The MOBI-Kids Study Protocol: Challenges in Assessing Childhood and Adolescent Exposure to Electromagnetic Fields from Wireless Telecommunication Technologies and Possible Association with Brain Tumor Risk

The rapid increase in mobile phone use in young people has generated concern about possible health effects of exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF). MOBI-Kids, a multinational case-control study, investigates the potential effects of childhood and adolescent exposure to EMF from mobile communications technologies on brain tumor risk in 14 countries. The study, which aims to include approximately 1,000 brain tumor cases aged 10-24 years and two individually matched controls for each case, follows a common protocol and builds upon the methodological experience of the INTERPHONE study. The design and conduct of a study on EMF exposure and brain tumor risk in young people in a large number of countries is complex and poses methodological challenges. This manuscript discusses the design of MOBI-Kids and describes the challenges and approaches chosen to address them, including: (1) the choice of controls operated for suspected appendicitis, to reduce potential selection bias related to low response rates among population controls; (2) investigating a young study population spanning a relatively wide age range; (3) conducting a large, multinational epidemiological study, while adhering to increasingly stricter ethics requirements; (4) investigating a rare and potentially fatal disease; and (5) assessing exposure to EMF from communication technologies. Our experience in thus far developing and implementing the study protocol indicates that MOBI-Kids is feasible and will generate results that will contribute to the understanding of potential brain tumor risks associated with use of mobile phones and other wireless communications technologies among young people

Wireless phone use in childhood and adolescence and neuroepithelial brain tumours: Results from the international MOBI-Kids study

In recent decades, the possibility that use of mobile communicating devices, particularly wireless (mobile and cordless) phones, may increase brain tumour risk, has been a concern, particularly given the considerable increase in their use by young people. MOBI-Kids, a 14-country (Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, the Netherlands, New Zealand, Spain) case-control study, was conducted to evaluate whether wireless phone use (and particularly resulting exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF)) increases risk of brain tumours in young people. Between 2010 and 2015, the study recruited 899 people with brain tumours aged 10 to 24 years old and 1,910 controls (operated for appendicitis) matched to the cases on date of diagnosis, study region and age. Participation rates were 72% for cases and 54% for controls. The mean ages of cases and controls were 16.5 and 16.6 years, respectively; 57% were males. The vast majority of study participants were wireless phones users, even in the youngest age group, and the study included substantial numbers of long-term (over 10 years) users: 22% overall, 51% in the 20-24-year-olds. Most tumours were of the neuroepithelial type (NBT; n = 671), mainly glioma. The odds ratios (OR) of NBT appeared to decrease with increasing time since start of use of wireless phones, cumulative number of calls and cumulative call time, particularly in the 15-19 years old age group. A decreasing trend in ORs was also observed with increasing estimated cumulative RF specific energy and ELF induced current density at the location of the tumour. Further analyses suggest that the large number of ORs below 1 in this study is unlikely to represent an unknown causal preventive effect of mobile phone exposure: they can be at least partially explained by differential recall by proxies and prodromal symptoms affecting phone use before diagnosis of the cases. We cannot rule out, however, residual confounding from sources we did not measure. Overall, our study provides no evidence of a causal association between wireless phone use and brain tumours in young people. However, the sources of bias summarised above prevent us from ruling out a small increased risk.Funding for the coordination of the MOBI-Kids study was obtained from the European Community's Seventh Framework Programme under grant agreements number 226873 and 603794, and from the Spanish Ministry of Science and Innovation (MINECO). In Spain, additional funding was obtained from the Spanish Health Research Fund (FIS) of the National Institute for Health Carlos III, and from the Junta de Andalucía, Consejería de Salud. Proyecto PI-0317-2010. ISGlobal also acknowledges support from the Spanish Ministry of Science, Innovation and Universities through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), support from the Generalitat de Catalunya through the CERCA Program and support from the Secretariat of Universities and Research of the Department of Business and Knowledge of the Generalitat of Catalonia through AGAUR (the Catalan Agency for Management of University and Research Grants) (Project 2017 SGR 1487). Australian participation in MOBI-Kids was supported by the Australian National Health and Medical Research Council with a five-year research grant (grant number: 546130). Austrian participation in MOBI-Kids was partly supported by a grant from the Ministry of Science. In Canada, participation in MOBI-Kids was supported by a university-industry partnership grant from the Canadian Institutes of Health Research (CIHR), reference number 110835, with the Canadian Wireless Telecommunications Association (CWTA) serving as the industrial partner. CWTA provides technical information on wireless telecommunications in Canada and facilitates access to billing records from Canadian network operators, but has no involvement in the design, conduct, analysis, or interpretation of the MOBI-KIDS study. French participation was also supported by the French National Agency for Sanitary Safety of Food, Environment and Labour (ANSES, contract FSRF2008-3), French National Cancer Institute (INCa), Pfizer Foundation and League against cancer. The German study centre received additional funding from the Federal Office for Radiation Protection (BfS) under grant number 3609S30010. In Greece, the study was partially supported by the Hellenic Society for Social Pediatrics and Health Promotion, ELKE (Special Account for Research Grants of the National and Kapodistrian University of Athens) and GGET (General Secretariat for Research and Technology). Mobi-Kids India was supported by Board of Research in Nuclear Sciences (BRNS, sanction no: 2013/38/01-BRNS)

Nonparticipation selection bias in the MOBI-Kids Study

Background: MOBI-Kids is a 14-country case-control study designed to investigate the potential effects of electromagnetic field exposure from mobile telecommunications devices on brain tumor risk in children and young adults conducted from 2010 to 2016. This work describes differences in cellular telephone use and personal characteristics among interviewed participants and refusers responding to a brief nonrespondent questionnaire. It also assesses the potential impact of nonparticipation selection bias on study findings. Methods: We compared nonrespondent questionnaires completed by 77 cases and 498 control refusers with responses from 683 interviewed cases and 1501 controls (suspected appendicitis patients) in six countries (France, Germany, Israel, Italy, Japan, and Spain). We derived selection bias factors and estimated inverse probability of selection weights for use in analysis of MOBI-Kids data. Results: The prevalence of ever-regular use was somewhat higher among interviewed participants than nonrespondent questionnaire respondents 10-14 years of age (68% vs. 62% controls, 63% vs. 48% cases); in those 20-24 years, the prevalence was ≥97%. Interviewed controls and cases in the 15- to 19- and 20- to 24-year-old age groups were more likely to have a time since start of use of 5+ years. Selection bias factors generally indicated a small underestimation in cellular telephone odds ratios (ORs) ranging from 0.96 to 0.97 for ever-regular use and 0.92 to 0.94 for time since start of use (5+ years), but varied in alternative hypothetical scenarios considered. Conclusions: Although limited by small numbers of nonrespondent questionnaire respondents, findings generally indicated a small underestimation in cellular telephone ORs due to selective nonparticipation.The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement number 226873—the MOBI-Kids project and the European Commission grant 603794-GERoNiMO project. The international coordination of the project was partly supported by a grant from the Spanish Ministry of Science and Innovation (MICCIN). France: this project received funds from the French National Agency for Sanitary Safety of Food, Environment and Labour (ANSES, contract FSRF2008-3), French National Cancer Institute (INCa), Pfizer Foundation, and League against cancer. Germany: The German branch of MOBI-Kids is supported by the Federal Office for Radiation Protection. Italy: Ministry of Health RF-2009-1546284. Japan: Japanese participation in MOBI-Kids is supported by the Ministry of Internal Affairs and Communications by Grant No. 0155-0007. Spain: Spanish participation was partially supported by the Spanish Health Research Fund (FISPI10/02981), the Andalusian Consejeria de Salud (PI-0317/2010), and Conselleria de Sanitat, Generalitat Valenciana under grant number 025/2010. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. M.C.T. was supported by the Departament de Salut, Generalitat de Catalunya (SLT002/16/00232)

Using software-modified smartphones to validate self-reported mobile phone use in young people : A pilot study

A newly developed smartphone application was piloted to characterize and validate mobile phone use in young people. Twenty-six volunteers (mean age 17.3 years) from France, Spain, and the Netherlands used a software-modified smartphone for 4 weeks; the application installed on the phone recorded number and duration of calls, data use, laterality, hands-free device usage, and communication system used for both voice calls and data transfer. Upon returning the phone, participants estimated their mobile phone use during those 4 weeks via an interviewer-administered questionnaire. Results indicated that participants on average underestimated the number of calls they made, while they overestimated total call duration. Participants held the phone for about 90% of total call time near the head, mainly on the side of the head they reported as dominant. Some limitations were encountered when comparing reported and recorded data use and speaker use. When applied in a larger sample, information recorded by the smartphone application will be very useful to improve radiofrequency (RF) exposure modeling from mobile phones to be used in epidemiological research. Bioelectromagnetics. 36:538-543, 2015. © 2015 Wiley Periodicals, Inc

Are Cal/OSHA Regulations Protecting Farmworkers in California From Heat-Related Illness?

ObjectiveDetermine compliance with and effectiveness of California regulations in reducing farmworkers' heat-related illness (HRI) risk and identify main factors contributing to HRI.MethodsIn a cross-sectional study of Latino farmworkers, core body temperature (CBT), work rate, and environmental temperature (WBGT) were monitored over a work shift by individual ingestible thermistors, accelerometers, and weather stations, respectively. Multiple logistic modeling was used to identify risk factors for elevated CBT.ResultsAlthough farms complied with Cal/OSHA regulations, worker training of HRI prevention and hydration replacement rates were insufficient. In modeling (AOR [95% CI]) male sex (3.74 [1.22 - 11.54]), WBGT (1.22 [1.08 - 1.38]), work rate (1.004 [1.002 - 1.006]), and increased BMI (1.11 [1.10 - 1.29]) were all independently associated with elevated CBT.ConclusionRisk of HRI was exacerbated by work rate and environmental temperature despite farms following Cal/OSHA regulations

Particulate Matter, Endotoxin, and Worker Respiratory Health on Large Californian Dairies

ObjectiveTo assess respiratory exposures and lung function in a cross-sectional study of California dairy workers.MethodsExposure of 205 dairy and 45 control (vegetable processing) workers to particulate matter and endotoxin was monitored. Pre- and postshift spirometry and interviews were conducted.ResultsGeometric mean inhalable and PM2.5 concentrations were 812 and 35.3 μg/m3 versus 481.9 and 19.6 μg/m3, respectively, for dairy and control workers. Endotoxin concentrations were 329 EU/m3 or 1122 pmol/m3 and 13.5 EU/m3 or 110 pmol/m3, respectively, for dairy and control workers. In a mixed-effects model, forced vital capacity decreased across a work shift by 24.5 mL (95% confidence interval, -44.7 to -4.3; P = 0.018) with log10 (total endotoxin) and by 22.0 mL (95% confidence interval, -43.2 to -0.08; P = 0.042) per hour worked.ConclusionsModern California dairy endotoxin exposures and shift length were associated with a mild acute decrease in forced vital capacity

The epidemiology of glioma in adults: a “state of the science” review

Gliomas are the most common primary intracranial tumor, representing 81% of malignant brain tumors. Although relatively rare, they cause significant mortality and morbidity. Glioblastoma, the most common glioma histology (∼45% of all gliomas), has a 5-year relative survival of ∼5%. A small portion of these tumors are caused by Mendelian disorders, including neurofibromatosis, tuberous sclerosis, and Li-Fraumeni syndrome. Genomic analyses of glioma have also produced new evidence about risk and prognosis. Recently discovered biomarkers that indicate improved survival include O⁶-methylguanine-DNA methyltransferase methylation, isocitrate dehydrogenase mutation, and a glioma cytosine-phosphate-guanine island methylator phenotype. Genome-wide association studies have identified heritable risk alleles within 7 genes that are associated with increased risk of glioma. Many risk factors have been examined as potential contributors to glioma risk. Most significantly, these include an increase in risk by exposure to ionizing radiation and a decrease in risk by history of allergies or atopic disease(s). The potential influence of occupational exposures and cellular phones has also been examined, with inconclusive results. We provide a “state of the science” review of current research into causes and risk factors for gliomas in adults

Patterns of cellular phone use among young people in 12 countries : Implications for RF exposure

Characterizing exposure to radiofrequency (RF) fields from wireless telecommunications technologies during childhood and adolescence is a research priority in investigating the health effects of RF. The Mobi-Expo study aimed to describe characteristics and determinants of cellular phone use in 534 young people (10-24years) in 12 countries. The study used a specifically designed software application installed on smartphones to collect data on the use of wireless telecommunications devices within this age group. The role of gender, age, maternal education, calendar period, and country was evaluated through multivariate models mutually adjusting for all variables. Call number and duration were higher among females compared to males (geometric mean (GM) ratio 1.17 and 1.42, respectively), among 20-24year olds compared to 10-14year olds (GM ratio 2.09 and 4.40, respectively), and among lowest compared to highest social classes (GM ratio 1.52 and 1.58, respectively). The number of SMS was higher in females (GM ratio 1.46) and the middle age group (15-19year olds: GM ratio 2.21 compared to 10-14year olds) and decreased over time. Data use was highest in the oldest age group, whereas Wi-Fi use was highest in the middle age group. Both data and Wi-Fi use increased over time. Large differences in the number and duration of calls, SMS, and data/Wi-Fi use were seen by country, with country and age accounting for up to 50% of the variance. Hands-free and laterality of use did not show significant differences by sex, age, education, study period, or country. Although limited by a convenience sample, these results provide valuable insights to the design, analysis, and interpretation of future epidemiological studies concerning the health effects of exposure resulting from cellular phone use in young people. In addition, the information provided by this research may be used to design strategies to minimize RF exposure

Recall of mobile phone usage and laterality in young people: The multinational Mobi-Expo study

OBJECTIVE: To study recall of mobile phone usage, including laterality and hands-free use, in young people. METHODS: Actual mobile phone use was recorded among volunteers aged between 10 and 24 years from 12 countries by the software application XMobiSense and was compared with self-reported mobile phone use at 6 and 18 months after using the application. The application recorded number and duration of voice calls, number of text messages, amount of data transfer, laterality (% of call time the phone was near the right or left side of the head, or neither), and hands-free usage. After data cleaning, 466 participants were available for the main analyses (recorded vs. self-reported phone use after 6 months). RESULTS: Participants were on average 18.6 years old (IQR 15.2-21.8 years). The Spearman correlation coefficients between recorded and self-reported (after 6 months) number and duration of voice calls were 0.68 and 0.65, respectively. Number of calls was on average underestimated by the participants (adjusted geometric mean ratio (GMR) self-report/recorded = 0.52, 95% CI = 0.47-0.58), while duration of calls was overestimated (GMR=1.32, 95%, CI = 1.15-1.52). The ratios significantly differed by country, age, maternal educational level, and level of reported phone use, but not by time of the interview (6 vs. 18 months). Individuals who reported low mobile phone use underestimated their use, while individuals who reported the highest level of phone use were more likely to overestimate their use. Individuals who reported using the phone mainly on the right side of the head used it more on the right (71.1%) than the left (28.9%) side. Self-reported left side users, however, used the phone only slightly more on the left (53.3%) than the right (46.7%) side. Recorded percentage hands-free use (headset, speaker mode, Bluetooth) increased with increasing self-reported frequency of hands-free device usage. Frequent (≥50% of call time) reported headset or speaker mode use corresponded with 17.1% and 17.2% of total call time, respectively, that was recorded as hands-free use. DISCUSSION: These results indicate that young people can recall phone use moderately well, with recall depending on the amount of phone use and participants' characteristics. The obtained information can be used to calibrate self-reported mobile use to improve estimation of radiofrequency exposure from mobile phones