Epigenetic Biomarkers of Brain Injury in Children on Extracorporeal Membrane Oxygenation (ECMO)

Tuesday, March 24, 2026

11:15 AM - 12:15 PM Central Time

Location: Connections Central - RST 06

Julie Xian, N/A (she/her/hers)

Maryland

Disclosure(s): No relevant financial relationship(s) to disclose.
MB

Michael Bell, MD

Professor and Chief of the Division of Pediatric Critical Care Medicine
UT Southwestern Medical Center

Disclosure information not submitted.
BB

Bonnie A. Brooks, MD

HS Assistant Clinical Professor, Pediatrics
UCLA

Disclosure information not submitted.
AE

Allen Everett, MD

Director of the Pediatric Proteome Center and Professor of Pediatrics
Johns Hopkins University School of Medicine

Disclosure information not submitted.
AH

Adam S. Himebauch, MD, MSCE

Associate Professor of Anesthesia and Critical Care
Childrens Hospital of Philadelphia

Disclosure information not submitted.
AK

Asavari Kamerkar, DO

Medical Director, ECMO Department
Children’s Hospital Los Angeles

Disclosure information not submitted.
KL

Kerri LaRovere, MD, MMSc

Medical Director, Neurocritical Care and Assistant Professor of Neurology
Boston Children’s Hospital

Disclosure information not submitted.
LL

Laura Loftis, MD

Associate Professor of Pediatrics, Section of Critical Care Medicine
Texas Children's Hospital and Baylor College of Medicine

Disclosure information not submitted.
MF

Matthew Friedman, MD

Associate Professor of Clinical Pediatrics
Riley Hospital for Children at Indiana University Health

Disclosure information not submitted.
DN

Derek Ng, PhD

Associate Professor of Epidemiology
Johns Hopkins University

Disclosure information not submitted.
JP

Jose A. Pineda, MD, MSc

Director of Pediatric Neurocritical Care and Health Sciences Clinical Professor of Pediatrics
UCLA

Disclosure information not submitted.
JR

Jennifer Roem, MSc

Senior Biostatistician
Johns Hopkins University

Disclosure information not submitted.
AS

Ahmed Said, MD, PhD

Assistant Professor of Pediatrics, Division of Critical Care Medicine
Institute of Informatics, Biostatistics and Data Science, Washington University, St. Louis School of Medicine

Disclosure information not submitted.
HS

Hitesh Sandhu, MBBS, MRCPCH

Associate Professor, The University of Tennessee Health Science Center and Medical Director, ECMO
Le Bonheur Children's Hospital

Disclosure information not submitted.
MW

Mark Wainwright, MD PhD

Professor
Seattle Children's Hospital

Disclosure information not submitted.
AW

Alina N. West, MD, PhD

Assistant Professor, Pediatric Critical Care
Le Bonheur Children's Hospital

Disclosure information not submitted.
Melania M. Bembea, MD, MPH, PhD

Johns Hopkins University, Maryland

Disclosure information not submitted.

Introduction: The use of ECMO in critically ill children with severe cardiopulmonary failure is associated with increased risk of acute brain injury (ABI) and mortality. The role of the epigenome in neuroinflammatory pathways remains unexplored.

Methods: We analyzed differences in methylation signatures from peripheral blood mononuclear cells across 38 pediatric patients enrolled in the BEAM study, a multicenter, prospective, observational study in children supported on ECMO. Methylation sequencing was performed with the Infinium EPICv2 microarray. Patients were stratified into two cohorts: pediatric patients with (n=18) vs without (n=20) ABI on ECMO. Individuals were matched based on age ( < 1 year of age) and ECMO indication. We analyzed differentially methylated probes (DMPs) and gene-set enrichment (GSEA) between children on ECMO with and without ABI and corrected for multiple testing with false discovery rate < 0.05.

Results: The final study included methylation sequencing data of 867,448 probes across the 38 pediatric patient samples. Primary ECMO indication included cardiac (n=22), ECPR (n=12), and pulmonary (n=4). After correction for multiple testing, there were no significant methylation differences between the ECMO groups with vs without ABI, likely due to a small sample size and possible effect of the ECMO course overshadowing any methylation signatures from brain injury specifically. However, GSEA on the 100 most nominally significant DMPs showed perturbation of immune response pathways (p=0.02), implicating genes including VSTM1, NPLOC4, WRNIP1, NR4A3, ZBP1, VAMP8. Of note, 7 nominally significant probes mapped to recognized transcription start site (TSS) regions and 5UTR/Exon 1 of VSTM1 and 6 to ZBP1, immune regulatory genes highly expressed in whole blood. Lower levels of methylation were universally found across these probes in the ECMO group with ABI compared to no ABI, suggesting an upregulation of an inflammatory process. We were not able to identify any specific signatures indicative of neuroinflammation.

Conclusions: ECMO support involves an altered inflammatory response that corresponds to changes in the epigenome. Methylation biomarkers of inflammation in these patients provide insight into the underlying biological pathways and risk-stratification for children requiring ECMO.