New Blood Protein Predicts Pre-eclampsia and Foetal Growth Restriction

Pre-eclampsia is a pregnancy-related condition that causes high blood pressure and poses serious risks to both mother and baby. While routine antenatal appointments typically check blood pressure and urine, early signs are rarely noticeable. On September 1, 2026, researchers at the University of Cambridge published findings in Nature Medicine pinpointing a specific protein in maternal blood that signals future complications. Out of 2,904 proteins tested from blood samples taken at roughly 12 weeks of pregnancy, isthmin-2 emerged as the strongest early predictor for both pre-eclampsia and foetal growth restriction.

Foetal growth restriction affects roughly 3 to 10 percent of pregnancies in high-income countries and up to one in five pregnancies worldwide. Professor Gordon Smith led the study, which analysed blood samples from the Pregnancy Outcome Prediction Study conducted at the Rosie Hospital, part of Cambridge University Hospitals NHS Foundation Trust, between 2008 and 2012. The team compared more than 200 women whose pregnancies were later affected by these conditions against a control group of more than 200 unaffected pregnancies.

Placental Function and the Role of Extravillous Trophoblasts

The placenta connects mother and baby to supply essential oxygen and nutrients throughout gestation. Early in pregnancy, specialized cells called extravillous trophoblasts burrow into the wall of the womb to establish a healthy blood supply. Both pre-eclampsia and foetal growth restriction occur when this placental invasion falls short. Humans possess the deepest placental invasion of any mammal, a trait linked by Professor Smith to the immense metabolic demands of developing the human brain.

Isthmin-2 is made almost exclusively within the placenta, predominantly by these invasive extravillous trophoblast cells. To determine whether the protein actively causes these developmental changes rather than simply correlating with them, the research team utilized human trophoblast stem cells first derived in 2018 and three-dimensional placental organoids developed the same year. When researchers switched off the isthmin-2 protein in trophoblast stem cells, the cells survived and grew normally but failed to transform into the invasive cells required to burrow into the womb wall. Similarly, mini-placentas lacking the protein stopped spreading into surrounding material.

Validation Across International Cohorts and Future Care Implications

To confirm the initial findings, the Cambridge team tested their results in a second pregnancy cohort from the same research programme and in a Swedish study involving more than 100 affected and 200 unaffected pregnancies. In all cohorts, low levels of isthmin-2 significantly outperformed five established placental markers measured in the same blood samples.

According to Professor Smith, early-pregnancy measurements of isthmin-2 are much better at predicting complications than existing tests.