Date of Award

5-2026

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Healthcare Genetics

Committee Chair/Advisor

Dr. Heide S. Temples

Committee Member

Dr. Sara M. Sarasua

Committee Member

Dr. Deborah Dewey

Committee Member

Dr. Gillian England-Mason

Committee Member

Dr. Vivian Haley-Zitlin

Abstract

The Developmental Origins of Health and Disease (DOHaD) framework posits that early life exposures can shape biological systems, influencing health and disease risk across the life course. A central tenet of this framework is developmental programming, which describes how exposures during critical developmental periods can alter physiological and metabolic pathways. Epigenetic processes, involving chemical modifications that regulate gene expression without altering the underlying DNA sequence, are proposed to mediate these programming effects. In this context, maternal nutrition represents a modifiable exposure with the potential to influence epigenetic regulation. During pregnancy, adequate nutrient availability supports optimal fetal growth. Omega-3 and omega-6 fatty acids are essential for placental health and fetal neurodevelopment. However, significant gaps remain in understanding the extent to which maternal fatty acid status during pregnancy is associated with infant epigenetic variation. Current research is primarily observational, and the mechanistic pathways underlying the associations between maternal fatty acids and infant epigenetic variation, as well as their implications for child development, remain insufficiently characterized.

The work presented in this dissertation offers an integrative approach to examining the associations between maternal fatty acid status and infant developmental programming. It comprises a concept analysis that presents an evidence-based conceptual definition of developmental programming; a policy analysis that recommends revisions to the policy governing the ethical conduct of research in Canada to be inclusive of genomic and epigenetic technologies; a critical narrative review that provides direction for the empirical research; and a novel study examining associations between maternal fatty acid status during pregnancy and infant epigenetic age acceleration.

This study analyzed data from 250 mother-infant pairs from the Canadian Alberta Pregnancy Outcomes and Nutrition (APrON) cohort using multivariable robust linear regression models to examine associations between maternal second-trimester fatty acid status and infant epigenetic age acceleration (EAA) at three months of age, measured by the Pediatric-Buccal-Epigenetic (PedBE) clock. Maternal levels of eicosapentaenoic acid (EPA) and total omega-3 fatty acids were positively associated with infant EAA, indicating faster biological aging than chronological aging. There was an inverse association between the total omega-6 to omega-3 fatty acid ratio and EAA. These findings suggest that maternal exposure to various fatty acids or fatty acid profiles during pregnancy may have divergent effects on epigenetic aging rates. Continued research, particularly in larger cohorts, is needed to understand the implications of deviations in infant epigenetic aging rates for children’s growth and development, and the mechanisms by which early exposure to modifiable risk factors, such as diet, may alter the epigenome during critical periods of development.

The dissertation concludes with a summary of the findings, limitations, and recommendations for future research. Overall, this research provides evidence that variation in maternal fatty acid status during pregnancy is associated with differences in infant epigenetic age acceleration, supporting the hypothesis that prenatal nutrition may influence early biological development through epigenetic mechanisms consistent with the DOHaD framework.

Author ORCID Identifier

0000-0003-2296-1016

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