Cambridge scientists find protein that predicts preeclampsia in first trimester

Researchers at the University of Cambridge have identified a protein that serves as a first-trimester predictor of preeclampsia and fetal growth restriction, a discovery that could lead to new screening tests and treatments for two of pregnancy's most dangerous complications.

The findings, published on Monday in Nature Medicine Springer Nature Group, reveal that low circulating levels of a protein called isthmin-2 (ISM2) around 12 weeks into pregnancy were the strongest indicator — out of 2,904 proteins analyzed — that a pregnancy would go on to develop preeclampsia or fetal growth restriction.cam+1

A Missing Piece of the Puzzle

Both preeclampsia and fetal growth restriction are linked to problems with the placenta failing to develop properly. Specialized placental cells known as extravillous trophoblasts normally invade the mother's uterus to establish a healthy blood supply for the fetus. Until now, the reason this process sometimes fails has been poorly understood.cam

The Cambridge team found that ISM2 is produced almost exclusively in the placenta and plays an essential role in enabling these cells to invade the uterine wall. When researchers switched off ISM2 production in human trophoblast stem cells in the laboratory, the cells survived but failed to become the invasive type needed to establish blood flow. In three-dimensional "mini-placentas," cells without ISM2 stopped spreading into surrounding material.cam

"Early pregnancy maternal levels of isthmin-2 are much better at predicting complications than existing tests, so it could enable us to develop better ways of identifying those pregnancies at greatest risk," said Professor Gordon Smith, head of the Department of Obstetrics and Gynaecology at Cambridge.cam

Scope and Implications

Preeclampsia, which causes dangerously high blood pressure and can lead to organ damage, affects roughly one in 20 pregnancies worldwide and remains a leading cause of maternal and fetal death. Fetal growth restriction affects up to one in five pregnancies globally and is a major contributor to stillbirth.www+1

The researchers studied more than 200 women who developed preeclampsia or fetal growth restriction and compared them with more than 200 women with normal pregnancies. The results were validated using samples from Swedish pregnant women, including over 100 cases and 200 controls.cam

Professor Steve Charnock-Jones, a co-author, said the discovery opens the door not only to better screening but also to potential prevention. "Now that we know what goes wrong, we may be in a better position to make a major difference to pregnancy outcomes, protecting the health and lives of millions of mothers and their babies every year," he said.cam

The research was largely funded by Wellcome Leap, with additional support from the National Institute for Health and Care Research Biomedical Research Centre and the Medical Research Council.cam