TOP 12 - Epigenetic Signatures of Neonatal Stress: Linking NICU Stress Exposure to DNA Methylation

Publication Number: 2764.TOP 12

Fulden Aycan, University of Iowa Stead Family Children's Hospital, Iowa City, IA, United States; Lindsey Rhea, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, United States; Emma Simpson, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, United States; Laura Jelliffe-Pawlowski, New York University, New York, NY, United States; Elizabeth E. Rogers, University of California, San Francisco, School of Medicine, San Francisco, CA, United States; John M M. Dagle, University of Iowa Stead Family Children's Hospital, Iowa City, IA, United States; Kelli Kae Ryckman, Indiana University, Bloomington, IN, United States; Allison Momany, University of Iowa Stead Family Children's Hospital, Iowa City, IA, United States

Background: Very preterm infants (VPT; < 32 weeks’ gestation) experience high levels of stress in the NICU due to painful medical procedures, serious morbidities, and environmental stimuli. Socioeconomic (SES) factors—such as racial or ethnic identity and social support—may further influence stress exposure, especially if they affect parental presence in the NICU. These early-life stressors occur during critical periods of brain and biological development and are linked to adverse neurodevelopmental outcomes. Epigenetic mechanisms like DNA methylation (DNAm) may explain how stress becomes biologically embedded. Prior studies have examined DNAm in relation to medical or SES factors separately and used samples collected at NICU discharge, limiting insight into whether DNAm changes preceded or resulted from morbidities. Examining how neonatal morbidities and SES interact to shape DNAm across hospitalization may clarify mechanisms driving neonatal health and later neurodevelopmental risk.

Objective: To examine how serious neonatal morbidities and socioeconomic context influence epigenetic programming in VPT infants. Specifically, we aim to examine the impact of serious neonatal morbidities and socioeconomic context on DNA methylation change across NICU hospitalization at candidate loci.

Design/Methods: VPT infants were enrolled in an IRB-approved study on genetics of preterm birth and neurodevelopment. VPT Infants with known genetic syndromes, congenital anomalies, or without English-language consent were excluded. Dried blood spot samples were collected at birth and every other week until discharge. Based on prior work (Evers, 2020), major morbidities—bronchopulmonary dysplasia, retinopathy of prematurity, serious brain injury, and infection—were abstracted from medical records. Socioeconomic context was assessed using demographic factors (Camerota, 2021), including infant race/ethnicity and maternal education, occupation, and relationship status at delivery. DNA will be extracted from dried blood samples, and DNAm quantified using the Illumina EPIC array. Loci previously linked to neonatal morbidities (Evers, 2020) will be examined for DNAm changes across hospitalization and in relation to SES–morbidity interactions, using linear mixed-effects models to account for repeated measures and confounders.
Preliminary DNA extraction and methylation analyses are underway, with completion expected by January 31, 2026.

Maternal and Neonatal Sociodemographic and Clinical Profiles
PAS abstract table 10.30.jpegMaternal and neonatal demographic and clinical characteristics of the study cohort