Hypospadias in a cohort of 1072 Danish newborn boys: Prevalence and relationship to placental weight, anthropometrical measurements at birth, and reproductive hormone levels at three months of age

Context: Hypospadias is one of the most frequent male congenital malformations and may be part of the testicular dysgenesis syndrome. Objective: The aim of the study was to investigate the prevalence of hypospadias in Denmark and evaluate the relationship to anthropometrical measurements at birth and reproductive hormone levels at 3 months of age. Design: A prospective cohort study was conducted with 3-yr follow-up ( 1997-2004). Setting: The population-based study was conducted at the University Hospital of Copenhagen. Participants: A total of 1072 Danish boys were consecutively recruited antenatally, with 74.4% completing the study. Main Outcome Measures: The study examined the position of the urethral meatus, anthropometrical measurements, placental weight, and reproductive hormone levels. Results: The Danish birth prevalence of hypospadias was significantly higher than in a concomitant Finnish study (1.03 vs. 0.27%; P = 0.012). At 3 yr, the true prevalence was found to be 4.64% because additional mild cases were detected when physiological phimosis dissolved. Weight for gestational age ( percentage deviation from expected mean) ( - 5.00 vs. - 0.59%; P = 0.030) and placental weight ( 567 vs. 658 g; P = 0.023) were significantly lower, and FSH was significantly higher (1.48 vs. 1.15 IU/liter; P = 0.007) in boys with hypospadias, compared with healthy boys. Conclusions: We found a surprisingly high total rate of hypospadias of 4.6% in this large prospective cohort study. Seventy-two percent of the cases were apparent only after the prepuce could be retracted. Hypospadias were associated with elevated serum FSH levels at 3 months. We also confirmed an association between fetal growth impairment and hypospadias; however, it is yet unknown whether this indicates a causal relationship or a shared pathogenic factor.