Hypospadias: risk factor patterns and different phenotypes

Abstract

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),

Maternal and paternal risk factors for anorectal malformations: A Dutch case‐control study

“…The control group was derived from a study on hypospadias (Brouwers et al, 2009) and recruited at the Departments of Otorhinolaryngology of the RUNMC and three general hospitals around Nijmegen, covering the referral area of the ARM cases. All controls were boys with persistent middle ear infection treated with ventilation tubes and born between 1996 and 2004.…”

Genetic and environmental factors in the aetiology of hypospadias

“…Other studies, although with a lesser increased risk, have confirmed this finding [35][36][37][38]. Proposed explanations include that DES may cause genetic or epigenetic changes in primordial oocytes, which are then transmitted to next generation, or changes in somatic cells of the DES daughters resulting in hormonal imbalance in adult life [34].…”

Prevalence of genital abnormalities in neonates

“…Nos anos mais recentes, tem se verificado tendência global de elevação da prevalência desse defeito, provavelmente relacionada com exposição ambiental a drogas com ação estrogênica ou antiandrogênica, com capacidade de desbalancear a relação andrógeno/estrógeno ou de interferir na biossíntese de esteroides sexuais 4,[19][20][21] . Embora esses fatores não tenham sido investigados no presente estudo, a ausência de diferenças estatisticamente significativas entre casos e controles em relação à procedência materna sugere a inexistência de exposição preferencial a fatores de risco para hipospádia na população residente na capital comparada à residente no interior de Alagoas.…”