Marijn M Brouwers

Publications of Marijn M Brouwers

• Estrogenic and androgenic activities in total plasma measured with reporter-gene bioassays: relevant exposure measures for endocrine disruptors in epidemiologic studies?

  Authors: Marijn M Brouwers, Harrie Besselink, Reini W Bretveld, Rob Anzion, Paul T J Scheepers, Abraham Brouwer, Nel Roeleveld

  Environment international. 04/2011; 37(3):557-64.

  Measurements of estrogenic and androgenic activities in total plasma with Chemically Activated LUciferase gene eXpression (CALUX®) bioassays could provide biologically relevant measures for exposureMeasurements of estrogenic and androgenic activities in total plasma with Chemically Activated LUciferase gene eXpression (CALUX®) bioassays could provide biologically relevant measures for exposure to endocrine disruptors in epidemiologic studies. The objective of this study was to explore the effects of a variety of sources of potential endocrine disruptors on estrogenic and androgenic activities in total plasma measured by CALUX®. Plasma samples and interview data on sources of potential endocrine disruptors were collected from 108 men with different exposures profiles. CALUX® measurements (BioDetection Services) involved human U2-OS cell lines controlled by the estrogen receptor alpha and the androgen receptor. Mean differences (beta) in 17β-estradiol equivalents (EEQs) and dihydrotestosterone equivalents (AEQs) between exposure groups were estimated using general linear models. Mean plasma AEQs and EEQs were 9.1×10(-1)ng/ml and 12.0pg/ml, respectively. Elevated AEQs were found in smokers (beta 1.9 (95%CI 0.1-3.6)×10(-1)ng/ml) and heavy drinkers (1.4 (0.2-3.1)×10(-1)ng/ml), and in men occupationally exposed to disinfectants (1.6 (0.3-3.5)×10(-1)ng/ml) or welding/soldering fumes (1.4 (-0.2-2.9)×10(-1)ng/ml). Occupational exposure to pesticides, disinfectants, and exhaust fumes seemed to be associated with increased plasma EEQs: 1.5 (-0.2-3.2)pg/ml, 2.1 (0.2-3.9)pg/ml, and 2.9 (0.6-5.2)pg/ml, respectively. Moderate to high plasma dioxin levels, measured in a subgroup by the dioxin-responsive CALUX®, were accompanied by a 20% increase in AEQs. This is the first study in which CALUX® was used to assess hormone activities in total plasma. Although the results are not yet readily interpretable, they indicate that these measurements can be valuable for epidemiologic studies on endocrine disruptors and give direction for further research.

• Occupational exposure to endocrine disruptors and time to pregnancy among couples in a large birth cohort study: the Generation R Study.

  Authors: Claudia A Snijder, Marijn M Brouwers, Vincent W V Jaddoe, Albert Hofman, Nel Roeleveld, Alex Burdorf

  Fertility and sterility. 03/2011; 95(6):2067-72.

  To study the influence of occupational exposure to endocrine disruptors (EDs) on time to pregnancy (TTP). Cross-sectional analysis within a prospective, population-based cohort study. MedicalTo study the influence of occupational exposure to endocrine disruptors (EDs) on time to pregnancy (TTP). Cross-sectional analysis within a prospective, population-based cohort study. Medical center. Mothers and fathers who filled out a questionnaire during mid-pregnancy (response 77% and 82% of enrollment, respectively) were selected if the pregnancy was planned and either parent performed paid employment. In total, 2,774 mothers and 2,728 partners were included in the statistical analyses. None. Self-reported TTP (months). There was no correlation between maternal and paternal exposure, because κ values for agreement for all exposure categories ranged from 0.03 to 0.13. Paternal occupational exposure to heavy metals (hazard ratio of pregnancy 0.83; 95% confidence interval 0.71-0.97) and overall exposure to EDs (hazard ratio 0.85; 95% confidence interval 0.75-0.96) was statistically significantly associated with an increased TTP. Maternal occupational exposure to all categories of EDs showed prolonged TTP, but the decreased hazard ratios were not statistically significant. This birth cohort study provides indications for adverse effects of parental occupational exposure to EDs on TTP.

• Risk factors for undescended testis.

  Authors: Marijn M Brouwers, Leonie M de Bruijne, Robert P E de Gier, Gerhard A Zielhuis, Wouter F J Feitz, Nel Roeleveld

  Journal of pediatric urology. 11/2010; 8(1):59-66.

  To contribute to the understanding of the etiology of undescended testis (UDT), by exploring a wide range of potential risk factors in a case-referent study. Cases and referents were recruited atTo contribute to the understanding of the etiology of undescended testis (UDT), by exploring a wide range of potential risk factors in a case-referent study. Cases and referents were recruited at five hospitals and included 200 boys with surgically corrected UDT and 629 boys with persistent middle ear effusion. Risk factor data were obtained by postal questionnaires to both parents. Clinical data were collected from medical files. Adjusted odds ratios (OR) with 95% confidence intervals (CI) were estimated using logistic regression. The main findings include associations between UDT and familial occurrence of the disorder: OR 3.1 (95%CI 1.9-4.9), low birth weight: 2.2 (1.1-4.3), twinning: 2.2 (0.9-5.4), gestational preeclampsia: 1.9 (0.8-4.4), use of oral contraceptives after conception: 3.6 (1.0-12.5), in vitro fertilization/intracytoplasmic sperm injection treatment: 2.2 (0.8-6.0), paternal subfertility: 1.8 (0.8-4.1), and maternal occupational exposure to cosmetics: 3.0 (0.9-10.0). Subgroup analyses indicated differences in ORs for several factors between cases with (n = 92) and without (n = 103) inguinal hernia or hydrocele. The findings point towards a role for genetic predisposition, placental insufficiency, and possibly exposure to specific endocrine disrupting substances in the etiology of UDT. Further research should take into account potential etiologic differences between subgroups of cases with UDT.

• Maternal and paternal risk factors for anorectal malformations: a Dutch case-control study.

  Authors: Iris A L M van Rooij, Charlotte H W Wijers, Paul N M A Rieu, Hester S Hendriks, Marijn M Brouwers, Nine V Knoers, Ivo de Blaauw, Nel Roeleveld

  Birth defects research. Part A, Clinical and molecular teratology. 03/2010; 88(3):152-8.

  Anorectal malformations (ARM) are major congenital malformations that usually require a multitude of surgical procedures at a very early age and have a large impact on the lives of patients and theirAnorectal malformations (ARM) are major congenital malformations that usually require a multitude of surgical procedures at a very early age and have a large impact on the lives of patients and their parents. The causes of ARM are still largely unknown, but they are assumed to have a multifactorial etiology. A few studies focused on environmental risk factors, but evidence is still scarce. In this Dutch case-control study (1996-2008), we investigated the role of maternal and paternal risk factors in the etiology of ARM. Parents of 85 ARM cases and 650 controls filled in a questionnaire. Controls were children treated with ear ventilation tubes. A higher occurrence of fever during the first trimester of pregnancy was found for case mothers compared to control mothers (odds ratio [OR], 5.1; 95% Confidence Interval [CI], 0.9, 28.1). Maternal occupational exposure to industrial cleaning agents and solvents increased the risk of ARM three times (OR, 2.9; 95% CI, 0.9, 9.3). Overweight (Body Mass Index [BMI] > or = 25 kg/m(2)) before pregnancy also seemed to be associated with ARM (OR, 1.8; 95% CI, 1.1, 2.8), as well as maternal multivitamin use during pregnancy (OR, 1.6; 95% CI, 1.0, 2.7), paternal smoking (OR, 1.8; 95% CI, 1.1, 2.9), and paternal occupational exposure to exhaust fumes (OR, 1.9; 95% CI, 1.0, 3.6). Reported ARM in at least one first- or second-degree family member greatly increased the risk of having a child with an ARM (OR, 40.3; 95% CI, 4.8, 342.8). This study revealed potential risk factors for ARM, including fever during pregnancy, maternal overweight, use of multivitamins, paternal smoking, and occupational exposures, but a familial component seems important as well.

• Hypospadias: risk factor patterns and different phenotypes.

  Authors: Marijn M Brouwers, Loes F M van der Zanden, Robert P E de Gier, Evert J Barten, Gerhard A Zielhuis, Wouter F J Feitz, Nel Roeleveld

  BJU international. 09/2009;

  OBJECTIVE To obtain more insight into the origin of hypospadias by exploring a wide range of potential risk factors in a case-referent study in which a distinction was made between differentOBJECTIVE To obtain more insight into the origin of hypospadias by exploring a wide range of potential risk factors in a case-referent study in which a distinction was made between different phenotypes. PATIENTS AND METHODS Cases and referents were 305 boys with hypospadias and 629 boys with middle ear effusion whose parents completed postal questionnaires. Hypospadias phenotype was classified as distal (195 boys), middle (67), and proximal (43). Adjusted odds ratios (OR) with 95% confidence intervals (CI) were estimated using logistic regression. RESULTS Low birth weight, being a twin or triplet, mother being a diethylstilbestrol-daughter, fertility treatments, paternal subfertility, obesity, prescriptive drug use, and familial occurrence of hypospadias or testicular cancer were associated with hypospadias in general. For familial occurrence of hypospadias, there were high risk estimates for the distal and middle phenotypes with an OR (95%CI) of 10.4 (4.5-24.1) and 9.0 (3.1-26.0), but not for the proximal type at 1.8 (0.2-14.9). By contrast, the association with low birth weight (a proxy for placental dysfunction) seemed much stronger for proximal hypospadias with an OR (95%CI) of 9.1 (3.4-24.2) compared with distal and middle hypospadias at 2.6 (1.4-5.0) and 2.3 (0.8-6.5). There were similar estimates for pre-eclampsia. CONCLUSION These findings indicate aetiological heterogeneity of hypospadias and provide indications for the possible mechanisms through which specific risk factors may interfere with penile development.

• Occupational exposure to potential endocrine disruptors: further development of a Job Exposure Matrix.

  Authors: Marijn M Brouwers, Martie van Tongeren, Adrian A Hirst, Reini W Bretveld, Nel Roeleveld

  Occupational and environmental medicine. 04/2009;

  OBJECTIVES: The aim was to develop a new up-to-date and comprehensive Job Exposure Matrix (JEM) for estimating exposure to potential endocrine disruptors in epidemiologic research. METHODS: ChemicalsOBJECTIVES: The aim was to develop a new up-to-date and comprehensive Job Exposure Matrix (JEM) for estimating exposure to potential endocrine disruptors in epidemiologic research. METHODS: Chemicals with endocrine disrupting properties were identified from the literature and classified into 10 chemical groups: polycyclic aromatic hydrocarbons (PAHs), polychlorinated organic compounds, pesticides, phthalates, organic solvents, bisphenol A, alkylphenolic compounds, brominated flame retardants, metals, and a miscellaneous group. Most chemical groups were divided into three to six subgroups. Focusing on the years 1996 - 2006, three experts scored the probability of exposure to each chemical group and subgroup for 353 job titles, in three levels: 'unlikely' (0), 'possible' (1), and 'probable' (2). Job titles with positive exposure probability scores were provided with exposure scenarios that described the reasoning behind the scores. RESULTS: For 238 job titles (67%), exposure to any chemical group was unlikely, whereas 102 (29%) job titles were classified as possibly (17%) or probably (12%) exposed to one or several endocrine disruptors. The remaining 13 job titles provided too little information to classify exposure. PAHs, pesticides, phthalates, organic solvents, alkylphenolic compounds, and metals were often linked to a job title in the JEM. The remaining chemical groups were found to involve very few occupations. CONCLUSIONS: Despite some important limitations, this JEM can be a valuable tool for exposure assessment in studies on health risks of endocrine disruptors, especially when task-specific information is incorporated. The documented exposure scenarios are meant to facilitate further adjustments to the JEM to allow more widespread use.

• Risk factors for hypospadias.

  Authors: Marijn M Brouwers, Wouter F J Feitz, Luc A J Roelofs, Lambertus A L M Kiemeney, Robert P E de Gier, Nel Roeleveld

  European journal of pediatrics. 08/2007; 166(7):671-8.

  Despite being one of the most common congenital defects in boys, the etiology of hypospadias remains largely unknown. In this case-referent study, we evaluated a wide spectrum of potential riskDespite being one of the most common congenital defects in boys, the etiology of hypospadias remains largely unknown. In this case-referent study, we evaluated a wide spectrum of potential risk factors for hypospadias. Cases were identified from the hospital information system, and referents were recruited through the parents of the cases. Both parents of cases and referents completed written questionnaires that they received through the mail. Logistic regression analyses were used to assess the independent contribution of different factors to the risk of hypospadias. The final database included 583 cases and 251 referents. Hypospadias more often occurred in children whose father had hypospadias (OR=9.7; 95%CI: 1.3-74.0) and in children with a low birth weight (OR=2.3; 95%CI: 1.2-4.2). Indications for elevated risks were found when mothers were DES-daughters (OR=3.5; 95%CI: 0.8-15.6), fathers were subfertile (OR=1.8; 95%CI: 0.7-4.5), the parents had undergone fertility treatment (OR=2.3; 95%CI: 0.9-5.8), and in twin or triplet pregnancies (OR=2.0; 95%CI: 0.8-5.1). Maternal use of iron supplements (OR=2.2; 95%CI: 0.8-6.0), maternal smoking (OR=1.5; 95%CI: 1.0-2.4), paternal prescriptive drug use (OR=2.6; 95%CI: 1.1-6.6), and paternal exposure to pesticides (OR=2.1; 95%CI: 0.6-7.1) during the 3 months immediately prior to conception or in the first trimester of pregnancy also appeared to increase the risk of hypospadias. The associations found in this study support the hypothesis that genetic predisposition, placental insufficiency, and substances that interfere with natural hormones play a role in the etiology of hypospadias.