Evidence map›Paper›PMID 33822234›Full record

ArticleJournal of tropical pediatrics2021

Associations of DNA Methylation Mortality Risk Markers with Congenital Microcephaly from Zika Virus: A Study of Brazilian Children Less than 4 Years of Age.

Jamaji C Nwanaji-Enwerem, Lars Van Der Laan, Elorm F Avakame, Kristan A Scott, Heather H Burris, Andres Cardenas

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of tropical pediatrics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 40% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
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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

6 authors at 5 institutions in 1 country.

Jamaji C Nwanaji-EnweremDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, and MD/PhD Program, Harvard Medical School, Boston, MA, USA.
Lars Van Der LaanDivision of Environmental Health Sciences, School of Public Health and Center for Computational Biology, University of California, Berkeley, CA, USA Berkeley.
Elorm F AvakameDepartment of Pediatrics, Children's National Medical Center, Washington, DC, USA.
Kristan A ScottDepartment of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
Heather H BurrisDepartment of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Andres CardenasDivision of Environmental Health Sciences, School of Public Health and Center for Computational Biology, University of California, Berkeley, CA, USA Berkeley.
University of California, Berkeley · USBeth Israel Deaconess Medical Center · USBoston Children's Hospital · USChildren's National · USHarvard University · US

Funding

PRENATAL AND POSTNATAL EXPOSURE TO ENVIRONMENTAL MIXTURES: NEURODEVELOPMENT AND DNA METHYLATION BIOMARKERSR01ES031259 · NIEHS · UNIVERSITY OF CALIFORNIA BERKELEY · PI CARDENAS, ANDRES · 2020 to 2024
$1.9M
Early life influences on Epigenetic Aging in Mexican-American childrenR03AG067064 · NIA · UNIVERSITY OF CALIFORNIA BERKELEY · PI HOLLAND, NINA T · 2020 to 2021
$159k
NIA NIH HHS R03 AG067064NIEHS NIH HHS R01 ES031259
6 · The paper itself

Abstract

backgroundZika virus (ZIKV)-associated congenital microcephaly is an important contributor to pediatric death, and more robust pediatric mortality risk metrics are needed to help guide life plans and clinical decision making for these patients. Although common etiologies of pediatric and adult mortality differ, early life health can impact adult outcomes-potentially through DNA methylation. Hence, in this pilot study, we take an early step in identifying pediatric mortality risk metrics by examining associations of ZIKV infection and associated congenital microcephaly with existing adult DNA methylation-based mortality biomarkers: GrimAge and Zhang's mortality score (ZMS).

methodsMortality measures were calculated from previously published HumanMethylationEPIC BeadChip data from 44 Brazilian children aged 5-40 months (18 with ZIKV-associated microcephaly; 7 normocephalic, exposed to ZIKV in utero; and 19 unexposed controls). We used linear models adjusted for chronological age, sex, methylation batch and white blood cell proportions to evaluate ZIKV and mortality marker relationships.

resultsWe observed significant decreases in GrimAge-component plasminogen activator inhibitor-1 [PAI-1; β = -2453.06 pg/ml, 95% confidence interval (CI) -3652.96, -1253.16, p = 0.0002], and ZMS-site cg14975410 methylation (β = -0.06, 95% CI -0.09, -0.03, p = 0.0003) among children with microcephaly compared to controls. PAI-1 (β = -2448.70 pg/ml, 95% CI -4384.45, -512.95, p = 0.01) and cg14975410 (β = 0.01, 95% CI -0.04, 0.06, p = 0.64) results in comparisons of normocephalic, ZIKV-exposed children to controls were not statistically significant.

conclusionOur results suggest that elements of previously-identified adult epigenetic markers of mortality risk are associated with ZIKV-associated microcephaly, a known contributor to pediatric mortality risk. These findings may provide insights for efforts aimed at developing pediatric mortality markers.

Indexed as

MicrocephalyPregnancy Complications, InfectiousZika VirusZika Virus InfectionAdultBrazilChildChild, PreschoolDNA MethylationFemaleHumansInfantPilot ProjectsPregnancycg14975410congenital microcephalyepigeneticsGrimAgemortality scorePAI-1Zika

Identifiers

PMID33822234
PMCPMC8022928
OpenAlexW3143967029

What OpenQuestion holds

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Registered trials

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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.