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.
and proximal (43). Adjusted odds ratios (OR) with 95% confidence intervals (CI) were estimated using logistic regression. RESULTSLow 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. CONCLUSIONThese findings indicate aetiological heterogeneity of hypospadias and provide indications for the possible mechanisms through which specific risk factors may interfere with penile development. KEYWORDShypospadias, risk factors, endocrine disruptors, phenotype, severity Study Type -Aetiologic (case-referent) Level of Evidence 2a OBJECTIVETo 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 METHODSCases 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),
The results confirm an increased risk of hypospadias when mothers were exposed to DES in utero. However, the excess risk appears to be of much smaller magnitude than in the 2002 study. Further research on the potential health risks for the third generation is of great importance.
The American Academy of Pediatrics recently released its new Technical Report and Policy Statement on male circumcision, concluding that current evidence indicates that the health benefits of newborn male circumcision outweigh the risks. The technical report is based on the scrutiny of a large number of complex scientific articles. Therefore, while striving for objectivity, the conclusions drawn by the 8 task force members reflect what these individual physicians perceived as trustworthy evidence. Seen from the outside, cultural bias reflecting the normality of nontherapeutic male circumcision in the United States seems obvious, and the report’s conclusions are different from those reached by physicians in other parts of the Western world, including Europe, Canada, and Australia. In this commentary, a different view is presented by non–US-based physicians and representatives of general medical associations and societies for pediatrics, pediatric surgery, and pediatric urology in Northern Europe. To these authors, only 1 of the arguments put forward by the American Academy of Pediatrics has some theoretical relevance in relation to infant male circumcision; namely, the possible protection against urinary tract infections in infant boys, which can easily be treated with antibiotics without tissue loss. The other claimed health benefits, including protection against HIV/AIDS, genital herpes, genital warts, and penile cancer, are questionable, weak, and likely to have little public health relevance in a Western context, and they do not represent compelling reasons for surgery before boys are old enough to decide for themselves.
Even in the hands of the experienced pediatric urologists the complication rate after hypospadias repair remains high, with an average of 54% at long-term followup. Our results clearly showed that additional complications can present after long-term followup (a first complication can present after more than 5 years with the longest interval being 14 years). Therefore, final outcome of hypospadias surgery can only be evaluated once the patient has reached adulthood. The results seem to depend on the severity of the abnormality, reflected in the complication distribution rather than operative technique.
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