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Biomarker may flag early pregnancy risk

A protein was linked experimentally to trophoblast invasion.

  • By

  • Andrea Surnit

  • September 4, 2026

  • 4 min

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Clinical Report: Biomarker may flag early pregnancy risk

Overview

Low maternal serum isthmin-2 (ISM2) levels in the first trimester may indicate an increased risk of preeclampsia and fetal growth restriction. This study analyzed samples from multiple pregnancy cohorts.

Background

Identifying biomarkers for early pregnancy complications such as preeclampsia and fetal growth restriction is crucial for improving maternal and fetal health outcomes. Current clinical practices rely on later-stage assessments.

Data Highlights

OutcomeISM2 Rank
Preeclampsia alone1
Fetal growth restriction alone1
Preeclampsia with fetal growth restriction2
Composite outcome1

Key Findings

  • Low ISM2 levels at approximately 12 weeks were associated with all four outcomes: preeclampsia, fetal growth restriction, preeclampsia with fetal growth restriction, and a composite of these outcomes.
  • ISM2 showed greater discrimination for composite outcomes resulting in preterm birth compared to established placental biomarkers.
  • In the POPS2 cohort, ISM2 had the lowest summed rank across the four outcomes and was the strongest signal for the composite outcome.
  • Lower ISM2 levels were linked to greater uterine artery resistance at about 20 weeks among cases.
  • Reducing ISM2 expression significantly impaired trophoblast differentiation and invasion capabilities.

Clinical Implications

The findings indicate that measuring ISM2 levels in the first trimester is associated with identifying pregnancies at risk for preeclampsia and fetal growth restriction.

Conclusion

Low ISM2 levels in early pregnancy are associated with adverse outcomes such as preeclampsia and fetal growth restriction.

Related Resources & Content

  1. Miao R., et al., Nature Medicine, 2026 -- Isthmin-2 is a first-trimester predictor of preeclampsia and fetal growth restriction
  2. the pathologist — Pregnancy Risk Predictor
  3. reuters — Can Cheek Swabs Predict Preeclampsia Risk?
  4. the analytical scientist — Proteomics Identifies Early Preeclampsia Biomarkers
  5. Frontiers in Neurology — Identification and validation of GNA12circle as a novel plasma eccDNA biomarker for early detection of first-trimester preeclampsia
  6. Pregnancy Risk Predictor
  7. Can Cheek Swabs Predict Preeclampsia Risk?
  8. Proteomics Identifies Early Preeclampsia Biomarkers
  9. Aspirin Use to Prevent Preeclampsia and Related Morbidity and Mortality: Preventive Medication
  10. Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia
  11. Isthmin-2 is a first-trimester predictor of preeclampsia and fetal growth restriction | Nature Medicine

Original Source(s)

Biomarker may flag early pregnancy risk

  • by Andrea Surnit

  • September 4, 2026

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