Risk factors for hypospadias.
ABSTRACT 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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ABSTRACT: Potential trans-generational influence of diethylstilbestrol (DES) exposure emerged with reports of effects in grandchildren of DES-treated pregnant women and of reproductive tract tumors in offspring of mice exposed in utero to DES. Accordingly, we examined the trans-generational influence of DES on development of external genitalia (ExG) and compared effects of in utero DES exposure in CD-1 and C57BL/6 mice injected with oil or DES every other day from gestational days 12 to 18. Mice were examined at birth, and on 5–120 days postnatal to evaluate ExG malformations. Of 23 adult (>60 days) prenatally DES-exposed males, features indicative of urethral meatal hypospadias (see text for definitions) ranged from 18% to 100% in prenatally DES-exposed CD-1 males and 31% to 100% in prenatally DES-exposed C57BL/6 males. Thus, the strains differed only slightly in the incidence of male urethral hypospadias. Ninety-one percent of DES-exposed CD-1 females and 100% of DES-exposed C57BL/6 females had urethral–vaginal fistula. All DES-exposed CD-1 and C57BL/6 females lacked an os clitoris. None of the prenatally oil-treated CD-1 and C57BL/6 male and female mice had ExG malformations. For the second-generation study, 10 adult CD-1 males and females, from oil- and DES-exposed groups, respectively, were paired with untreated CD-1 mice for 30 days, and their offspring evaluated for ExG malformations. None of the F1 DES-treated females were fertile. Nine of 10 prenatally DES-exposed CD-1 males sired offspring with untreated females, producing 55 male and 42 female pups. Of the F2 DES-lineage adult males, 20% had exposed urethral flaps, a criterion of urethral meatal hypospadias. Five of 42 (11.9%) F2 DES lineage females had urethral–vaginal fistula. In contrast, all F2 oil-lineage males and all oil-lineage females were normal. Thus, prenatal DES exposure induces malformations of ExG in both sexes and strains of mice, and certain malformations are transmitted to the second-generation.Differentiation 09/2014; · 2.84 Impact Factor
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ABSTRACT: Background Hypospadias is a frequent birth defect with three phenotypic subtypes. With data from the National Birth Defects Prevention Study, a large, multi-state, population-based, case–control study, we compared risk factors for second and third degree hypospadias.MethodsA wide variety of data on maternal and pregnancy-related risk factors for isolated second and third degree hypospadias was collected by means of computer-assisted telephone interviews to identify potential etiological differences between the two phenotypes. Logistic regression was used to calculate odds ratios including a random effect by study center.ResultsIn total, 1547 second degree cases, 389 third degree cases, and 5183 male controls were included in our study. Third degree cases were more likely to have a non-Hispanic black or Asian/Pacific Islander mother, be delivered preterm, have a low birth weight, be small for gestational age, and be conceived with fertility treatments than second degree cases and controls. Associations with both second and third degree hypospadias were observed for maternal age, family history, parity, plurality, and hypertension during pregnancy. Risk estimates were generally higher for third degree hypospadias except for family history.Conclusion Most risk factors were associated with both or neither phenotype. Therefore, it is likely that the underlying mechanism is at least partly similar for both phenotypes. However, some associations were different between second and third degree hypospadias, and went in opposite directions for second and third degree hypospadias for Asian/Pacific Islander mothers. Effect estimates for subtypes of hypospadias may be over- or underestimated in studies without stratification by phenotype. Birth Defects Research (Part A), 2014. © 2014 Wiley Periodicals, Inc.Birth Defects Research Part A Clinical and Molecular Teratology 09/2014; · 2.27 Impact Factor
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ABSTRACT: This case-controlled study was designed to evaluate the association between various baseline parental factors and the risk of hypospadias in China. Patients were selected from tertiary referral hospitals in Anhui, a province in mid-eastern China. A questionnaire was given to the parents of each patient. The final database included 193 cases and 835 controls. The incidence of additional coexistent anomalies was 13.0%, primarily cryptorchidism (9.8%). Ten patients (5.1%) were from families with genital anomaly, including five families (2.6%) with hypospadias. The risks of hypospadias was higher for children of mothers > 35 (odds ratio [OR] =1.47) and < 18 (OR = 2.95) years of age, and in mothers who had consumed alcohol (OR = 2.67), used drugs (OR = 1.53) and had an infection (OR = 1.87) during pregnancy. The risk of hypospadias was also higher when mothers (OR = 1.68) and fathers (OR = 1.74) were engaged in agriculture. Other factors assessed were not associated with the risk of hypospadias.Asian Journal of Andrology 05/2014; · 2.53 Impact Factor