Molecular epidemiology of hypospadias: review of genetic and environmental risk factors.
A descriptive epidemiological study of hypospadias has been made utilizing data from seven malformation surveillance systems round the world: Denmark, Hungary, Italy, Mexico, South America, Spain, and Sweden. The joint material represents 8,122 boys with hypospadias, 7,419 of which were "isolated", that is, with no other known malformation except those obviously related to hypospadias (undescended testis, hydrocele, scrotum anomalies). The main study was based on the infants with isolated hypospadias, but an analysis of multimalformed infants with hypospadias was also made. The registered birth prevalence of isolated hypospadias varied much among the seven programs. For the years 1980-1981, the lowest recorded birth prevalence was 0.26 (Mexico) and the highest, 2.11 (Hungary). An analysis of ascertainment was made for three programs: Denmark, Hungary, and Sweden. While some uncorrect registration of infants as hypospadiac were detected, a strong underascertainment of varying degree was seen. In Hungary and Sweden, where the highest birth prevalences were recorded, there was a 30-40% underascertainment of cases later operated on; in Denmark underascertainment was still larger. When correction was made for underascertainment, the Danish and Swedish birth prevalences of isolated hypospadias were very similar. No information on ascertainment was available for the other systems, but it seems very unlikely that the low birth prevalences recorded in Mexico and South America can be solely explained by underascertainment. Therefore, it appears that true differences in the prevalence at birth of hypospadias do exist. There are no indications that the different birth prevalences depend on inclusion or exclusion of mild (distal) forms of hypospadias. There is an apparent inverse correlation between fertility in a population (estimated from mean parity in control women) and the birth prevalence of isolated hypospadias. Within each program geographical variations in birth prevalence could be seen, but the interprogram variation was larger than the intraprogram one. There is an effect of maternal age and parity on the intensity ratio of isolated hypospadias. This effect varies among programs. The variability for mothers under 20, parity 1, seems to be inversely related to the proportion of delivered women belonging to that age class. With increasing maternal age, especially within parity 1, an increased hypospadias intensity ratio is seen. Infants with isolated hypospadias show a lower birth weight and to some extent also a shorter gestational length than do controls.(ABSTRACT TRUNCATED AT 400 WORDS)