Maternal Smoking, Alcohol, and Caffeine Exposures and Risk of Hypospadias.

BACKGROUND: We examined the association of hypospadias risk with maternal smoking and consumption of alcohol and caffeine.

METHODS: We analyzed data from mothers of 2437 moderate/severe cases and 5472 nonmalformed controls born from 1997 to 2011 who participated in the National Birth Defects Prevention Study (NBDPS). Exposures were assessed by maternal telephone interviews. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) adjusted for mother's age, parity, race-ethnicity, education, vitamin/mineral supplement intake, obesity, and study center.

RESULTS: Active smoking during the first month of pregnancy was associated with reduced risk, with smaller ORs for increasing quantity smoked; the OR for smoking >1/2 pack/day was 0.7 (95% CI, 0.5-0.9). Among nonsmokers, the OR for any secondhand smoke exposure was 0.8 (95% CI, 0.7-0.9). ORs for alcohol and caffeine consumption were near one and CIs included 1.0. In an analysis of joint exposures to smoking and alcohol and caffeine consumption, the only OR for which the 95% CI excluded 1.0 was for women who smoked, drank, and had low caffeine consumption (OR, 0.6; 95% CI, 0.4-0.8).

CONCLUSION: Maternal exposure to cigarette smoke was associated with reduced risk, and women who smoked, drank, and had low caffeine intake were at lowest risk. We do not interpret these results to suggest that these exposures have overall benefit to a pregnant woman or developing fetus. They may, however, offer clues to help us understand mechanisms that lead to hypospadias. Birth Defects Research 109:1127-1133, 2017. © 2017 Wiley Periodicals, Inc.