Biomarker may flag early pregnancy risk

A protein was linked experimentally to trophoblast invasion.

By
Andrea Surnit
September 4, 2026
4 min

MDSpire News

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

Outcome	ISM2 Rank
Preeclampsia alone	1
Fetal growth restriction alone	1
Preeclampsia with fetal growth restriction	2
Composite outcome	1

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.