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

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

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

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

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

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

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

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

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

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

Pilot test of a peer-led small-group video intervention to promote mammography screening among Chinese American immigrants.

This study evaluated the feasibility, acceptability, and potential effect of a small-group video intervention led by trained Chinese American lay educators who recruited Chinese American women not up to date on mammography screening. Nine lay educators conducted 14 Breast Health Tea Time Workshops in community settings and private homes that started with watching a culturally tailored video promoting screening followed by a question-and-answer session and distribution of print materials. Many group attendees did not have health insurance or a regular doctor, had low levels of income, and were not proficient in English. Forty-four percent of the attendees reported receipt of a mammogram within 6 months after the small-group session, with higher odds of screening among women who had lived in the United States less than 10% of their lifetime. Four of the educators were very interested in conducting another group session in the next 6 months.

Peer navigation improves diagnostic follow-up after breast cancer screening among Korean American women: results of a randomized trial.

OBJECTIVE: To test an intervention to increase adherence to diagnostic follow-up tests among Asian American women. METHODS: Korean American women who were referred for a diagnostic follow-up test (mainly diagnostic mammograms) and who had missed their follow-up appointment were eligible to participate in the study. Women from two clinics (n = 176) were randomly allocated to a usual care control arm or a peer navigator intervention arm. A 20-min telephone survey was administered to women in both study arms six months after they were identified to assess demographic and socio-economic characteristics and the primary outcome, self-reported completion of the recommended follow-up exam. RESULTS: Among women who completed the survey at six-month follow-up, self-reported completion of follow-up procedures was 97% in the intervention arm and 67% in the control arm (p < 0.001). Based on an intent-to-treat analysis of all women who were randomized and an assumption of no completion of follow-up exam for women with missing outcome data, self-reported completion of follow-up was 61% in the intervention arm and 46% in the usual care control arm (p < 0.069). CONCLUSIONS: Our results suggest that a peer navigator intervention to assist Korean American women to obtain follow-up diagnostic tests after an abnormal breast cancer screening test is efficacious.

Handheld Ultrasound as a Novel Predictive Tool in Atrial Fibrillation: Prediction of Outcomes Following Electrical Cardioversion.

BACKGROUND: Atrial fibrillation (AF) recurrence after successful direct current cardioversion (CV) is common, and clinical predictors may be useful. We evaluated the risk of early AF recurrence according to inferior vena cava (IVC) measurements by handheld ultrasound (HHU) at the time of CV. OBJECTIVE: Assess HHU and objectively obtained measurements acquired at the point of care as potential clinical predictors of future clinical outcomes in patients with AF undergoing CV. METHODS: Maximum IVC diameter (IVCd) and collapsibility with inspiration were measured by the Vscan HHU (General Electric Healthcare Division) in 128 patients immediately before and after successful CV for AF. Patients were followed by chart review for recurrence of AF. RESULTS: Mean IVCd was 2.16 cm in AF pre-CV and 2.01 cm in sinus rhythm post-CV (P<.001). AF recurred within 30 days of CV in 34 of 128 patients (26.6%). Among patients with IVCd <2.1 cm pre-CV and decrease in IVCd post-CV, AF recurrence was 12.1%, compared to 31.6% in patients not meeting these parameters (odds ratio [OR] 0.299, P=.04). This association persisted after adjustment for age, ejection fraction <50%, left atrial enlargement, and amiodarone use (adjusted OR 0.185, P=.01). Among patients with IVCd post-CV <1.7 cm, AF recurrence was 13.5%, compared to 31.9% in patients not meeting this parameter (OR 0.185, P=.01). IVC parameters did not predict AF recurrence at 180 or 365 days. CONCLUSIONS: The presence of a normal IVCd pre-CV that becomes smaller post-CV and the presence of a small IVCd post-CV were each independently associated with reduced likelihood of early, but not late, AF recurrence. HHU assessment of IVCd at the time of CV may be useful to identify patients at low risk of early recurrence of AF after CV.

Maternal cell phone use during pregnancy and child cognition at age 5 years in 3 birth cohorts.

BACKGROUND: There have been few studies of children's cognitive development in relation to mothers' cell phone use, and most were limited to outcomes at age 3 years or younger. We examined the relationship between maternal cell phone use during pregnancy and cognitive performance in 5-year old children. METHODS: This study included data from 3 birth cohorts: the Danish National Birth Cohort (DNBC) (n = 1209), Spanish Environment and Childhood Project (INMA) (n = 1383), and Korean Mothers and Children's Environment Health Study (MOCEH) (n = 497). All cohorts collected information about maternal cell phone use during pregnancy and cognitive performance in children at age 5. We performed linear regression to compute mean differences (MD) and 95% confidence intervals (CI) in children's general, verbal, and non-verbal cognition scores comparing frequency of maternal prenatal cell phone use with adjustments for numerous potential confounding factors. Models were computed separately for each cohort and using pooled data in meta-analysis. RESULTS: No associations were detected between frequency of prenatal cell phone use and children's cognition scores. Scores tended to be lower in the highest frequency of use category; MD (95% CI) in general cognition scores were 0.78 (-0.76, 2.33) for none, 0.11 (-0.81, 1.03) for medium, and -0.41 (-1.54, 0.73) for high compared to low frequency of use. This pattern was seen across all cognitive dimensions, but the results were imprecise overall. CONCLUSION: We observed patterns of lower mean cognition scores among children in relation to high frequency maternal prenatal cell phone use. The causal nature and mechanism of this relationship remain unknown.

Re-examining the association between residential exposure to magnetic fields from power lines and childhood asthma in the Danish National Birth Cohort.

BACKGROUND: A study reported an increased risk of asthma in children whose mothers were exposed to magnetic field (MF) levels above 0.2 µT during pregnancy. We re-examined this association using data from mothers and children in the Danish National Birth Cohort (DNBC). METHODS: This study included 92,676 singleton-born children and their mothers from the DNBC. MF exposure from power lines was estimated for all residences where the mothers lived during pregnancy and for all children from birth until the end of follow up. Exposure was categorized into 0 µT, 0.1 µT, and ≥ 0.2 µT for analysis. Definitive and possible asthma cases were identified using data from three independent data sources: 1) mothers' reports, 2) a national hospitalization register, 3) a national prescription drug register. We calculated hazard ratios (HR) and 95% confidence intervals (CI) for the association between the highest level of exposure during pregnancy and asthma in children, adjusting for several potential confounding factors. We also examined the sensitivity of the risk estimates to changes in exposure and outcome definitions. RESULTS: No differences or trends in the risk of asthma development were detected between children with different levels of MF exposure regardless of the asthma case definition or outcome data source. For definitive cases, the HR (95% CI) for those with any exposure was 0.72 (0.27-1.92), and it was 0.41 (0.06-2.92) for those exposed to ≥ 0.2 µT. Adjustments for confounding and variations in the exposure definition did not appreciably alter the results. CONCLUSION: We did not find evidence that residential exposure to MF during pregnancy or early childhood increased the risk of childhood asthma. This interpretation is in line with the lack of an established biological mechanism directly linking MF exposure to asthma, but high exposure was very rare in this cohort.

Usefulness of Serial Measurements of Inferior Vena Cava Diameter by VscanTM to Identify Patients With Heart Failure at High Risk of Hospitalization.

Estimation of volume status is integral to heart failure (HF) management. Measurement of inferior vena cava (IVC) diameter (IVCd) by ultrasound provides a noninvasive estimate of right atrial pressures. The GE Vscan is a handheld ultrasound (HHU) device that allows for point-of-care measurements to assess volume status. We hypothesize that IVCd measurements using HHU can predict the risk of HF admission. We retrospectively analyzed a cohort of patients with HF treated in an ambulatory care setting over 17 months. Serial measurements of IVCd were obtained using HHU in the supine position from the subcostal window. Log-binomial regression models were used to compare IVCd measurements between patients with and without HF admissions and to estimate the association between IVCd and risk of HF admission. Of the 355 patients with systolic (38%) and diastolic HF (62%) who were analyzed, 45% were women with a mean age of 73 years at the time of the first IVCd measurement. Overall, 3,488 measurements were obtained, and 32.4% of patients were hospitalized during follow-up. Patients with at least 1 hospital admission had a greater mean IVCd than those who were not admitted (2.0 vs 1.8 cm, p <0.01). In our analysis, every 0.5-cm increase in the mean IVCd was associated with a 38% increase in risk of HF admission (risk ratio [RR] 1.38, 95% CI 1.16 to 1.62, p <0.01). The risk of HF admission was also significantly increased in patients with IVCd 2.0 to 2.49 cm (RR 1.79, 95% CI 1.27 to 2.52, p <0.01) and ≥2.5 cm (RR 2.39, 95% CI 1.55 to 3.67, p <0.01), compared with patients with an IVCd < 2.0 cm. Increasing IVCd as measured by HHU at the point-of-care is associated with an increased risk of HF admission and may provide clinically useful information at the point-of-care to guide HF management.

Maternal cell phone use during pregnancy and child behavioral problems in five birth cohorts.

INTRODUCTION: Previous studies have reported associations between prenatal cell phone use and child behavioral problems, but findings have been inconsistent and based on retrospective assessment of cell phone use. This study aimed to assess this association in a multi-national analysis, using data from three cohorts with prospective data on prenatal cell phone use, together with previously published data from two cohorts with retrospectively collected cell phone use data. METHODS: We used individual participant data from 83,884 mother-child pairs in the five cohorts from Denmark (1996-2002), Korea (2006-2011), the Netherlands (2003-2004), Norway (2004-2008), and Spain (2003-2008). We categorized cell phone use into none, low, medium, and high, based on frequency of calls during pregnancy reported by the mothers. Child behavioral problems (reported by mothers using the Strengths and Difficulties Questionnaire or Child Behavior Checklist) were classified in the borderline/clinical and clinical ranges using validated cut-offs in children aged 5-7years. Cohort specific risk estimates were meta-analyzed. RESULTS: Overall, 38.8% of mothers, mostly from the Danish cohort, reported no cell phone use during pregnancy and these mothers were less likely to have a child with overall behavioral, hyperactivity/inattention or emotional problems. Evidence for a trend of increasing risk of child behavioral problems through the maternal cell phone use categories was observed for hyperactivity/inattention problems (OR for problems in the clinical range: 1.11, 95%CI 1.01, 1.22; 1.28, 95%CI 1.12, 1.48, among children of medium and high users, respectively). This association was fairly consistent across cohorts and between cohorts with retrospectively and prospectively collected cell phone use data. CONCLUSIONS: Maternal cell phone use during pregnancy may be associated with an increased risk for behavioral problems, particularly hyperactivity/inattention problems, in the offspring. The interpretation of these results is unclear as uncontrolled confounding may influence both maternal cell phone use and child behavioral problems.

Trends in cell phone use among children in the Danish national birth cohort at ages 7 and 11 years.

We prospectively examined trends in cell phone use among children in the Danish National Birth Cohort. Cell phone use was assessed at ages 7 and 11 years, and we examined use patterns by age, by year of birth, and in relation to specific individual characteristics. There was an increase in cell phone use from age 7 (37%) to 11 years (94%). There was a clear pattern of greater reported cell phone use among children at age 7 years with later birth year, but this trend disappeared at age 11. Girls and those who used phones at age 7 talked more often and for longer durations at age 11 years. Low socio-economic status and later year of birth were associated with voice calls at age 7 but not at age 11 years. At age 11 most used cell phones for texting and gaming more than for voice calls. Further, children who started using cell phones at age 7 years were more likely to be heavy cell phone voice users at age 11 years, making early use a marker for higher cumulative exposure regardless of year of birth. As cell phone technology continues to advance, new use patterns will continue to emerge, and exposure assessment research among children must reflect these trends.

Prospective cohort analysis of cellphone use and emotional and behavioural difficulties in children.

BACKGROUND: We previously reported associations between cellphone exposure and emotional and behavioural difficulties in children in the Danish National Birth Cohort using cross-sectional data. To overcome the limitations of cross-sectional analysis, we re-examined these associations with prospectively collected data. METHODS: Based on maternal reports, prenatal and postnatal cellphone exposures were assessed at age 7 years, and emotional and behavioural difficulties were assessed at 7 and 11 years with the Strengths and Difficulties Questionnaire. We used multivariable-adjusted logistic regression models to estimate ORs and 95% CIs relating prenatal exposure and age-7 cellphone use to emotional and behavioural difficulties at age 11 years. RESULTS: Children without emotional and behavioural difficulties at age 7 years, but who had cellphone exposures, had increased odds of emotional and behavioural difficulties at age 11 years, with an OR of 1.58 (95% CI 1.34 to 1.86) for children with both prenatal and age-7 cellphone exposures, 1.41 (95% CI 1.20 to 1.66) for prenatal exposure only, and 1.36 (95% CI 1.14 to 1.63) for age-7 use only. These results did not materially change when early adopters were excluded, or when children with emotional and behavioural difficulties at age 7 years were included in the analysis. CONCLUSIONS: Our findings are consistent with patterns seen in earlier studies, and suggest that both prenatal and postnatal exposures may be associated with increased risks of emotional and behavioural difficulties in children.

Characterization of extremely low frequency magnetic fields from diesel, gasoline and hybrid cars under controlled conditions.

This study characterizes extremely low frequency (ELF) magnetic field (MF) levels in 10 car models. Extensive measurements were conducted in three diesel, four gasoline, and three hybrid cars, under similar controlled conditions and negligible background fields. Averaged over all four seats under various driving scenarios the fields were lowest in diesel cars (0.02 µT), higher for gasoline (0.04-0.05 µT) and highest in hybrids (0.06-0.09 µT), but all were in-line with daily exposures from other sources. Hybrid cars had the highest mean and 95th percentile MF levels, and an especially large percentage of measurements above 0.2 µT. These parameters were also higher for moving conditions compared to standing while idling or revving at 2500 RPM and higher still at 80 km/h compared to 40 km/h. Fields in non-hybrid cars were higher at the front seats, while in hybrid cars they were higher at the back seats, particularly the back right seat where 16%-69% of measurements were greater than 0.2 µT. As our results do not include low frequency fields (below 30 Hz) that might be generated by tire rotation, we suggest that net currents flowing through the cars' metallic chassis may be a possible source of MF. Larger surveys in standardized and well-described settings should be conducted with different types of vehicles and with spectral analysis of fields including lower frequencies due to magnetization of tires.

Epidemiology of childhood leukemia in the presence and absence of Down syndrome.

Down syndrome (DS) is a common congenital anomaly, and children with DS have a substantially higher risk of leukemia. Although understanding of genetic and epigenetic changes of childhood leukemia has improved, the causes of childhood leukemia and the potential role of environmental exposures in leukemogenesis remain largely unknown. Although many epidemiologic studies have examined a variety of environmental exposures, ionizing radiation remains the only generally accepted environmental risk factor for childhood leukemia. Among suspected risk factors, infections, exposure to pesticides, and extremely low frequency magnetic fields are notable. While there are well-defined differences between leukemia in children with and without DS, studies of risk factors for leukemia among DS children are generally consistent with trends seen among non-DS (NDS) children. We provide background on DS epidemiology and review the similarities and differences in biological and epidemiologic features of leukemia in children with and without DS. We propose that both acute lymphoblastic and acute myeloblastic leukemia among DS children can serve as an informative model for development of childhood leukemia. Further, the high rates of leukemia among DS children make it possible to study this disease using a cohort approach, a powerful method that is unfeasible in the general population due to the rarity of childhood leukemia.

Complexities of sibling analysis when exposures and outcomes change with time and birth order.

In this study, we demonstrate the complexities of performing a sibling analysis with a re-examination of associations between cell phone exposures and behavioral problems observed previously in the Danish National Birth Cohort. Children (52,680; including 5441 siblings) followed up to age 7 were included. We examined differences in exposures and behavioral problems between siblings and non-siblings and by birth order and birth year. We estimated associations between cell phone exposures and behavioral problems while accounting for the random family effect among siblings. The association of behavioral problems with both prenatal and postnatal exposure differed between siblings (odds ratio (OR): 1.07; 95% confidence interval (CI): 0.69-1.66) and non-siblings (OR: 1.54; 95% CI: 1.36-1.74) and within siblings by birth order; the association was strongest for first-born siblings (OR: 1.72; 95% CI: 0.86-3.42) and negative for later-born siblings (OR: 0.63; 95% CI: 0.31-1.25), which may be because of increases in cell phone use with later birth year. Sibling analysis can be a powerful tool for (partially) accounting for confounding by invariant unmeasured within-family factors, but it cannot account for uncontrolled confounding by varying family-level factors, such as those that vary with time and birth order.

Prenatal and Postnatal Cell Phone Exposures and Headaches in Children.

OBJECTIVE: Children today are exposed to cell phones early in life, and may be at the greatest risk if exposure is harmful to health. We investigated associations between cell phone exposures and headaches in children. STUDY DESIGN: The Danish National Birth Cohort enrolled pregnant women between 1996 and 2002. When their children reached age seven years, mothers completed a questionnaire regarding the child's health, behaviors, and exposures. We used multivariable adjusted models to relate prenatal only, postnatal only, or both prenatal and postnatal cell phone exposure to whether the child had migraines and headache-related symptoms. RESULTS: Our analyses included data from 52,680 children. Children with cell phone exposure had higher odds of migraines and headache-related symptoms than children with no exposure. The odds ratio for migraines was 1.30 (95% confidence interval: 1.01-1.68) and for headache-related symptoms was 1.32 (95% confidence interval: 1.23-1.40) for children with both prenatal and postnatal exposure. CONCLUSIONS: In this study, cell phone exposures were associated with headaches in children, but the associations may not be causal given the potential for uncontrolled confounding and misclassification in observational studies such as this. However, given the widespread use of cell phones, if a causal effect exists it would have great public health impact.