Abstract

Objectives: Hypospadias is a urogenital birth defect affecting infant boys. Periconceptual parental occupational exposure to endocrine disrupting chemicals (EDCs) with oestrogenic or anti-androgenic properties may adversely affect male genital development in-utero. The aim of this study was to investigate the association between both maternal and paternal occupational exposure to endocrine disrupting chemicals and hypospadias.

Methods: This registry-based case-control study considered all 1202 cases of hypospadias born in Western Australia between 1980 and 2000 and a cohort of 2583 male controls randomly selected from birth records for whom information regarding parental occupation was available from the Western Australian Maternal and Child Health Research Database. Occupational exposures to seven groups of potential EDCs were independently coded by two researchers according to a validated job-exposure matrix.

Results: Multivariable analysis showed a strong association with potential maternal occupational exposure to heavy metals with an over two-fold increased risk of hypospadias (Odds Ratio (OR) 2.6, 95%CI 1.3 to 5.2) and women exposed to phthalates were more likely to have an affected son (1.2, 0.8 to 1.7). Compared with mild or isolated cases, the risk of moderate-severe hypospadias or multiple defects were increased up to 2 and 5-fold, respectively with maternal exposure to most types of EDC. Paternal occupational exposure to polychlorinated organic (OR 1.3, 95%CI 1.0 to 1.8) and bi-phenolic (OR 1.6, 95%CI 1.0 to 2.6) compounds were also possible risk factors.

Conclusions: Findings provide preliminary evidence regarding exposure to chemicals with oestrogenic or anti-androgenic properties of EDCs and increased risk of hypospadias. Further studies taking into account more detailed parental occupational exposure and possibly, assessment of the effect of genetic susceptibility, are required to elucidate the underlying aetiology of hypospadias.