# Epigenetic biomarkers of preeclampsia risk among mothers with chronic hypertension

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2022 · $642,616

## Abstract

Preeclampsia (preE), defined as the onset of hypertension paired with proteinuria and/or other
organ complication after 20 weeks of gestation, is a common pregnancy complication affecting
2-8% of pregnancies worldwide. The condition is even more common among mothers with
chronic mild hypertension at pregnancy onset (affecting >25%). Importantly, preE confers a
significantly increased risk of maternal and fetal morbidity including cardiovascular
complications, preterm delivery, low birth weight and even death. Furthermore, recent studies
demonstrate that a history of a preE is associated with an increased risk of cardiovascular
disease for the mother later in life. The pathophysiology of preE is not completely understood
but abnormal placentation, vascular dysfunction and oxidative stress is thought to cause
maternal endothelial dysfunction resulting in the onset of clinical symptoms. To date the only
definitive diagnosis is through blood pressure and urine protein measurement in the second or
third trimester. However, the pathology is suspected to start in the first trimester and earlier
identification can allow for better treatment and outcomes. The epigenome is recognized as an
important driver of the gene expression changes necessary to support pregnancy. Numerous
epigenomic studies of placental tissue have identified differentially methylated regions (DMRs, a
type of epigenetic modification) associated with preE in genes and pathways suspected to
underlie disease. A handful of studies have identified changes in the maternal epigenome from
blood which could be identifiable earlier in pregnancy. Overall, additional research is needed to
determine if methylation sites in maternal blood cells are useful to understand preE risk. This
study will leverage the rich resource of the Chronic Hypertension And Pregnancy (CHAP) study
designed to determine the efficacy and safety of antihypertensive treatment during pregnancy.
Our ancillary study will use a nested case-control design (650 cases and 650 controls) to
discover CpGs and DMRs for preE using existing data and blood samples. Findings will be
replicated among participants from the Magee Obstetric Maternal & Infant Biobank database
(N~650). PreE CpGs and DMRs (validated through replication) will be further tested for
association with maternal cardiovascular outcomes in CHAP as well as in parous women from
observational cohorts with existing metylation data from the National Heart Lung and Blood
Institute’s Transomics for Precision Medicine (TOPMed) Program. The proposed research
seeks to better understand the pathophysiology of preE and identify potential new biomarkers to
facilitate early detection, management, and treatment of this serious pregnancy condition.

## Key facts

- **NIH application ID:** 10366753
- **Project number:** 1R01HL155127-01A1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Bertha Hidalgo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $642,616
- **Award type:** 1
- **Project period:** 2022-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10366753

## Citation

> US National Institutes of Health, RePORTER application 10366753, Epigenetic biomarkers of preeclampsia risk among mothers with chronic hypertension (1R01HL155127-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10366753. Licensed CC0.

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