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Risk factors for different phenotypes of hypospadias: results from a Dutch case-control study.

Abstract：

UNLABELLED:WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The various phenotypes of hypospadias may result from disturbances of dissimilar embryonic processes in different time windows, suggesting aetiological heterogeneity; however, only a few studies have investigated the risk factors for the different hypospadias phenotypes. The study confirmed that genetic predisposition possibly plays a role in anterior and middle hypospadias, as shown by the large effect estimates for familial occurrence of these forms of hypospadias. By contrast, the posterior phenotype was more often associated with pregnancy-related factors, such as primiparity, preterm delivery, and being small for gestational age. New findings were that hormone-containing contraceptive use after conception increased the risk of middle and posterior hypospadias, while multiple pregnancies were associated with the posterior form in particular. OBJECTIVE:To identify specific risk factors for different phenotypes of hypospadias that may arise as a result of dissimilar embryonic processes in different time windows. PATIENTS AND METHODS:A total of 405 hypospadias cases and 627 male controls were included in a Dutch case-control study. Medical records of cases were reviewed to determine the anatomical location of the urethral opening, while demographic, lifestyle and pregnancy-related risk factor data were obtained from self-administered questionnaires. Multivariable and multinomial logistic regression analyses were used to calculate effect estimates for the group containing all cases of hypospadias and for the different hypospadias phenotypes. RESULTS:Cases were subdivided into anterior (glandular and coronal; 59%), middle (penile; 29%) and posterior (penoscrotal, scrotal and perineal; 12%) hypospadias. Being a twin/triplet, primiparity, preterm delivery, and being small for gestational age were associated with hypospadias, particularly in posterior cases. Family history of hypospadias increased the risk of hypospadias, an effect that seemed to be more predominant in anterior and middle forms. Maternal obesity seemed to increase the risk of hypospadias in general, and hormone-containing contraceptive use during pregnancy especially increased the risk of middle and posterior hypospadias. CONCLUSIONS:Our study provides some indications for aetiological heterogeneity of hypospadias, separating anterior and middle phenotypes from posterior hypospadias. Future research should continue to try to establish which specific risk factors and mechanisms may differ according to hypospadias phenotype.

journal_name

BJU Int

journal_title

BJU international

authors

van Rooij IA,van der Zanden LF,Brouwers MM,Knoers NV,Feitz WF,Roeleveld N

doi

10.1111/j.1464-410X.2012.11745.x

subject

Has Abstract

pub_date

2013-07-01 00:00:00

pages

121-8

issue

eissn

1464-4096

issn

1464-410X

journal_volume

112

pub_type

杂志文章

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Risk factors for different phenotypes of hypospadias: results from a Dutch case-control study.