Evaluating Differences in Nonsyndromic Orofacial Clefts by Infant Sex: National Birth Defects Prevention Study,...

To investigate nongenetic factors that may contribute to observed differences in nonsyndromic orofacial clefts by infant sex.

Using data for 1997-2011 deliveries from the National Birth Defects Prevention Study, a case-control study, we separately examined associations between 23 maternal factors and cleft lip with or without cleft palate (CL/P) and cleft palate alone (CP) using multivariable logistic regression stratified by infant sex.

We compared 2986 infants with CL/P and 1557 with CP to 11 271 control infants without birth defects. After adjusting for maternal age at conception and education, lower odds of nonsyndromic orofacial clefts were observed among male infants of non-Hispanic Black mothers (CL/P adjusted odds ratio [aOR]: 0.36; 95% confidence interval [CI]: 0.28-0.45; CP aOR: 0.56; 95% CI: 0.41-0.76) and of Hispanic mothers (CL/P aOR: 0.84; 95% CI: 0.73-0.96; CP aOR: 0.57; 95% CI: 0.45-0.72) compared with non-Hispanic White mothers. Similar, though attenuated, lower odds of nonsyndromic orofacial clefts were observed among female infants of non-Hispanic Black mothers, but no association was observed among female infants of Hispanic mothers. Differences in associations between maternal education and nutrient intake (carbohydrate, energy, total lipids/fat, vitamin E, and zinc) and CL/P, as well as maternal vitamin C intake and CP, were also observed by infant sex.

Associations between nonsyndromic orofacial clefts and minority racial and ethnic groups were attenuated or nonexistent among female infants compared with male infants. Sex-specific differences of CL/P appear more susceptible to environmental factors (eg, maternal education and nutrient intake) than sex-specific differences of CP.