Evidence map›Paper›PMID 35764815›Full record

ArticlePediatric research2023

CpG methylation patterns in placenta and neonatal blood are differentially associated with neonatal inflammation.

Lauren A Eaves, Adam E Enggasser, Marie Camerota, Semsa Gogcu, William A Gower, Hadley Hartwell, Wesley M Jackson, Elizabeth Jensen, Robert M Joseph, Carmen J Marsit and 8 more

Open access · greenAbstract read
In one paragraph

Article in Pediatric research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.6field-weighted citation impact, top 36% 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

8 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
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

18 authors at 8 institutions in 1 country.

Lauren A EavesDepartment of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Adam E EnggasserDepartment of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Marie CamerotaDepartment of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA.
Semsa GogcuDivision of Neonatology, Department of Pediatrics, Wake Forest School of Medicine, Winston-Salem, NC, USA.
William A GowerDepartment of Pediatrics, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
Hadley HartwellDepartment of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Wesley M JacksonDepartment of Pediatrics, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
Elizabeth JensenDepartment of Epidemiology and Prevention, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Robert M JosephDepartment of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, USA.
Carmen J MarsitGangarosa Department of Environmental Health, Emory University Rollins School of Public Health, Atlanta, GA, USA.
Kyle RoellDepartment of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Hudson P SantosInstitute for Environmental Health Solutions, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jeffrey S ShenbergerDivision of Neonatology, Department of Pediatrics, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Lisa SmeesterDepartment of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Diana YanniDepartment of Neonatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Karl C K KubanDivision of Pediatric Neurology, Department of Pediatrics, School of Medicine, Boston University Medical Center, Boston, MA, USA.
T Michael O'SheaDepartment of Pediatrics, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
Rebecca C FryDepartment of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. rfry@unc.edu.
University of North Carolina at Chapel Hill · USWake Forest University · USBeth Israel Deaconess Medical Center · USBoston Medical Center · USBoston University · USBrown University · USEmory University · USUniversity of Miami · US

Funding

UNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Hazel B Nichols · 2001 to 2026
$36.3M
The Role of the Placenta-Brain Axis in Children's NeurodevelopmentUH3OD023348 · OD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Rebecca Fry, Michael O'SHEA · 2018 to 2026
$21.9M
Placental Epigenome and Brain Dysfunction after Preterm BirthR01HD092374 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FRY, REBECCA, O'SHEA, MICHAEL · 2017 to 2021
$3.2M
Enriching the Rhode Island Child Health StudyU24ES028507 · NIEHS · EMORY UNIVERSITY · PI MARSIT, CARMEN JOSEPH, STROUD, LAURA R · 2023 to 2025
$1.0M
NICHD NIH HHS R01 HD092374NIEHS NIH HHS P30 ES010126NIEHS NIH HHS U24 ES028507NIH HHS UH3 OD023348
6 · The paper itself

Abstract

backgroundInfants born extremely premature are at increased risk for health complications later in life for which neonatal inflammation may be a contributing biological driver. Placental CpG methylation provides mechanistic information regarding the relationship between prenatal epigenetic programming, prematurity, neonatal inflammation, and later-in-life health.

methodsWe contrasted CpG methylation in the placenta and neonatal blood spots in relation to neonatal inflammation in the Extremely Low Gestational Age Newborn (ELGAN) cohort. Neonatal inflammation status was based on the expression of six inflammation-related proteins, assessed as (1) day-one inflammation (DOI) or (2) intermittent or sustained systemic inflammation (ISSI, inflammation on ≥2 days in the first 2 postnatal weeks). Epigenome-wide CpG methylation was assessed in 354 placental samples and 318 neonatal blood samples.

resultsPlacental CpG methylation displayed the strongest association with ISSI (48 CpG sites) but was not associated with DOI. This was in contrast to CpG methylation in blood spots, which was associated with DOI (111 CpG sites) and not with ISSI (one CpG site).

conclusionsPlacental CpG methylation was strongly associated with ISSI, a measure of inflammation previously linked to later-in-life cognitive impairment, while day-one neonatal blood methylation was associated with DOI. IMPACT: Neonatal inflammation increases the risk of adverse later-life outcomes, especially in infants born extremely preterm. CpG methylation in the placenta and neonatal blood spots were evaluated in relation to neonatal inflammation assessed via circulating proteins as either (i) day-one inflammation (DOI) or (ii) intermittent or sustained systemic inflammation (ISSI, inflammation on ≥2 days in the first 2 weeks). Tissue specificity was observed in epigenetic-inflammatory relationships: placental CpG methylation was associated with ISSI, neonatal blood CpG methylation was associated with DOI. Supporting the placental origins of disease framework, placental epigenetic patterns are associated with a propensity for ISSI in neonates.

Indexed as

DNA MethylationPlacentaCpG IslandsEpigenesis, GeneticFemaleGestational AgeHumansInfant, NewbornInfant, PrematureInflammationPregnancy

Identifiers

PMID35764815
PMCPMC10289042
OpenAlexW4283712799

What OpenQuestion holds

Textmetadata
LicenceTDM
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.