Date of Award
1-1-2023
Language
English
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
College/School/Department
Department of Epidemiology and Biostatistics
Content Description
1 online resource (vii, 133 pages) : illustrations (some color)
Dissertation/Thesis Chair
Allison Appleton
Committee Members
Melissa Tracy, Gabriel Schlomer
Keywords
Epigenetics, Prenatal influences, Fetus
Subject Categories
Epidemiology
Abstract
Development Origins of Health (DOHaD) evidence suggests that prenatal exposures have an important impact on offspring health throughout the life course. Environmental and psychosocial exposures during fetal development are associated with a range of health outcomes for offspring, and effects are often sex specific. One of the mechanisms which may explain differences in health outcomes is epigenetic alterations, which are the molecular mechanisms that regulate gene expression and can be modified during fetal development. Many studies have shown that psychosocial stress and social adversity can modulate epigenetic mechanisms and affect health. While there are several methods for measuring epigenetic alterations, this dissertation was focused on gestational epigenetic aging. It examined the effects of maternal stress and socioeconomic status during pregnancy on gestational epigenetic age of the offspring. Specifically, this dissertation examined how whether prenatal exposure to stressful life events, and individual and area level indicators of socioeconomic status (SES) affect epigenetic aging and how epigenetic aging in turn affects birth size and growth in early childhood. Gestational epigenetic age can be estimated by a number of epigenetic clock variables. Epigenetic clocks are built by taking a panel of informative CpG sites and methylation extents into consideration and creating a measure of biologic age in a given tissue. When epigenetic age is greater than chronological age (according to birthdate), such epigenetic age is said to be accelerated and thus indicative of accelerated development of body tissue. From a DOHaD perspective, this gestational age acceleration (GAA) could be indicative of fetal response to an adverse in utero environment. Thus, GAA may have implications for health risk later in life. Using data from the Albany Infant and Mother Study (AIMS), we explored the association of psychosocial stress and SES with GAA, in addition to the association of GAA and infant/age 2 size measures. AIMS is a prospective examination of 300 pregnant women and their infants. During the enrollment visit, each participant completed a self-report questionnaire to assess exposures (including stress scales) during pregnancy and prior to pregnancy. Umbilical cord blood samples were collected and sequenced, allowing for the calculation of GAA. Paper 1 tested the association between GAA and SES at the individual and area levels. We hypothesized that children born to mothers of a lower SES would experience accelerated GAA. Paper 2 examined the association between GAA and maternal psychosocial stress. We hypothesized that children of mothers with higher stress levels during pregnancy would experience accelerated GAA. Additionally, we fitted a model testing for effect modification by SES to determine whether the effect of psychosocial stress on GAA varies according to SES. Paper 3 examined GAA and birth size and age 2 growth and body size. We hypothesized that infants with higher GAA will experience more adverse birth size measures and higher BMI percentiles at age 2. In addition, as most DOHaD programming effects tend to be sex specific, we tested for effect modification by sex. In paper 1, we found that individual and neighborhood level socioeconomic status was not associated with GAA. Testing for joint effects of individual and neighborhood level socioeconomic status yielded null results. This was similar to previous research that found that socioeconomic status, measured by parental education, is not associated with GAA. In paper 2, stress was not associated with GAA in our study. Additionally, testing for statistical interaction between stress scores and maternal education yielded null results. We found that depression scores were associated with a decrease in GAA in all regression models, suggesting that depression may be influential in epigenetic patterning of offspring. Prior studies have also found associations between depression and GAA. In paper 3, GAA was associated with birthweight and cephalization index score (a marker of intrauterine growth restriction), but not with age 2 BMI, in this study. Finally, testing for statistical interaction between sex and GAA yielded null results. Our findings suggested that there is a relation between GAA and birth size, but the effect may fall away over time. Previous research has also found mixed associations between GAA and size over time, suggesting a role for postnatal environmental influence. Together, these papers contribute to existing literature that seeks to explain the role of prenatal psychosocial adversity and epigenetic methylation patterns in offspring growth and development. This literature helps to inform how social-environmental and psychosocial factors may affect offspring programming in utero, an important aspect of the Developmental Origins of Health and Disease theory. Ultimately, the gestational epigenetic methylation mechanism could provide biological evidence of of what forms of stress and socioeconomic status affect GAA at the earliest time in the life course. This can strengthen the rationale for providing support and resources to individuals and offspring who are at higher risk of the adverse outcomes associated with environmental and psychosocial outcomes.
Recommended Citation
Pawlowski, Emilia, "Gestational epigenetic aging : prenatal influences and early life associations" (2023). Legacy Theses & Dissertations (2009 - 2024). 3215.
https://scholarsarchive.library.albany.edu/legacy-etd/3215
