Evidence map›Paper›PMID 42680952›Full record

ArticleNature medicine2026

Isthmin-2 is a first-trimester predictor of preeclampsia and fetal growth restriction.

Ruoyu Miao, Sungsam Gong, Ulla Sovio, Irving L M H Aye, Giulia Avellino, Jacqueline Guettler, Stephanie N Rogers, Emma Cook, Ana Toribio, Lina Bergman and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

16 authors.

Ruoyu Miao *Department of Obstetrics and Gynaecology, University of Cambridge; NIHR Cambridge Biomedical Research Centre, Cambridge, UK.ORCID http://orcid.org/0000-0001-6125-4467
Sungsam Gong *Department of Obstetrics and Gynaecology, University of Cambridge; NIHR Cambridge Biomedical Research Centre, Cambridge, UK.ORCID http://orcid.org/0000-0001-5796-4423
Ulla Sovio *Department of Obstetrics and Gynaecology, University of Cambridge; NIHR Cambridge Biomedical Research Centre, Cambridge, UK.ORCID http://orcid.org/0000-0002-0799-1105
Irving L M H Aye *Department of Obstetrics and Gynaecology, University of Cambridge; NIHR Cambridge Biomedical Research Centre, Cambridge, UK.ORCID http://orcid.org/0000-0003-3400-5005
Giulia AvellinoDepartment of Obstetrics and Gynaecology, University of Cambridge; NIHR Cambridge Biomedical Research Centre, Cambridge, UK.ORCID http://orcid.org/0000-0002-7413-0217
Jacqueline GuettlerDepartment of Obstetrics and Gynaecology, University of Cambridge; NIHR Cambridge Biomedical Research Centre, Cambridge, UK.ORCID http://orcid.org/0000-0002-8141-5712
Stephanie N RogersDepartment of Obstetrics and Gynaecology, University of Cambridge; NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
Emma CookDepartment of Obstetrics and Gynaecology, University of Cambridge; NIHR Cambridge Biomedical Research Centre, Cambridge, UK.ORCID http://orcid.org/0000-0002-6142-4443
Ana ToribioStratified Medicine Core Laboratory, Department of Genomic Medicine, University of Cambridge, Cambridge, UK.
Lina BergmanDepartment of Obstetrics and Gynecology, Institute of Clinical Sciences, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden.
Susanne LagerDepartment of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
Anna-Karin WikströmDepartment of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
IMPACT Consortium
Paul D W KirkMRC Biostatistics Unit, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-5931-7489
D Stephen Charnock-JonesDepartment of Obstetrics and Gynaecology, University of Cambridge; NIHR Cambridge Biomedical Research Centre, Cambridge, UK. dscj1@cam.ac.uk.ORCID http://orcid.org/0000-0002-2936-4890
Gordon C S SmithDepartment of Obstetrics and Gynaecology, University of Cambridge; NIHR Cambridge Biomedical Research Centre, Cambridge, UK. gcss2@cam.ac.uk.ORCID http://orcid.org/0000-0003-2124-0997

Funding

RCUK | Medical Research Council (MRC) MR/W027046/1RCUK | Medical Research Council (MRC) MR/Z504440/1Wellcome TrustWellcome Trust (Wellcome) 215524/Z/19/Z
6 · The paper itself

Abstract

Preeclampsia and fetal growth restriction (FGR) are major causes of global morbidity and mortality. Both conditions are associated with impaired invasion of the uterus by extravillous trophoblast (EVT). We performed proteomics in maternal serum obtained at ~12 weeks of gestational age in a prospective pregnancy cohort (Pregnancy Outcome Prediction Study). Here we show that low maternal serum isthmin-2 (ISM2) was the strongest protein signal (out of 2,904) in the first trimester of pregnancy for preeclampsia or FGR. We validated the association in two independent cohorts (Pregnancy Outcome Prediction Study 2 and Improving Maternal Pregnancy And Child ouTcomes study). ISM2 protein and mRNA are almost exclusively produced in the placenta, and, within the placenta, ISM2 mRNA is highly enriched in EVT. Knocking down ISM2 in cultured human trophoblast stem cells profoundly inhibited EVT invasion. Conversely, expressing ISM2 in a cell line lacking endogenous ISM2 (HEK293 cells) promoted migration. We conclude that ISM2 may be causally involved in the early pathophysiology of failed trophoblast invasion and that the protein and its associated pathways are potential targets for the prediction and prevention of preeclampsia and FGR.

Indexed as

Fetal Growth RetardationPre-EclampsiaPregnancy Trimester, FirstAdultCell MovementExtravillous TrophoblastsFemaleHEK293 CellsHumansPlacentaPregnancyProspective StudiesRNA, MessengerTrophoblastsRNA, Messenger

Identifiers

PMID42680952
PMCPMC13577898

What Socratic holds

Textmetadata
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 Socratic graph.