Date of Award

1-1-2019

Language

English

Document Type

Master's Thesis

Degree Name

Master of Science (MS)

College/School/Department

Department of Epidemiology and Biostatistics

Program

Epidemiology

Content Description

1 online resource (iii, 32 pages) : color illustrations.

Dissertation/Thesis Chair

Allison A Appleton

Committee Members

Eli S Rosenberg

Keywords

gestational age, Leptin, maternal diet, methylation, RPMM, Pregnancy, Fetus, Food habits, Prenatal Nutritional Physiological Phenomena, Fetal Development

Subject Categories

Biostatistics | Epidemiology | Genetics

Abstract

The health of a newborn baby is inextricably linked to the health status of its mother and in turn the mother’s diet during pregnancy. Leptin (LEP) is an adipokine hormone involved in metabolism regulation and has been linked fetal development through the hypothalamic-pituitary-adrenal axis (HPA). Prior work suggests that gestational epigenetic alterations the LEP gene may be sensitive to adverse exposures during pregnancy, which in turn could explain variation in neonate outcomes. However, no prior work has examined this possibility explicitly. The objective of this study was to investigate the association between dietary patterns of mothers during pregnancy and their effect on gestational LEP methylation patterns, and associations between LEP methylation and dietary factors with gestational age. We also explored sex-specific patterning in LEP methylation and in neonate outcomes. By use of factor analysis, the items of a food frequency questionnaire were classified into three groups; western food items, prudent food items, and meat food items. A model-based clustering algorithm was used to identify four distinct classes of LEP methylation. Logistic regression was used to model the probability of membership in each of four classes according to dietary type, while adjusting for covariates. Each diet had a negative association with LEP class one and each diet had a positive association with LEP class three. There were clear methylation patterns across locations on the LEP gene which indicated similarities and differences between the classes. The strongest effect was a negative association was between the meat diet and LEP class one (OR = 0.93, 95%CI: 0.87, 0.98). The most significant positive association was between prudent diet and LEP class three (OR = 1.15, 95%CI: 1.06, 1.26). Significant differences in methylation levels and differing effects of diet on gestational age were found between male and female neonates. These results demonstrate a link between maternal diet habits and LEP methylation and a link between diet habits and gestational age, with some sex-specific pattering. Taken together, these findings demonstrate that maternal diet during pregnancy, a modifiable risk factor, could have the potential to mediate pathologies associated with LEP methylation and gestational age.

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