Sunday, May 15, 2022

MOBI-KIDS: Childhood Brain Tumor Risk & Mobile Phone Use Study




A critical analysis of the MOBI-Kids study of wireless phone use 
in childhood and adolescence and brain tumor risk 

Lennart Hardell, Joel M. Moskowitz. A critical analysis of the MOBI-Kids study of wireless phone use in childhood and adolescence and brain tumor risk. Reviews on Environmental Health. May 5, 2022. https://doi.org/10.1515/reveh-2022-0040.

Abstract

The MOBI-Kids case-control study on wireless phone use and brain tumor risk in childhood and adolescence included the age group 10–24 years diagnosed between 2010 and 2015. Overall no increased risk was found although for brain tumors in the temporal region an increased risk was found in the age groups 10–14 and 20–24 years. Most odds ratios (ORs) in MOBI-Kids were <1.0, some statistically significant, suggestive of a preventive effect from RF radiation; however, this is in contrast to current knowledge about radiofrequency (RF) carcinogenesis. The MOBI-Kids results are not biologically plausible and indicate that the study was flawed due to methodological problems. For example, not all brain tumor cases were included since central localization was excluded. Instead, all brain tumor cases should have been included regardless of histopathology and anatomical localization. Only surgical controls with appendicitis were used instead of population-based controls from the same geographical area as for the cases. In fact, increased incidence of appendicitis has been postulated to be associated with RF radiation which makes selection of control group in MOBI-Kids questionable. Start of wireless phone use up to 10 years before diagnosis was in some analyses included in the unexposed group. Thus, any important results demonstrating late carcinogenesis, a promoter effect, have been omitted from analysis and may underestimate true risks. Linear trend was in some analyses statistically significant in the calculation of RF-specific energy and extremely low frequency (ELF)-induced current in the center of gravity of the tumor. Additional case-case analysis should have been performed. The data from this study should be reanalyzed using unconditional regression analysis adjusted for potential confounding factors to increase statistical power. Then all responding cases and controls could be included in the analyses. In sum, we believe the results as reported in this paper seem uninterpretable and should be dismissed.

Summary

  • In our opinion, the results as reported in the MOBI-Kids paper seem uninterpretable and should be dismissed.
  • All brain tumor cases should have been included regardless of histopathology and anatomical localization.

  • Only surgical controls with suspected appendicitis were used. Yet, increased incidence of appendicitis has been postulated to be associated with RF radiation.

  • Start of wireless phone use up to 10 years before diagnosis was in some analyses included in the unexposed group. This would bias the ORs towards unity.

  • The results indicate an increased risk for tumors in the temporal brain region in spite of methodological issues based on low numbers in several categories.

  • Linear trend was in some analyses statistically significant in the calculation of RF-specific energy and ELF-induced current in the center of gravity of the tumor. Additional case-case analysis should have been performed.

  • The data from this study should be reanalyzed using unconditional regression analysis adjusted for potential confounding factors to increase the statistical power.

Finally, it is unfortunate that after such a major investment of resources that little can be learned at this time from the MOBI-Kids study about the risk of brain tumors from wireless phone use in young people. Since the study addresses an issue critical to public health and the majority of the funding was from the European Commission, the MOBI-Kids data set should be publicly archived making it available to the scientific community to enable the data to be re-analyzed using different assumptions and methods.


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Feb 2, 2022

My Comments on the International MOBI-Kids Study

In December 2021, almost seven years after data collection was completed, the main outcome paper for the International MOBI-Kids study was finally published. This case-control study examined brain tumor risk from wireless phone use among young people 10-24 years of age (Castaño-Vinyals et al, 2022) (see abstract below).

Conducting a multinational epidemiologic study involving more than 50 scientists with data collected in 14 nations is a complex endeavor with a substantial risk of failure. Although the investigators made an exemplary effort to salvage the study via supplemental sub-studies and post-hoc analyses, after reviewing their paper, we believe they were unsuccessful in overcoming serious methodological problems. Hence, in our opinion, the data seem uninterpretable, and the study's results should be dismissed.

The authors of the MOBI-Kids study appear to agree with our assessment because they concluded in the paper’s abstract:

"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."

Based upon our review of the research on brain tumor risk among adults who use mobile phones (Choi et al., 2020), we recommend that those who must use mobile phones should keep their use as low as reasonably achievable (ALARA) and should follow safety guidelines. These guidelines especially apply to children and adolescents whose brains and bodies are still developing.

Specific concerns re: the MOBI-Kids study methodology

We believe there is an explanation for the many risk estimates less than 1 in the MOBI-Kids study. The study had substantially lower participation rates for controls (54%) than cases (72%) that likely biased brain tumor risk estimates downward. The investigators conducted a non-participation study to estimate the amount of this bias, but this study also had serious limitations (i.e., small sample sizes; differential participation rates) and likely underestimated the amount of selection bias in the current paper.

The original study design called for recruitment of 2,000 cases (Sadetzki et al., 2014). Due to problems with recruitment, the study managed to enroll only 898 cases. Moreover, the primary analyses in the outcome paper included only 671 cases with neuroepithelial brain tumors (NBT). Hence, the study had inadequate sensitivity (i.e., statistical power) to detect even a moderate-sized effect (let alone a small effect) from mobile phone use on brain tumor risk.

In a case-control study, controls should be selected that have equal risk for the study outcome as the cases. We question whether using youth diagnosed with appendicitis as controls constitutes a suitable choice for a study of cell phone users. Why didn't the study include a population-based control group like the INTERPHONE study which preceded it (Cardis et al., 2007)?

During the data collection period (2010-2015), many young people in this study may have used smart phones. Whereas earlier cellphones had antennas at the top of the phone, many smart phones have cellular transmission antennas in the bottom of the phones exposing the neck to the greatest radio frequency radiation, not the head. This may increase the risk of other tumors, especially thyroid gland tumors, but reduce the brain tumor risk.

Finally, ten or fewer years of mobile phone use may not be a sufficient amount of time before a mobile phone-related brain tumor is diagnosed in this young population. However, the CEFALO study (Aydin et al., 2011) of children's mobile use and brain tumor risk did find a significant dose-response relationship for the number of years of cellphone use in a subsample of participants with mobile phone operator (i.e. telephone company) data. The MOBI-Kids study also had mobile phone operator data on 25% of participants but did not report the outcome results for this subsample.

MOBI-Kids and CEFALO differed in important ways. MOBI-Kids used hospital controls whereas CEFALO selected controls from the general population. Whereas MOBI-Kids included only neuroepithelial brain tumors (NBT) in its primary analyses, CEFALO did not exclude any brain tumors. MOBI-Kids collected data years later when different cellular technology was popular, and mobile phone towers likely were located more proximal to users which may have resulted in less exposure to RFR emitted by cellphones. Although MOBI-Kids collected data in 14 countries, most of the data were from five countries, Spain, Italy, France, Israel, and Germany, and none was from the four CEFALO countries, Denmark, Norway, Sweden, and Switzerland.

In sum, it is unfortunate that after such a major investment of resources and time that little can be learned from the MOBI-Kids study about the risk of brain tumors from wireless phone use in young people. Since the study addresses an issue critical to public health and the majority of the funding was from the European Commission, the MOBI-Kids data set should be made available to the scientific community for secondary analysis to enable the data to be re-analyzed using different assumptions and methods.

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

Castaño-Vinyals G, Sadetzki S, Vermeulen R, Momoli F, Kundi M, Merletti F, Maslanyj M, Calderon C, Wiart J, Lee AK, Taki M, Sim M, Armstrong B, Benke G, Schattner R, Hutter HP, Krewski D, Mohipp C, Ritvo P, Spinelli J, Lacour B, Remen T, Radon K, Weinmann T, Petridou ET, Moschovi M, Pourtsidis A, Oikonomou K, Kanavidis P, Bouka E, Dikshit R, Nagrani R, Chetrit A, Bruchim R, Maule M, Migliore E, Filippini G, Miligi L, Mattioli S, Kojimahara N, Yamaguchi N, Ha M, Choi K, Kromhout H, Goedhart G, 't Mannetje A, Eng A, Langer CE, Alguacil J, Aragonés N, Morales-Suárez-Varela M, Badia F, Albert A, Carretero G, Cardis E. Wireless phone use in childhood and adolescence and neuroepithelial brain tumours: Results from the international MOBI-Kids study. Environ Int. 2021 Dec 30;160:107069. doi: 10.1016/j.envint.2021.

Abstract

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.

Highlights

• Increasing use of mobile technologies by young people is a topic of public health concern.

• MOBI-Kids studied brain tumour risk and wireless phone use (and EMF) in 14 countries.

• The study includes 899 brain tumour cases aged 10–24 years old and 1,910 controls.

• We have no evidence of a causal association between wireless phone use and brain tumours.

• Because of likely biases we cannot rule out a small increased risk.

 Open access paper: https://www.sciencedirect.com/science/article/pii/S0160412021006942?via%3Dihub

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February 18, 2021

When will we learn whether mobile phone use was associated with increased risk of brain tumors or neurological disorders in the Mobi-Kids study?

February 15 was #InternationalChildhoodCancerDay which reminded me that we have yet to see publication of the most important results from the Mobi-Kids Childhood Brain Tumor Risk & Mobile Phone Use Study.

This project is the largest case-control study to examine the risk of a young person developing brain cancer in relation to his/her exposure to electromagnetic fields and wireless radiation from mobile phones. This 14-nation case-control study was funded by the European Commission (EC) from March 2009 to February 2016. The EC contributed 58% of the total budget for this €6.1 million ($7.4 million) project. The EC funding for this 7-year project ended five years ago!

Was mobile phone use associated with increased risk of brain tumors or neurological disorders among these youth?

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Clinical presentation of young people (10-24 years old) with brain tumors: results from the international MOBI-Kids study

Angela Zumel-Marne et al. 
Clinical presentation of young people (10-24 years old) with brain tumors: results from the international MOBI-Kids study. J Neurooncol. 2020 Apr;147(2):427-440. doi: 10.1007/s11060-020-03437-4. Epub 2020 Mar 3. DOI: 10.1007/s11060-020-03437-4.

Abstract

Introduction: We used data from MOBI-Kids, a 14-country international collaborative case-control study of brain tumors (BTs), to study clinical characteristics of the tumors in older children (10 years or older), adolescents and young adults (up to the age of 24).

Methods: Information from clinical records was obtained for 899 BT cases, including signs and symptoms, symptom onset, diagnosis date, tumor type and location.

Results: Overall, 64% of all tumors were low-grade, 76% were neuroepithelial tumors and 62% gliomas. There were more males than females among neuroepithelial and embryonal tumor cases, but more females with meningeal tumors. The most frequent locations were cerebellum (22%) and frontal (16%) lobe. The most frequent symptom was headaches (60%), overall, as well as for gliomas, embryonal and 'non-neuroepithelial' tumors; it was convulsions/seizures for neuroepithelial tumors other than glioma, and visual signs and symptoms for meningiomas. A cluster analysis showed that headaches and nausea/vomiting was the only combination of symptoms that exceeded a cutoff of 50%, with a joint occurrence of 67%. Overall, the median time from first symptom to diagnosis was 1.42 months (IQR 0.53-4.80); it exceeded 1 year in 12% of cases, though no particular symptom was associated with exceptionally long or short delays.

Conclusions: This is the largest clinical epidemiology study of BT in young people conducted so far. Many signs and symptoms were identified, dominated by headaches and nausea/vomiting. Diagnosis was generally rapid but in 12% diagnostic delay exceeded 1 year with none of the symptoms been associated with a distinctly long time until diagnosis.

Open access paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136306/

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January 26, 2019

The MOBI-Kids project is the largest case-control study to examine the risk of a young person developing brain cancer in relation to his/her exposure to electromagnetic fields and wireless radiation from mobile phones.

The study was funded by the European Commission from March, 2009 to February, 2016. The EU contributed 58% of the total budget for this €6.1 million project.

Although the EU project ended three years ago, the authors have not yet published the most important outcomes from this study.

Following is the executive summary from the authors' final report to the European Commission:

Final Report Summary: MOBI-KIDS (Risk of brain cancer from exposure 
to radiofrequency fields in childhood & adolescence)

Executive Summary

"The overall objective of the current project was to assess the potential carcinogenic effects of childhood and adolescent exposure to radio frequency (RF) and extremely low frequency (ELF) from mobile telephones on tumours of the central nervous system.


In order to achieve this, the operational objectives were:

- To conduct a multinational epidemiological case-control study of brain tumours diagnosed in young people in relation to electro-magnetic fields (EMF) exposure from mobile telephones and other sources of RF in eight countries under the current grant, and, subject to funds being secured separately, in a number of non-European countries;

- To develop and validate improved indices of RF and extremely low frequency (ELF) exposure, and assess related uncertainties, for all subjects in the study;

- To analyse the relation between risk of brain tumours and exposures to RF and ELF from mobile phones and other relevant and important sources of exposure in young people’s general environment.

The MOBI-KIDS project was conducted in 14 countries (Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, New Zealand, Spain, The Netherlands) between 2010 and 2015. It used a case-control study design, recruiting 898 eligible cases aged 10 to 24 years old and 1 912 controls matched to the cases on reference date, study region and age. 

Each participant completed a face-to-face interview that included information on socio-demographic factors; complete residential history; exposure to farm and domestic animals; mobile phone use; use of other wireless communication devices including cordless phones and Wi-Fi; exposure to other environmental and occupational sources of EMF; occupational history of the subject and his/her parents during the peri-conception, pregnancy and peri-natal period; occupational exposures to ionising radiation and chemicals; medical radiation exposure; medical history of the subject and mother and water and disinfection by-products exposure (the later only in 6 countries). Interviewers completed a questionnaire regarding responsiveness of the interviewee and quality of recall. 

Validation studies were conducted, as well as various sub studies, to assess the validity and accuracy of the information collected and identify and characterise possible recall and selection biases which may affect the interpretation of study results. Extensive work went into characterising, modelling and validating ELF and RF exposure from different types of mobile and cordless phones, different communication systems and other environmental sources of EMF. The mobile and cordless phones ELF and RF algorithms, to estimate amount of exposure at the location of the tumour, have been completed and validated. Estimation of occupational and environmental exposures to EMF and other factors is underway.

Most brain tumours were of the neuroepithelial type mainly gliomas. Mean age of cases and controls at the reference date is 16.53 and 16.67 respectively with 56% of male participants. There were similar proportions of childhood (10-14) adolescent and young adult cases and controls. Tumour localisation was made by neuro radiologists in each country using standardised age-specific 3D grids for over 90% of cases. Validation of tumour localisation and of diagnosis is underway.

Among regular users of mobile phones, the mean time since start of mobile phone use was 6.2 years for controls, with high differences by age group: 3.2 years for the younger age group (10-14) and 9.2 years for the older age group (20-24), respectively; in the latter group, 37% of controls reported using a phone for 10 years or more. Average number of calls per month was 43 for cases and 49 for controls – with 5% of cases and 4% of controls making more than 10 calls per day on average –, and average hours per month talking on the mobile phone were 2.1 and 2.6 respectively – 4% of case and 3% of controls used the phone for calling more than 1 hour per month on average. In both indicators of mobile phone use, we observed an increasing trend in number of calls and average call time with age. 

Analyses of the association between mobile phone use and brain tumour risk, as well as between estimated RF and ELF exposure at the location of the tumour and risk of brain tumour have been conducted and a publication is in preparation. Results however cannot be made public until publication in a peer-reviewed scientific journal.
This is by far the largest epidemiological study on the effects of EMF on brain tumour risk in young people."

Funded by European Commission FP-7/Environment grant agreement: 226873
Project start date: March 1, 2009
Project end date: February 29, 2016 (closed project)
Overall budget: € 6 078 765,80 
EU contribution: € 3 499 748


Grant Recipients




Feb 1, 2017

Research on the adverse effects of mobile phone radiation has focused on the radiofrequency (RF) emissions from cell phones and cordless phones and has ignored the effects of the extremely low frequency fields (ELF) produced by the phones. Yet ELF was labelled "possibly carcinogenic to humans" by the WHO International Agency for Research on Cancer a decade earlier than RF.


The paper below indicates that the MOBI-Kids research team is studying the effects of exposure to ELF as well as RF on children's cancer risk from mobile and cordless phone use.



ELF exposure from mobile and cordless phones 
for the epidemiological MOBI-Kids study

Calderón C, Ichikawa H, Taki M, Wake K, Addison D, Mee T, Maslanyj M, Kromhout H, Lee AK, Sim MR, Wiart J, Cardis E. ELF exposure from mobile and cordless phones for the epidemiological MOBI-Kids study. Environ Int. 2017 Jan 23. pii: S0160-4120(17)30047-8. doi: 10.1016/j.envint.2017.01.005. [Epub ahead of print]

Abstract

This paper describes measurements and computational modelling carried out in the MOBI-Kids case-control study to assess the extremely low frequency (ELF) exposure of the brain from use of mobile and cordless phones. Four different communication systems were investigated: Global System for Mobile (GSM), Universal Mobile Telecommunications System (UMTS), Digital Enhanced Cordless Telecommunications (DECT) and Wi-Fi Voice over Internet Protocol (VoIP). The magnetic fields produced by the phones during transmission were measured under controlled laboratory conditions, and an equivalent loop was fitted to the data to produce three-dimensional extrapolations of the field. Computational modelling was then used to calculate the induced current density and electric field strength in the brain resulting from exposure to these magnetic fields. Human voxel phantoms of four different ages were used: 8, 11, 14 and adult. The results indicate that the current densities induced in the brain during DECT calls are likely to be an order of magnitude lower than those generated during GSM calls but over twice that during UMTS calls. The average current density during Wi-Fi VoIP calls was found to be lower than for UMTS by 30%, but the variability across the samples investigated was high. Spectral contributions were important to consider in relation to current density, particularly for DECT phones. This study suggests that the spatial distribution of the ELF induced current densities in brain tissues is determined by the physical characteristics of the phone (in particular battery position) while the amplitude is mainly dependent on communication system, thus providing a feasible basis for assessing ELF exposure in the epidemiological study. The number of phantoms was not large enough to provide definitive evidence of an increase of induced current density with age, but the data that are available suggest that, if present, the effect is likely to be very small.

https://www.ncbi.nlm.nih.gov/pubmed/28126406


May, 2016

According to the European Commission, the EU-funded project "Risk of brain cancer from exposure to radiofrequency fields in childhood and adolescence" (MOBI-Kids) was "closed" on Feb 29, 2016. The study will make an important contribution to assessing the association, if any, between electromagnetic field exposure due to use of mobile communication devices and the development of brain cancer in youth.


The last Mobi-Kids Consortium meeting was held February 16-17, 2016. The meeting was attended by investigators from 15 countries. Preliminary results from the study were discussed.

From December, 2010 through February, 2015, about 800 cases and 1,600 controls were interviewed for this study.

The project cost 6 million Euros with 3.5 million Euros from the European Commission.


June, 2014

My comments:

This is a difficult case-control study to undertake as it involves 14 nations and about 60 senior investigators. The original goal was to recruit 2,000 cases. The authors revised the original goal to 1,000 cases because recruitment of cases has been much more difficult than anticipated. As of June, 2014, only 686 cases were recruited, and 566 were interviewed. Only six more months remain for participant recruitment. Thus, even the reduced recruitment goal may be difficult to achieve.

I am concerned that the MOBI-Kids study will fail to have adequate statistical power to detect the association between EMF exposure and brain tumor risk. The CEFALO study of brain tumor risk in children was seriously under-powered with 352 cases (Aydin et al., 2011; http://bit.ly/1pW4ulA). The four nation CEFALO study found a 36% increased relative risk of brain tumors with any mobile phone use, but this was not statistically significant due to the small sample size (OR = 1.36; 95% CI = 0.92 to 2.02) so the authors dismissed this overall finding. (See my supplementary comments below because CEFALO found some statistically significant evidence for increased brain tumor risk which the study authors also dismissed.)

Only four of the 58 authors of the MOBI-Kids study declared conflicts of interest (see below). The funding sources for this study are listed below. I will leave it to others to determine how much of the funding originated from industry and whether funneling the funds through intermediary organizations or agencies eliminated potential conflicts of interest.

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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

Sadetzki S, Langer CE, Bruchim R, Kundi M, Merletti F, Vermeulen R, Kromhout H, Lee A-K, Maslanyj M, Sim MR, Taki M, Wiart J, Armstrong B, Milne E, Benke G, Schattner R, Hutter H-P, Woehrer A, Krewski D, Mohipp C, Momoli F, Ritvo P, Spinelli J, Lacour B, Delmas D, Remen T, Radon K, Weinmann T, Klostermann S, Heinrich S, Petridou E, Bouka E, Panagopoulou P, Dikshit R, Nagrani R, Even-Nir H, Chetrit A, Maule M, Migliore E, Filippini G, Miligi L, Mattioli S, Yamaguchi N, Kojimahara N, Ha M, Choi K-H, Mannetje A’, Eng A, Woodward A, Carretero G, Alguacil J, Aragones N, Suare-Varela MM, Goedhart G, Schouten-van Meeteren AAYN, Reedijk AAMJ and Cardis E (2014) 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. Front. Public Health 2:124. Sep 23, 2014. doi: 10.3389/fpubh.2014.00124.

Abstract

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.

Open Access: http://bit.ly/1pVKGyS

Excerpts

The original expected number of cases in the target age range was of the order of 2,000. With the implementation of the study, however, it became apparent that the number of eligible cases is, in fact, much lower, in large part due to an underestimation of the number of midline tumors in the study population and, to a lesser extent, the failure of busy medical staff to notify eligible patients in some centers. In most centers, it is difficult to know exactly how many cases are ineligible as doctors/hospital staff will generally not inform study staff of ineligible cases. However, centers with access to detailed, reliable registry information or hospital records have excluded from one-third to more than one-half of cases due to an ineligible (midline) diagnosis. Table 1 indicates the revised expected number of eligible cases per year; the revised expected total number of cases to be included in MOBI-Kids is around 1,000, based on each center’s length of time in the field and other factors such as number of participating hospitals and accessibility to eligible cases. Fortunately, the MOBI-Kids study still has sufficient statistical power despite the reduced number of cases (see Study Power below).

Study Power


As discussed above, despite our best efforts to reach the original expected sample size of approximately 2,000 cases, the revised projected number of case is just under 1,000. However, preliminary results on mobile phone use among controls indicate that 77 and 83% of males and females, respectively, were defined as ever using a mobile phone regularly (data not shown). In keeping with the INTERPHONE study, subjects who had used a mobile phone for <1 year were considered “never” regular users. Further, approximately 14% of all subjects in MOBI-Kids have used a mobile phone for 10 years or longer, the threshold for long-term use in INTERPHONE. As this was a higher proportion than originally expected, our power calculations were revised based on the updated expected number of subjects and updated exposure indicators. Assuming that 971 cases are included in matched analyses, the study has 79% power to detect an increased risk of 40% [the estimated increase in the risk of glioma seen in the highest decile of phone use in INTERPHONE (10)], assuming 10% have used a mobile phone for 10 years or longer; power increases to 90% assuming 15% are “long-term” mobile phone users.

Conclusion

In spite of its challenges, the advantages of MOBI-Kids include its large sample size – it will be the largest study to date on this topic in young people – covering 14 participating countries. Subjects are being identified and recruited in a time period in which mobile phone use in young people has become more prevalent, thus, increasing the statistical power and overall representativeness and generalizability of the results. In addition, MOBI-Kids includes extensive exposure assessment work and validation studies using both historical provider records and SMPS to counteract potential recall bias. Despite the various challenges faced by the study team (which have implications for other epidemiological studies), our experience thus far in developing and implementing the study protocol indicates that MOBI-Kids is feasible and will generate results contributing to the understanding of potential brain tumor risks associated with use of mobile phones and other wireless communication technologies among young people.

Conflict of Interest Statement

Daniel Krewski has conducted contract work for the federal government of Canada (specifically, the Public Health Agency of Canada and Industry Canada) involving systematic review and summary of scientific information on potential health effects of radiofrequency fields. Malcolm R. Sim – wife had shares of Cell Phone Company. Masao Taki’s department received a grant to support numerical modeling work under a university–industry partnership. Joe Wiart works at Whist Laboratory funded by Orange. None of this funding was used to support the research described in this paper. The other authors declare that they have no conflict of interest.

Funding: the research leading to these results has received funding from by the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement number 22687 3 – the MOBI-Kids project. International coordination of the project is partly supported by a grant from the Spanish Ministry of Science and Innovation (MICCIN). Australia: Australian participation in MOBI-Kids is supported by the Australian National Health and Medical Research Council with a five-year research grant (grant number: 546130 and Chief Investigators are: Malcolm R. Sim, Bruce Armstrong, Elizabeth Milne, and Geza Benke). Austria: Austrian participation in MOBI-Kids is partly supported by a grant from the Ministry of Science. Canada: Canadian participation in MOBI-Kids is supported by a university–industry partnership grant from the Canadian Institutes of Health Research (CIHR), 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. Health Canada has also provided financial support to facilitate coordination between Canadian and international MOBI-Kids investigators. Daniel Krewski is the Natural Sciences and Engineering Research Council of Canada Chair in Risk Science at the University of Ottawa. France: this project received funds from the French National Agency for Sanitary Safety of Food, Environment and Labour (ANSES, contract FSRF 2008-3), 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. Greece: Greek participation is partially supported by ELKE (Special Account for Research Grants of the National and Kapodistrian University of Athens) and GGET (General Secretariat for Research and Technology). India: MOBI-Kids India is supported by the Board of Research in Nuclear Sciences (BRNS). Italy: Ministry of Health RF-2009-1546284. Japan: Japanese participation in MOBI-Kids is supported by the Ministry of Internal Affairs and Communications. Korea: MOBI-Kids Korea is financially supported by the Ministry of Science, ICT and Future Planning (MSIP), Korea in the ICT R&D Program. New Zealand: MOBI-Kids New Zealand is supported by grants from Cure Kids New Zealand and the New Zealand Health Research Council. Spain: Spanish participation is partially supported by the Spanish Health Research Fund (FIS PI10/02981), the Andalusian Consejeria de Salud (PI-0317/2010) and Conselleria de Sanitat, Generalitat Valenciana under grant number 025/2010. The Netherlands: Dutch participation in MOBI-KIDS is partly supported by The Netherlands Organisation for Health Research and Development (ZonMw) within the program Electromagnetic Fields and Health Research under grant number 85800001, and by the ODAS foundation, a private foundation supporting activities in the field of pediatric oncology and visual disabilities.

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MOBI-Kids Key Facts

Study Design (http://bit.ly/1ycxo9o):

Fourteen participating nations: Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, Netherlands, New Zealand, and Spain.

Diagnostic period: May, 2010 through December, 2014.

Participation rates (to date) (http://bit.ly/1CYvnO7):
78-83% of cases and 60-69% of controls.

Main characteristics of 566 cases and 1074 controls (thru June, 2014) (http://bit.ly/1BXvbfr):
Sex: 55% male, 45% female.

Years of age: 40% 10-14; 35% 15-19;  24% 20-24.

Most of the cases came from six countries: Spain (145), Italy (106), Germany (71), Israel (65) , France (63), or Greece (42).  The eight other countries have so far only contributed 2 to 23 cases each.

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'Cellphones Don't Increase Kids' Cancer Risk' Study Flawed, Experts Say 

Natalie Wolchover, LiveScience, July 28, 2011 

<SNIP>

"It's a very peculiar paper and even more peculiar that it's published in a journal sponsored by the National Cancer Institute," Joel Moskowitz, director of the Center for Family and Community Health at the University of California-Berkeley, told Life's Little Mysteries. A red flag, he said, is that the research was funded in part by the cellphone industry, and some of the investigators also do other industry-funded research.

In Moskowitz's opinion, the conclusions drawn by study leader Martin Röösli, an environmental epidemiologist at the Swiss Tropical and Public Health Institute, and his colleagues were biased to downplay concerns about cellphone use among children and adolescents.

<SNIP>

In a response sent to the media, Moskowitz pointed out what he considers several flaws in Röösli's logic, starting with how little cellphone use (one call per week) counted as "regular." This parameter flooded the pool of truly regular cellphone users with almost-non-users, he said, skewing the results. "Such a loose definition of regular use would be expected to reduce the association between cellphone use and tumor risk," Moskowitz wrote.  [FAQ: Cellphone Radiation and Brain Cancer]

When a subset of the data corresponding only to heavy cellphone users is analyzed, he pointed out, the results become much more striking. From the journal's paper itself: "[There] was a highly significant association between the time since first subscription and brain tumor risk. Children who used cellphones for at least 2.8 years were more than twice as likely to have a brain tumor than those who never regularly used cellphones." The authors went on to state: "As compared to never regular users, those who used cellphones for 4 or more years based on phone company records were 3.7 to 4.0 times more likely to have brain tumors, and those who made 2,638 or more calls were 2.9 to 4.8 times more likely to have brain tumors."

http://www.livescience.com/15290-cellphones-increase-kids-cancer-risk-study-flawed-experts.html

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MOBI-Kids Original Post (May 10, 2013)


Brain tumors are the second most common cancer in young people under 20 years of age. The incidence has been increasing recently. (1)

CEFALO, a small, four-country, case-control study of brain tumors in children, found in a subgroup for whom phone company data were available that brain tumor risk was related to the number of years the children had a mobile phone subscription. The study found elevated risks (though not statistically significant) for children who used mobile phones in three of the four countries (Denmark, Sweden and Switzerland), but not in Norway or overall. The study had 352 young people 7-19 years of age with brain tumors and 646 healthy young people. (2)


In a case-control study, persons who have developed a disease are identified and their past exposure to potential etiological factors is compared to persons who do not have the disease. (1)

MOBI-KIDS is a large, 16-country, case-control study that will evaluate the association between mobile phone and other communication technology use, other environmental exposures, and the risk of brain tumors in young people. MOBI-KIDS will include about 2.000 young people 10-24 years of age with brain tumors and about 4.000 healthy young people. Results will be available in 2015/2016. (3)


Just like the INTERPHONE study which examined brain tumors in adults, Canada is participating in the MOBI-KIDS study, but the U.S. is not. (4) 

Why has the U.S. failed to participate in these international studies? Why does the U.S. fund so little research on the health risks of exposure to electromagnetic radiation?

http://www.mbkds.com/home



References

(1) Frequently Asked Questions | MOBI-KIDS. http://www.mbkds.com/frequently-asked-questions-0

(2)  Aydin D., et al. Mobile phone use and brain tumors in children and adolescents: a multicenter case-control study.J Natl Cancer Inst. 2011 Aug 17;103(16):1264-76. doi: 10.1093/jnci/djr244. Epub 2011 Jul 27. http://jnci.oxfordjournals.org/content/103/16/1264.long

(3) Welcome | MOBI-KIDS: Study on Communication Technology, Environment, and Brain Tumours in Young People. http://www.mbkds.com/home

(4) Partners | MOBI-KIDS. http://www.mbkds.com/list-of-partners

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Revital Bar-Sade Bruchim, Ph.D., 

Fieldwork Coordinator, Mobi-Kids Israel

May 12, 2015

"Another paper published by Prof. Sadetzki and Prof. Cardis in 2011 entitled: "Indications of possible brain-tumor risk in mobile-phone studies: should we be concerned?" (Occup Environ Med. 2011 Mar;68(3):169-71), discusses the main issues in the interpretation of the findings reported in published studies of brain tumors in relation to mobile-phone use, particularly the largest of these, Interphone, and their potential public-health implications. 

The authors concluded that while more studies are needed to confirm or refute these results, indications of an increased risk in high- and long-term users from Interphone and other studies are of concern. 

Since more than 4 billion people, including children, using mobile phones even a small risk at the individual level could eventually result in a considerable number of tumors and become an important public-health issue. 

The authors suggested that until definitive scientific answers are available, simple and low-cost measures, such as the use of text messages, hands-free kits and/or the loud-speaker mode of the phone should be used to reduce exposure to the brain from mobile phones."


http://www.crealradiation.com/index.php/en/news-about-mobi-kids-project/feature-of-the-month-israel

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Assessment of extremely low frequency magnetic field exposure from GSM mobile phones


Calderón C, Addison D, Mee T, Findlay R, Maslanyj M, Conil E, Kromhout H, Lee AK, Sim MR, Taki M, Varsier N, Wiart J, Cardis E. Assessment of extremely low frequency magnetic field exposure from GSM mobile phones. Bioelectromagnetics. 2014 Apr;35(3):210-21. doi: 10.1002/bem.21827.

Abstract

Although radio frequency (RF) electromagnetic fields emitted by mobile phones have received much attention, relatively little is known about the extremely low frequency (ELF) magnetic fields emitted by phones. This paper summarises ELF magnetic flux density measurements on global system for mobile communications (GSM) mobile phones, conducted as part of the MOBI-KIDS epidemiological study. The main challenge is to identify a small number of generic phone models that can be used to classify the ELF exposure for the different phones reported in the study. Two-dimensional magnetic flux density measurements were performed on 47 GSM mobile phones at a distance of 25 mm. Maximum resultant magnetic flux density values at 217 Hz had a geometric mean of 221 (+198/-104) nT. Taking into account harmonic data, measurements suggest that mobile phones could make a substantial contribution to ELF exposure in the general population. The maximum values and easily available variables were poorly correlated. However, three groups could be defined on the basis of field pattern indicating that manufacturers and shapes of mobile phones may be the important parameters linked to the spatial characteristics of the magnetic field, and the categorization of ELF magnetic field exposure for GSM phones in the MOBI-KIDS study may be achievable on the basis of a small number of representative phones. Such categorization would result in a twofold exposure gradient between high and low exposure based on type of phone used, although there was overlap in the grouping.



Excerpts

From the perspective of the main epidemiological study, thus far the data suggest the most favourable grouping to be based on distinguishing bar phones for given manufacturers and flip/slide phones. The proposed a priori grouping approach is relatively easy to apply and when adopted will result in a reasonable twofold exposure gradient between high and low exposure based on type of phone used.

Because the ELF signal has a burst-like waveform, harmonic components are also an important factor. The relative importance of the harmonics can be considered in terms of the wellestablished biophysical mechanism of electrical stimulation of nervous tissue, which forms the basis for the exposure guidelines of the International Commission on Non-Ionizing Radiation Protection [ICNIRP, 2010].
 
The study demonstrates that the phones emit magnetic flux densities at 217 Hz and associated harmonics, and could contribute substantially to ELF exposure in the general population. It is therefore not unreasonable to include a measure of this exposure in epidemiological studies assessing the potential risk of EMF exposure and brain tumor, particularly for young people, for whom the time weighted average exposure, over lifetime, may be greater than in adults.

Due to the technological advancements in mobile telecommunications during the study period of interest (2000–2013), it will also be necessary to assess 2.5–3.5 G phones; Enhanced Data rates for GSM Evolution (EDGE), Universal Mobile Telecommunications System (UMTS), High Speed Packet Access (HSPA) and Digital Enhanced Cordless Telecommunications (DECT) phones as well as the 2G phones. 

Conflicts of interest: Prof. Masao Taki's department received a grant to support numerical modeling work under a university-industry partnership. Whist Lab is funded by France Telecom. None of this funding was used to support the research described in this paper.

Wednesday, May 11, 2022

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