Klaus Schlaefer

Malformations in newborn: results based on 30940 infants and fetuses from the Mainz congenital birth defect monitoring system (1990-1998)

Abstractu2002Prevalence rates of birth defects in the Federal Republic of Germany are informative to assess the general background risk of having a child with a birth defect. They provide basic figures to determine temporal and regional prevalence trends, to evaluate and initiate preventive measures and to initiate research projects. To avoid observer, definition and collection bias, active monitoring systems are required. Data collected in the active monitoring system of the Mainz Birth Defects Registry are presented. From 1990–1998, 30940 livebirths, stillbirths and abortions underwent standardized physical and sonographic examinations. Anamnestic data were collected from prenatal care records, maternity files and hospital records. Major malformations were diagnosed in 2144 (6.9%) and mild errors of morphogenesis in 11104 (35.8%) of all infants. Risk factors associated with the occurrence of major malformations were identified by comparing anamnestic data from infants with and without major malformations. Using multivariate regression models, statistically significant associations were established for 9 risk factors. Causally related risk factors were parents or siblings with malformations, parental consanguinity, more than 3 minor errors of morphogenesis in the proband, maternal diabetes mellitus and ingestion of antiallergic drugs in the first trimester of pregnancy. Conjunctional risk factors were polyhydramnios, oligohydramnios and gestational age <32 weeks at birth. Using these risk factors, populations at risk for the occurrence of major malformation can be identified.

Serial examination of 20,248 newborn fetuses and infants: Correlations between drug exposure and major malformations

Maternal medication during the first trimester of pregnancy has been discussed as a risk factor for development of birth defects. The correlation between maternal drug use and major malformations was investigated in a population-based case-control study in Mainz. Over a period of 5 years (1990-1994), 20,248 livebirths, stillbirths, and abortions underwent physical and sonographic examination, and anamnestic data were collected. A total of 1,472 births with congenital anomalies (cases) and 9,682 births without major and minor malformations (controls) were analyzed. We distinguished between 30 different drug categories, which were divided into medication taken continuously (before and during pregnancy; CM) and acute medication (drugs given within the first 3 months of gravidity; AM). Statistically highly-significant results [CM: Odds Ratios (OR) 1.2, Confidence Intervals (CI) 1.1-1.4, P = 0.008; AM: OR 1.2, CI 1.1-1.3, P = 0.008] were established for maternal drug use in correlation to birth defects. For the majority of combinations between drugs and specific malformations no teratogenic risks were found. However, statistically significant associations were recorded for antiallergics and heart anomalies (CM, AM) as well as musculoskeletal anomalies (AM); for bronchodilators and heart anomalies (CM, AM); for antiepileptics and anomalies of the internal urogenital system (CM), as well as cleft palate/cleft lips (AM); for thyroid hormones and anomalies of the nervous system (CM, AM), as well as anomalies of the external urogenital system (CM, AM); for insulin and anomalies of the musculoskeletal system (CM); for digitalis and anomalies of the musculoskeletal system (AM).

History of allergic disease and epilepsy and risk of glioma and meningioma (INTERPHONE study group, Germany)

The aim of the present analysis was to examine the association of a medical history of asthma, hay fever, eczema, or epilepsy with the risk of glioma and meningioma. Data of a German population-based case–control study included 381 meningioma cases, 366 glioma cases, and 1,494 controls. Participants’ histories of asthma, hay fever, eczema, and epilepsy and the respective ages at onset were asked during a personal interview. A small inverse association between allergic condition and both glioma (odds ratio: 0.92; 95% CI: 0.70–1.22) and meningioma (odd ratio: 0.87; 95% CI: 0.66–1.14) was found. For glioma, this inverse association was more pronounced in persons reporting to have asthma compared to other allergic conditions. The positive association between epilepsy and particularly glioma suggests that epilepsy is an early symptom of the disease. As the association was seen also for epilepsies occurring more than a decade before the diagnosis of glioma, this might indicate either an aetiological role of epilepsy, or a relatively long preclinical phase. In conclusion our study confirms previous findings of case control studies but not those from cohort studies. However, possible selection bias in case control studies might not explain the different results in its entirety.

Occupational Exposure to Extremely Low-Frequency Magnetic Fields and Brain Tumor Risks in the INTEROCC Study

Background: Occupational exposure to extremely low-frequency magnetic fields (ELF) is a suspected risk factor for brain tumors, however the literature is inconsistent. Few studies have assessed whether ELF in different time windows of exposure may be associated with specific histologic types of brain tumors. This study examines the association between ELF and brain tumors in the large-scale INTEROCC study. Methods: Cases of adult primary glioma and meningioma were recruited in seven countries (Australia, Canada, France, Germany, Israel, New Zealand, and the United Kingdom) between 2000 and 2004. Estimates of mean workday ELF exposure based on a job exposure matrix were assigned. Estimates of cumulative exposure, average exposure, maximum exposure, and exposure duration were calculated for the lifetime, and 1 to 4, 5 to 9, and 10+ years before the diagnosis/reference date. Results: There were 3,761 included brain tumor cases (1,939 glioma and 1,822 meningioma) and 5,404 population controls. There was no association between lifetime cumulative ELF exposure and glioma or meningioma risk. However, there were positive associations between cumulative ELF 1 to 4 years before the diagnosis/reference date and glioma [odds ratio (OR) ≥ 90th percentile vs. < 25th percentile, 1.67; 95% confidence interval (CI), 1.36–2.07; PLinear trend < 0.0001], and, somewhat weaker associations with meningioma (OR ≥ 90th percentile vs. < 25th percentile, 1.23; 95% CI, 0.97–1.57; PLinear trend = 0.02). Conclusions: Results showed positive associations between ELF in the recent past and glioma. Impact: Occupational ELF exposure may play a role in the later stages (promotion and progression) of brain tumorigenesis. Cancer Epidemiol Biomarkers Prev; 23(9); 1863–72. ©2014 AACR.

Validity of self-reported occupational noise exposure.

In all epidemiological studies the validity of self-reported questionnaire data is an important issue as the exposure assessment based on such data is a major source of bias in the risk estimation. A validation study was conducted based on a case–control study including 94 acoustic neuroma cases and 191 matched controls from the German Interphone Study to investigate the level of agreement between self-reported occupational noise exposure and a job-exposure-matrix (JEM) on noise exposure derived from a lifetime occupation calendar. The JEM was generated based on measurement data collected in the literature for various occupations. Level of agreement was investigated by using sensitivity, specificity, kappa coefficient and the Youden-Index. The receiver operating characteristics curve yielded an optimal cut point of 80xa0decibel(Acoustic) (dB(A)) to dichotomize noise exposure, displaying a moderate agreement between self-reported exposure and the JEM-based exposure (kappa of 0.53) that was slightly higher for cases than controls (kappas of 0.62 and 0.48). The agreement was only slightly lower if the longest held job or the last held job were used instead of the loudest job of the lifetime job history. The cut point of 80xa0dB(A) corresponds with regulations for workers safety with a recommendation to wear noise protection. The good levels of agreement between self-reported high occupational noise exposure compared with JEM-data, together with no substantial differences between cases and controls, suggest that self-reported data on occupational noise exposure is a valid exposure metric. Noise exposure appears to be appropriate if only exposure information on the last or the longest held job is available.

Occupation and risk of glioma, meningioma and acoustic neuroma: Results from a German case–control study (Interphone Study Group, Germany)

BACKGROUNDnSeveral epidemiological studies have investigated the association between occupation and brain tumour risk, but results have been inconclusive. We investigated the association between six occupational categories defined a priori: chemical, metal, agricultural, construction, electrical/electronic and transport, and the risk of glioma, meningioma and acoustic neuroma.nnnMETHODSnIn a population-based case-control study involving a total of 844 cases and 1688 controls conducted from 2000 to 2003, detailed information on life-long job histories was collected during personal interviews and used to create job calendars for each participant. Job title, job activity, job number, and the starting and ending dates of the activity were recorded for all activities with duration of at least 1 year. Reported occupational activities were coded according to the International Standard Classification of Occupations 1988 (ISCO 88). For the analyses we focused on six a priori defined occupational sectors, namely chemical, metal, agricultural, construction, electrical/electronic and transport. Multiple conditional logistic regression analysis was used to estimate odds ratios and their 95% confidence intervals.nnnRESULTSnMost of the observed odds ratios were close to 1.0 for ever having worked in the six occupational sectors and risk of glioma, meningioma and acoustic neuroma. Sub-group analyses according to duration of employment resulted in two elevated odds ratios with confidence intervals excluding unity.nnnCONCLUSIONSnWe did not observe an increased risk of glioma or meningioma for occupations in the agricultural, construction, transport, chemical, electrical/electronic and metal sectors. The number of significant odds ratios is consistent with an overall null-effect.

INTEROCC case-control study: lack of association between glioma tumors and occupational exposure to selected combustion products, dusts and other chemical agents

BackgroundThe aim was to investigate possible associations between glioma (an aggressive type of brain cancer) and occupational exposure to selected agents: combustion products (diesel and gasoline exhaust emissions, benzo(a)pyrene), dusts (animal dust, asbestos, crystalline silica, wood dust) and some other chemical agents (formaldehyde, oil mist, sulphur dioxide).MethodsThe INTEROCC study included cases diagnosed with glioma during 2000–2004 in sub-regions of seven countries. Population controls, selected from various sampling frames in different centers, were frequency or individually matched to cases by sex, age and center. Face-to-face interviews with the subject or a proxy respondent were conducted by trained interviewers. Detailed information was collected on socio-economic and lifestyle characteristics, medical history and work history. Occupational exposure to the 10 selected agents was assessed by a job exposure matrix (JEM) which provides estimates of the probability and level of exposure for different occupations. Using a 25% probability of exposure in a given occupation in the JEM as the threshold for considering a worker exposed, the lifetime prevalence of exposure varied from about 1% to about 15% for the different agents. Associations between glioma and each of the 10 agents were estimated by conditional logistic regression, and using three separate exposure indices: i) ever vs. never; ii) lifetime cumulative exposure; iii) total duration of exposure.ResultsThe study sample consisted of 1,800 glioma cases and 5,160 controls. Most odds ratio estimates were close to the null value. None of the ten agents displayed a significantly increased odds ratio nor any indication of dose–response relationships with cumulative exposure or with duration of exposure.ConclusionThus, there was no evidence that these exposures influence risk of glioma.

Radiofrequency Electromagnetic Fields Emitted from Base Stations of DECT Cordless Phones and the Risk of Glioma and Meningioma (Interphone Study Group, Germany)

Abstract Schüz, J., Böhler, E., Schlehofer, B., Berg, G., Schlaefer, K., Hettinger, I., Kunna-Grass, K., Wahrendorf, J. and Blettner, M. Radiofrequency Electromagnetic Fields Emitted from Base Stations of DECT Cordless Phones and the Risk of Glioma and Meningioma (Interphone Study Group, Germany). Radiat. Res. 166, 116–119 (2006). The objective of this study was to test the hypothesis that exposure to continuous low-level radiofrequency electromagnetic fields (RF EMFs) increases the risk of glioma and meningioma. Participants in a population-based case-control study in Germany on the risk of brain tumors in relation to cellular phone use were 747 incident brain tumor cases between the ages of 30 and 69 years and 1494 matched controls. The exposure measure of this analysis was the location of a base station of a DECT (Digital Enhanced Cordless Telecommunications) cordless phone close to the bed, which was used as a proxy for continuous low-level exposure to RF EMFs during the night. Estimated odds ratios were 0.82 (95% confidence interval: 0.29–2.33) for glioma and 0.83 (0.29–2.36) for meningioma. There was also no increasing risk observed with duration of exposure to DECT cordless phone base stations. Although the study was limited due to the small number of exposed subjects, it is still a first indication that residential low-level exposure to RF EMFs may not pose a higher risk of brain tumors.

Occupational solvent exposure and risk of meningioma: results from the INTEROCC multicentre case-control study

Objective To examine associations between occupational exposure to selected organic solvents and meningioma. Methodology A multicentre case–control study conducted in seven countries, including 1906 cases and 5565 controls. Occupational exposure to selected classes of organic solvents (aliphatic and alicyclic hydrocarbons, aromatic hydrocarbons, chlorinated hydrocarbons and ‘other’ organic solvents) or seven specific solvents (benzene, toluene, trichloroethylene, perchloroethylene, 1,1,1-trichloroethylene, methylene chloride and gasoline) was assessed using lifetime occupational histories and a modified version of the FINJEM job-exposure matrix (INTEROCC-JEM). Study participants were classified as ‘exposed’ when they had worked in an occupation for at least 1u2005year, with a 5-year lag, in which the estimated prevalence of exposure was 25% or greater in the INTEROCC-JEM. Associations between meningioma and each of the solvent exposures were estimated using conditional logistic regression, adjusting for potential confounders. Results A total of 6.5% of study participants were ever exposed to ‘any’ solvent, with a somewhat greater proportion of controls (7%) ever exposed compared with cases (5%), but only one case was ever exposed to any chlorinated hydrocarbon (1,1,1-trichloroethane). No association was observed between any of the organic solvents and meningioma, in either men or women, and no dose–response relationships were observed in internal analyses using either exposure duration or cumulative exposure. Discussion We found no evidence that occupational exposure to these organic solvents is associated with meningioma.

Birth defects in the vicinity of nuclear power plants in Germany

Living in the vicinity of nuclear power plants (NPP) is discussed here in terms of adverse health effects. A prospective population-based cohort study was conducted to evaluate whether the prevalence of birth defects in the vicinity of NPPs is elevated and scrutinize a possible distance correlation. A birth cohort born to mothers living within 10xa0km of two selected NPPs (study region) was compared to a region without NPP (comparison region), and an active surveillance of all live births, stillbirths, and induced abortions in the defined regions was performed. Between 01/2007 and 02/2008, all newborns were examined by specially trained study paediatricians according to the protocols of the Birth Registry Mainz Model. The cohort consisted of 5,273 infants (90% completeness). The outcome measure was an infant with birth defect(s). The prevalence of infants with birth defects was 4.5% in the study region and 4.7% in the comparison region, which corresponds to a relative risk (RR) of 0.94 (lower 95% confidence level (CL): 0.76). Thus, the prevalence of birth defects in the regions surrounding NPPs was not increased compared to those of the comparison region. Adjustment for potential confounders did not substantially change the result (RR 0.90, lower 95% CL 0.73). The adjusted and unadjusted distance approach (1/distance in km) did not show any correlation to vicinity to a NPP (pxa0=xa00.38). Specifically, within the study region, the prevalence of birth defects showed no upward trend with decreasing distance. Birth defect prevalence and most descriptive parameters in the comparison region were identical to those in the Birth Registry Mainz Model.