PlGF blood test can predict early preeclampsia in SCD pregnancies
Patients are at higher risk for placental complications
A blood test measuring a protein called placental growth factor (PlGF) may help identify women with sickle cell disease (SCD) who are at risk of developing early-onset preeclampsia, a new study shows.
Preeclampsia is a disorder marked by high blood pressure and excess protein in the urine, which is an indicator of kidney damage. It can be dangerous for both the pregnant woman and her fetus, and typically occurs after 20 weeks of gestation.
“Patients with sickle cell disease are at higher risk for placental complications, so the ability to predict this risk is important for better pregnancy management,” Kinga Malinowski, MD, the study’s senior author and the head of the Hematology-Focused Maternal Fetal Medicine Clinic at Hamilton Health Sciences, in Canada, said in a press release from the American Society of Hematology (ASH). “With appropriate care, it is absolutely possible for patients with sickle cell disease to have a healthy, safe pregnancy for mom and baby.”
The study, “Utility of Placental Growth Factor (PlGF) for preeclampsia prediction in pregnancies complicated by Sickle Cell Disease,” was published in Blood Advances, an ASH journal.
Why SCD makes preeclampsia monitoring difficult
Monitoring for preeclampsia during pregnancy is important for everyone but is crucial for people with SCD. Those with this genetic disorder are more than twice as likely to experience this complication.
The placenta is the main source of PlGF, a protein that promotes the development of blood vessels. Previous studies have shown a close association between low PlGF levels and preeclampsia. Testing for low PlGF levels has been used to monitor for preeclampsia in the general population.
However, it remained unclear whether the cutoffs used to detect low PlGF in the general population could also be applied to SCD. This was mostly because SCD is often marked by chronic inflammation, which can boost PlGF production by red blood cells.
“Patients with sickle cell disease are at high risk for developing preeclampsia, but the challenge is that these patients produce placental growth factor even when they aren’t pregnant,” said Malinowski, who is also a professor at McMaster University, in Canada.
Another challenge is that most studies on PlGF levels have focused on people of European descent. SCD predominantly affects people who are Black or of African descent, who “have higher circulating PlGF levels than other racial groups in the 3rd trimester,” the researchers wrote.
To explore whether low PlGF levels could be used to predict risk of preeclampsia in SCD patients, Malinowski and colleagues retrospectively looked at data from 83 Black women with SCD and 149 Black women without it who served as controls. Each had at least one PlGF measurement taken between 20 and 36 weeks of gestation.
The study was conducted at Mount Sinai Hospital in Canada, where Malinowski was co-director of the Hematology in Pregnancy Program at the time.
The challenge of using PlGF in sickle cell disease
During the study, four pregnant women with SCD developed early-onset preeclampsia (starting before 34 weeks of gestation), seven developed late-onset preeclampsia (starting at or after 34 weeks of gestation), and the remaining participants did not have preeclampsia.
Women with SCD and early-onset preeclampsia had significantly lower median PlGF levels (78 picograms/mL) relative to those with late-onset preeclampsia (158 picograms/mL) and those without the complication (435 picograms/mL). A similar pattern was seen in the control group.
Previous research in the general population has shown PlGF levels below 100 picograms/mL between 20 and 24 weeks of pregnancy can signal preeclampsia. Using this cutoff was 100% accurate for distinguishing SCD patients with early-onset preeclampsia from those without the complication.
However, most women with SCD and late-onset preeclampsia had PlGF levels above this preestablished threshold. The cutoff level had to be raised to 832 picograms/mL to ensure 100% accuracy.
These data indicate that, “as in the non-SCD pregnant population, low circulating PlGF may be used as a diagnostic test for suspected preeclampsia, especially early-onset,” the researchers concluded, adding that PlGF testing for pregnant SCD patients “has the capacity to enhance safety and improve [pregnancy] outcomes.”
The researchers also found that, in all the women, early-onset preeclampsia was associated with earlier gestational age at delivery, lower birth weights, and higher rates of cesarean deliveries.
Pregnant women with SCD also had higher rates of maternal vascular malperfusion (MVM), which is inadequate blood flow from the mother to the placenta, compared with the controls. MVM is the most common placental issue linked to preeclampsia and restricted fetal growth.
The rates were even higher among women with preeclampsia. Lower PlGF levels were significantly associated with MVM in SCD pregnancies across all gestational stages, “further emphasizing its utility as a marker of placental health,” the researchers wrote.
“Future studies should focus on validating these findings in larger, multicentre [studies] of pregnant individuals with SCD and exploring the integration of PlGF with other biomarkers, to enhance its predictive accuracy,” they concluded.
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