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

• Published in: The journal of clinical endocrinology and metabolism 2005-07, Vol.90 (7), p.4041-4046
• Main Authors: Boisen, K. A., Chellakooty, M., Schmidt, I. M., Kai, C. M., Damgaard, I. N., Suomi, A.-M., Toppari, J., Skakkebaek, N. E., Main, K. M.
• Format: Article
• Language: English
• Subjects: Age; Biological and medical sciences; Birth; Birth Weight; Cohort analysis; Cohort Studies; Congenital defects; Endocrinopathies; Follicle Stimulating Hormone - blood; Follicle-stimulating hormone; Fundamental and applied biological sciences. Psychology; Gestational age; Humans; Hypospadias - epidemiology; Hypospadias - etiology; Infant; Infant, Newborn; Inhibins - blood; Male; Medical sciences; Organ Size; Placenta; Placenta - anatomy & histology; Population studies; Prevalence; Prospective Studies; Vertebrates: endocrinology; Weight
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2005-0302

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.