Placental growth factor testing highlighted at obstetrics conference

At a recent meeting, hosted by the RCPI, attendees heard how PlGF testing can help to reduce stillbirths

The RCPI welcomed obstetricians and gynaecologists to No 6, Kildare Street for a cross-border conference on Friday 7 March. The RCPI Institute of Obstetricians and Gynaecologists (IOG) annual Spring Conference is a key meeting in the College calendar, showcasing the latest research and practice in the area.

During the conference, Dr Suzanne O’Sullivan was appointed as the new IOG Chair, taking over from Prof Sam Coulter-Smith. Dr O’Sullivan is an accomplished obstetrician, gynaecologist, and sub-specialist urogynaecologist at Cork University Maternity Hospital. She has served as an elected Fellow on the RCPI Council, National Specialty Director for basic specialist training and higher specialist training, and National Director of Training at the IOG, where she led the development of an advanced simulation programme.

Among the eminent conference speakers was Dr John Kingdom, an obstetrician at Mount Sinai Hospital in Toronto, Canada, and co-founder of one of the world’s first dedicated placenta clinics .

Dr Kingdom argued that the inclusion of placental growth factor (PlGF) testing could transform pregnancy screening tests, with an estimated potential of lowering the tragedy of stillbirth by up to 50 per cent.

He recalled his time as an obstetrics trainee at the Queen Mother’s Hospital in Glasgow in the late 1980s and early 1990s.

Later, with the encouragement of a young consultant, he successfully applied for a Fellowship with the UK’s Medical Research Council to do research at its blood pressure unit in London.

“That’s where I got my interest in the placenta,” he said.

After two years of research, Dr Kingdom sub-specialised in foetal medicine at University College Hospital London, but soon decided to relocate.

“I didn’t want to do private practice. I wanted to do academia and make a difference.”

He secured an obstetrician position at Mount Sinai Hospital, where he was reunited with a peer from college, Dr Rory Windrim. Both had studied undergraduate medicine together at Trinity College Dublin in the early 1980s.

“He and I started a placenta clinic within a year of me arriving and we’ve done it together every Tuesday for 27 years, with women all over Ontario with placenta problems,” Dr Kingdom said.

Research

With a long-time interest in the molecular biology of placental damage, he was very familiar with PlGF – a protein made in the placenta and secreted into the maternal blood. In 2013, he followed with interest a study from King’s College London, which observed a group of 625 women across seven different maternity units.

Known as the PELICAN Study, it suggested that measuring PlGF could help accurately diagnose pre-eclampsia. Over the next four years, Dr Kingdom managed to persuade the chief of pathology at Mount Sinai to explore PlGF testing.

An opportunity for a cohort study finally presented itself in 2020, during the first months of the Covid-19 pandemic. A call-out was issued for grant proposals to fund innovative new methods to reconcile healthcare needs with Covid-19 safety measures.

“You have got to show up for a blood test at 24 weeks anyway to check for diabetes. Why don’t we tag on a placental blood test?” he said.

“If your blood test is normal at 24 weeks, we can do remote, Zoom-based antenatal care and education safely, from week 24-36. We can therefore strip out a lot of patients coming to hospital for care who are scared to come, and make sure they’re safe and that their babies don’t die from undetected growth restriction and placental insufficiency.

“We ultimately screened 10,000 patients. Between one to two per 100 people would be considered having a low [placental] blood test [level]. For those people, we said we’re going to educate them, monitor their blood pressure, treat and prevent pre-eclampsia from becoming serious for the mother, introduce high-quality ultrasound imaging to monitor the baby, and, if necessary, step in early to deliver the baby and prevent [the baby] from dying inside the mother, so it will be a premature live-born baby that will do well. From this blood test, we’re able to identify 60 per cent of patients who are destined to deliver prematurely before 34 weeks.”

As the evidence of potential links between preventable stillbirth and placental insufficiencies and low PlGF levels become more compelling, new interest has emerged in dedicated placenta and PlGF testing services.

Dr Kingdom spoke fondly of being a medical student in Dublin during the early 1980s, (“I lived above the neonatal unit in the old part of the Rotunda. There were so many beautiful historical buildings as hospitals.”). While in Dublin for the RCPI conference, he visited the National Maternity Hospital and Rotunda Hospital – both have interest in setting up placenta programmes.

“These approaches we expanded 25 years ago are really coming into play in Irish hospitals as well,” he said.

Stillbirth rate

“The stillbirth rate in Ireland is about three or four per 1,000. That’s pretty similar to Canada. What we’re trying to do is minimise the risk of preventable tragedies in pregnancy. What counts is that the placental insufficiencies that killed the baby a week before labour could have been detected much earlier from this blood test, and the patient then could then have been monitored and perhaps had a caesarean delivery or induction of labour two weeks earlier, and therefore have a live-born child that’s healthy.

“The placental complications of pregnancy are the common things doctors and midwives fear. They’re scared of a patient having an eclamptic fit or a stillbirth, or a sudden placental separation where they start bleeding. Here’s a simple way for all of us to substantially lower our fear of these big complications of pregnancy. We can substantially lower the tragedy of stillbirth by, I’d say, 50 per cent,” he said.

During his presentation, Dr Kingdom argued that including PlGF testing could transform pregnancy screening tests. The dominant multi-modal intervention model – combining information about a patient’s ethnic background, weight, pregnancy history, etc, into a sequential algorithm – could be replaced by a more universal, uni-modal blood test. “I think it can make a real difference in obstetrics and maternal foetal medical care,” he said.

Themed ‘Celebrating Obstetrics and Gynaecology’, the conference marked the first time that RCPI’s IOG hosted a joint meeting in No 6, Kildare Street, Dublin, with the Royal College of Obstetricians and Gynaecologists (RCOG) UK, and the Ulster Obstetrical and Gynaecological Society (UOGS), Northern Ireland.

UOGS President Dr Kristine Steele presented on a new category of ectopic pregnancy that is asymptomatic. She urged against gynaecologists feeling pressure to perform unnecessary intervention and recommended expectant management as a treatment.

Dr Ranee Thakar, RCOG President, gave an update on how her college was addressing women’s health priorities through several new projects, including a new Race Equity Project (feedback revealed that 75 per cent of the College’s membership witnessed racial discrimination at work) and a new Avoiding Brain Injury in Childbirth programme co-designed with Royal College of Midwives.

“We have seen nearly a 60 per cent increase in gynaecology referrals in three years up to 2022,” said RCPI IOG Chair, Dr O’Sullivan. Noting the upcoming seventh anniversary of the HSE’s pause on vaginal mesh implants, she thanked Dr Thakar and Dr Lucia Dolan, who volunteered their free weekends to help provide vaginal mesh removal training in the Republic of Ireland. Dr O’Sullivan also said that all 19 recommendations made by the Chief Medical Officer have been addressed.

“I feel our specialty is good at collegiality. If we reach out to each other, there’s a lot we can do,” said Dr O’Sullivan.

This article was produced by the RCPI.