Date of Award:

Summer 2017

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Nutrition, Dietetics, and Food Sciences

Advisor/Chair:

Ronald G. Munger

Abstract

Orofacial clefts (OFCs) are among the most common congenital birth defects and are characterized by incomplete development of the lip or the palate or both. The lip and palate develop separately at different times during the first trimester of pregnancy. The etiology of OFCs is multifactorial and includes a combination of genetic and environmental factors. This project aims to examine role of maternal diabetes mellitus in orofacial clefts through studies of medical histories, biomarkers, and genes.

In a study of Utah birth certificates, mothers with pre-existing diabetes and gestational diabetes mellitus (GDM) had an increased risk of OFCs, and obese mothers also had an increased risk. Mothers of children with OFCs were more likely than mothers of unaffected children to develop obesity, metabolic syndrome and gestational diabetes mellitus later in life. These result were more strongly related to cleft palate than cleft lip. Many genes related to GDM were associated with OFCs through genetic effects alone and gene-environment interaction effects with periconceptional maternal multivitamin use, maternal smoking, and environmental tobacco smoke. These results support the hypothesis that GDM may be causally related to OFCs via multiple GDM susceptibility genes and interactions with environmental factors.

Individuals with OFCs face both physical and mental health problem, which require multi-specialty team care. OFC prevention and prediction are important to public health. This dissertation reported that maternal diabetes mellitus, maternal pre-pregnancy weight and genes related to GDM had an association with the risk of OFCs. Mothers having an OFC child had an increased risk of developing metabolic abnormalities later in life. Potential risk factors were reported in this dissertation that may be useful for OFC prevention. This dissertation also reported potential biomarkers for predicting OFCs. Moreover, mothers having an OFC child may require regular monitoring of metabolic abnormalities later in life.

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