Using placental growth factor to predict preeclampsia risk in pregnant women with sickle cell disease

In pregnant women with sickle cell disease, the risk of developing early-onset preeclampsia can be determined by measuring levels of a protein associated with placental function and development. These findings provide insight that may help clinicians to anticipate and mitigate adverse pregnancy outcomes and were published in the journal Blood Advances. 

"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," explained the lead study author, Kinga Malinowski, MD, MSc, who initiated the work as co-director of the Hematology in Pregnancy Program at Mount Sinai Hospital and assistant professor at the University of Toronto, both in Canada. 

"This has raised the question of whether we can use low placental growth factor levels to predict preeclampsia in this patient population, and our study finds that, yes, we can, and with the same threshold that we use for patients without sickle cell disease," said Dr. Malinowski, who now leads the Hematology-Focused Maternal Fetal Medicine Clinic at Hamilton Health Sciences and is a professor in the Department of Obstetrics and Gynaecology at McMaster University. 

Placental growth factor (PlGF) is a protein produced by the placenta that supports the development of blood vessels. Measuring PlGF levels can help assess the risk of preeclampsia, a potentially deadly pregnancy complication that usually arises after 20 weeks and is characterized by high blood pressure and protein in the urine. Women with sickle cell disease are more than 2.4 times likely to develop preeclampsia during pregnancy when compared to women without this condition. This complication can inhibit growth of the fetus, result in premature birth, and is associated with stroke and potential organ damage in the mother. 

In their study, the researchers retrospectively evaluated data on 83 pregnant women with sickle cell disease compared to 149 Black women without sickle cell disease, all patients at Mount Sinai Hospital in Toronto. All pregnancies had at least one PlGF measurement between 20- and 36-weeks' gestation. 

The researchers observed that median PlGF levels in individuals with sickle cell disease and early-onset preeclampsia were substantially lower at 20-24 weeks (78 pg/mL) compared to pregnancies with late-onset preeclampsia (158 pg/mL) or no preeclampsia (435 pg/mL). This trend mirrored that of the control group, with median PlGF levels of 55 pg/mL, 448 pg/mL, and 322 pg/mL for early-onset preeclampsia, late-onset preeclampsia, and no preeclampsia, respectively. 

Low PlGF levels were effective at predicting the onset of preeclampsia in the pregnant women with sickle cell disease. Specifically, a prediction of early-onset preeclampsia achieved 100% sensitivity and specificity with a PlGF threshold of 87 pg/mL at 20 – 24 weeks, while a cut-off of 832 pg/mL at 20-24 weeks achieved 100% sensitivity and specificity for predicting late-onset preeclampsia. Additionally, the researchers found that pregnant women with sickle cell disease faced a particularly high risk of maternal vascular malperfusion, or inadequate blood flow, which is the most common placental injury linked to preeclampsia and fetal growth restriction. This risk was even higher in the presence of preeclampsia and was consistently associated with lower PlGF levels across all gestational stages. 

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. With appropriate care, it is absolutely possible for patients with sickle cell disease to have a healthy, safe pregnancy for mom and baby." 

Dr. Kinga Malinowski, MD, MSc, lead study author

The study has some limitations, including that it was a single center study. Furthermore, other factors in addition to placental health can contribute to adverse pregnancy outcomes in women with sickle cell disease. 

Dr. Malinowski and her colleagues are currently conducting an international study to validate a risk assessment calculator for pregnant patients with sickle cell disease, designed to identify those at highest risk of complications and guide timely interventions to reduce adverse outcomes. 

Sickle cell disease is the most common inherited blood disorder and is marked by abnormally shaped red blood cells that can block blood vessels, leading to pain and infection. The condition affects more than 100,000 people in the United States and about one in every 365 Black or African American births.