Risk factors for hypospadias

Department of Epidemiology and Biostatistics (133), Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
European Journal of Pediatrics (Impact Factor: 1.89). 08/2007; 166(7):671-8. DOI: 10.1007/s00431-006-0304-z
Source: PubMed


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 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.

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    • "Studies suggest that intra-uterine growth restriction (IUGR) in itself is a determining risk factor for hypospadias rather than the absolute birth weight (Hussain et al., 2002; Jensen et al., 2012; Yinon et al., 2010). Furthermore, twinning is a risk factor consistently associated with hypospadias (Brouwers et al., 2007; Jensen et al., 2012; Nordenvall et al., 2014; van Rooij et al., 2013). In a large case-control study about structural birth defects in twins, hypospadias occurred more often in twins compared "
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    ABSTRACT: Hypospadias is associated with twinning. The incidence of hypospadias in monochorionic and dichorionic male twins is, however, yet to be determined. All medical records of monochorionic and dichorionic twins admitted to our neonatal nursery between January 2004 and August 2013 were reviewed for the presence of hypospadias. A total of 350 monochorionic and 303 dichorionic male twins were included in the study. The incidence of hypospadias in monochorionic and dichorionic groups was 4% (14/350) and 1% (3/303) (p = .016) respectively. In 11 of the 15 twin couples, hypospadias occurred in the twin with the lowest birth weight. The rate of hypospadias in twin infants small-for-gestational-age group was 10% (6/60) compared with 2% (11/593) in the appropriate-for-gestational-age group (p = .002). In a multivariate analysis, both monochorionicity and small-for-gestational-age were independently associated with hypospadias, odds ratio 4.1 (95% confidence interval (CI): 1.1-14.7) and 6.1 (95% CI: 2.2-17.2) respectively. The incidence of hypospadias is four-fold higher in monochorionic twins compared with dichorionic twins. Hypospadias is also independently associated with small-for-gestational-age.
    Twin Research and Human Genetics 08/2015; 18(5):1-4. DOI:10.1017/thg.2015.55 · 2.30 Impact Factor
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    • "We identified 14 case-control studies2032395051525354555657585960 published from 1990 to 2010 and one meta-analysis42 on the association between maternal cigarette smoking during pregnancy and hypospadias. "
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    ABSTRACT: Maternal cigarette smoking may affect the intrauterine hormonal environment during pregnancy and this early fetal exposure may have detrimental effects on the future trajectory of reproductive health. In this review, we discuss the epidemiological literature on the association between prenatal exposure to maternal cigarette smoking and several aspects of reproductive health. The literature points towards an increased risk of the urogenital malformation cryptorchidism, but a potential protective effect on the risk of hypospadias in sons following prenatal cigarette smoking exposure. Studies on sexual maturation find a tendency towards accelerated pubertal development in exposed boys and girls. In adult life, prenatally exposed men have impaired semen quality compared with unexposed individuals, but an influence on fecundability, that is, the biological ability to reproduce, is less evident. We found no evidence to support an association between prenatal cigarette smoking exposure and testicular cancer. Among adult daughters, research is sparse and inconsistent, but exposure to cigarette smoking in utero may decrease fecundability. In conclusion, prenatal exposure to cigarette smoking may cause some long-term adverse effects on the reproductive health.
    Asian Journal of Andrology 01/2014; 16(1):39-49. DOI:10.4103/1008-682X.122351 · 2.60 Impact Factor
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    • "Hypospadias is thought to be associated with a transgenerational effect because treatment of pregnant mothers with diethylstilboestrol (DES) increased the incidence of hypospadias in the second generation.55 Some studies have reported that paternal exposure to pesticides prior to pregnancy does not seem to be associated with hypospadias.5657 A large study in the United Kingdom based on the birth defects registry data reported that hypospadias was not more likely among infants born to women with any particular occupational exposures.58 "
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    ABSTRACT: During the past few decades, scientific evidence has been accumulated concerning the possible adverse effects of the exposure to environmental chemicals on the well-being of wildlife and human populations. One large and growing group of such compounds of anthropogenic or natural origin is referred to as endocrine-disrupting chemicals (EDCs), due to their deleterious action on the endocrine system. This concern was first focused on the control of reproductive function particularly in males, but has later been expanded to include all possible endocrine functions. The present review describes the underlying physiology behind the cascade of developmental events that occur during sexual differentiation of males and the specific role of androgen in the masculinization process and proper organogenesis of the external male genitalia. The impact of the genetic background, environmental exposures and lifestyle factors in the etiology of hypospadias, cryptorchidism and testicular cancer are reviewed and the possible role of EDCs in the development of these reproductive disorders is discussed critically. Finally, the possible direct and programming effects of exposures in utero to widely use therapeutic compounds, environmental estrogens and other chemicals on the incidence of reproductive abnormalities and poor semen quality in humans are also highlighted.
    Asian Journal of Andrology 01/2014; 16(1):50-9. DOI:10.4103/1008-682X.122199 · 2.60 Impact Factor
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