Male gender significantly increases risk of major congenital anomalies in the USA non-diabetic population

Oxidative stress (OS) is emerging as a major mechanism of teratogenesis. Male fetuses may have heightened sensitivity to OS. We investigated whether male gender was a significant risk factor for common major congenital anomalies (CA). CDC-National Center for Health Statistics data for 19 states (49% of US births) for the year 2006 were reviewed. Exclusion criteria were chromosomal anomalies and all diabetic pregnancies. Major CA evaluated were anencephaly, spina bifida, cyanotic CHD (CCHD), congenial diaphragmatic hernia (CDH), omphalocele, gastroschisis, limb defects, cleft lip with or without cleft palate (CL) and isolated cleft palate. Stepwise logistic regression was used to control for the impact of the following confounders: maternal age, race/ethnicity, first trimester smoking, education and multiple gestation. Adjusted ORs (95% CI) for CA in males using females as the reference category were calculated. There were a total of 1,974,945 eligible cases of which there were 3,886 (0.2%) relevant anomalies. Males had a significantly higher risk for major CA overall, adjusted OR (95% CI) = 1.18(1.1,1.27) , p< 0.001. There were significantly increased adjusted odds (95% CI) for CCHD: 1.198 (1.027, 1.397), CDH: 1.487 (1.078, 2.051) and CL: 1.431 (1.24, 1.651). In no category did female sex significantly increase the risk of CA. Based on a large number of cases drawn from the USA population, male gender appears to be a significant independent risk factor for some common major CA in newborns. These findings appear consistent with male gender being an important risk factor for major congenital anomaly in the non-diabetic population.