Evidence map›Paper›PMID 31887212›Full record

ArticlePloS one2019

Lower S-adenosylmethionine levels and DNA hypomethylation of placental growth factor (PlGF) in placental tissue of early-onset preeclampsia-complicated pregnancies.

Sandra G Heil, Emilie M Herzog, Pieter H Griffioen, Bertrand van Zelst, Sten P Willemsen, Yolanda B de Rijke, Regine P M Steegers-Theunissen, Eric A P Steegers

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 2 pooled it
1.4field-weighted citation impact, top 17% 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, 2 syntheses or guidelines pooled it, 18 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Second-trimester multimetabolite panel for early preeclampsia rule-out.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2026
    Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. An Atherogenic Diet DisturbsBiomedicines · 2021
    Article
  10. Article
  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

8 authors at 1 institution in 1 country.

Sandra G HeilErasmus MC University Medical Center, Rotterdam, The Netherlands, Department of Clinical Chemistry.ORCID 0000-0003-4737-5865
Emilie M HerzogErasmus MC University Medical Center, Rotterdam, The Netherlands, Department of Obstetrics and Gynaecology.
Pieter H GriffioenErasmus MC University Medical Center, Rotterdam, The Netherlands, Department of Clinical Chemistry.
Bertrand van ZelstErasmus MC University Medical Center, Rotterdam, The Netherlands, Department of Clinical Chemistry.
Sten P WillemsenErasmus MC University Medical Center, Rotterdam, The Netherlands, Department of Obstetrics and Gynaecology.
Yolanda B de RijkeErasmus MC University Medical Center, Rotterdam, The Netherlands, Department of Clinical Chemistry.
Regine P M Steegers-TheunissenErasmus MC University Medical Center, Rotterdam, The Netherlands, Department of Obstetrics and Gynaecology.
Eric A P SteegersErasmus MC University Medical Center, Rotterdam, The Netherlands, Department of Obstetrics and Gynaecology.
Erasmus MC · NL

Funding

Medical Research Council MR/S03658X/1
6 · The paper itself

Abstract

introductionThe pathophysiology of preeclampsia is largely unknown. Serum placental induced growth factor (PlGF) levels are decreased during second trimester pregnancy. Aberrant DNA methylation is suggested to be involved in the etiology of preeclampsia (PE). We hypothesize that DNA methylation is altered in PE placentas determined the methylation index by measuring placental S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) levels. In addition, we assessed global DNA methylation status by long-interspersed nuclear element-1 (LINE-1) and DNA methylation status of the PlGF gene.

methodsPlacental tissue of 11 early onset PE (EOPE), 11 late onset PE (LOPE) and 60 controls consisting of 25 uncomplicated controls 20 fetal growth restriction (FGR) and 15 preterm births (PTB) controls was collected from a nested case-control study of The Rotterdam Periconceptional Cohort. RNA and DNA was isolated from placental tissue and DNA was treated with sodium bisulfite. SAM and SAH levels were measured by LC-ESI-MS/MS. Methylation of LINE-1 and PlGF genes was analyzed by Sequenom Epityper and. mRNA expression of PlGF was assessed with qPCR. Differences were assessed by analysis of covariance (ANCOVA) corrected for gestational age and birth weight.

resultsPlacental SAM levels were significantly lower in placental tissue of EOPE pregnancies compared to PTB controls (mean difference -240 ± 71.4 nmol/g protein, P = 0.01). PlGF DNA methylation was decreased in placental tissue of EOPE cases versus LOPE (mean difference -17.4 ± 5.1%, P = 0.01), uncomplicated controls (mean difference -23.4 ± 5.4%%, P <0.001), FGR controls (mean difference -17.9 ± 4.6%, P = 0.002) and PTB controls (mean difference -11.3 ± 3.8% P = 0.04). No significant differences were observed in SAH, SAM:SAH ratio, LINE-1 DNA methylation and PlGF mRNA expression between groups. DISCUSSION: The hypomethylation state of the placenta in EOPE, which is reflected by lower SAM and PlGF DNA hypomethylation underlines the possible role of placental DNA hypomethylation in the pathophysiology of EOPE, which needs further investigation.

Indexed as

DNA MethylationAdultCase-Control StudiesFemaleHumansPlacentaPlacenta Growth FactorPre-EclampsiaPregnancyS-AdenosylhomocysteineS-AdenosylmethioninePGF protein, humanPlacenta Growth FactorS-AdenosylhomocysteineS-Adenosylmethionine

Identifiers

PMID31887212
PMCPMC6936822
OpenAlexW2997020264

What OpenQuestion holds

Textmetadata
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.