Innovative research by King’s academics has addressed an unmet meet need for strategies to identify women and babies at risk of serious complications of pregnancy, saving lives and easing the burden on women.

Every year around 130 000 births in the UK are affected by the most common gestational disorders: preterm birth, hypertension or pre-eclampsia, and intrahepatic cholestasis of pregnancy. When evaluated globally this number rises to 20 million.

With these disorders responsible for 10% of maternal and fetal illness, disability and death, it is both a national and global priority to reduce the number of pregnant women at risk.

By improving understanding of the underlying causes of these disorders, King’s researchers have developed diagnostic markers and tools that are able to better identify pregnant women at greatest risk and determine their pathways to care.

The work – undertaken over a decade by King’s Professors Lucy Chappell, Laura Magee, Kypros Nicolaides, Liona Poon, Lucilla Poston, Jane Sandall, Andrew Shennan, Rachel Tribe, Peter von Dadelszen, Catherine Williamson and Dr Caroline Ovadia – demonstrates that novel tools and personalised care can lead to reductions in maternal and fetal morbidity and mortality.

New tests combine with new technology to prevent spontaneous preterm birth (PTB)

In 2014 King’s established an evidence-based research clinic for women at risk of prematurity at Guys and St Thomas NHS Trust. The new tests offered at this clinic (quantification of cervico-vaginal fetal fibronectin and measurement of cervical length) were combined with maternal health history to create an algorithm that determines whether a woman is at risk of preterm birth. This algorithm has subsequently been incorporated into an app, QUiPP, which is widely used to guide clinical management and support pregnant women.

The results of this research influenced a Department of Health report (now Department of Health and Social Care) which recommended a reduction in preterm birth from 8% to 6% by 2025, while prediction tests and intervention strategies developed and validated by the research have been incorporated into national guidance.

Encouragingly, the specialist clinic model pioneered by our academics was recommended for rollout by the NHS and there are now 50 clinics like it in the UK, with more planned.

Methods for early detection of pre-eclampsia widely adopted

While raised blood pressure and detection of urinary protein have traditionally signalled pre-eclampsia in pregnant women, these markers are not always reliable to ensure accurate diagnosis.

Previous research led by King’s academics determined that when low placental growth factor (PlGF) measured in the blood is combined with clinical history, blood pressure and ultrasound, it can accurately predict in early pregnancy those women that will subsequently develop pre-eclampsia. They were also able to show that treatment with aspirin following risk assessment with an algorithm including PlGF reduced the incidence of early-onset pre-eclampsia by 80%.

King’s researchers led a clinical trial which revealed that PlGF measurement in the second half of pregnancy in high-risk women reduced the time to diagnosis and maternal complications of pre-eclampsia. This persuasive evidence for PIGF testing resulted in its inclusion in 2016 and 2019 NICE guidelines here in the UK, while in Mozambique the government has introduced PIGF screening as a national policy.

Early aspirin treatment for prevention of pre-eclampsia in high-risk women has also been incorporated into NICE and International Federation of Gynaecology and Obstetrics guidelines, amongst others.

The research has had significant impact at a global health level. King’s researchers developed CRADLE VSA, a blood pressure monitor with a novel traffic light alert system. The Sierra Leonean government has rolled out 3000 of these devices, associated with a greater than 50% reduction in maternal mortality in the country. The device was one of the top 30 high impact innovations in global health in 2015 and has been recommended for use in refugee camps.

Increased knowledge of Intrahepatic cholestasis of pregnancy (ICP) enables prediction of complications of pregnancy

King’s researchers uncovered that maternal serum bile acid concentrations above a specific threshold can identify those with ICP at increased risk of stillbirth. As a result, health care providers are able to make more accurate decisions about timing of delivery, reducing the risk of this devastating complication.

Further whole genome sequencing identified pathological mutations in liver transporter genes in 20% of women with pregnancy cholestasis, with real impact on clinical management and planning.

Evidence that serum bile acids play a role in stillbirth has been included in a number of influential guidelines and the published research was voted the most impactful paper of 2019 by the North American Society of Obstetric Medicine.

With a direct bearing on women’s lives, this research resulted in approval of screening of women with ICP by the NHS Genomic Medicine Service to identify those with mutations in hepatobiliary disease genes, and at risk of cirrhosis, gallstone pancreatitis or biliary malignancy in later life.

Research with real-world impact

As is evident, King’s-led research into these three widespread gestational disorders has had a substantial impact on the lives of pregnant women both in the UK and around the world. At the same time it has equipped health care professionals to provide better management for women and plan for adverse outcomes, informing national and international policy and guidelines on high risk pregnancy.