Biomarker may flag early pregnancy risk - Summary - MDSpire
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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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Objective:

To investigate the association of low maternal serum isthmin-2 (ISM2) levels in the first trimester with the risk of preeclampsia (PE) and fetal growth restriction (FGR).

Approach:
  • Study Design: Analyzed samples from 3 prospective pregnancy cohorts, including the POPS study with 4,512 nulliparous patients, measuring 2,904 maternal serum proteins at approximately 12 weeks.
  • Outcomes Evaluated: Four outcomes were assessed: PE without FGR, FGR without PE, PE with FGR, and a composite of any of the three outcomes.
  • Statistical Analysis: Compared ISM2 with established placental biomarkers and evaluated its association with uterine artery blood flow.
  • Functional Studies: Investigated ISM2 expression and function using human trophoblast stem cells and placental organoids.
Key Findings:
  • Low ISM2 levels at 12 weeks were associated with all four outcomes: PE without FGR, FGR without PE, PE with FGR, and a composite of any of the three outcomes.
  • ISM2 showed greater discrimination for composite outcomes compared to five established placental biomarkers.
  • Lower ISM2 at 12 weeks was associated with greater uterine artery resistance at 20 weeks.
  • In the IMPACT study, lower ISM2 levels were observed in those who experienced PE complicated by preterm birth or FGR.
Limitations:
  • The study focused on northern European cohorts, requiring validation in other populations.
  • The reasons for lower ISM2 levels in patients who developed PE or FGR were not determined.
  • Mechanisms underlying the effects of ISM2 on trophoblast invasion and migration remain unknown.
Conclusion:

Low ISM2 in the first trimester had the strongest association with subsequent PE and/or FGR among the proteins studied.

Sources:

Original Source(s)

Biomarker may flag early pregnancy risk

  • by Andrea Surnit

  • September 4, 2026

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