OBJECTIVE: To 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 METHODS: Cases 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), and proximal (43). Adjusted odds ratios (OR) with 95% confidence intervals (CI) were estimated using logistic regression. RESULTS: Low 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. CONCLUSION: These findings indicate aetiological heterogeneity of hypospadias and provide indications for the possible mechanisms through which specific risk factors may interfere with penile development.
OBJECTIVE: To 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 METHODS: Cases 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), and proximal (43). Adjusted odds ratios (OR) with 95% confidence intervals (CI) were estimated using logistic regression. RESULTS:Low 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. CONCLUSION: These findings indicate aetiological heterogeneity of hypospadias and provide indications for the possible mechanisms through which specific risk factors may interfere with penile development.
Authors: Alissa R Van Zutphen; Martha M Werler; Marilyn M Browne; Paul A Romitti; Erin M Bell; Louise-Anne McNutt; Charlotte M Druschel; Allen A Mitchell Journal: Obstet Gynecol Date: 2014-02 Impact factor: 7.661
Authors: Cilla Söderhäll; Izabella Baranowska Körberg; Hanh T T Thai; Jia Cao; Yougen Chen; Xufeng Zhang; Zu Shulu; Loes F M van der Zanden; Iris A L M van Rooij; Louise Frisén; Nel Roeleveld; Ellen Markljung; Ingrid Kockum; Agneta Nordenskjöld Journal: Eur J Hum Genet Date: 2014-07-02 Impact factor: 4.246
Authors: Sander Groen In 't Woud; Iris A L M van Rooij; Marleen M H J van Gelder; Richard S Olney; Suzan L Carmichael; Nel Roeleveld; Jennita Reefhuis Journal: Birth Defects Res A Clin Mol Teratol Date: 2014-09-02
Authors: Suzan L Carmichael; Chen Ma; Marcia L Feldkamp; Ronald G Munger; Richard S Olney; Lorenzo D Botto; Gary M Shaw; Adolfo Correa Journal: Paediatr Perinat Epidemiol Date: 2012-05-17 Impact factor: 3.980