Maternal intake of vitamin E and birth defects, national birth defects prevention study, 1997 to 2005.

BACKGROUND: In a recent study, high maternal periconceptional intake of vitamin E was found to be associated with risk of congenital heart defects (CHDs). To explore this association further, we investigated the association between total daily vitamin E intake and selected birth defects. METHODS: We analyzed data from 4525 controls and 8665 cases from the 1997 to 2005 National Birth Defects Prevention Study. We categorized estimated periconceptional energy-adjusted total daily vitamin E intake from diet and supplements into quartiles (referent, lowest quartile). Associations between quartiles of energy-adjusted vitamin E intake and selected birth defects were adjusted for demographic, lifestyle, and nutritional factors. RESULTS: We observed a statistically significant association with the third quartile of vitamin E intake (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.01-1.35) and all CHDs combined. Among CHD sub-types, we observed associations with left ventricular outflow tract obstruction defects, and its sub-type, coarctation of the aorta and the third quartile of vitamin E intake. Among defects other than CHDs, we observed associations between anorectal atresia and the third quartile of vitamin E intake (OR, 1.66; 95% CI, 1.01-2.72) and hypospadias and the fourth quartile of vitamin E intake (OR, 1.42; 95% CI, 1.09-1.87). CONCLUSION: Selected quartiles of energy-adjusted estimated total daily vitamin E intake were associated with selected birth defects. However, because these few associations did not exhibit exposure-response patterns consistent with increasing risk associated with increasing intake of vitamin E, further studies are warranted to corroborate our findings.

Lack of defects in androgen production in children with hypospadias.

Formation of the male urethra requires the synthesis of testosterone, its activation to dihydrotestosterone (DHT) in genital skin, and binding of DHT to the androgen receptor. Defects in any of those steps can cause hypospadias. To determine whether defects exist in the production of androgens in individuals with hypospadias, we examined enzymatic function of 3beta-hydroxysteroid dehydrogenase (3betaHSD), P450c17 (17alpha-hydroxylase and 17,20 lyase activity), and type 3 17betaHSD. Sixty-eight subjects participated in the study: 48 patients had hypospadias, and 20 had normal male genitalia. Subjects were stratified into groups based on age and severity of hypospadias, as defined by location of the urethral meatus after correction of penile curvature. Hormonal values in boys with hypospadias were compared by nonparametric analysis with those in age-matched controls. Controls excluded individuals with cryptorchidism, micropenis, known endocrine defects, or receiving steroid supplementation. Morning fasting serum levels of pregnenolone, progesterone, 11-deoxycorticosterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, dehydroepiandrosterone, androstenedione, androstenediol, testosterone, and DHT were determined. To focus on the proximal steps in androgen biosynthesis, 12 individuals with hypospadias underwent standard ACTH stimulation. No significant differences in the androgen precursors and metabolites were found between controls and individuals with hypospadias. The response to ACTH was variable without a significant difference between the patients with different degrees of hypospadias and/or published controls. These data indicate that enzymatic defects in the steroidogenic steps from cholesterol to DHT are not a common etiology of hypospadias. Routine abnormalities in the androgen biosynthetic pathway are an unlikely cause of any degree of hypospadias in boys without accompanying cryptorchidism or genital malformations.