Evidence map›Paper›PMID 35410447›Full record

ArticleClinical epigenetics2022

Selective hypermethylation is evident in small intestine samples from infants with necrotizing enterocolitis.

Misty Good, Tianjiao Chu, Patricia Shaw, Lila S Nolan, Joseph Wrobleski, Carlos Castro, Qingqing Gong, Olivia DeWitt, David N Finegold, David Peters

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.0field-weighted citation impact, top 28% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Necrotizing enterocolitis.Nature reviews. Disease primers · 2026
    Review
  5. Review
  6. Necrotizing Enterocolitis: What's New and What's Next?International journal of molecular sciences · 2025
    Review
  7. Article
  8. Article
  9. Review
  10. DNA methylation in necrotizing enterocolitis.Expert reviews in molecular medicine · 2024
    Review
  11. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Misty GoodDivision of Neonatal-Perinatal Medicine, Department of Pediatrics, University of North Carolina at Chapel Hill, 101 Manning Drive, Campus Box 7596, Chapel Hill, NC, 27599, USA. mistygood@unc.edu.
Tianjiao ChuDepartment of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, 204 Craft Avenue, Pittsburgh, PA, 15213, USA.
Patricia ShawDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, USA.
Lila S NolanDepartment of Pediatrics, Washington University School of Medicine, St. Louis, USA.
Joseph WrobleskiDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, USA.
Carlos CastroDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, USA.
Qingqing GongDepartment of Pediatrics, Washington University School of Medicine, St. Louis, USA.
Olivia DeWittDepartment of Pediatrics, Washington University School of Medicine, St. Louis, USA.
David N FinegoldDepartment of Human Genetics, University of Pittsburgh, Pittsburgh, USA.
David PetersDepartment of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, 204 Craft Avenue, Pittsburgh, PA, 15213, USA. dgp6@pitt.edu.ORCID 0000-0003-4354-1125
University of Pittsburgh · USWashington University in St. Louis · USUniversity of North Carolina at Chapel Hill · US

Funding

Non-invasive analysis of methylated cell free DNA in necrotizing enterocolitisR01DK124614 · NIDDK · WASHINGTON UNIVERSITY · PI GOOD, MISTY L, PETERS, DAVID GERARD · 2021 to 2024
$2.5M
Neonatal gut-on-a-chip platform for high content drug testing and precision medicineR01HD105301 · NICHD · WASHINGTON UNIVERSITY · PI GOOD, MISTY L, MAGNESS, SCOTT T · 2021 to 2024
$2.4M
Modulation of the Intestinal Immune Response in Necrotizing EnterocolitisR01DK118568 · NIDDK · WASHINGTON UNIVERSITY · PI GOOD, MISTY L · 2018 to 2022
$1.8M
Regulation of Intestinal Immunity by Aryl Hydrocarbon Receptor Signaling in Necrotizing EnterocolitisF32DK130248 · NIDDK · WASHINGTON UNIVERSITY · PI NOLAN, LILA · 2021 to 2022
$154k
Medical Research Council MR/V035401/1NICHD NIH HHS R01 HD105301NIDDK NIH HHS F32 DK130248NIDDK NIH HHS R01 DK118568NIDDK NIH HHS R01 DK124614
6 · The paper itself

Abstract

objectiveNecrotizing enterocolitis (NEC) is the most common and lethal gastrointestinal disease affecting preterm infants. NEC develops suddenly and is characterized by gut barrier destruction, an inflammatory response, intestinal necrosis and multi-system organ failure. There is currently no method for early NEC detection, and the pathogenesis of NEC remains unclear.

designTo further understand the molecular mechanisms that support NEC, we used solution phase hybridization and next-generation DNA sequencing of bisulfite converted DNA to perform targeted genome-wide analysis of DNA methylation at high read depth.

resultsWe found that ileal samples from surgical NEC infants (n = 5) exist in a broadly hypermethylated state relative to their non-NEC counterparts (n = 9). These trends were not uniform, with hypermethylation being most consistently observed outside CpG islands and promoters. We further identified several biologically interesting gene promoters that displayed differential methylation in NEC and a number of biological pathways that appear dysregulated in NEC. We also found that DNA methylation patterns identified in ileal NEC tissue were correlated with those found and published previously in stool samples from NEC-affected infants.

conclusionWe confirmed that surgical NEC is associated with broad DNA hypermethylation in the ileum, and this may be detectable in stool samples of affected individuals. Thus, an epigenomic liquid biopsy of stool may have significant potential as a biomarker with respect to the diagnostic/predictive detection of NEC. Our findings, along with recent similar observations in colon, suggest that epigenomic dysregulation is a significant feature of surgical NEC. These findings motivate future studies which will involve the longitudinal screening of samples obtained prior to the onset of NEC. Our long-term goal is the development of novel screening, diagnostic and phenotyping methods for NEC.

Indexed as

Enterocolitis, NecrotizingInfant, Newborn, DiseasesCpG IslandsDNA MethylationHumansInfantInfant, NewbornInfant, PrematureIntestine, SmallDNA methylationEpigeneticsIleumIntestineNecrotizing enterocolitisNeonatal

Identifiers

PMID35410447
PMCPMC8996588
OpenAlexW4223517703

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.