Nel Roeleveld

Publications of Nel Roeleveld

• Interobserver reliability and diagnostic performance of Chiari II malformation measures in MR imaging-part 2.

  Authors: Niels Geerdink, Ton van der Vliet, Jan J Rotteveel, Ton Feuth, Nel Roeleveld, Reinier A Mullaart

  Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery. 05/2012;

  PURPOSE: Brain MR imaging is essential in the assessment of Chiari II malformation in clinical and research settings concerning spina bifida. However, the interpretation of MR images of thePURPOSE: Brain MR imaging is essential in the assessment of Chiari II malformation in clinical and research settings concerning spina bifida. However, the interpretation of MR images of the malformation is not always straightforward. Morphometric analyses of the extent of Chiari II malformation may improve the assessment. In an attempt to select appropriate morphometric measures for this purpose, we investigated the interobserver reliability and diagnostic performance of several morphometric measures of Chiari II malformation on MR images. METHODS: Brain MR images of 79 children [26 with open spinal dysraphism, 17 with closed spinal dysraphism, and 36 without spinal dysraphism; mean age 10.6 (SD 3.2; range, 6-16) years] were evaluated. All children had been assessed for Chiari II malformation (defined as cerebellar herniation in combination with open spinal dysraphism; n = 23). Three observers blindly and independently reviewed the MR images for 21 measures of the cerebellum, brainstem, and posterior fossa in three planes. The interobserver reliability was assessed by an agreement index (AI = 1 - RRE) and the diagnostic performance by receiver operating characteristic analyses. RESULTS: Reliability was good for most measures, except for the degree of herniation of the vermis and tonsil. Most values differed statistically significantly between children with and without Chiari II malformation. The measures mamillopontine distance and cerebellar width showed excellent diagnostic performance. CONCLUSIONS: Morphometric measures may reliably quantify the morphological distortions of Chiari II malformation on MR images and provide additional tools to assess the severity of Chiari II malformation in clinical and research settings.

• Essential features of Chiari II malformation in MR imaging: an interobserver reliability study-part 1.

  Authors: Niels Geerdink, Ton van der Vliet, Jan J Rotteveel, Ton Feuth, Nel Roeleveld, Reinier A Mullaart

  Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery. 05/2012;

  PURPOSE: Brain MR imaging is essential in the assessment of Chiari II malformation in clinical and research settings concerning spina bifida. However, the interpretation of morphological features ofPURPOSE: Brain MR imaging is essential in the assessment of Chiari II malformation in clinical and research settings concerning spina bifida. However, the interpretation of morphological features of the malformation on MR images may not always be straightforward. In an attempt to select those features that unambiguously characterize the Chiari II malformation, we investigated the interobserver reliability of all its well-known MR features. METHODS: Brain MR images of 79 children [26 presumed to have Chiari II malformation, 36 presumed to have no cerebral abnormalities, and 17 children in whom some Chiari II malformation features might be present; mean age 10.6 (SD 3.2; range, 6-16) years] were blindly and independently reviewed by three observers. They rated 33 morphological features of the Chiari II malformation as present, absent, or indefinable in three planes (sagittal, axial, and coronal). The interobserver reliability was assessed using κ statistics. RESULTS: Twenty-three of the features studied turned out to be unreliable, whereas the interobserver agreement was almost perfect (κ value > 0.8) for nine features (eight in the sagittal plane and one in the axial plane, but none in the coronal plane). CONCLUSIONS: This study presents essential features of the Chiari II malformation on MR images by ruling out the unreliable features. Using these features may improve the assessment of Chiari II malformation in clinical and research settings.

• Occupational exposure to chemical substances and time to pregnancy: a systematic review.

  Authors: Claudia A Snijder, Egbert Te Velde, Nel Roeleveld, Alex Burdorf

  Human reproduction update. 03/2012;

  BACKGROUNDFertility problems are an important health issue, as 10-15% of couples have difficulties conceiving. Reproductive function is thought to be compromised by lifestyle behaviours, butBACKGROUNDFertility problems are an important health issue, as 10-15% of couples have difficulties conceiving. Reproductive function is thought to be compromised by lifestyle behaviours, but environmental contaminants and work-related factors are also thought to play a role. The objective of this review was to systematically summarize the available evidence concerning the influence of occupational exposure to chemicals on time to pregnancy (TTP).METHODSA structured search on occupational exposure to chemicals and TTP was carried out in PubMed and Embase. Studies were included if TTP was used as outcome measure and exposure to chemicals at the job level was described. In total, 49 studies were included in this review.RESULTSStudies varied widely in characterization of exposure, hampering a meta-analytic approach across all studies. For lead, strong indications for adverse effects on TTP were present, supporting the mandatory provisions for pregnant women being exposed to lead in many countries. These indications were also found for pesticide exposure, and one could argue that couples working in agriculture or horticultural trades must be informed about the risks of pesticide exposure. Epidemiologic evidence on other chemicals, such as organic solvents, and other metals remains equivocal, hampering clear counselling of couples who are trying to become pregnant.CONCLUSIONSDespite some uncertainties in the evidence base, it may still be prudent to advise against lead and pesticide exposure at the workplace for couples trying to conceive. This review also identifies several priorities for future studies in the field of occupational epidemiology.

• Occupational exposure to chemicals and fetal growth: the Generation R Study.

  Authors: Claudia A Snijder, Nel Roeleveld, Egbert Te Velde, Eric A P Steegers, Hein Raat, Albert Hofman, Vincent W V Jaddoe, Alex Burdorf

  Human reproduction (Oxford, England). 01/2012; 27(3):910-20.

  BACKGROUND Developmental diseases, such as birth defects, growth restriction and preterm delivery, account for >25% of infant mortality and morbidity. Several studies have shown that exposure toBACKGROUND Developmental diseases, such as birth defects, growth restriction and preterm delivery, account for >25% of infant mortality and morbidity. Several studies have shown that exposure to chemicals during pregnancy is associated with adverse birth outcomes. The aim of this study was to identify whether occupational exposure to various chemicals might adversely influence intrauterine growth patterns and placental weight. METHODS Associations between maternal occupational exposure to various chemicals and fetal growth were studied in 4680 pregnant women participating in a population-based prospective cohort study from early pregnancy onwards in the Netherlands (2002-2006), the Generation R Study. Mothers who filled out a questionnaire during mid-pregnancy (response: 77% of enrolment) were included if they conducted paid employment during pregnancy and had a spontaneously conceived singleton live born pregnancy (n = 4680). A job exposure matrix was used, linking job titles to expert judgement on exposure to chemicals in the workplace. Fetal growth characteristics were repeatedly measured by ultrasound and were used in combination with measurements at birth. Placental weight was obtained from medical records and hospital registries. Linear regression models for repeated measurements were used to study the associations between maternal occupational exposure to chemicals and intrauterine growth. RESULTS We observed that maternal occupational exposure to polycyclic aromatic hydrocarbons, phthalates, alkylphenolic compounds and pesticides adversely influenced several domains of fetal growth (fetal weight, fetal head circumference and fetal length). We found a significant association between pesticide and phthalate exposure with a decreased placental weight. CONCLUSIONS Our results suggest that maternal occupational exposure to several chemicals is associated with impaired fetal growth during pregnancy and a decreased placental weight. Further studies are needed to confirm these findings and to assess post-natal consequences.

• Reproductive health characteristics of marijuana and cocaine users: results from the 2002 National Survey of Family Growth.

  Authors: Marleen M H J van Gelder, Jennita Reefhuis, Anne M Herron, Mark L Williams, Nel Roeleveld

  Perspectives on sexual and reproductive health. 09/2011; 43(3):164-72.

  Illicit drug use is associated with risky sexual behaviors in adolescents and young adults. However, few studies have examined these associations among drug users of all reproductive ages, using aIllicit drug use is associated with risky sexual behaviors in adolescents and young adults. However, few studies have examined these associations among drug users of all reproductive ages, using a control group of nonusers. Associations between marijuana and cocaine use, and outcomes related to sexual behaviors and reproductive health, were assessed using data from the 2002 National Survey of Family Growth. Overall, 4,928 men and 7,643 women aged 15-44 were interviewed. Chi-square tests, t tests and multivariable logistic regression analyses were used; in supplementary analyses, men and women were stratified by age-group (25 or younger, and older than 25), to capture the understudied older adults who use drugs. Twenty-seven percent of men and 16% of women reported use of marijuana or cocaine in the last year. Drug users were younger than nonusers at first vaginal sex (mean, 15.2-16.1 vs. 17.3-17.5 years) and were more likely to have engaged in risky sexual behaviors in the last year, including having had sex with a nonmonogamous partner (odds ratios, 3.3-5.2 for men and 2.9-6.5 for women), while high on alcohol or drugs (10.1-18.0 and 8.1-24.2), or in exchange for money or drugs (2.7-2.8 and 2.3-9.2). They also were more likely to have undergone STD testing or treatment. Drug use was associated with risky sexual behaviors in both age-groups. Programs aimed at reducing sexual risks among drug users should address the behaviors of men and women of all reproductive ages.

• 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.

• Corrigendum: Common variants in DGKK are strongly associated with risk of hypospadias.

  Authors: Loes F M van der Zanden, Iris A L M van Rooij, Wout F J Feitz, Jo Knight, A Rogier T Donders, Kirsten Y Renkema, Ernie M H F Bongers, Sita H H M Vermeulen, Lambertus A L M Kiemeney, Joris A Veltman, Alejandro Arias-Vásquez, Xufeng Zhang, Ellen Markljung, Liang Qiao, Laurence S Baskin, Agneta Nordenskjöld, Nel Roeleveld, Barbara Franke, Nine V A M Knoers

  Nature genetics. 03/2011; 43(3):277.

• 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.

• Influence of birth mode on early neurological outcome in infants with myelomeningocele.

  Authors: Inge Cuppen, Alex J Eggink, Fred K Lotgering, Jan J Rotteveel, Reinier A Mullaart, Nel Roeleveld

  European journal of obstetrics, gynecology, and reproductive biology. 02/2011; 156(1):18-22.

  The aim of the study was to determine whether route of birth affects early neurological outcome in infants with myelomeningocele. In a retrospective cohort study, 95 neonates with myelomeningoceleThe aim of the study was to determine whether route of birth affects early neurological outcome in infants with myelomeningocele. In a retrospective cohort study, 95 neonates with myelomeningocele evaluated at the Radboud University Nijmegen Medical Centre between 1990 and 2006 were reviewed. The effect of delivery mode on early neurological outcome was assessed as the difference between the functional neurological level of the defect and the X-ray level (ΔFAX). Early neurological outcome was better in the vaginally delivered infants (ΔFAX 0.96 ± 2.1) than in those delivered by cesarean section (ΔFAX 0.20 ± 2.5). After correction for confounders, multiple regression analysis demonstrated that vaginal delivery was associated with significantly better early neurological outcome as compared to cesarean section (β=1.21; 95% CI 0.16; 2.27; p=0.03) for infants in vertex and breech position combined. Subgroup analysis revealed a non-significant trend towards better outcome after vaginal delivery that was more pronounced in infants in breech position than in vertex position. In infants with myelomeningocele, born in either vertex or breech position, there is no clinical evidence that early neurological outcome is improved by cesarean section.

• Reporting on the modes of data collection.

  Authors: Marleen M H J van Gelder, Reini W Bretveld, Nel Roeleveld

  Lancet. 01/2011; 377(9759):30.

• Common variants in DGKK are strongly associated with risk of hypospadias.

  Authors: Loes F M van der Zanden, Iris A L M van Rooij, Wout F J Feitz, Jo Knight, A Rogier T Donders, Kirsten Y Renkema, Ernie M H F Bongers, Sita H H M Vermeulen, Lambertus A L M Kiemeney, Joris A Veltman, Alejandro Arias-Vásquez, Xufeng Zhang, Ellen Markljung, Liang Qiao, Laurence S Baskin, Agneta Nordenskjöld, Nel Roeleveld, Barbara Franke, Nine V A M Knoers

  Nature genetics. 01/2011; 43(1):48-50.

  Hypospadias is a common congenital malformation of the male external genitalia. We performed a genome-wide association study using pooled DNA from 436 individuals with hypospadias (cases) and 494Hypospadias is a common congenital malformation of the male external genitalia. We performed a genome-wide association study using pooled DNA from 436 individuals with hypospadias (cases) and 494 controls of European descent and selected the highest ranked SNPs for individual genotyping in the discovery sample, an additional Dutch sample of 133 cases and their parents, and a Swedish series of 266 cases and 402 controls. Individual genotyping of two SNPs (rs1934179 and rs7063116) in DGKK, encoding diacylglycerol kinase κ, produced compelling evidence for association with hypospadias in the discovery sample (allele-specific odds ratio (OR) = 2.5, P = 2.5 × 10⁻¹¹ and OR = 2.3, P = 2.9 × 10⁻⁹, respectively) and in the Dutch (OR = 3.9, P = 2.4 × 10⁻⁵ and OR = 3.8, P = 3.4 × 10⁻⁵) and Swedish (OR = 2.5, P = 2.6 × 10⁻⁸ and OR = 2.2, P = 2.7 × 10⁻⁶) replication samples. Expression studies showed expression of DGKK in preputial tissue of cases and controls, which was lower in carriers of the risk allele of rs1934179 (P = 0.047). We propose DGKK as a major risk gene for hypospadias.

• Exposure to non-steroidal anti-inflammatory drugs during pregnancy and the risk of selected birth defects: a prospective cohort study.

  Authors: Marleen M H J van Gelder, Nel Roeleveld, Hedvig Nordeng

  PloS one. 01/2011; 6(7):e22174.

  Since use of non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy is common, small increases in the risk of birth defects may have significant implications for public health. Results ofSince use of non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy is common, small increases in the risk of birth defects may have significant implications for public health. Results of human studies on the teratogenic risks of NSAIDs are inconsistent. Therefore, we evaluated the risk of selected birth defects after prenatal exposure to prescribed and over-the-counter NSAIDs. We used data on 69,929 women enrolled in the Norwegian Mother and Child Cohort Study between 1999 and 2006. Data on NSAID exposure were available from a self-administered questionnaire completed around gestational week 17. Information on pregnancy outcome was obtained from the Medical Birth Registry of Norway. Only birth defects suspected to be associated with NSAID exposure based upon proposed teratogenic mechanisms and previous studies were included in the multivariable logistic regression analyses. A total of 3,023 women used NSAIDs in gestational weeks 0-12 and 64,074 women did not report NSAID use in early pregnancy. No associations were observed between overall exposure to NSAIDs during pregnancy and the selected birth defects separately or as a group (adjusted odds ratio 0.7, 95% confidence interval 0.4-1.1). Associations between maternal use of specific types of NSAIDs and the selected birth defects were not found either, although an increased risk was seen for septal defects and exposure to multiple NSAIDs based on small numbers (2 exposed cases; crude odds ratio 3.9, 95% confidence interval 0.9-15.7). Exposure to NSAIDs during the first 12 weeks of gestation does not seem to be associated with an increased risk of the selected birth defects. However, due to the small numbers of NSAID-exposed infants for the individual birth defect categories, increases in the risks of specific birth defects could not be excluded.

• Validation of maternal self-report in retrospective studies.

  Authors: Marleen M H J van Gelder, Nel Roeleveld

  Early human development. 11/2010; 87(1):43-4.

  Case-control studies are frequently performed in prenatal and perinatal epidemiology. For data collection, these studies often rely on self-administered questionnaires or personal interviews.Case-control studies are frequently performed in prenatal and perinatal epidemiology. For data collection, these studies often rely on self-administered questionnaires or personal interviews. Although of importance, validation of these measurement instruments received little attention in epidemiologic research so far. In this letter, we stress the need for more well-conducted validation studies in the field of prenatal and perinatal epidemiology. In addition, we comment on a validation study that was previously published in this journal.

• 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.

• Research perspectives in the etiology of congenital anorectal malformations using data of the International Consortium on Anorectal Malformations: evidence for risk factors across different populations.

  Authors: Charlotte H W Wijers, Ivo de Blaauw, Carlo L M Marcelis, Rene M H Wijnen, Han Brunner, Paola Midrio, Piergiorgio Gamba, Maurizio Clementi, Ekkehart Jenetzky, Nadine Zwink [......] Stefan Holland-Cunz, Stuart Hosie, Stefanie Märzheuser, Eberhard Schmiedeke, Célia Crétolle, Sabine Sarnacki, Marc A Levitt, Nine V A M Knoers, Nel Roeleveld, Iris A L M van Rooij

  Pediatric surgery international. 11/2010; 26(11):1093-9.

  The recently established International Consortium on Anorectal Malformations aims to identify genetic and environmental risk factors in the etiology of syndromic and nonsyndromic anorectalThe recently established International Consortium on Anorectal Malformations aims to identify genetic and environmental risk factors in the etiology of syndromic and nonsyndromic anorectal malformations (ARM) by promoting collaboration through data sharing and combined research activities. The consortium attempts to recruit at least 1,000 ARM cases. DNA samples are collected from case-parent triads to identify genetic factors involved in ARM. Several genetic techniques will be applied, including SNP arrays, gene and whole exome sequencing, and a genome-wide association study. Questionnaires inquiring about circumstances before and during pregnancy will be used to obtain environmental risk factor data. Currently, 701 ARM cases have been recruited throughout Europe. Clinical data are available from all cases, and DNA samples and questionnaire data mainly from the Dutch and German cases. Preliminary analyses on environmental risk factors in the Dutch and German cohort found associations between ARM and family history of ARM, fever during first trimester of pregnancy and maternal job exposure to cleaning agents and solvents. First results show that both genetic and environmental factors may contribute to the multifactorial etiology of ARM. The International Consortium on Anorectal Malformations will provide possibilities to study and detect important genes and environmental risk factors for ARM, ultimately resulting in better genetic counseling, improved therapies, and primary prevention.

• Web-based questionnaires: the future in epidemiology?

  Authors: Marleen M H J van Gelder, Reini W Bretveld, Nel Roeleveld

  American journal of epidemiology. 09/2010; 172(11):1292-8.

  The traditional epidemiologic modes of data collection, including paper-and-pencil questionnaires and interviews, have several limitations, such as decreasing response rates over the last decades andThe traditional epidemiologic modes of data collection, including paper-and-pencil questionnaires and interviews, have several limitations, such as decreasing response rates over the last decades and high costs in large study populations. The use of Web-based questionnaires may be an attractive alternative but is still scarce in epidemiologic research because of major concerns about selective nonresponse and reliability of the data obtained. The authors discuss advantages and disadvantages of Web-based questionnaires and current developments in this area. In addition, they focus on some practical issues and safety concerns involved in the application of Web-based questionnaires in epidemiologic research. They conclude that many problems related to the use of Web-based questionnaires have been solved or will most likely be solved in the near future and that this mode of data collection offers serious benefits. However, questionnaire design issues may have a major impact on response and completion rates and on reliability of the data. Theoretically, Web-based questionnaires could be considered an alternative or complementary mode in the range of epidemiologic methods of data collection. Practice and comparisons with the traditional survey techniques should reveal whether they can fulfill their expectations.

• Is human fecundity declining in Western countries?

  Authors: Egbert te Velde, Alex Burdorf, Eberhard Nieschlag, René Eijkemans, Jan A M Kremer, Nel Roeleveld, Dik Habbema

  Human reproduction (Oxford, England). 06/2010; 25(6):1348-53.

  Since Carlsen and co-workers reported in 1992 that sperm counts have decreased during the second half of the last century in Western societies, there has been widespread anxiety about the adverseSince Carlsen and co-workers reported in 1992 that sperm counts have decreased during the second half of the last century in Western societies, there has been widespread anxiety about the adverse effects of environmental pollutants on human fecundity. The Carlsen report was followed by several re-analyses of their data set and by many studies on time trends in sperm quality and on secular trends in fecundity. However, the results of these studies were diverse, complex, difficult to interpret and, therefore, less straightforward than the Carlsen report suggested. The claims that population fecundity is declining and that environmental pollutants are involved, can neither be confirmed nor rejected, in our opinion. However, it is of great importance to find out because the possible influence of widespread environmental pollution, which would adversely affect human reproduction, should be a matter of great concern triggering large-scale studies into its causes and possibilities for prevention. The fundamental reason we still do not know whether population fecundity is declining is the lack of an appropriate surveillance system. Is such a system possible? In our opinion, determining total sperm counts (as a measure of male reproductive health) in combination with time to pregnancy (as a measure of couple fecundity) in carefully selected populations is a feasible option for such a monitoring system. If we want to find out whether or not population fecundity will be declining within the following 20-30 years, we must start monitoring now.

• Genetics of hypospadias: are single-nucleotide polymorphisms in SRD5A2, ESR1, ESR2, and ATF3 really associated with the malformation?

  Authors: Loes F M van der Zanden, Iris A L M van Rooij, Wout F J Feitz, Sita H H M Vermeulen, Lambertus A L M Kiemeney, Nine V A M Knoers, Nel Roeleveld, Barbara Franke

  The Journal of clinical endocrinology and metabolism. 03/2010; 95(5):2384-90.

  Hypospadias is a common congenital malformation of the male external genitalia with a multifactorial etiology. Little is known about the genes involved in hypospadias. A few genetic associations haveHypospadias is a common congenital malformation of the male external genitalia with a multifactorial etiology. Little is known about the genes involved in hypospadias. A few genetic associations have been reported but mainly in studies of small sample size. Most of these associations have not been replicated. The aim of this study was to investigate whether previously reported associations for four single-nucleotide polymorphisms (SNPs) in genes involved in hormonal pathways could be replicated in a large Dutch hypospadias sample. The SNPs investigated are rs523349 in steroid-5 alpha-reductase (SRD5A2), rs6932902 in estrogen receptor 1 (ESR1), rs2987983 in ESR2, and rs11119982 in activating transcription factor 3 (ATF3). DESIGN, PARTICIPANTS, AND METHODS: We genotyped 620 Caucasian hypospadias cases and 596 controls for these SNPs using TaqMan-based genotyping. We did not replicate the associations of the SNPs in SRD5A2 and ESR1 with hypospadias. The SNPs in ESR2 and ATF3 were borderline associated with hypospadias [odds ratios 0.9 (95% confidence interval 0.7-1.0) and 1.2 (95% confidence interval 1.0-1.4), respectively] but in the opposite direction compared with earlier publications. Stratification according to localization of the urethral opening produced comparable results in the subgroups. The lack of consistency between our and previously performed studies might represent spurious results or chance findings in our or the earlier studies, differences in criteria used to select the study populations, or a real difference between populations, i.e. different genes contributing to disease risk. These results once again confirm the importance of replication in genetic association approaches.

• 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.

• Thickened saliva after effective management of drooling with botulinum toxin A.

  Authors: Corrie E Erasmus, Karen Van Hulst, Frank Ja Van Den Hoogen, Jacques Van Limbeek, Nel Roeleveld, Enno Ci Veerman, Jan J Rotteveel, Peter H Jongerius

  Developmental medicine and child neurology. 02/2010; 52(6):e114-8.

  The aim of this study was to evaluate the rheological properties of saliva after submandibular botulinum toxin type A (BoNT-A) injections. We enrolled 15 children (11 males and six females; age rangeThe aim of this study was to evaluate the rheological properties of saliva after submandibular botulinum toxin type A (BoNT-A) injections. We enrolled 15 children (11 males and six females; age range 3-17 y, mean age 9 y 10 mo) diagnosed with spastic (n=9) or dyskinetic (n=6) quadriplegic cerebral palsy (CP); Gross Motor Function Classification System level IV or V; and two children with intellectual disability (IQ<70) who experienced moderate to severe drooling. Salivary flow rate and drooling quotient were measured at baseline and at different times after BoNT-A injections up to 24 weeks. The mucin concentration of saliva was analysed before and after BoNT-A treatment. Both submandibular salivary flow rate (baseline 0.38 mL/min; 24 wks after injection 0.26 mL/min) and drooling quotient (baseline 42.5%; 24 wks 28.80%) were substantially reduced, with a concomitant increase in mucin concentration within 8 weeks after BoNT-A injection (from 0.612 to 1.830 U/mL). The parents of nine children observed thickened saliva. Swallowing and chewing were problematic in seven children. Two of these children needed treatment with mucolytics because of pooling of thickened saliva in the throat. When making decisions about the use of BoNT-A, the risk of problems with masticatory and swallowing functions as a result of thickening of saliva after BoNT-A treatment should be taken into account.