Author ORCID Identifier
https://orcid.org/0000-0002-1050-5470
Date of Award
2025
Document Type
Thesis (Ph.D.)
Department or Program
Quantitative Biomedical Sciences
First Advisor
Caitlin G. Howe
Abstract
Diabetes and hypertension during pregnancy adversely impact maternal and offspring health. Altered placental function is hypothesized to be involved, but impacts of elevated glucose and blood pressure (BP) within the subclinical range are unknown. The objective of this thesis is to evaluate how elevated glucose and BP, above and below diagnostic thresholds, impact measures of placental development and function including gross morphology (Aim 1), histopathology (Aim 2), and maternal circulating miRNAs (Aim 3), many of which originate in the placenta. Gross morphology and histopathology data from the New Hampshire Birth Cohort Study were used for Aims 1 and 2, and circulating miRNA data from the Maternal And Developmental Risks from Environmental and Social Stressors cohort were used for Aim 3. To measure elevated glucose and BP within the subclinical range, continuous glucose concentrations and longitudinal BP trajectories were evaluated. Diabetes was associated with an earlier delivery and larger birth weight but was not associated with measures of placental gross morphology or histopathology. Participants with type 2 diabetes had lower circulating levels of placenta-specific miRNAs involved in insulin regulation, metabolism, and placental development. In the subclinical range, elevated glucose was associated with earlier delivery, placental histopathological features indicative of delayed maturation, consistent with prior literature for diabetes, and lower levels of miRNAs associated with longer gestational duration. Preeclampsia was associated with lower placental weight, reduced placental efficiency, higher odds of preterm delivery, and lower circulating levels of miRNAs in involved in inflammation, cardiac cell differentiation, and placental function. Conversely, chronic hypertension was associated with larger placental weight and upregulation of a placenta-specific miRNA associated with shorter gestational duration. Elevated BP below diagnostic thresholds was associated with shorter gestation, altered circulating levels of miRNAs involved in placenta function and, paradoxically, higher placental efficiency. Collectively, these findings support that elevated glucose and BP, above and below diagnostic thresholds, are associated with earlier delivery and measures of placental structure, function, and molecular signaling, including markers previously associated with earlier delivery. This research supports the hypothesis that altered placental function may contribute to the adverse effects of elevated glucose and BP, including within the subclinical range.
Recommended Citation
Anderson, Elizabeth Cook, "Beyond Diagnostic Thresholds: Measures of the Maternal Cardiometabolic Health Continuum and their Association with Placental Function" (2025). Dartmouth College Ph.D Dissertations. 444.
https://digitalcommons.dartmouth.edu/dissertations/444
