Date of Award:


Document Type:


Degree Name:

Doctor of Philosophy (PhD)


Nutrition, Dietetics, and Food Sciences

Committee Chair(s)

Ronald G. Munger


Ronald G. Munger


Heidi J. Wengreen


Christopher D. Corcoran


Korry Hintze


Adele Cutler


Orofacial clefts (OFCs) are facial malformations that happen during early pregnancy and have a complex and heterogeneous etiology, involving both genetic and environmental risk factors. This project examined the association between maternal nutrition, folate-related biomarkers, candidate genes involved in one-carbon metabolism (OCM), and OFCs in order to achieve more comprehensive knowledge of how nutrition and genetics influence OFC risk. All studies performed in this project used the data collected in the Utah Child and Family Health Study (UCFHS) and the Johns Hopkins International Cleft Consortium.

Neither maternal periconceptional multivitamin use nor healthy dietary pattern score alone was individually associated with OFC risk. However, the combination of PCMV use and a higher score reflecting the ideal Dietary Approach to Stop Hypertension (DASH) diet was associated with 55% reduction in risk of isolated OFCs, evidence that the prevention of OFCs may require attention to both prenatal vitamin use and improving maternal diets. Mothers who had an OFC-affected pregnancy were observed to have a lower blood folate reduced levels, in both multivitamin users and non-users, evidence that they have a reduced ability compared with control mothers to utilize supplemental folic acid. Higher folic acid intake levels may be required for mothers with a history of an OFC-affected pregnancy. The ability to utilize supplement folic acid might be modified by MTHFR C677T genotype. Several genes in the OCM pathway were found to influence risk for OFCs with some through genetic effects and most through gene-environment interaction effects with maternal multivitamin supplementation during periconceptional period and maternal biomarker concentrations for OCM-related nutrients. These results emphasize the need to consider gene-environment interactions when searching for genes influencing OFCs.

Reduction in the prevalence of OFCs could have tremendous importance. The results of this dissertation may help identify factors important to OFCs etiology and in turn, provide valuable targets for preventive intervention. Children born with an OFC require medical care from birth until adulthood and encounter a higher mortality rate. The costs incurred from caring for children born with OFCs not only include the clinical care of many disciplines but also involve the emotional disturbance and social and employment exclusion for affected individuals. Reducing the risk of OFCs would lessen considerable financial and emotional burdens to families and societies.