Date of Award:

2014

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Nutrition, Dietetics, and Food Sciences

Advisor/Chair:

Ronald G. Munger

Co-Advisor/Chair:

Christopher Corcoran

Abstract

Orofacial clefts (OFCs) are among the most common structural birth defects and a public health problem. Several studies suggest that maternal obesity pre-existing diabetes mellitus (DM), and the underlying metabolic abnormalities, may be involved in the pathogenesis of cleft lip (CL) and cleft palate (CP) birth defects. Although hypertension and gestational diabetes mellitus (GDM) have been associated in a few studies with congenital birth defects, studies examining the risk associated with OFCs are limited. The overall objective of this dissertation was to examine the association between maternal obesity, DM, GDM, and hypertension and the risk of OFCs in case-control studies.

Analyses of data from an international consortium revealed that maternal obesity (pre-pregnancy BMI >30), compared to normal weight (18.525), was associated with an increased risk of cleft palate with or without cleft lip (CP/L) (adjusted odds ratio (aOR) =1.13 [95% confidence intervals (CI) 1.01-1.25]). We also found a marginal association between maternal underweight and CP/L (1.0 [reference]; aOR=1.14 [0.97-1.34]. CL only was not associated with maternal bodyweight. Interestingly, among college-graduates, there was no increased risk of CP, but mothers with less than a completed college education had an increased risk of CP for underweight and obesity.

Investigation of the Utah OFC data provided evidence that maternal GDM is significantly associated with isolated (aOR=2.63 [1.30-5.34]) and non-isolated clefts (aOR=2.66 [1.02-6.97]). Maternal hypertension is significantly associated with non-isolated clefts (aOR=6.56 [2.18-19.77]). We found a further elevated risk of OFCs among GDM mothers and those with hypertension who were also obese.

The analyses of data from an international consortium revealed significant associations between maternal diabetes and the risk of OFCs. The estimated relative risk of DM for isolated OFCs was 1.33 [1.14-1.54] and was slightly higher for multiple OFCs (aOR=1.86 [1.44-2.40]). Diabetic mothers with abnormal body-mass-index had an increased risk for having inborn with OFCs.

Throughout the dissertation, we demonstrated the extent in which maternal obesity, pre-existing DM, GDM, and maternal hypertension may increase the risk of OFC birth defects. The results highlight the need for pre-conceptional program planning for the prevention of OFCs with screening for abnormal glucose tolerance and hypertension.

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