Abstract
BackgroundHypospadias is a frequently occurring congenital anomaly in male infants, in which the opening of the urethra is located along the ventral side of the penis. Although various studies attempted to identify its causes, the aetiology of the majority of hypospadias cases remains poorly understood. Maternal hypertensive disorders are believed to be associated with hypospadias, but the results of previous studies are not consistent, especially for subtypes of hypospadias.ObjectivesTo investigate the associations between maternal hypertensive disorders, stratified by pharmacological treatment, and the occurrence of hypospadias divided into subtypes in a large population‐based case‐control study.MethodsWe included 887 hypospadias cases and 1005 male controls from the AGORA data‐ and biobank. Cases and controls were born in the periods 1975‐2016 and 1990‐2011, respectively. All data were collected in the period 2004‐2018. Maternal questionnaires were used to obtain information on hypertensive disorders during pregnancy, antihypertensive medication treatment, and potential confounders. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for the associations between hypertensive disorders and hypospadias were estimated using logistic regression.ResultsHypertensive disorders were reported by 15.3% of the women in this study. Maternal hypertensive disorders in general, chronic hypertension, and gestational hypertension were not associated with hypospadias or its subtypes. Preeclampsia was associated with posterior hypospadias (aOR 3.09, 95% CI 1.49, 6.43), whether it was untreated (aOR 2.81, 95% CI 1.24, 6.38) or pharmacologically treated preeclampsia (aOR 4.96, 95% CI 1.08, 22.80).ConclusionsOur findings indicate that preeclampsia is associated with posterior hypospadias, irrespective of pharmacological treatment. This result supports the hypothesis of aetiological heterogeneity among the subtypes of hypospadias, with pregnancy‐related risk factors being associated with the more severe types of hypospadias.
Highlights
| BACKGROUNDHypospadias is one of the most frequently occurring congenital anomalies in male infants.[1,2] Boys diagnosed with hypospadias have a displaced opening of the urethra on the ventral side of the penis, due to incomplete fusion of the urethral folds in the third and fourth months of gestation.[3,4,5] Based on the location of the meatus, subtypes of hypospadias can be defined as anterior hypospadias (glandular, coronal, and sub-coronal), middle hypospadias (distal penile, midshaft, and proximal penile), and posterior hypospadias (penoscrotal, scrotal, and perineal),[6,7,8] similar but not equivalent to first, second, and third-degree hypospadias and other classifications that are being used.[9]
Hypospadias is a frequently occurring congenital anomaly in male infants, in which the opening of the urethra is located along the ventral side of the penis
Previous studies suggest that associations with hypospadias are dependent on the type of hypertensive disorder, maternal exposure to antihypertensive medication during pregnancy, and the subtypes of hypospadias
Summary
Hypospadias is one of the most frequently occurring congenital anomalies in male infants.[1,2] Boys diagnosed with hypospadias have a displaced opening of the urethra on the ventral side of the penis, due to incomplete fusion of the urethral folds in the third and fourth months of gestation.[3,4,5] Based on the location of the meatus, subtypes of hypospadias can be defined as anterior hypospadias (glandular, coronal, and sub-coronal), middle hypospadias (distal penile, midshaft, and proximal penile), and posterior hypospadias (penoscrotal, scrotal, and perineal),[6,7,8] similar but not equivalent to first, second, and third-degree hypospadias and other classifications that are being used.[9]. A few studies investigated these associations in more detail by looking at antihypertensive medication use during pregnancy and subtypes of hypospadias. Previous studies showed rather consistent results, but suggest that associations with hypospadias are dependent on the type of hypertensive disorder, maternal exposure to antihypertensive medication during pregnancy, and subtype of hypospadias. A few studies explored these associations further by looking at antihypertensive medication use during pregnancy and/or the subtypes of hypospadias. Previous studies suggest that associations with hypospadias are dependent on the type of hypertensive disorder, maternal exposure to antihypertensive medication during pregnancy, and the subtypes of hypospadias. All three of these factors.[23] we explored the associations between the separate maternal hypertensive disorders, stratified by pharmacological treatment, and the occurrence of hypospadias including its subtypes in a large population-based case-control study
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