Preeclampsia is a serious multisystem disorder that typically manifests as hypertension and proteinuria after 20 weeks’ gestation. The condition is multifactorial and involves placental, immunological, genetic, vascular, and maternal factors.
In Spain, preeclampsia affects about 1%-3% of pregnancies and, if not detected and managed early, can have severe or fatal consequences for both the mother and fetus.
Screening
First-trimester screening identifies patients at risk for early preeclampsia, defined as onset before 34 weeks of gestation, but there is no routine screening in the second or third trimester to detect late preeclampsia.
Standard first-trimester assessment combines maternal history, such as age, BMI, personal and family history of preeclampsia, diabetes, chronic hypertension, blood pressure measurement, uterine artery Doppler, and maternal blood testing for placental growth factor and pregnancy-associated plasma protein A.
These data were entered into the Fetal Medicine Foundation algorithm to estimate the probability of preterm preeclampsia (before 37 weeks); an estimated probability of > 1% typically prompts low-dose aspirin (150 mg/day).
Preeclampsia is diagnosed from 20 weeks’ gestation onward based on sustained elevated systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg on two readings at least 4 hours apart with signs of organ dysfunction such as proteinuria, renal or hepatic impairment, neurologic or hematologic complications, or evidence of uteroplacental dysfunction identified by clinical exam, laboratory tests, or ultrasound.
“Both clinical symptoms and test results can be nonspecific, which increases the risk for misdiagnosis,” said Carmen Garrido Giménez, MD, PhD, Clinical Head of Obstetrics at the Hospital de la Santa Creu i Sant Pau in Barcelona, Spain, and a researcher with the Women and Perinatal Health Research Group at the Institut de Recerca Sant Pau (IR Sant Pau), Barcelona.
“The soluble fms-like tyrosine kinase 1 to placental growth factor (sFlt-1/PlGF) angiogenic ratio is highly useful for ruling out preeclampsia, but elevated values can also appear in other placental disorders,” said Madalina Nicoleta Nan, MD, Specialist in Clinical Biochemistry at the Hospital de la Santa Creu i Sant Pau and researcher in Clinical Biochemistry at IR Sant Pau, who discussed the findings with Univadis Spain, a Medscape Network platform.
However, its limited availability in many laboratories, especially in emergency departments, hampers its systematic application in clinical practice beyond tertiary hospitals.
As clinical signs and standard tests can be nonspecific, researchers have explored alternative or complementary biomarkers. One promising avenue is the use of cardiovascular biomarkers, given the bidirectional link between cardiovascular diseases and preeclampsia. “Women with cardiovascular risk factors, such as chronic hypertension, diabetes, obesity, or kidney disease, are more likely to develop preeclampsia, and a history of preeclampsia increases the risk for cardiovascular disease. Researchers have therefore evaluated the role of cardiovascular biomarkers, particularly natriuretic peptides, B-type natriuretic peptide (BNP), and N-terminal pro-BNP (NT-proBNP), for the early detection and risk for preeclampsia,” explained Garrido Giménez and Nan.
Most studies using this approach have focused on whether these markers are elevated in women with clinically confirmed preeclampsia, with higher levels observed in earlier and more severe cases of preeclampsia. None have compared their performance with that of the sFlt-1/PlGF ratio, which is the most specific diagnostic standard. The researchers also did not assess the ability of these markers to predict preeclampsia in the week before clinical diagnosis.
Study Insights
A multicenter prospective study led by the Hospital de la Santa Creu i Sant Pau and the IR Sant Pau, with collaborators at four other Catalan hospitals, assessed whether NT-proBNP could predict the onset of early preeclampsia within 1 week of assessment in women with clinical suspicion at 24 weeks of gestation. The study enrolled 316 pregnant women from March 2018 to December 2020 (mean maternal age, 34 years; 86.4% Caucasian); 74 women (23.4%) developed preeclampsia.
The study found that NT-proBNP levels increased sharply in the days before symptom onset, making it a potential early warning marker. Levels of 116 pg/mL or higher predicted early preeclampsia with 90.9% sensitivity and 94.3% specificity.
This performance matched that of the sFlt-1/PlGF ratio, the current standard test; however, NT-proBNP offers the advantage of being less expensive and more widely available.
These results were unexpected. “We knew the cardiac biomarker would be elevated in women with preeclampsia because of its link to cardiovascular dysfunction,” said the physicians.
“We did not expect the predictive performance to match that of the angiogenic factor ratio (sFlt-1/PlGF) when the diagnosis was imminent. This short-term equivalence suggests the biomarker could serve as a complementary or alternative diagnostic option where angiogenic markers are unavailable.”
This predictive value could enable closer monitoring of at-risk women and allow timely preventive measures, such as administering corticosteroids to accelerate fetal lung maturation or hospital admission when necessary.
Detection of Complicated Cases
Beyond early preeclampsia, NT-proBNP also predicted complicated cases involving fetal growth restriction, placental abruption, or stillbirth, with a performance similar to that of the sFlt-1/PlGF ratio.
The sensitivity for these complications was 84.2%, and the specificity was 91.4%, supporting the potential for broader clinical use. This integrated approach could be especially valuable in obstetric pathology or intermediate care units, where anticipating complications may improve both maternal and fetal outcomes.
Clinical Translation
The study aimed to assess whether NT-proBNP could serve as a diagnostic alternative in settings lacking access to more specific markers, such as the sFlt-1/PlGF ratio, which is typically limited to tertiary hospitals.
However, the physicians said, “NT-proBNP cannot replace the angiogenic ratio, which is more reliable for ruling out preeclampsia in the longer term.”
For NT-proBNP to become a real diagnostic tool, “further prospective studies in diverse populations are needed to validate the proposed cutoff value. Trials incorporating NT-proBNP into diagnostic and clinical decision-making processes are required to determine its application in the early diagnosis of preeclampsia and improved clinical management. Standardized protocols and integration into existing clinical guidelines are also essential,” said the physicians.
“We are now studying whether combining NT-proBNP with the sFlt-1/PlGF ratio can improve the prediction of preeclampsia and maternal-fetal complications. We are also considering the possibility of randomized trials to assess the clinical utility of this biomarker in decision-making, although expanding this research beyond Spain is not currently planned,” the physicians concluded.
Elisa Llurba reported receiving consulting fees from the Spanish advisory board of Roche Diagnostics. The other authors declared having no conflicts of interest.
This story was translated from Univadis Spain.