Meta-analysis of childhood leukaemia : Reports and publications

C. Brabant, G. Honvo, C. Demonceau, E. Tirelli, D. Cataldo, O. Bruyère

Many in vitro and animal studies have been performed to examine the carcinogenic potential of extremely low frequency magnetic fields (ELF-EMF) in rodents and the impact of ELF-MF on DNA, but with conflicting results. Therefore, we are performing a systematic review and meta-analysis to synthetize the scientific studies on the carcinogenic effects of ELF-MF performed with animals and with the comet assay.
We have used Medline, Scopus and Embase to find all the studies that have examined the carcinogenic potential of extremely low frequency magnetic fields. Our search strategy produced 5138 references without the duplicates. We have used Covidence to screen the abstracts and the full texts. 384 abstracts potentially met our inclusion criteria. Two investigators (Dr. Christian Brabant and PhD student Céline Demonceau) have read the 384 full texts to determine which ones met our inclusion criteria. 68 articles with complete data met our inclusion criteria. Three articles have been eliminated because they were at least partially based on the same data. 65 articles have been included in the qualitative synthesis of our work. We are currently performing the data extraction using a standardized data extraction form. The assessment of methodological quality is performed independently by the two reviewers. We are using the SYRCLE’s risk of bias tool to evaluate the methodological quality of the animal studies.

C. Brabant, G. Honvo, C. Demonceau, E. Tirelli, D. Cataldo, O. Bruyère

We have performed a meta-analysis that supports an increased risk of leukemia in children after exposure to extremely low frequency magnetic fields (ELF-MF) and we have published our work in Reviews on Environmental Health (Brabant et al., 2022, Reviews on Environmental Health, doi: 10.1515/reveh-2021-0112). However, the conditions under which ELF-MF represent a risk factor for leukemia are still unclear. For example, the duration of the magnetic field exposure seems to play a critical role for the development of cancers but this is difficult to demonstrate in human studies. Almost all the studies included in our meta-analysis were case-control studies but variables like the magnetic flux density, the frequency and the duration of the magnetic field exposure cannot be manipulated experimentally in these case-control studies. In vitro and animal studies could be relevant to clarify the role of these variables. Since most cancers are initiated by damage to the genome of the cells, several in vitro studies have been conducted to examine the genotoxic effects of magnetic fields on DNA and chromosomal structure. Furthermore, many animal studies have been performed to determine whether exposure to ELF-MF can increase the risk of developing cancer in mammals. Animal models provide the opportunity to investigate the carcinogenetic potential of ELF-MF experimentally and manipulate variables like the magnetic flux density and duration of magnetic field exposure. Nevertheless, there are many discrepancies in this research field. Therefore, we are performing a systematic review and meta-analysis on the carcinogenic effects of ELF-MF based on studies performed with animals and in vitro to clarify the conditions under which ELF-MF can promote cancer and leukemia development. In this report, we describe our protocol, our search strategy and the methods we have used to select studies. Our protocol describes the methods used in our systematic review and has been published in Prospero in May 2022 (Registration number: CRD42022321862). Medline, Scopus and Embase database searches have been performed to identify relevant articles. Using these databases, we have detected all the studies that have examined the carcinogenic potential of ELF-EMF (EMF ≤ 100 Hz). All articles written in English and French will be reviewed. Two independent reviewers (Dr. Christian Brabant and PhD student Céline Demonceau) are currently performing the study selection.

Prof. O. Bruyère, Dr. C. Brabant, Dr. A. Geerinck, Dr. C. Beaudart, Prof. E. Tirelli, Prof. C. Geuzaine

Exposure to magnetic fields and childhood Leukemia: a systematic review and meta-analysis of case-control and cohort studies
Introduction The association between childhood leukemia and extremely low frequency magnetic fields (ELF-MF) generated by power lines and various electric appliances has been studied extensively during the past forty years. However, the conditions under which ELF-MF represent a risk factor for leukemia are still unclear. Therefore, we have performed a systematic review and meta-analysis to clarify the relation between ELF-MF from several sources and childhood leukemia.
Methods We have systematically searched Medline, Scopus, Cochrane Database of Systematic Review and DARE to identify each article that has examined the relationship between ELF-MF and childhood leukemia. We have performed a global meta-analysis that takes into account the different measures used to assess magnetic field exposure: magnetic flux density measurements (< 0.2 μT vs > 0.2 μT), distances between the child’s home and power lines (> 200 m vs < 200 m) and the wire codings defined by Wertheimer et Leeper in 1979 (low current configuration vs high current configuration, cf. Am J Epidemiol 109, 273-84). Moreover, meta-analyses either based on magnetic flux densities, on proximity to power lines or on wire codings have been performed. The association between electric appliances and childhood leukemia has also been examined.
Results Of the 861 references identified, 39 studies have been included in our systematic review. Our global meta-analysis supports an association between childhood leukemia and ELF-MF (21 studies, OR = 1.24; 95% CI 1.06 – 1.46), an association mainly explained by the studies conducted before 2000 (earlier studies: OR = 1.46; 95% CI 1.20 – 1.77 vs later studies: OR = 1.05; 95% CI 0.88 – 1.26). Our meta-analyses based only on magnetic field measurements indicated that the magnetic flux density threshold associated with childhood leukemia is higher than 0.4 μT (13 studies, > 0.4 μT: OR = 1.47; 95% CI 1.12 – 1.92; acute lymphoblastic leukemia alone: 7 studies, > 0.4 μT: OR = 1.88; 95% CI 1.31- 2.70). Lower magnetic fields were not associated with leukemia (14 studies, 0.1 – 0.2 μT: OR = 1.05; 95% CI 0.88 – 1.24; 0.2 – 0.4 μT: OR = 1.05; 95% CI 0.87 – 1.28). Our meta-analyses based only on distances (5 studies) showed that the estimated summary OR for living within 200 m of power lines and within 50 m of power lines were 0.98 (95 % CI 0.85-1.12) and 1.11 (95% CI 0.81, 1.52), respectively. The OR for living within 50 m of power lines and acute lymphoblastic leukemia analyzed separately was 1.44 (95% CI 0.72-2.88). Our meta-analyses based only on wire codings (5 studies) indicated that the estimated summary OR for the very high current configuration was 1.23 (95% CI 0.72-2.10). Finally, the risk of childhood leukemia was increased after exposure to bedside electric blankets (4 studies, OR = 2.75; 95% CI 1.71 – 4.42; 4 studies) and, to a lesser extent, electric clocks (4 studies, OR = 1.27; 95% CI 1.01 – 1.60).
Conclusion Our results indicate that only ELF-MF higher than 0.4 μT increase the risk of developing leukemia in children, very likely acute lymphoblastic leukemia. Magnetic flux density measurements should be performed if children live within 200 m of overhead power lines to guarantee that they are not exposed to ELF-MF higher than 0.4 μT. However, living more than 200 m away from power lines is likely a safe distance for children not associated with a higher leukemia risk. Children should not use electric blankets that generate magnetic fields higher than 0.4 μT. Finally, “bedside” electric clocks should be located at least one meter away from the bed of the child, because the magnetic flux density generated by electric clocks is lower than 0.4 μT at this distance.

The Research Unit in Public Health, Epidemiology and Health Economics has extensive expertise in conducting systematic reviews and meta-analyses. This research unit is composed of twenty researchers active in various fields ranging from pregnant women’s health to the well-being of residents of nursing homes and including the epidemiological evaluation of health determinants.

>>> Publications on Public Health

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PRISMA website: http://www.bmj.com/content/339/bmj.b2700

Rabenda V, Beaudart C, Bruyère, O (2017) Il n’est jamais trop tard pour apprendre à (bien) lire … La Méta-Analyse. Ortho-Rhumato 15: 27-32.

• Meta-analysis of childhood leukaemia: Objectives
• Childhood leukaemia studies

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