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Research Article Alert

PlGF (Placental Growth Factor) Testing in Clinical Care: Evidence From a Canadian Hospital


Kelsey McLaughlin, PhD

In April 2021, Hypertension published a research article that examined the integration of placental growth factor (PlGF) testing into clinical care of high-risk pregnancies at Mount Sinai Hospital in Toronto, Canada.

 

Dr. Kelsey McLaughlin was the lead author of this article, with Dr. Melanie Audette as a co-author.

Keep reading to learn more about this study!

What is placental growth factor (PlGF)?

 

Placental growth factor (PlGF) is a protein that is produced by the placenta and released into the mother’s blood.

 

Scientists believe that the main reason that the placenta produces PlGF in normal pregnancy is to help the placenta grow and develop properly. PlGF is also thought to help the mother’s blood vessels around the body to relax and adapt to pregnancy, keeping the mother’s blood pressure at normal levels.

 

In normal pregnancy, levels of PlGF in the mother’s blood starts to increase in the first trimester and levels continue to rise until the third trimester. As the third trimester progresses, PlGF levels begin to drop; scientists believe this may be to protect the mother against excessive bleeding at delivery.

What is the role of PlGF in preeclampsia?

 

This research article mainly focuses on the relationship between PlGF levels and hypertensive disorders of pregnancy, including preeclampsia.

 

Preeclampsia is a serious disorder of pregnancy, where pregnant patients develop high blood pressure with organ damage. This hypertensive disorder impacts approximately 1 in 20 pregnancies and is associated with increased risk of health concerns for both mom and baby.

 

Scientists believe that a major cause of preeclampsia is abnormal levels of proteins produced by the placenta circulating in the mother’s blood. Patients with preeclampsia commonly have some degree of placental abnormality or dysfunction. Placental dysfunction can also lead to fetal growth restriction and/or stillbirth. The placentas of patients with preeclampsia release proteins into the mother’s blood in an abnormal manner as early as the first trimester. Abnormal levels of placental proteins can then be measured through screening blood tests.

 

Recent research has determined that measuring PlGF levels in pregnant patient’s blood is an important clinical advancement for two reasons:

  1. PlGF testing as early as the second trimester can accurately predict which pregnant patients are at increased risk of developing preeclampsia, and

  2. PlGF testing can help doctors to diagnose preeclampsia in pregnant patients in a more timely manner

 

Improving the prediction and diagnosis of preeclampsia can the potential to improve the health and pregnancy outcomes of both the mother and baby.

 

Despite this promising research, PlGF testing has not been widely integrated into standard clinical care in North America. This is mainly due to the lack of evidence investigating PlGF testing in real-world clinical settings. Real-world research is important to provide insight into how useful innovations like PlGF testing are outside of a tightly controlled research study and to provide health care providers with a more realistic sense of how this innovation can be used.

Summary of this research article

Purpose

The purpose of this investigation was to study the relationship between PlGF levels in high-risk pregnant patients and pregnancy outcomes in the real-world clinical setting.

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Methods

In March 2017, PlGF testing was integrated into real-world clinical care of high-risk pregnancies at Mount Sinai Hospital in Toronto, Canada. Doctors taking care of high-risk pregnant patients could order a PlGF blood test.

 

If the result of the PlGF blood test was equal to or over 100 pg/mL, patients were considered to have ‘normal’ PlGF levels. If the result of the PlGF blood test was below 100 pg/mL, patients were considered to have ‘low’ or ‘abnormal’ PlGF levels.

 

Doctors could order PlGF testing for pregnant patients between 20 – 36 weeks of gestation if patients were thought to be at risk of placental dysfunction, hypertensive disorders of pregnancy (including preeclampsia) or fetal growth restriction. Pregnant patients presenting with symptoms of these pregnancy complications could also have a PlGF test completed; an example would be if a pregnant patient presented to triage with a headache (a common symptom of preeclampsia).

 

Between March 2017 – December 2019, 979 high-risk pregnant patients with a single fetus completed PlGF testing between 20 – 36 weeks of gestation and delivered at Mount Sinai Hospital.

Results

 

Information about the high-risk pregnant patients who completed PlGF testing

  • 30% of high-risk pregnant patients had low PlGF levels

  • Patients with low PlGF levels delivered earlier than patients with normal PlGF levels (31 vs 37 weeks)

  • Babies born to patients with low PlGF levels had a lower birthweight centile than patients with normal PlGF levels (7th percentile vs 47th percentile)

Associations between PlGF levels and maternal pregnancy outcomes:

  • 62% of patients who completed PlGF testing were diagnosed with a hypertensive disorder of pregnancy, including gestational hypertension, late-onset preeclampsia or early-onset preeclampsia

  • 54% of patients who completed PlGF testing had a preterm birth (delivery before 37 weeks of gestation)

  • Patients with low PlGF levels were more likely to have a preterm birth than patients with normal PlGF levels (92% vs 38%)

  • Within 4 weeks of PlGF testing, over 60% of the patients with low PlGF levels had delivered preterm vs 1% of patients with normal PlGF levels

  • Pregnant patients with low PlGF levels were at strikingly higher risk of being diagnosed with a hypertensive disorder of pregnancy, specifically early-onset preeclampsia

 

Associations between PlGF levels and fetal pregnancy outcomes:

  • 6% of patients who completed PlGF testing had a stillbirth

  • Pregnant patients with low PlGF levels were at significantly higher risk of having a stillbirth

  • Stillbirth in patients with low PlGF levels was mainly due to placental dysfunction, while stillbirth in patients with low PlGF levels was mainly due to a fetal complication (such as genetic or anatomical anomalies)

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What do the results of this research article mean?

 

This research article represents a critical step in supporting the wide integration of PlGF testing into clinics and hospitals across Canada and internationally. Combining PlGF testing with current standard investigations for high-risk pregnant patients, including ultrasound and other blood tests, has the potential to improve clinical care and pregnancy outcomes.

 

In high-risk patients, PlGF testing can inform health care providers regarding which patients are at increased of preterm birth, early-onset preeclampsia and stillbirth. This is of great clinical value, as patients with low PlGF levels could then be offered higher levels of maternal-fetal care, monitoring and possibly additional clinical interventions.

 

PlGF testing could also provide clinical value to high-risk pregnant patients with normal PlGF levels, as these patients are at low risk of associated adverse pregnancy outcomes and could avoid unnecessary clinical intervention.

 

Importantly, PlGF testing could be a useful tool for remote communities that lack readily accessible maternal-fetal care. Pregnant patients with low PlGF levels could be referred to outside clinical centers with expert care due to the increased risk of preterm birth, early-onset preeclampsia and stillbirth.

Limitations of this research article

 

The results of this research article were generated from one high-risk hospital in downtown Toronto, which may not represent the experiences of other clinical centers across Canada. Similarly, the demographic of patients at this downtown center may not represent populations in different centers. Lastly, this investigation was not able to assess the pre-pregnancy health of these patients, which previous research has shown can have an impact on pregnancy outcomes (including obesity, diabetes, chronic hypertension).

Summary

 

This research article provides data to support the integration of PlGF testing for high-risk pregnant patients into Canadian clinical centers. Low PlGF levels in high-risk pregnant patients was associated with increased risk of preterm birth, preeclampsia and stillbirth.

 

Further research is needed to investigate the usefulness of PlGF testing across a wide range of Canadian clinical centers.

 

Disclaimer

Every woman and every pregnancy is unique. Pregnant women should speak to their healthcare provider to ensure maternal and fetal safety. This article is meant to provide readers with current information and opinions. All medical and treatment decisions should be discussed with your healthcare provider.

This article was written by Dr. Kelsey McLaughlin and edited by Dr. Melanie Audette.