Frank J, Melnick R, Moskowitz J, on behalf of the International Commission on the Biological Effects of Electromagnetic Fields (ICBE-EMF). A critical appraisal of the WHO 2024 systematic review of the effects of RF-EMF exposure on tinnitus, migraine/headache, and non-specific symptoms. Reviews on Environmental Health. 2024. doi: 10.1515/reveh-2024-0069. Open access paper:
We examined one of the first published of the several systematic reviews being part of WHO’s renewed initiative to assess the evidence of associations between man-made radiofrequency electromagnetic radiation (RF-EMF) and adverse health effects in humans. The examined review addresses experimental studies of pregnancy and birth outcomes in non-human mammals. The review claims that the analyzed data did not provide conclusions certain enough to inform decisions at a regulatory level. Our objective was to assess the quality of this systematic review and evaluate the relevance of its conclusions to pregnant women and their offspring. The quality and relevance were checked on the review’s own premises: e.g., we did not question the selection of papers, nor the chosen statistical methods. While the WHO systematic review presents itself as thorough, scientific, and relevant to human health, we identified numerous issues rendering the WHO review irrelevant and severely flawed. All flaws found skew the results in support of the review’s conclusion that there is no conclusive evidence for nonthermal effects. We show that the underlying data, when relevant studies are cited correctly, support the opposite conclusion: There are clear indications of detrimental nonthermal effects from RF-EMF exposure. The many identified flaws uncover a pattern of systematic skewedness aiming for uncertainty hidden behind complex scientific rigor. The skewed methodology and low quality of this review is highly concerning, as it threatens to undermine the trustworthiness and professionalism of the WHO in the area of human health hazards from man-made RF-EMF.
EHC2023 is a systematic review, including meta-analyses as to 14 different endpoints related to pregnancy and birth outcomes, based on selected experimental laboratory studies on effects on pregnancy and birth from RF-EMF exposure of non-human mammals. EHC2023 is a massive work, carried out under the banner of objectivity, thoroughness and scientific rigor by the use of statistical refinement and technicalities, arguably in order to reach a sound and solid conclusion. The final conclusion of the report is (EHC2023, p. 31, bold added):
In spite of the large number of studies collected, our systematic review could only partly answer the PECO question and did not provide conclusions certain enough to inform decisions at a regulatory level, but it can be considered a solid starting point to direct future research on this topic.
Our objective with this paper is, contrary to this conclusion, to document as clearly as possible, that the conclusion of the EHC2023 review is far from supported, but contradicted, by the scientific literature analyzed by its authors. What seems to be supportive, appears so due to the many irrelevant studies included, to important methodological choices not being documented or discussed, and due to significant errors and flaws. By our stepwise testing, we found that with flaws corrected, the original data and the EHC2023 methodology led to an opposite conclusion: Evidence of hazard from subthermal exposure to RF-EMF is well underpinned by its reviewed literature."
"The authors of EHC2023 considered 88 papers to be relevant and of sufficient quality for their review. Parts of our analysis have been carried out using the data from all these 88 papers."
"For a detailed quality assessment of the performed calculations in
EHC2023, we chose the procedure for doing calculations of the pooled
effects size based on Cohen’s d and its confidence intervals used for
nine of the 14 of the endpoints. To make the work manageable, we chose
the endpoint with the most studies reviewed: the “fetal weight” endpoint
(EHC2023 Figure 6), based on 44 papers, assuming this would be
representative for the EHC2023 meta-analyses. The assessment was done by
closely reviewing 43 of these papers and how they are handled in
EHC2023."
"Our main result: many flaws in EHC2023, all contributing to the conclusion “no conclusion can be drawn”
"More than half the studies included in EHC2023 are irrelevant for humans protected by IEEE/ICES and ICNIRP guidelines, making the results irrelevant"
"For the EHC2023 review to be relevant for the assessment of hazards to pregnant women and their fetuses in everyday situations, the exposure conditions in the studies reviewed should mimic – or at least to a reasonable extent be transferable to – everyday situations pregnant women will encounter when in an environment with (manmade) RF-EMFs/wireless technology. This means that only studies with “Low nonthermal SAR” are relevant." ... "To be considered relevant, a study should therefore use subthermal exposure conditions, and over several days. We found that over half the studies selected for the EHC2023 review do not meet these criteria: They are experiments with irrelevant exposure conditions."
The Systematic Review (SR) used a "A pooled effect size open for interpretation" ... "The equations used for relative weighting of the studies have the potential of skewing the results in any direction, and are neither documented nor discussed"
"The Risk of Bias (RoB) assessment of EHC2023 is highly biased towards thermal studies" .... Hence, by favoring thermal studies, the RoB analysis is also skewed toward favoring old studies, while discrediting modern studies."... we see that of the total papers reviewed, the majority is published before 2001 (50 vs. 38 papers). Of papers published 1975–2000, 22 % were rated High Concern for Risk of Bias (HC), while 52 % of the newer studies (2001–2021) are rated HC. We also see that the newer papers are almost all nonthermal, and as much as more than half of them are rated (HC), while for older studies, published before 2001, a majority of the papers are thermal, and that more nonthermal than thermal are rated HC." ... " The overall conclusion from this analysis is that the RoB analysis is biased, in particular as it downgrades modern studies of nonthermal effects due to RoB questions unfit for quality assessment of such studies." ... The biased RoB analysis of the EHC2023 has the overall effect of increasing the number of thermal studies used in the meta-analysis – thereby reducing relevance, increasing heterogeneity and adding uncertainty, and is then further used in a biased and flawed line of logic to claim that the resulting small pooled effect sizes then found are uncertain."
"Our in-depth analysis of the “fetal weight” meta-analysis reveals misciting and miscalculation behind the pooled effect size" ... "
"We found, in total nine studies (27 %) cited erroneously or with unjustified divergences, and “cherry picking” experiments from 12 studies (36 %). In some cases, several flaws applied to the same study. In total we found flawed handling of 19 (58 %) of the 33 nonthermal studies analyzed in EHC2023 for the fetal weight endpoint....All of the flaws described skew the results in the direction of a lower pooled effect size and/or higher uncertainty. The flaws make the meta-analysis useless, unless for just that purpose."
"Misreporting of significant detrimental effects found in reviewed papers due to choice of endpoints not used in modern, nonthermal studies" ... we limited our analysis to the 28 relevant, nonthermal papers selected for the EHC2023 fetal weight meta-analysis. We found that significant detrimental effects were not reported, or misreported in various ways: Of the 28 papers, eight report no effects found. Of the remaining 20 papers, significant results are reported in 13 papers (65 %) but omitted in EHC2023 Table 3 (A very few of these omitted effects are superficially mentioned elsewhere in EHC2023)....Only for the remaining seven of the 28 nonthermal papers are all effects reported in EHC2023 Table 3, although they are still downplayed in most cases." ... "Using biochemical parameters as endpoints is part of modern approaches to assess health risks from subthermal exposure. Since such effects are relevant to all mammals, they offer better assessments also as to human health risks when experiments are carried out on animals. By disregarding findings at such endpoints and downgrading such modern approaches in their RoB assessment, the authors of EHC2023 favor old, irrelevant studies. Also, by their endpoints chosen, they effectively eliminate the huge majority of modern research observing physiological changes clearly caused from subthermal exposures [8]."
"Relevant correlated factors not taken into account" ... "EHC2023 checks for fetal weight reduction as an effect from RF-EMF exposure. However, the well-known inverse correlation between fetal weight and litter size has not been taken into account by the EHC2023 authors" ... " It Is alarming that the two single endpoints" [fetal weight and brain weight] "in EHC2023 that we checked, are so “saturated” with serious flaws, rendering the meta-analyses useless, although both endpoints should have been rather simple to evaluate."
"Sub-group analyses of non-thermal effects not made, although prescribed in protocol" ... "The protocol for EHC2023 specifies that sub-group analyses should be made for subthermal RF-EMF exposure – for parameters such as frequency, duration and modulation (the protocol, p. 9). EHC2023 deviates from its protocol by only doing sub-group analysis for animal species, SAR-values (SAR<0.1, 0.1≤SAR<5, SAR≥5 W/kg) and animal core temperature increase." ... "Leaving out sub-group analyses for frequency, duration and modulation means missed opportunities to spot effects on health from subthermal exposure and their possible causes, as such analyses would do so better than sub-groups for averaged SAR values from heterogeneous experiments."
"EHC2023 claims the effects found stem from the thermal studies. But when corrected, the strongest effects are in the nonthermal" ... " This result shows that of all the nonthermal studies in the EHC2023 fetal weight analysis, those with the lowest SAR show the highest reductions of fetal weight and therefore contribute the most to the increase in pooled effect size for the “fetal weight” endpoint. It is also significantly higher than the pooled effect size presented in EHC2023 for the thermal, LSC studies (1.01 compared to 0.51)."
"Discussion: how may all the flaws in EHC2023 be explained?" ... "EHC2023’s many flaws strip the study of legitimacy and the results of any credibility or trustworthiness, even when evaluated on the premises of the so-called “thermal only tradition”....On the top of this, the authors of EHC2023 falsely claim that all effects found be caused by results of experiments with thermal exposure conditions and therefore, falsely inferring that realistic conditions are harmless....A substantial part of the flaws may well be explained as resulting from all the authors of the review belonging to “the thermal only tradition:"
"The WHO EHC undertaking is organized by a group of 21 experts selected by WHO’s office “The International EMF Project” (TIEP). All but three of these experts are either affiliated with the guidelines issuing foundation ICNIRP [9] or connected through co-authorships linked to a tiny self-referencing network of authors mainly affiliated with ICNIRP and IEEE/ICES or both [10]. Both ICNIRP and IEEE/ICES defend exposure limits based on tissue overheating as sufficient for EMF protection, the thermal only tradition. ICNIRP is closely connected to TIEP. IEEE/ICES issues guidelines for RF-EMF used in USA, in co-ordination with ICNIRP." // ... The 21 experts selected the authors for the protocol and EHC2023. All these experts are proponents of the thermal only view."
Conclusions
"The rigorous protocol and extensive analyses presented in EHC2023 and its protocol, convey an impression of serious science, credibility, and reliability. However, we have shown that this is not the case.
We found EHC2023 to be a massive work with a rigorous and complex protocol and extensive and complex statistical analyses. A consequence of the complexity is that it can be assumed that no average reader – not even professionals – will check the results of the review, if not for other reasons, because of the major effort needed. Thereby, scientific exchange, debate and control is impeded and reduced to a matter of trust.
We had the opportunity to spend time on an in-depth analysis of representative parts of EHC2023 to assess its quality based to the extent possible on the review’s own premises – that is, independent of our opinion about the professional premises chosen.
We cannot prove that the flaws and omissions are deliberately added to reach wanted conclusions, as we have next to no information about the authors, neither of the process behind the authoring EHC2023 or its protocol. Anyhow, and whatever the cause, the EHC2023 review is clearly of such a low quality, also when evaluated within the thermal only tradition, that its conclusions are without scientific value.
Our findings show that the conclusion of EHC2023 is not well-founded, and therefore the final conclusions of EHC2023 that no conclusion can be drawn that are (EHC2023, p. 31) “certain enough to inform decisions at a regulatory level” cannot be trusted. The errors, flaws and omissions are grave enough to render EHC2023 unscientific and unethical, and it should therefore be retracted.
As it now stands, the conclusion of ECH2023 stands out as what appears to be a manufactured argument for current regulations being adequate to protect the health of human mothers and their offspring. Manipulating and skewing research results in order to manufacture a wanted conclusion is a well-known strategy to avoid stricter regulations [11], [12], [13], [14], [15]. Further investigations and better sources would be needed to prove such an assault on humanity to be the case as to EHC2023.
EHC2023 is just one of several studies commissioned by the same organization (WHO EHC no. 137) and states clearly that consistency has been assured in the protocols for these studies. Our analysis of EHC2023 may in this view be seen as a case study of the results of the entire WHO EHC undertaking: Since many of our concerns are related to core elements of the protocol, there are good reasons also to question the quality of all present and forthcoming results being part of the WHO EHC undertaking unless a thorough revision of its course is made."
Open access paper: https://www.degruyter.com/document/doi/10.1515/reveh-2024-0089/html
Microwave News, Dec 15, 2022
https://microwavenews.com/
World Health Organization, Dec 15, 2022
To download the WHO public notice: https://cdn.who.int/media/
Overview
In order to enhance its management of conflicts of interest as well as strengthen public trust and transparency in connection with WHO meetings and activities involving the provision of technical/normative advice, the names and brief biographies of individuals (“Published Information”) being considered for participation in a WHO-convened Guideline Development Group are disclosed for public notice and comment.
The Published Information is provided by the experts themselves and is the sole responsibility of the individuals concerned. WHO is not responsible for the accuracy, veracity and completeness of the Published Information provided. Furthermore, in no event will WHO be responsible or liable for damages in relation to the use of, and reliance upon, the Published Information.
The comments received by WHO through the public notice and comment process are treated confidentially. Any comments should be sent to this e-mail address: emfproject@who.int. Comments brought to the attention of WHO through this process are an integral component of WHO’s conflict of interest assessment process and are carefully reviewed. WHO reserves the right to discuss information received through this process with the relevant expert and disclose to this expert the name and affiliation of the provider of such information. Upon review and assessment of the information received through this process, WHO, in its sole discretion, may take appropriate management action in accordance with its policies.
Guideline Development Groups provide technical and/or normative advice and recommendations to WHO. Participation in a Guideline Development Group convened by WHO does not necessarily mean that the views expressed by the expert concerned are shared by WHO and/or represent the decisions or stated policy of WHO.
The list of participating experts, a summary of relevant interests disclosed by such experts, and any appropriate mitigation measures taken by WHO relating to the management of conflicts of interests, will be reported publicly in accordance with WHO policies.
https://www.who.int/
WHO Headquarters, Geneva, Switzerland
Expertise: Epidemiologist
Qualifications: MSc, MD, PhD
Current position: Professor of Epidemiology
Institutional affiliation: Leibniz-Institute for Prevention Research and Epidemiology-BIPS (Bremen, Germany) and University of Bremen (Germany)
Expertise: Occupational Physician by training, specialized in systematic reviews and guidelines of environmental and occupational health issues
Qualifications: MD, PhD
Current position: Senior Researcher
Institutional affiliation: University Medical Centers Amsterdam, Public and Occupational Health Department, Netherlands; Cochrane Work
Expertise: Clinician - Neurosurgeon
Qualifications: MD, PhD
Current position: Professor of Neurosurgery
Institutional affiliation: Ajou University School of Medicine, Ajou University Hospital, Korea
Qualifications: MD, PhD (epidemiology)
Current position: Professor of epidemiology
Institutional affiliation: Tampere University, Tampere, Finland
Expertise: Epidemiologist
Qualifications: PhD
Current position: Professor of Epidemiology, Head Radiation Programme
Institutional affiliation: Barcelona Institute of Global Health (ISGlobal), Spain
Expertise: researcher, background in physics and medicine; expertise in human and vivo studies, focused on the nervous and the endocrine system, and recently on thermal regulation and perception
Qualifications: MD, PhD, Docent
Current position: Senior scientist, end February 28th, 2023
Institutional affiliation: National Institute of Industrial Environment and Risks, under the umbrella of the Environment Ministry (Ecology), France
Expertise: Researcher
Institutional affiliation: Rosemead School of Psychology, Biola University, USA
Expertise: Bioelectromagnetics, EMF computational exposure assessment
Qualifications: PhD (Bioengineering)
Current position: Research Scientist
Institutional affiliation: CNR – National Research Council, Institute of Electronics, Information Engineering and Telecommunications (IEIIT), Italy
Expertise: Clinician and Researcher
Qualifications: MD, PhD
Current positions: Senior Consultant in Neuroradiology, Professor of Epidemiology
Institutional affiliation: Department of Neuroradiology, Karolinska University Hospital, Institute of Environmental Medicine, Karolinska Institute, Sweden
Expertise: Epidemiologist/exposure scientist
Qualifications: PhD, MSc
Current position: Full Professor
Institutional affiliation: Utrecht University, Institute for Risk Assessment Sciences, Netherlands
Expertise: Researcher
Current position: Assistant Professor, Department of Electrical Engineering and Automation
Institutional affiliation: Aalto University, Finland
Expertise: Researcher
Qualifications: DVM, PhD
Current position: Principal Researcher
Institutional affiliation: Korea Institute of Radiological & Medical Sciences
Expertise: Research Scientist
Qualifications: PhD
Current position: Director, Radiation Research and Advice
Institutional affiliation: Australian Radiation Protection and Nuclear Safety Agency (ARPANSA)
Expertise: Thermal Physiology; Integrative Human Physiology
Qualifications: PhD
Current Position: Research Scientist; Adjunct Professor
Institutional Affiliation: Non-Ionizing Radiation Health Sciences Division, Consumer and Clinical Radiation
Protection Bureau, Health Canada; School of Human Kinetics, Faculty of Health Sciences, University of Ottawa
Expertise: occupational medicine, occupational epidemiology
Qualifications: PhD, MD
Current position: Occupational Physician, Post-Doc Researcher, Secretary of the ICOH Scientific Committee “Radiation and Work”
Institutional affiliation: a) Department of biomedical, metabolic and Neural Science, University of Modena & Reggio emilia, Italy; b) International Commission on Occupational Health (ICOH) – Scientific Committee “Radiation and Work”
Expertise: public health physician, clinical lecturer, environmental epidemiologist
Qualifications: MD, PhD
Current position: Chief consultant; senior lecturer; Caldwell Research Fellow, NCEPH, Australian National University.
Institutional affiliation: University of Calabar, Nigeria; National Centre for Epidemiology and Population Health, Australian National University.
Expertise: Epidemiologist
Current position: Professor of Epidemiology
Institutional affiliation: Brown University School of Public Health, Rhode Island, USA
Expertise: Biologist
Qualifications: Diploma, Dr. rer. nat. (PhD in Science)
Current position: Senior Scientist, Competence Center for Electromagnetic fields
Institutional affiliation: German Federal Office for Radiation Protection (BfS)
Expertise: in vivo experiment
Qualifications: PhD, MPH
Current position: Director
Institutional affiliation: National Institute of Public Health, Japan
Expertise: RF EMF exposure expert
Qualifications: Doctor of Engineering
Current position: Director
Institutional affiliation: Electromagnetic Compatibility Laboratory, Electromagnetic Standards Research Center, Radio Research Institute, National Institute of Information and Communications Technology, Japan
Expertise: Exposure expert
Qualifications: PhD
Current position: Professorate senior engineer
Institutional affiliation: China Academy of Information and Communications Technology
"A recent study found that tools that use an overall risk of bias rating may reduce the available evidence to evaluate the health effects of chemical exposures by excluding studies based on only one methodological or reporting limitation, leading to an inaccurate conclusion [136, 137]. These findings are consistent with the 2021 NAS report on the IRIS Program, which found, based on data from recent IRIS assessments that used such a risk of bias approach, that the proportion of human studies excluded from further consideration ranged from 0 to 50 percent for human epidemiological studies, and 0 to 41.5 percent for animal studies [70]. Recognizing this concern, two separate 2021 NAS reports recommended that “study evaluation ratings should not be used to exclude studies” [70], “Do not exclude studies based on risk of bias, study quality, or reporting quality” and “Do not use numeric scores to evaluate studies; replace them with domain-based scoring as is done in the tools used in the Navigation Guide and OHAT” [124].
To avoid discarding valuable information, risk of bias assessments should be performed for each individual study, and the evidence base should then be assessed in its entirety. This allows an exploration of the potential effects of various biases. The 2021 NAS report makes this point: “While there is inevitably variation in the internal validity and risk of bias across individual studies, it is standard practice to include all studies, even the studies with a high risk of bias into the evidence synthesis… Once a study is determined to be eligible, the study could be included in the synthesis and the risk-of-bias assessment and its limitations accounted for in any qualitative or quantitative synthesis… In the synthesis step, low-quality studies may be excluded as a sensitivity analysis, but it is inappropriate to leave them out of synthesis completely” [124]." (4)
"The extent to which particular scientific results constitute progress in knowledge or contribute to societal well-being is often contested. This is especially the case when scientific findings are uncertain or controversial and when they can be interpreted to support controversial policy choices....Assessing science, no matter how rigorous the methods that may be used, is ultimately a matter of interpretation. The possibility of competing interpretations of evidence is ever-present when using science indicators or applying any other analytic method for measuring the progress and impact of science." (5)
(1) National Toxicology Program. Handbook for Conducting Systematic Reviews for Health Effects Evaluations. https://ntp.niehs.nih.gov/whatwestudy/assessments/ noncancer/handbook/index.html
(2) National Toxicology Program. Handbook for Conducting a Literature-Based Health Assessment Using OHAT Approach for Systematic Review and Evidence Integration (March 4, 2019): https://ntp.niehs.nih.gov/ntp/ohat/pubs/handbookmarch2019_ 508.pdf
(3) National Toxicology Program. 2019 OHAT Handbook Update and Clarification Summary Document (March 4, 2019). https://ntp.niehs.nih.gov/ntp/ohat/pubs/ handbookclarificationmarch2019 _508.pdf
(4) Chartres N, Sass JB, Gee D, Bălan SA, Birnbaum L, Cogliano VJ, Cooper C, Fedinick KP, Harrison RM, Kolossa-Gehring M, Mandrioli D, Mitchell MA, Norris SL, Portier CJ, Straif K, Vermeire T. Conducting evaluations of evidence that are transparent, timely and can lead to health-protective actions. Environ Health. 2022 Dec 5;21(1):123. doi: 10.1186/s12940-022-00926-z. https://ehjournal.biomedcentral.com/articles/10.1186/s12940-022-00926-z
(5) National Research Council. 2007. A Strategy for Assessing Science: Behavioral and Social Research on Aging. Washington, DC: The National Academies Press. https://doi.org/10.17226/11788
.
Research Protocols for Radiofrequency EHC Reviews;
Susanna Lagorio, Maria Blettner, Dan Baaken, Maria Feychting, Ken Karipidis, Tom Loney, Nicola Orsini, Martin Röösli, Marilia Silva Paulo, Mark Elwood. The effect of exposure to radiofrequency fields on cancer risk in the general and working population: A protocol for a systematic review of human observational studies. Environ Int. 2021 Aug 22;157:106828. doi: 10.1016/j.envint.2021.106828.
• A systematic review of all subject-relevant epidemiological studies is now needed.
• A detailed protocol ensures the review's transparency, utility and credibility.
• Original study validity will be evaluated with a customized OHAT risk of bias tool.
• Internal coherence and external plausibility will inform conclusions.
Abstract
Background: The World Health Organization (WHO) has an ongoing project to assess potential health effects of exposure to radiofrequency electromagnetic fields (RF-EMF) in the general and working population. Here we present the protocol for a systematic review of the scientific literature on cancer hazards from exposure to RF-EMF in humans, commissioned by the WHO as part of that project.
Objective: To assess the quality and strength of the evidence provided by human observational studies for a causal association between exposure to RF-EMF and risk of neoplastic diseases.
Eligibility criteria: We will include cohort and case-control studies investigating neoplasia risks in relation to three types of exposure to RF-EMF: near-field, head-localized, exposure from wireless phone use (SR-A); far-field, whole body, environmental exposure from fixed-site transmitters (SR-B); near/far-field occupational exposures from use of handheld transceivers or RF-emitting equipment in the workplace (SR-C). While no restriction on tumour type will be applied, we will focus on selected neoplasms of the central nervous system (brain, meninges, pituitary gland, acoustic nerve) and salivary gland tumours (SR-A); brain tumours and leukaemias (SR-B, SR-C).
Information sources: Eligible studies will be identified through Medline, Embase, and EMF-Portal.
Risk-of-bias assessment: We will use a tailored version of the OHAT's tool to evaluate the study's internal validity.
Data synthesis: We will consider separately studies on different tumours, neoplasm-specific risks from different exposure sources, and a given exposure-outcome pair in adults and children. When a quantitative synthesis of findings can be envisaged, the main aims of the meta-analysis will be to assess the strength of association and the shape of the exposure-response relationship; to quantify the degree of heterogeneity across studies; and explore the sources of inconsistency (if any). When a meta-analysis is judged inappropriate, we will perform a narrative synthesis, complemented by a structured tabulation of results and appropriate visual displays.
Evidence assessment: Confidence in evidence will be assessed in line with the GRADE approach.
Funding: This project is supported by the World Health Organization. Co-financing was provided by the New Zealand Ministry of Health; the Istituto Superiore di Sanità in its capacity as a WHO Collaborating Centre for Radiation and Health; ARPANSA as a WHO Collaborating Centre for Radiation Protection.
Registration: PROSPERO CRD42021236798.
Ryan P.W. Kenny, Evelyn Barron Millar, Adenike Adesanya, Catherine Richmond, Fiona Beyer, Carolina Calderon, Judith Rankin, Mireille Toledano, Maria Feychting, Mark S Pearce, Dawn Craig, Fiona Pearson. The effects of radiofrequency exposure on male fertility and adverse reproductive outcomes: A protocol for two systematic reviews of human observational studies with meta-analysis. Environ Int. 158, 2022, 106968. doi: 10.1016/j.envint.2021.106968.
Abstract
Background The World Health Organization (WHO) is bringing together evidence on radiofrequency electromagnetic field (RF-EMF) exposure in relation to health outcomes, previously identified as priorities for evaluation by experts in the field, to inform exposure guidelines. A suite of systematic reviews are being undertaken by a network of topic experts and methodologists in order to collect, assess and synthesise data relevant to these guidelines. Here, we present the protocol for the systematic review on the effect of exposure to RF on adverse reproductive outcomes (human observational studies), also referred to as Systematic Review (SR) 3 within the series of systematic reviews currently being commissioned.
Objectives Following the WHO handbook for guideline development and the COSTER conduct guidelines, we will systematically review the effect of RF-EMF exposure on both male fertility (SR3A) and adverse pregnancy outcomes (SR3B) in human observational studies. Herein we adhere to the PRISMA-P reporting guidelines.
Data sources We will conduct a broad search for potentially relevant records relevant for both reviews within the following bibliographic databases: MEDLINE; Embase; and EMF Portal. We will also conduct searches of grey literature through relevant databases and organisational websites. RF-EMF experts will also be consulted. We will hand search citation and reference lists of included study records.
Study eligibility criteria We will include quantitative human observational studies on the effect of RF-EMF exposure: (in SR3A) in adult male participants on infertility, sperm morphology, concentration or total sperm count or motility; and (in SR3B) in preconception adults or pregnant women on preterm birth, small for gestational age (associated with intrauterine growth restriction), miscarriage, stillbirth and congenital anomalies.
Study appraisal and synthesis methods Titles, abstracts and then full texts will be screened in blinded duplicate against eligibility criteria with input from a third reviewer as required. Data extraction from included studies will be completed by two reviewers as will risk of bias assessment using the Office of Health Assessment and Translation (OHAT) tool. If appropriate we will undertake meta-analysis to pool effect measures and explore heterogeneity using sub-group analyses or meta-regression as feasible. We will conduct sensitivity analysis to assess the impact of any assumptions made throughout the review process. The OHAT methodology, based on the GRADE guidelines for evidence assessment, will be used to evaluate the certainty of evidence per outcome and to conclude the level of evidence of a health effect.
Conclusion This manuscript details the protocols for two systematic reviews. The aims of publishing details of both protocols are to: pre-specify their scope and methods; reduce the impact of reviewer bias; promote transparency and replicability; and improve the review process.
Prospero registration CRD42021265401 (SR3A), CRD42021266268 (SR3B).
Declaration of Competing Interest
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Maria Feychting has a permanent position as Professor of Epidemiology at Karolinska Institutet, Stockholm Sweden since 2005. She has served as advisor to a number of national and international public advisory and research steering groups concerning the potential health effects of exposure to non-ionizing radiation, including the WHO (ongoing), Public Health England Advisory Group on Non-ionising Radiation - AGNIR (2009–2017), the Norwegian Public Health Institute (2010–2012), the Swedish Council for Working Life and Social Research (2003–2012), the Swedish Radiation Safety Authority’s independent scientific expert group on electromagnetic fields (2003–2011). She was member of the International Commission on Non-Ionizing Radiation Protection (ICNIRP), an independent body setting guidelines for non-ionizing radiation protection (2008–May 2020), and vice chairman of the Commission (May 2016–May 2020).
Mireille Toledano has been involved in funded research assessing mobile phone and other wireless technologies usage on health outcomes. The SCAMP (study cognition adolescents and mobile phones) prospective cohort study which is currently ongoing (2015–2021). The COSMOS (cohort study of mobile phone use and health) a longitudinal cohort study which is completed (2019).
Open access paper: https://www.sciencedirect.com/science/article/pii/S0160412021005936
• Male infertility and adverse pregnancy outcomes are relevant human health problems.
• Radiofrequency electromagnetic fields are widespread in the human environment.
• A link between radiofrequency and adverse reproductive outcomes is controversial.
• This is the protocol of WHO-funded systematic review and meta-analysis on this issue.
Abstract
Background Radiofrequency Electromagnetic Fields (RF-EMF) at environmental level have been reported to induce adverse effects on the male reproductive system and developing embryos. However, despite the number of experiments conducted since the 1970s, the diversity of testing approaches and exposure conditions, inconsistencies among results, and dosimetric flaws have not yet permitted a solid assessment of the relationship between RF-EMF exposure and such effects, warranting a more systematic and methodologically rigorous approach to the evaluation of available data.
Objectives This study aims at evaluating the effects of RF-EMF exposure on male fertility and pregnancy outcomes by a systematic review (SR) of experimental studies, conducted in compliance with international guidelines. The evidence will be organized into three streams: 1) Studies evaluating the impact of RF-EMF on the male reproductive system of experimental mammals; 2) studies evaluating the impact of RF-EMF on human sperm exposed in vitro; 3) studies evaluating the impact of RF-EMF on adverse pregnancy, birth outcomes and delayed effects in experimental mammals exposed in utero.
Study eligibility and criteria Eligible studies will include peer-reviewed articles reporting of original results about effects of controlled exposures to RF-EMF in the frequency range 100 kHz–300 GHz on the selected outcomes without any language or year-of-publication restrictions. Eligible studies will be retrieved by calibrated search strings applied to three electronic databases, PubMed, Scopus and EMF Portal and by manual search of the list of references of included papers and published reviews.
Study appraisal and synthesis method The internal validity of the studies will be evaluated using the Risk of Bias (RoB) Rating Tool developed by National Toxicology Program/Office of Health Assessment and Translation (NTP/OHAT) integrated with input from the SYRCLE RoB tool. Given sufficient commensurate data, meta-analyses will be performed, otherwise narrative syntheses will be produced. Finally, the certainty of the effects of RF-EMF exposure on male fertility and pregnancy and birth outcomes will be established following GRADE.
Funding The study is financially supported by the World Health Organization.
Registration OSF Registration DOI https://doi.org/10.17605/OSF.
• This protocol outlines the steps required for a systematic review of the effect of long-term radiofrequency exposure on cognition in human observational studies.
Abstract
Background: The long term effects of exposure to radiofrequency (RF) electromagnetic fields (EMF) for frequencies from 100 kHz to 300 GHz on cognitive performance are best assessed using observational studies. In recent years, the use of mobile (cell) phones has been the main source of RF EMF exposure to the brain, although other sources of exposure may be significant. Cognitive function includes various mental and psychological abilities, which can be measured in a range of domains, such as learning, memory, reasoning, problem solving, decision making and attention. Although effects on cognitive function may be most evident later in life, in the experimental setting acute and immediate effects can only be studied. Observational studies are needed when effects are observed after months or years following short or long-term exposure. The importance of the effects of exposure on children has also been recently identified.
Objectives: To assess the long-term effects of RF EMF local and whole-body exposure compared to no or a lower level of exposure on indicators of cognition, including complex attention, executive function, learning and memory, perceptual motor ability and social cognition, but excluding cognitive effects caused by neurodegenerative diseases or neurodevelopmental disorders, and to assess if there is evidence of a dose response relationship.
Study eligibility and criteria: We will include observational studies that have evaluated cognitive effects of RF energy including a comparator group with a different level of exposure. Studies must report at least one validated measure of cognitive function, including global or domain specific measures, or cognitive impairment, with a minimum follow-up of 6 months. Cohort or case-control studies published in the peer review literature in any language are eligible. We will exclude cross-sectional studies and any that only report brain structure or biomarkers.
Study appraisal and synthesis method: We will conduct searches of PubMed, Embase, PsycINFO and the EMF-Portal. At least two authors will independently screen the titles/abstracts of all records, with any conflicts resolved by a third reviewer. Full-text screening will also be conducted independently by two authors with conflicts resolved by consensus. Data will be extracted from the studies included, such as identifiers and characteristics of the study design, exposure and comparator groups, participants, outcomes assessed and results. Risk of bias will be assessed with the Office of Health Assessment and Translation (OHAT) tool. We will conduct a meta-analysis of similar studies with a random effects model in STATA or similar software, if two or more studies are available for a given exposure-outcome combination. Confidence in the body evidence will be judged using GRADE methods as adapted by OHAT for reviews of environmental exposures.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Blanka Pophof, Jacob Burns, Heidi Danker-Hopfe, Hans Dorn, Cornelia Egblomassé-Roidl, Torsten Eggert, Kateryna Fuks, Bernd Henschenmacher, Jens Kuhne, Cornelia Sauter, Gernot Schmid. The effect of exposure to radiofrequency electromagnetic fields on cognitive performance in human experimental studies: A protocol for a systematic review. Environ Int. 2021 Jul 29;157:106783. doi: 10.1016/j.envint.2021.106783.
Abstract
Background: The World Health Organization (WHO) is currently assessing the potential health effects of exposure to radiofrequency electromagnetic fields (RF-EMFs) in the general and working population. Related to one such health effect, there is a concern that RF-EMFs may affect cognitive performance in humans. The systematic review (SR) aims to identify, summarize and synthesize the evidence base related to this question. Here, we present the protocol for the planned SR.
Objectives: The main objective is to present a protocol for a SR which will evaluate the associations between short-term exposure to RF-EMFs and cognitive performance in human experimental studies.
Data sources: We will search the following databases: PubMed, Embase, Web of Science, Scopus, and the EMF-Portal. The reference lists of included studies and retrieved review articles will be manually searched.
Study eligibility and criteria: We will include randomized human experimental studies that assess the effects of RF-EMFs on cognitive performance compared to no exposure or lower exposure. We will include peer-reviewed articles of any publication date in any language that report primary data.
Data extraction and analysis: Data will be extracted according to a pre-defined set of forms developed and piloted by the review author team. To assess the risk of bias, we will apply the Rating Tool for Human and Animal Studies developed by NTP/OHAT, supplemented with additional questions relevant for cross-over studies. Where sufficiently similar studies are identified (e.g. the heterogeneity concerning population, exposure and outcome is low and the studies can be combined), we will conduct random-effects meta-analysis; otherwise, we will conduct a narrative synthesis.
Assessment of certainty of evidence: The certainty of evidence for each identified outcome will be assessed according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Performing the review according to this protocol will allow the identification of possible effects of RF-EMFs on cognitive performance in humans. The protocol has been registered in PROSPERO, an open-source protocol registration system, to foster transparency.
Registration PROSPERO CRD42021236168.
Highlights
• No up to date comprehensive systematic review is available.
• Priority outcomes for head exposure are tinnitus, migraine, and headaches.
• Further priority outcomes are sleep disturbances and composite symptom scores.
Abstract
Background Applications emitting radiofrequency electromagnetic fields (RF-EMF; 100 kHz to 300 GHz) are widely used for communication (e.g. mobile phones), in medicine (diathermy) and in industry (RF heaters). Concern has been raised that RF-EMF exposure affects health related quality of life, because a part of the population reports to experience a variety of symptoms related to low exposure levels below regulatory limits.
Objectives To systematically review the effects of longer-term or repeated local and whole human body RF-EMF exposure on the occurrence of symptoms evaluating migraine, tinnitus, headaches, sleep disturbances and composite symptom scores as primary outcomes.
Methods We will follow the WHO handbook for guideline development. For the development of the systematic review protocol we considered handbook for conducting systematic reviews for health effects evaluations from the National Toxicology Program-Office of Health Assessment and Translation (NTP-OHAT) and COSTER (Recommendations for the conduct of systematic reviews in toxicology and environmental health research).
Eligibility criteria Peer-reviewed epidemiological studies in the general population or workers aiming to investigate the association between local or whole-body RF-EMF exposure for at least one week and symptoms are eligible for inclusion. Only cohort, case-control and panel studies will be included.
Information sources We will search the scientific literature databases Medline, Web of Science, PsycInfo, Cochrane Library, Epistemonikos and Embase, using a predefined search strategy. This search will be supplemented by a search in the EMF-Portal and checks of reference lists of relevant papers and reviews.
Study appraisal and synthesis method Data from included papers will be extracted according to predefined forms. Findings will be summarized in tables, graphical displays and in a narrative synthesis of the available evidence, complemented with meta-analyses. We will separately review effects of local, far field and occupational exposure.
Risk of bias The internal validity of included studies will be assessed using the NTP-OHAT Risk of Bias Rating Tool for Human and Animal Studies, elaborated to observational RF-EMF studies.
Evidence appraisal To rate certainty of the evidence, we will use the OHAT GRADE-based approach for epidemiological studies.
Framework and funding This protocol concerns one of the ten different systematic reviews considered in a larger systematic review of the World Health Organization to assess potential health effects of exposure to RF-EMF in the general and working population.
Registration PROSPERO CRD42021239432.
Open access paper: https://www.sciencedirect.com/science/article/pii/S0160412021004773?via%3Dihub
Bernd Henschenmacher, Annette Bitsch, Tonia de las Heras Gala, Henry Jay Forman, Athanassios Fragoulis, Pietro Ghezzi, Rupert Kellner, Wolfgang Koch, Jens Kuhne, Dmitrij Sachno, Gernot Schmid, Katya Tsaioun, Jos Verbeek, Robert Wright. The effect of radiofrequency electromagnetic fields (RF-EMF) on biomarkers of oxidative stress in vivo and in vitro: A protocol for a systematic review. Environ Int. 158, 2022, 106932. doi: 10.1016/j.envint.2021.106932.
Background Oxidative stress is conjectured to be related to many diseases. Furthermore, it is hypothesized that radiofrequency fields may induce oxidative stress in various cell types and thereby compromise human and animal health. This systematic review (SR) aims to summarize and evaluate the literature related to this hypothesis.
Objectives The main objective of this SR is to evaluate the associations between the exposure to radiofrequency electromagnetic fields and oxidative stress in experimental models (in vivo and in vitro).
Methods The SR framework has been developed following the guidelines established in the WHO Handbook for Guideline Development and the Handbook for Conducting a Literature-Based Health Assessment). We will include controlled in vivo and in vitro laboratory studies that assess the effects of an exposure to RF-EMF on valid markers for oxidative stress compared to no or sham exposure. The protocol is registered in PROSPERO.
We will search the following databases: PubMed, Embase, Web of Science Core Collection, Scopus, and the EMF-Portal. The reference lists of included studies and retrieved review articles will also be manually searched.
Study appraisal and synthesis method Data will be extracted according to a pre-defined set of forms developed in the DistillerSR online software and synthesized in a meta-analysis when studies are judged sufficiently similar to be combined. If a meta-analysis is not possible, we will describe the effects of the exposure in a narrative way.
Risk of bias The risk of bias will be assessed with the NTP/OHAT risk of bias rating tool for human and animal studies.
We will use GRADE to assess the certainty of the conclusions (high, moderate, low, or inadequate) regarding the association between radiofrequency electromagnetic fields and oxidative stress.
Funding This work was funded by the World Health Organization (WHO).
Registration The protocol was registered on the PROSPERO webpage on July 8, 2021.
Open access paper: https://www.sciencedirect.com/science/article/pii/S0160412021005572
Jos Verbeek, Gunnhild Oftedal, Maria Feychting, Eric van Rongen, Maria Rosaria Scarfì, Simon Mann, Rachel Wong, Emilie van Deventer. Prioritizing health outcomes when assessing the effects of exposure to radiofrequency electromagnetic fields: A survey among experts. Environ Int. 146, 2021. 106300. doi:10.1016/j.envint.2020.106300.
• RF EMF may lead to other than heat-related health effects by yet unknown mechanisms
• Prioritizing health effects is needed for review utility and resource efficiency.
• RF EMF experts prioritized all peer-reviewed published biological and health outcomes.
• Cancer, heat-related effects, and adverse birth outcomes were rated most critical.
• WHO commissioned ten systematic reviews of the most critical health outcomes.
Abstract
Exposure to radiofrequency (RF) electromagnetic fields (EMF) (frequencies of 100 kHz to 300 GHz) has been steadily increasing. In addition to heat-related effects of RF EMF, other yet-unspecified biological effects, might exist which could possibly lead to health effects. Given the large number of health endpoints that have been studied, we wanted to prioritize those that would merit systematic reviews.
We developed a survey listing of all health endpoints reported in the literature and we asked 300 RF EMF experts and researchers to prioritize these health effects for systematic review as critical, important or unimportant. We also asked the experts to provide the rationale for their prioritization.
Of the 300 RF EMF experts queried, 164 (54%) responded. They rated cancer, heat-related effects, adverse birth outcomes, electromagnetic hypersensitivity, cognitive impairment, adverse pregnancy outcomes and oxidative stress as outcomes most critical regarding RF EMF exposure. For these outcomes, systematic reviews are needed. For heat-related outcomes, the experts based their ranking of the critical outcomes on what is known from human or animal studies, and for cancer and other outcomes, they based their rating also on public concern.
Declaration of Competing Interest
MF was vice chairman (May 2016 – May 2020) of the International Commission on Non-Ionizing Radiation Protection, an independent body setting guidelines for non-ionizing radiation protection. She has served as advisor to several national and international public advisory and research steering groups concerning the potential health effects of exposure to non-ionizing radiation.
MRS is in the Scientific Council of the Swedish Radiation Safety Authority for preparing reports on the evaluation of the scientific literature related to electromagnetic fields and health.
GO is member of the International Commission on Non-Ionizing Radiation Protection. She has been member of groups appointed by Norwegian authorities to evaluate potential health effects of non-ionizing electromagnetic fields.
EvR was chairman (May 2016 – May 2020) of the International Commission on Non-Ionizing Radiation Protection and is currently vice-chairman. He is also member of the Scientific Council of the Swedish Radiation Safety Authority.
SM is a member of the International Commission on Non-Ionizing Radiation Protection’s Scientific Expert Group. Within the UK, he is Secretary to the Committee on Medical Aspects of Radiation in the Environment and he was Secretary (until 2017) to the Advisory Group on Non-Ionising Radiation.
All other authors have declared no conflict of interest.
Stephanie M. Eick, Dana E. Goin, Nicholas Chartres, Juleen Lam, Tracey J. Woodruff. Assessing risk of bias in human environmental epidemiology studies using three tools: different conclusions from different tools. Syst Rev 9, 249 (2020). doi: 10.1186/
Abstract
Background Systematic reviews are increasingly prevalent in environmental health due to their ability to synthesize evidence while reducing bias. Different systematic review methods have been developed by the US National Toxicology Program’s Office of Health Assessment and Translation (OHAT), the US Environmental Protection Agency’s (EPA) Integrated Risk Information System (IRIS), and by the US EPA under the Toxic Substances Control Act (TSCA), including the approach to assess risk of bias (ROB), one of the most vital steps which is used to evaluate internal validity of the studies. Our objective was to compare the performance of three tools (OHAT, IRIS, TSCA) in assessing ROB.
Methods We selected a systematic review on polybrominated diphenyl ethers and intelligence quotient and/or attention deficit hyperactivity disorder because it had been endorsed by the National Academy of Sciences. Two reviewers followed verbatim instructions from the tools and independently applied each tool to assess ROB in 15 studies previously identified. We documented the time to apply each tool and the impact the ROB ratings for each tool had on the final rating of the quality of the overall body of evidence.
Results The time to complete the ROB assessments varied widely (mean = 20, 32, and 40 min per study for the OHAT, IRIS, and TSCA tools, respectively). All studies were rated overall “low” or “uninformative” using IRIS, due to “deficient” or “critically deficient” ratings in one or two domains. Similarly, all studies were rated “unacceptable” using the TSCA tool because of one “unacceptable” rating in a metric related to statistical power. Approximately half of the studies had “low” or “probably low ROB” ratings across all domains with the OHAT and Navigation Guide tools.
Conclusions Tools that use overall ROB or study quality ratings, such as IRIS and TSCA, may reduce the available evidence to assess the harms of environmental exposures by erroneously excluding studies, which leads to inaccurate conclusions about the quality of the body of evidence. We recommend using ROB tools that circumvent these issues, such as OHAT and Navigation Guide.
"Following on the publication of the INTERPHONE study (May 2010) and the IARC classification of RF fields (May 2011), the health risk assessment of radiofrequency fields by WHO was started with a kick-off meeting in January 2012. A core group of 6 experts has been gathered to help with the development of the monograph. They, in turn, have enlisted the help of close to 30 experts to develop different sections of the first draft. Monthly conference calls have been held over the past year. A face-to-face meeting was convened in Istanbul in May 2015.A number of systematic reviews have been performed based on published peer-reviewed data. Search strategies, inclusion/exclusion criteria and quality criteria have been developed for the different types of studies. A first draft was uploaded on the WHO website in the Fall of 2014. Over 90 entries were filed electronically through the consultation providing around 700 comments to different chapters and section of the draft. Over 300 missing papers were identified through this useful step. Each submission has been carefully considered by the Core Group and the draft has been revised to take account of relevant comments and of papers published since December 2012. As a result of the consultation, a new chapter on biochemical and biological effects was added.The drawing of conclusions from the literature and the drafting of these chapters is the remit of a formal Task Group that will be convened by WHO following due process. The meeting of the Task Group is currently slated to be held in the Fall of 2016."
==
In March 1993, almost 30 years ago, the WHO published the last EHC monograph on radiofrequency radiation:
Electromagnetic fields (300 Hz to 300 GHz)
Environmental Health Criteria Monograph No.137
Overview
"WHO's assessment of any health risks produced by EMF emitting technologies falls within the responsibilities of the International EMF Project. One of the goals of the International EMF Project is therefore to carry out health risk assessments of RF, ELF and static fields, published in the Environmental Health Criteria.
The health risk assessments are
the result of in-depth critical reviews conducted through independent,
scientific peer-review groups. The are usually undertaken if new data
are available that would substantially change the evaluation, if there
is public concern for health or environmental effects of the agent
because of greater exposure, or if an appreciable time period has
elapsed since the last evaluation."
