This study examined the association of hypospadias risk with several maternal reproductive and demographic characteristics: age, parity, body mass index (BMI), nausea and vomiting of pregnancy (NVP), multiple pregnancy, fertility treatments and procedures, education and race-ethnicity. The study included data on deliveries with estimated due dates from October 1997 to December 2000 that were part of the National Birth Defects Prevention Study, a multi-state case–control study of many birth defects. The analysis included 502 cases with second or third degree hypospadias (i.e. the urethra opened at the penile shaft, scrotum or perineum) and 1286 male, liveborn, non-malformed controls. Risks were estimated from a multivariable logistic regression model that included all exposures of interest.
Results indicated particularly elevated risks among births to women who were primiparae, aged ≥35 years and had a BMI of >26, compared with women who were multiparae, aged <30 years and had a BMI of ≤26 [adjusted OR 12.5, 95% CI 5.1, 30.8]. NVP at least once per day during the second or third month of pregnancy vs. no NVP was associated with slightly reduced risk [OR 0.8, 95% CI 0.6, 1.1]. Multiple birth, fertility treatments and college education were associated with increased risks, and Hispanic race-ethnicity was associated with reduced risk. Although the potential contribution of underlying maternal endocrine parameters to the current findings are unknown, the results do provide clues regarding hypospadias aetiology that merit further investigation.