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

Abstract

Hypospadias is one of the most frequent male congenital malformations and may be part of the testicular dysgenesis syndrome. 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. A prospective cohort study was conducted with 3-yr follow-up (1997-2004). The population-based study was conducted at the University Hospital of Copenhagen. A total of 1072 Danish boys were consecutively recruited antenatally, with 74.4% completing the study. The study examined the position of the urethral meatus, anthropometrical measurements, placental weight, and reproductive hormone levels. 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. 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.