Role of maternal smoking and maternal reproductive history in the etiology of hypospadias in the offspring.

BACKGROUND: This study was undertaken to evaluate some possible risk factors for hypospadias with special regard to parity, subfertility and maternal smoking. METHODS: With the use of the Swedish health registries, 3,262 infants with a diagnosis of hypospadias were identified among 1,413,811 infants born in 1983-96 with prospectively collected smoking exposure during pregnancy. Odds ratios (OR) and 95% confidence intervals (CI) were calculated after adjustment for various possible confounders. RESULTS: A negative association between hypospadias and maternal smoking was found (OR: 0.83 95% CI: 0.76-0.90), but this association was only observed among mothers of Parity 1 or 4+, and the possibility of the results being due to confounding was suspected. Primiparity (vs. Parity 2) was positively associated with hypospadias (OR: 1.29 95% CI: 1.19-1.40), and so was subfertility (defined here as at least 1 year of attempts to conceive) (OR for subfertility: 1.16 95% CI: 1.01-1.33). The OR for smoking and primiparity, respectively, were of the same magnitude irrespective of whether subfertility was present or not, and no evidence was found that subfertility in the parents of infants with hypospadias seriously confounded the analyses. CONCLUSIONS: No explanation was found for the negative association between maternal smoking and hypospadias or the positive association between primiparity and hypospadias. Possible causal mechanisms are discussed. Teratology 66:185-191, 2002