At-risk pregnancies can be linked to a new biomarker

“The discovery helps to explain why placental cells fail to ‘invade’ the wall of the womb adequately in these two related conditions. The discovery could also lead to the development of tests to identify women who are at the greatest risk of developing these conditions, as well as new treatments,” says Lina Bergman, Professor at the University of Gothenburg and affiliated researcher at Uppsala University.

Pre-eclampsia affects about one in 20 pregnancies worldwide and is a significant cause of health complications in both mother and child, and is a major cause of maternal and infant mortality globally.

Fetal growth restriction, a condition that results in the baby not reaching its biological growth potential in the womb, affects about 3 to 10 per cent of all pregnancies in high-income countries, and up to one in five pregnancies globally. It is one of the main causes of complications during pregnancy and in newborns, including stillbirth.

Both of these conditions are known to be linked to problems in the development of the placenta at an early stage in the pregnancy; in particular, that specialised placental cells fail to invade the wall of the womb and establish a good blood supply.

When this process fails, it can lead to the placenta and the foetus being deprived of nutrients and oxygen, which in turn causes pre-eclampsia and fetal growth restriction. Until now, the reason for this invasion failing has been obscure.

Analysed samples from women in the UK and Sweden

To better understand this process, researchers at the University of Cambridge analysed serum samples taken from 600 pregnant women in the UK. The samples were taken at around 12 weeks of pregnancy. These samples were then validated in an extensive Swedish multi-centre study called the IMPACT study. The study included women in the first trimester of pregnancy from the cities of Uppsala, Stockholm, Falun, Eskilstuna, Karlstad, Örebro, Gothenburg and Lund. For the current study, the researchers selected all women who went on to develop pre-eclampsia for analysis, along with random controls (pregnant women who did not go on to develop the condition). A total of 400 samples from Sweden were analysed.

“Having such a diverse cohort of women from Sweden included in this study means that we can extrapolate the results to Sweden more broadly,” says Anna Karin Wikström, professor at Uppsala University, and principal researcher for the IMPACT study.

Protein level can reveal the risk of complications at an early stage

The researchers investigated the presence of 'red flags’ in the form of biomarkers in those women whose pregnancies were later affected by pre-eclampsia or fetal growth restriction. They found that low levels of a protein known as isthmin-2 (ISM2) in the blood at around three months into the pregnancy was the strongest indicator that the pregnancy would later go on to develop complications in the form of pre-eclampsia or fetal growth restriction.

“Since we could see a similar connection in both the UK and Swedish populations, it suggests that this protein plays an important role in the development of pre-eclampsia in diverse population groups. Hopefully, this can lead to an important test during the first trimester to identify women at high risk of pre-eclampsia and fetal growth restriction,” says Lina Bergman.

In laboratory experiments, the researchers switch off ISM2 in placental stem cells and were able to see that the cells no longer developed into the invasive cells that burrow into the wall of the womb. But when they added ISM2 to other cells, they became more invasive. This suggests that ISM2 plays a vital role in the development of the placenta.

“We hope that this new knowledge will not only allow us to develop tests to predict at-risk pregnancies, but also to prevent these conditions by stimulating the production of the protein in the placenta,” says Anna Karin Wikström.

Sandra Gunnarsson