magnetic fields of homes near transmission lines in the California Power Line Study.

The California Power Line Study is a case-control study investigating the relation between residences near transmission lines and risk of childhood leukemia. It includes 5788 childhood leukemia cases and 5788 matched primary controls born between 1986 and 2007. We describe the methodology for estimating magnetic fields at study residences as well as for characterizing sources of uncertainty in these estimates. Birth residences of study subjects were geocoded and their distances to transmission lines were ascertained. 302 residences were deemed sufficiently close to transmission lines to have non-zero magnetic fields attributable to the lines. These residences were visited and detailed data, describing the physical configuration and dimensions of the lines contributing to the magnetic field at the residence, were collected. Phasing, loading, and directional load flow data for years of birth and diagnosis for each subject as well as for the day of site visit were obtained from utilities when available; when yearly average load for a particular year was not available, extrapolated values based on expert knowledge and prediction models were obtained. These data were used to estimate the magnetic fields at the center, closest and farthest point of each residence. We found good correlation between calculated fields and spot measurements of fields taken on site during visits. Our modeling strategies yielded similar calculated field estimates, and they were in high agreement with utility extrapolations. Phasing was known for over 90% of the lines. Important sources of uncertainty included a lack of information on the precise location of residences located within apartment buildings or other complexes. Our findings suggest that we were able to achieve high specificity in exposure assessment, which is essential for examining the association between distance to or magnetic fields from power lines and childhood leukemia risk.

Cell phone exposures and hearing loss in children in the Danish National Birth Cohort.

BACKGROUND: Children today are exposed to cell phones early in life, and may be the most vulnerable if exposure is harmful to health. We investigated the association between cell phone use and hearing loss in children. METHODS: The Danish National Birth Cohort (DNBC) enrolled pregnant women between 1996 and 2002. Detailed interviews were conducted during gestation, and when the children were 6 months, 18 months and 7 years of age. We used multivariable-adjusted logistic regression, marginal structural models (MSM) with inverse-probability weighting, and doubly robust estimation (DRE) to relate hearing loss at age 18 months to cell phone use at age 7 years, and to investigate cell phone use reported at age 7 in relation to hearing loss at age 7. RESULTS: Our analyses included data from 52 680 children. We observed weak associations between cell phone use and hearing loss at age 7, with odds ratios and 95% confidence intervals from the traditional logistic regression, MSM and DRE models being 1.21 [95% confidence interval [CI] 0.99, 1.46], 1.23 [95% CI 1.01, 1.49] and 1.22 [95% CI 1.00, 1.49], respectively. CONCLUSIONS: Our findings could have been affected by various biases and are not sufficient to conclude that cell phone exposures have an effect on hearing. This is the first large-scale epidemiologic study to investigate this potentially important association among children, and replication of these findings is needed.

Electric shocks at work in Europe: development of a job exposure matrix.

OBJECTIVES: Electric shocks have been suggested as a potential risk factor for neurological disease, in particular for amyotrophic lateral sclerosis. While actual exposure to shocks is difficult to measure, occurrence and variation of electric injuries could serve as an exposure proxy. We assessed risk of electric injury, using occupational accident registries across Europe to develop an electric shock job-exposure-matrix (JEM). MATERIALS AND METHODS: Injury data were obtained from five European countries, and the number of workers per occupation and country from EUROSTAT was compiled at a 3-digit International Standard Classification of Occupations 1988 level. We pooled accident rates across countries with a random effects model and categorised jobs into low, medium and high risk based on the 75th and 90th percentile. We next compared our JEM to a JEM that classified extremely low frequency magnetic field exposure of jobs into low, medium and high. RESULTS: Of 116 job codes, occupations with high potential for electric injury exposure were electrical and electronic equipment mechanics and fitters, building frame workers and finishers, machinery mechanics and fitters, metal moulders and welders, assemblers, mining and construction labourers, metal-products machine operators, ships' decks crews and power production and related plant operators. Agreement between the electrical injury and magnetic field JEM was 67.2%. CONCLUSIONS: Our JEM classifies occupational titles according to risk of electric injury as a proxy for occurrence of electric shocks. In addition to assessing risk potentially arising from electric shocks, this JEM might contribute to disentangling risks from electric injury from those of extremely low frequency magnetic field exposure.

Patterns and predictors of early mortality in incident hemodialysis patients: new insights.

BACKGROUND: Incident hemodialysis patients have the highest mortality in the first several months after starting dialysis treatments. We hypothesized that the patterns and risk factors associated with this early mortality differ from those in later dialysis therapy periods. METHODS: We examined mortality patterns and predictors during the first several months of hemodialysis treatment in 18,707 incident patients since the first week of hemodialysis therapy and estimated the population attributable fractions for selected time periods in the first 24 months. RESULTS: The 18,707 incident hemodialysis patients were 45% women and 54% diabetics. The standardized mortality ratios (95% confidence interval) in the 1st to 3rd month of hemodialysis therapy were 1.81 (1.74-1.88), 1.79 (1.72-1.86), and 1.34 (1.27-1.40), respectively. The standardized mortality ratio reached prevalent mortality only by the 7th month. No survival advantage for African Americans existed in the first 6 months. Patients with low albumin <3.5 g/dl had the highest proportion of infection-related deaths while patients with higher albumin levels had higher cardiovascular deaths including 76% of deaths during the first 3 months. Use of catheter as vascular access and hypoalbuminemia <3.5 g/dl explained 34% (17-54%) and 33% (19-45%) of all deaths in the first 90 days, respectively. CONCLUSIONS: Incident hemodialysis patients have the highest mortality during the first 6 months including 80% higher death risk in the first 2 months. The presence of a central venous catheter and hypoalbuminemia <3.5 g/dl each explain one third of all deaths in the first 90 days.