Evidence map›Paper›PMID 32438913›Full record

ArticleBMC medicine2020

Circulating mRNAs are differentially expressed in pregnancies with severe placental insufficiency and at high risk of stillbirth.

Natalie J Hannan, Owen Stock, Rebecca Spencer, Clare Whitehead, Anna L David, Katie Groom, Scott Petersen, Amanda Henry, Joanne M Said, Sean Seeho and 10 more

Open access · goldAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.5field-weighted citation impact, top 7% 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

25 citing papers in PubMed, 40 citations in OpenAlex.

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  13. Improving Development of Drug Treatments for Pregnant Women and the Fetus.Therapeutic innovation & regulatory science · 2022
    Review
  14. Review
  15. Article
  16. The Update of Fetal Growth Restriction Associated with Biomarkers.Maternal-fetal medicine (Wolters Kluwer Health, Inc.) · 2022
    Review
  17. Article
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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

20 authors at 8 institutions in 3 countries.

Natalie J HannanTranslational Obstetrics Group, Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Level 4, Studley Rd, Heidelberg, Victoria, 3084, Australia.
Owen StockTranslational Obstetrics Group, Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Level 4, Studley Rd, Heidelberg, Victoria, 3084, Australia.
Rebecca SpencerElizabeth Garrett Anderson Institute for Women's Health, University College London, London, WC1E 6BT, UK.
Clare WhiteheadTranslational Obstetrics Group, Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Level 4, Studley Rd, Heidelberg, Victoria, 3084, Australia.
Anna L DavidElizabeth Garrett Anderson Institute for Women's Health, University College London, London, WC1E 6BT, UK.
Katie GroomDepartment of Maternal Fetal Medicine, Royal Women's Hospital, Parkville, Victoria, 3052, Australia.
Scott PetersenLiggins Institute, University of Auckland, Auckland, 1023, New Zealand.
Amanda HenryCentre for Maternal Fetal Medicine, Mater Mothers' Hospital, South Brisbane, Queensland, 4101, Australia.
Joanne M SaidDepartment of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, 3010, Australia.
Sean SeehoMaternal Fetal Medicine, Joan Kirner Women's & Children's Sunshine Hospital, St Albans, Victoria, 3021, Australia.
Stefan C KaneDepartment of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, 3010, Australia.
Lavinia GordonUniversity of Melbourne Centre for Cancer Research, Parkville, Victoria, 3010, Australia.
Sally BeardTranslational Obstetrics Group, Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Level 4, Studley Rd, Heidelberg, Victoria, 3084, Australia.
Kantaraja ChinderaElizabeth Garrett Anderson Institute for Women's Health, University College London, London, WC1E 6BT, UK.
Smita KaregodarElizabeth Garrett Anderson Institute for Women's Health, University College London, London, WC1E 6BT, UK.
Richard HiscockDepartment of anesthesia, Mercy Hospital for Women, Heidelberg, Victoria, 3084, Australia.
Natasha PritchardTranslational Obstetrics Group, Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Level 4, Studley Rd, Heidelberg, Victoria, 3084, Australia.
Tu'uhevaha J Kaitu'u-LinoTranslational Obstetrics Group, Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Level 4, Studley Rd, Heidelberg, Victoria, 3084, Australia.
Susan P WalkerTranslational Obstetrics Group, Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Level 4, Studley Rd, Heidelberg, Victoria, 3084, Australia.
Stephen TongTranslational Obstetrics Group, Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Level 4, Studley Rd, Heidelberg, Victoria, 3084, Australia. stong@unimelb.edu.au.
Mercy Hospital for Women · AUUniversity College London · GBUniversity of Melbourne · AUNorthern Sydney Local Health District · AUMater Mothers' Hospital · AURoyal Women's Hospital · AUSunshine Hospital · AUUniversity of Auckland · NZ

Funding

FP7 Ideas: European Research Council () 305823National Health and Medical Research Council of Australia 1028521;1183854;1055795;1146128;1159261;11364118
6 · The paper itself

Abstract

backgroundFetuses affected by placental insufficiency do not receive adequate nutrients and oxygenation, become growth restricted and acidemic, and can demise. Preterm fetal growth restriction is a severe form of placental insufficiency with a high risk of stillbirth. We set out to identify maternal circulating mRNA transcripts that are differentially expressed in preterm pregnancies complicated by very severe placental insufficiency, in utero fetal acidemia, and are at very high risk of stillbirth.

methodsWe performed a cohort study across six hospitals in Australia and New Zealand, prospectively collecting blood from 128 pregnancies complicated by preterm fetal growth restriction (delivery < 34 weeks' gestation) and 42 controls. RNA-sequencing was done on all samples to discover circulating mRNAs associated with preterm fetal growth restriction and fetal acidemia in utero. We used RT-PCR to validate the associations between five lead candidate biomarkers of placental insufficiency in an independent cohort from Europe (46 with preterm fetal growth restriction) and in a third cohort of pregnancies ending in stillbirth.

resultsIn the Australia and New Zealand cohort, we identified five mRNAs that were highly differentially expressed among pregnancies with preterm fetal growth restriction: NR4A2, EMP1, PGM5, SKIL, and UGT2B1. Combining three yielded an area under the receiver operative curve (AUC) of 0.95. Circulating NR4A2 and RCBTB2 in the maternal blood were dysregulated in the presence of fetal acidemia in utero. We validated the association between preterm fetal growth restriction and circulating EMP1, NR4A2, and PGM5 mRNA in a cohort from Europe. Combining EMP1 and PGM5 identified fetal growth restriction with an AUC of 0.92. Several of these genes were differentially expressed in the presence of ultrasound parameters that reflect placental insufficiency. Circulating NR4A2, EMP1, and RCBTB2 mRNA were differentially regulated in another cohort destined for stillbirth, compared to ongoing pregnancies. EMP1 mRNA appeared to have the most consistent association with placental insufficiency in all cohorts.

conclusionsMeasuring circulating mRNA offers potential as a test to identify pregnancies with severe placental insufficiency and at very high risk of stillbirth. Circulating mRNA EMP1 may be promising as a biomarker of severe placental insufficiency.

Indexed as

AdultCohort StudiesFemaleHumansInfant, NewbornPlacental InsufficiencyPregnancyRisk FactorsRNA, MessengerStillbirthRNA, MessengerCirculating mRNAFetal growth restrictionFetal hypoxiaPregnancy

Identifiers

PMID32438913
PMCPMC7243334
OpenAlexW3026204726

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.