Researchers in the UK have identified a protein in maternal blood that could change how doctors detect and manage two serious pregnancy complications: preeclampsia and fetal growth restriction. Published in Nature Medicine, the study focuses on istmin-2 (ISM2), which appears as a warning sign months before symptoms develop.
The timing matters. Scientists at the University of Cambridge found that low ISM2 levels in the third month of pregnancy were the strongest early signal for both preeclampsia and fetal growth restriction, outperforming current early screening tools. This could help doctors identify high-risk pregnancies well before complications develop.
Xinhua News reported that the study’s validation included approximately 600 British and 400 Swedish pregnancy samples. Together, the results confirmed ISM2’s predictive value across independent cohorts.
Preeclampsia affects about one in twenty pregnancies worldwide. Fetal growth restriction affects up to 10% of pregnancies in high-income countries and as many as one in five globally. Both are linked to abnormal placental development early in pregnancy and can have serious consequences if not detected in time.
The Cambridge team studied a type of placental cell called extravillous trophoblasts (EVT). These cells invade uterine tissue and establish the blood supply the fetus needs. If this process fails, the placenta and fetus do not receive enough oxygen and nutrients, which can lead to complications.
To investigate ISM2’s role, the researchers analyzed blood samples from women at about 12 weeks of pregnancy. The samples were collected as part of the Pregnancy Outcome Prediction Study (POPS) at the Rosie Hospital in Cambridge. They compared women who later developed preeclampsia or fetal growth restriction with those who had healthy pregnancies, and found that low ISM2 levels were a clear early warning.
Information from MedPage Today, the Cambridge-led team screened 2,904 different proteins before identifying ISM2 as the most powerful early predictor of preeclampsia and fetal growth restriction in the first trimester. The findings were also validated in independent cohorts, including POPS 2 and the Improving Maternal Pregnancy And Child ouTcomes study.
Further laboratory work showed that ISM2 and its messenger RNA are produced almost exclusively in the placenta, especially in EVT cells. When scientists blocked ISM2 production in human trophoblast stem cells, those cells could not develop into the invasive EVT type needed for proper placental development. The same happened in lab-grown placental organoids: cells without ISM2 could not invade simulated uterine tissue.
In another experiment, human kidney cells, which are not normally involved in placental invasion, were engineered to produce ISM2. These cells then acquired invasive properties in cell cultures. The findings point to ISM2 as a basic driver of the cellular behavior needed for healthy placental implantation.
Measuring ISM2 levels could make early screening for high-risk pregnancies more accurate. That could allow closer monitoring and earlier intervention. The Cambridge team found that maternal ISM2 levels in early pregnancy outperformed existing tests in predicting complications. Therapies that increase ISM2 production in the placenta could also help prevent these conditions.
To check their results, the researchers examined samples from more than 200 women who developed preeclampsia or fetal growth restriction and more than 200 controls. They then confirmed the findings in a Swedish group, strengthening the case for ISM2 as a universal marker.
The discovery remains in the research phase, but it offers new understanding into why placental invasion fails in some pregnancies. If future studies confirm the results, ISM2 testing could become a routine part of prenatal care, giving more women and babies a better chance of a healthy outcome.
In Spain, where early and effective prenatal screening is a public health priority, ISM2-based tests could help reduce maternal and newborn complications. The research also opens the way for targeted therapies that address the root causes of these conditions, beyond treating their symptoms. The next step is to turn the findings into practical tools for clinics and hospitals, making early detection and prevention a reality for families across Europe.
