Preeclampsia discovery could lead to new test and treatments for at-risk pregnancies

Cambridge scientists have discovered a protein that could potentially predict preeclampsia and fetal growth restriction, two major causes of stillbirth and illness in mothers and newborns. This breakthrough offers hope for early identification of at-risk pregnancies and the development of new treatments. Preeclampsia affects about one in 20 pregnancies globally and is a significant contributor to maternal and fetal health complications worldwide.

Fetal growth restriction, affecting 3% to 10% of pregnancies in high-income countries and up to one in five globally, is a leading cause of pregnancy complications and newborn health issues. These conditions are primarily linked to improper placental development, particularly the failure of specialized placental cells called extravillous trophoblasts (EVT) to invade the mother's womb.

Professor Gordon Smith, head of the University of Cambridge's Department of Obstetrics and Gynecology, explained that the placenta normally invades the mother's tissues, with humans having the deepest placental invasion among mammals. When this process fails, the placenta and fetus become deprived of essential nutrients and oxygen, leading to preeclampsia and fetal growth restriction.

To investigate the underlying cause of this failure, the researchers analyzed blood samples from pregnant women recruited to the Pregnancy Outcome Prediction Study (POPS) at the Rosie Hospital, part of Cambridge University Hospitals NHS Foundation Trust. They discovered that low levels of a protein called isthmin-2 (ISM2), predominantly produced in the placenta, were the strongest indicator of future preeclampsia or fetal growth restriction around three months into pregnancy.

Further experiments showed that without ISM2, trophoblast cells failed to develop into invasive EVT cells and spread into surrounding maternal tissue. This finding suggests that ISM2 plays a crucial role in the proper invasion of placental cells and the establishment of a healthy blood supply. If ISM2 levels can be increased in the placenta, it may prevent preeclampsia and fetal growth restriction, and potentially reduce the need for surgical interventions in cases of implantation complications.