Hypospadias and Intake of Nutrients Related to One-Carbon Metabolism

Purpose: We examined whether hypospadias is associated with maternal intake of folic acid containing vitamin/mineral supplements or dietary intake of nutrients related to one-carbon metabolism (folate, choline, vitamins B12 and B6, thiamine, riboflavin, methionine and zinc). Materials and Methods: The study included births from October 1997 to December 2003 that were part of the National Birth Defects Prevention Study. Diet was assessed by food frequency questionnaire during maternal telephone interviews. Analyses included 915 cases with second or third degree hypospadias (urethra opened at the penile shaft, scrotum or perineum) and 2,266 male, liveborn, nonmalformed controls. All ORs and 95% CIs were estimated from logistic regression models that included several potential confounders. Nutrient based analyses also included energy intake. Results: Hypospadias risk was not associated with supplement use (adjusted ORs were 1.2, 95% Cl 0.9-1.6 for intake beginning in the month before or the first month of pregnancy and 1.1, 95% Cl 0.8-1.4 for intake beginning in the second or third month, relative to no intake). Among women who took supplements reduced hypospadias risk was associated with higher dietary intakes of choline, methionine and vitamin B12. The respective ORs (CIS) for the highest vs lowest quartiles were 0.7 (0.5-1.1), 0.6 (0.4-0.9) and 0.7 (0.5-1.0). Among women who did not take supplements increased risk of hypospadias was associated with higher vitamin B12 intake. The OR (101) for the highest vs lowest quartile was 3.1 (1.1-9.0). Conclusions: This study suggests an association of hypospadias with intake of certain nutrients related to one-carbon metabolism.