Association of Placental Epigenetic Age Acceleration with Birthweight and Postnatal Growth in the First 2 Years of Life in the GLOWING Cohort (n=153) Restricted; Files Only

Abstract

 

 

Background: Epigenetic age acceleration has been linked to several adverse health outcomes in adults; however, only a few studies have examined its effects in newborns. Over the past decade, novel epigenetic clocks derived from placental tissue have proven to be highly accurate estimators of gestational age. To understand how patterns of newborn growth and development are influenced by gestational epigenetic age acceleration (GAA), we used a placenta epigenetic clock to investigate the association between GAA and newborn birthweight, as well as postnatal growth trajectories through the first two years of life.

 

Methods: We utilized data from 153 mother-infant pairs enrolled in the Glowing Life Optimizing Wellness (GLOWING) Study conducted in central Arkansas. Gestational Epigenetic age was estimated using Lee’s control placental clock (CPC). Birthweight and placental tissue were collected upon delivery. Postnatal growth trajectories were assessed through repeated measurements of weight until 2 years of age. Weight gain was modeled using SITAR and patterns were described using two model generated parameters. We regressed birthweight z-scores and SITAR size and intensity parameters on GAA, controlling for potential confounders. Sex-specific effects were also explored.

 

Results: Infants subjected to higher placental GAA had higher birthweights, yet concurrently lower size and intensity parameter values, thus signifying slower rates and lower amounts of postnatal weight gain. We found little evidence for sex-specific differential effects.

 

Conclusions: Our analyses revealed associations between GAA and birthweight and infant growth trajectories consistent with previous research. Our finding suggest higher placental GAA may be an indicator of heathier infants, but further research in larger, more diverse cohorts are needed to confirm observed associations and characterize sex-specific effects.

 

Table of Contents

Table of Contents

1. INTRODUCTION 1

The Placenta 1

Birthweight and Postnatal Growth Patterns 1

Ageing 2

Epigenetic Age as a Surrogate Measure of Biological Age 3

Current Research in Gestational Epigenetic Age Acceleration 4

Research Gaps 5

2. METHODS 5

Subjects 5

Institutional Review Board (IRB) Approval 6

Anthropometry 6

Self-Reported Variables 6

Gestational Age 6

Placental Sample Collection 6

Placental DNA Isolation 7

Genome-wide Methylation Profiling (GWMP) 7

Placental Cellular Heterogeneity 7

Epigenetic Age Estimation Methods 8

Statistical Analyses 8

3. RESULTS 10

Study Population 10

Epigenetic Age and Chronological Age 10

Growth Trajectory Modeling 11

Associations Between Acceleration with Birthweight, Size, and Intensity 11

Secondary Analyses 12

4. DISCUSSION 13

Previous Research 13

Strengths and Limitations 15

5. CONCLUSION 16

6. REFRENCES 17

7. TABLES & FIGURES 21

About this Master's Thesis

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School	Rollins School of Public Health
Department	Environmental Health
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Environmental Health Health Sciences, Aging
Palavra-chave	Epigenetics Age Acceleration Postnatal Growth Placenta
Committee Chair / Thesis Advisor	Todd M. Everson, Emory University

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