Occupation and risk of glioma, meningioma and acoustic neuroma: results from a German case-control study (interphone study group, Germany).

BACKGROUND: Several 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. METHODS: In 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. RESULTS: Most 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. CONCLUSIONS: We 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'.

Environmental risk factors for sporadic acoustic neuroma (Interphone Study Group, Germany).

The only known risk factor for sporadic acoustic neuroma is high-dose ionising radiation. Environmental exposures, such as radiofrequency electromagnetic fields and noise are under discussion, as well as an association with allergic diseases. We performed a population-based case-control study in Germany investigating these risk factors in 97 cases with acoustic neuroma, aged 30 to 69 years, and in 194 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in multiple logistic regression models. Increased risks were found for exposure to persistent noise (OR=2.31; 95% CI 1.15-4.66), and for hay fever (OR=2.20; 95% CI 1.09-4.45), but not for ionising radiation (OR=0.91; 95 % CI 0.51-1.61) or regular mobile phone use (OR=0.67; 95% CI 0.38-1.19). The study confirms results of recently published studies, although the pathogenetic mechanisms are still unknown.

[Pre- and postnatal kidney screening compared: an analysis of 34,450 newborn infants of the Mainz model birth register]. / Prä- und postnatales Nierenscreening im Vergleich: eine Analyse von 34.450 Neugeborenen des Geburtenregisters Mainzer Modell.

UNLABELLED: Malformations of the internal urogenital system are common. The birth registry "Mainz Model" reflects population-based prevalence of renal malformations, calculates sensitivity rates of the prenatal ultrasonographic findings and demonstrates rates of surgery needed. METHOD AND MATERIAL: During the study period (1990-2001) all newborns of the area of Mainz were examined according to a standardized procedure including ultrasonography of the kidneys. Pathology reports were reviewed for stillbirth, abortions (> 15.SSW) and induced abortions. Beside these clinical findings, since 1996 (after implementation of a special ultrasonographic malformation screening according to the german maternity guidelines) the results of prenatal as well as postnatal ultrasonographic examinations of the kidney were recorded. All children with pathologic diagnoses of the kidneys were retrospectively analysed. Data about the follow up and surgery if needed, were collected. RESULTS: During the study period from 1990-2001 34.450 newborns were examined. 407 of the neonates (1.2%) had a malformation of the kidney. During the study period from 1996-2001 13.162 neonates were examined. 194 neonates (1.5%) had pathologic and 225 neonates (2.07%) had controllable findings. The most common diagnoses were supernumerary kidney, hydronephroses und megaureter. 22 neonates (12.8%) underwent surgery. The sensitivity of the prenatal ultrasonography was 36% and the specificity was 99%. CONCLUSION: Both, the prenatal as well as the postnatal ultrasonographic screening of the kidneys are ingenious examinations. The prenatal examination detects life threatening malformations of the kidneys. The postnatal examination completes early diagnosis of renal defects by uncovering the malformations, which have been missed prenatally. The prevalence of malformations of the kidney is comparable to the one of hip dislocation. We therefore conclude, that ultrasonographic screening of the kidneys is needed.

Malformations in newborn: results based on 30,940 infants and fetuses from the Mainz congenital birth defect monitoring system (1990-1998).

Prevalence 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, 30,940 live-births, 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 11,104 (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.

Repression of phenobarbital-dependent CYP2B1 mRNA induction by reactive oxygen species in primary rat hepatocyte cultures.

Xenobiotic-metabolizing cytochrome P-450 (P-450) enzymes not only play a pivotal role in elimination of foreign compounds but also contribute to generation of toxic intermediates, including reactive oxygen species, that may elicit cellular damage if produced excessively. Expression of several xenobiotic-metabolizing P-450 enzymes is induced by phenobarbital (PB). Pronounced induction is observed for the rat CYP2B1 isoform. A primary rat hepatocyte culture system was used to investigate whether reactive oxygen species might modulate PB-dependent CYP2B1 induction. In cells cultivated for 3 days with 1.5 mM PB, substantial CYP2B1 mRNA induction was observed (100%). Addition of H(2)O(2) or of the catalase inhibitor 3-amino-1,2,4-triazole (AT) to the medium repressed induction to approximately 30% (at 1 mM H(2)O(2) and 2 mM AT, respectively). Accordingly, treatment of hepatocytes with PB and the glutathione precursor N-acetylcysteine (NAC) led to enhanced PB-dependent induction (to over 1000% at 10 mM NAC). In primary hepatocyte cultures transfected with a CYP2B1 promoter-luciferase construct containing approximately 2.7 kilobase pairs of the native CYP2B1 promoter sequence, PB-dependent reporter gene activation was repressed by AT and stimulated by N-acetylcysteine. Furthermore, a 263-base pair CYP2B1 promoter fragment encompassing the phenobarbital-responsive enhancer module conferred suppression of PB-dependent luciferase expression by AT and activation by NAC in a heterologous SV40-promoter construct. In summary, these data demonstrate a regulatory mechanism that is dependent on the cellular redox status, which modulates CYP2B1 mRNA induction by PB on the transcriptional level, thus representing a feedback mechanism preventing further P-450-dependent production of reactive oxygen intermediates under oxidative stress.

Prenatal diagnosis of major malformations: quality control of routine ultrasound examinations based on a five-year study of 20,248 newborn fetuses and infants.

Antenatal ultrasound screening for birth defects is increasingly becoming a routine procedure of prenatal care. Prenatal detection of malformations and subsequent adjustment of obstetric management are essential for secondary prevention. It is unknown whether ultrasound screening is effective in all pregnant women, or should only be performed in high risk populations. From 1990-1994, 20,248 livebirths, stillbirths and abortions underwent physical and sonographic examinations and anamnestic data were collected. To identify the high risk group, case control analyses of births with one of the 23 selected major malformations (controls) were performed with respect to anamnestic risk factors. All women had at least three routine ultrasound scans. The selected malformations were diagnosed in 298 children; 95 (30.3 per cent) were diagnosed antenatally. Detection rates were: CNS (68.6 per cent), gastro-intestinal tract (42.3 per cent), urinary system (24.1) per cent), heart (5.9 per cent). Complications during pregnancy were calculated as indicators of congenital anomalies: premature labour (< 28 week) OR 4.7 (3.8-5.9), placental insufficiency OR 1.9 (1.1-2.7) and vaginal bleeding OR 1.5 (1.2-1.8), etc. Antenatal routine ultrasound screening is not effective risk populations. Anamnestic risk factors risk factors during pregnancy may be essential indicators for identifying high risk populations. We propose screening of the described high risk pregnancies (about 22 per cent of all pregnancies) to be performed by specially trained and highly experienced ultrasonographers to increase sensitivity rates and benefit cost effectiveness.

[Does maternal obesity increase the risk of fetal abnormalities? Analysis of 20,248 newborn infants of the Mainz Birth Register for detecting congenital abnormalities]. / Erhöht mütterliche Adipositas das Risiko für kindliche Fehlbildungen? Analyse von 20,248 Neugeborenen des Mainzer Geburtenregisters zur Erfassung angeborener Fehlbildungen.

AIM: To investigate the risk of congenital malformations for newborn of obese women (BMI > or = 30) compared with women of average prepregnancy weight. METHODS: We performed a prospective, population-based case-control study of 20,248 newborn born in the city of Mainz. A total of 1,451 infants (cases) with and 8,088 without congenital malformations (controls) were analysed. The relative risks of associations between obesity and malformations were calculated as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: The prevalence of malformations in children of obese mothers is 11.1% and thus approximately 4% higher than those of the total study population. There is a significant odds ratio for major malformations (OR 1.3; KI 1.0-1.7). Statistically significant associations were calculated for malformations of the internal urogenital system (OR 1.7; 1.1-2.8), the eyes (OR 5.0; 1.3-20.0) and for orofacial clefts (OR 1.7; 1.1-2.8). Among the specific malformations the highest associations occurred for encephalocele (OR 7.3; 1.1-50.6), common truncus arteriosus (OR 6.3; 1.6-24.8) and Potter sequence (OR 6.3; 1.6-24.8). Adjustment for confounding factors (e.g. maternal diabetes mellitus and age) did not change the odds ratios. CONCLUSIONS: Our data demonstrate that newborn of obese mothers are at an increased risk for malformations. An adequate prenatal examination of these pregnancies should include ultrasound screening by specially trained ultrasonographers in tertiary units (DEGUM II/DEGUM III) and serum alpha-fetoprotein measurements. Public health campaigns for prevention are advised.

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).