A new biomedical test showed promise in for predicting the "short-term absence" of preeclampsia in women in whom the syndrome was suspected clinically,according to Austrian researchers.
However,it was less successful in determining which women would go on to develop that condition,reported Harald Zeisler,MD,of Medical University Vienna,and colleagues.
In women with suspected preeclampsia,the Elecsys immunoassay was able to pinpoint those who would not develop preeclampsia,eclampsia,or HELLP syndrome (hemolysis,elevated liver enzymes and low platelet count) in the subsequent week. Using a previously developed cutoff point,the test had a negative predictive value of 99.3% (95% CI 97.9-99.9),with 80.0% sensitivity (95% CI 51.9-95.7) and 78.3% specificity (95% CI 74.6-81.7),they wrote in the New England Journal of Medicine.
But the test was not as accurate at predicting whether these women went on to develop preeclampsia or any associated adverse fetal outcomes within the next 4 weeks. Its positive predictive value using that same cutoff was 36.7% (95% CI 28.4-45.7),with 66.2% sensitivity (95% CI 54.0-77.0) and 83.1% specificity (95% CI 79.4-86.3).
The PROGNOSIS (Prediction of Short-Term Outcome in Pregnant Women) study used immunoassay comprised of a ratio of vascular growth factors in the blood thought to be indicators of preeclampsia: an increase in soluble fms-like tyrosine kinase 1 (sFlt-1) and a decrease in placental growth factor (PlGF).
Women with a sFlt-1:PlGF ratio under the cutoff point of 38 would have a lower risk of developing preeclampsia or other adverse fetal outcomes than those with a ratio of more than 38,the authors noted.
Co-author Stefan Verlohren,MD,PhD,of Charité Berlin in Germany,said that the ratio should not be used by itself,but in conjunction with other diagnostic and clinical information.
"[It] is not a 'standalone test' but should be considered as an additional tool for aiding decision making in cases of suspected pre-eclampsia," he wrote in an email to MedPage Today.
The predictive performance of sFlt-1 and PlGF separately was not superior to that of the sFlt-1:PlGF ratio,the authors noted. But a post hoc analysis did suggest the addition of proteinuria and blood-pressure assessments improved both the positive and negative predictive values of the test.
Two adverse maternal outcomes were reported. A patient with a sFlt-1:PlGF ratio of 143.7 had severe preeclampsia and cerebral hemorrhage within 1 week,while another with a ratio of 64.4 had cerebral thrombosis within 4 weeks.
The median sFlt-1:PlGF ratio was 87.8 and 59.4 for participants who developed pre-eclampsia in 1 week and 4 weeks,respectively. The median ratios were 8.0 and 6.4,respectively,for the participants who did not develop pre-eclampsia.
Zeisler's team examined two cohorts of women. There were 500 in the development phase cohort (where the ratio was developed) and 550 in the validation phase. These women were from 14 countries and were all within 24 weeks to 36 weeks,6 days of gestation. There was no significant difference in age,gestational age,body mass index before pregnancy,and smoking status in those participants who developed preeclampsia and those who did not.
Limitations of the study included its observational nature. Also,the optimal cutoff for this immunoassay may be different when other assays.
While not involved with the study,Mary L. Rosser,MD,PhD,of Montefiore Medical Center in New York City,characterized these findings as "very exciting." She said that te test would be a positive influence to have in practice due to the potential time it would save for both doctors and patients.
"This could improve your clinical decisions with regards whether you hospitalize the patient,or monitor them as an outpatient,as well as the intensity of outpatient monitoring," she told MedPage Today. "If you don't have them in the hospital,and you have them in the office,how often do you have them come back? If you can safely say 'There's less of a probability that you will develop pre-eclampsia in the next week,' then you may not bring them back for monitoring several times during that 1 week."
preeclampsia often presents a complicated diagnostic problem for physicians,because the symptoms may mimic those found in normal pregnancy. In addition,it requires constant monitoring of the patient to see if the symptoms develop or worsen.
This is not the first time an elevated sFlt-1:PlGF ratio has been examined to aid in the detection of preeclampsia. An accompanying editorial by Ellen W. Seely,MD,and Caren G. Solomon,MD,both of Brigham and Women's Hospital in Boston,point out that while these values have not shown to be predictive earlier in pregnancy (prior to 20 weeks),studies of women later in pregnancy have shown more promise.
"Prospective single-center studies have suggested that the sFlt-1: PlGF ratio may be useful as a diagnostic aid for triaging women with singleton pregnancies and suspected pre-eclampsia," they wrote. "A test that could help clinicians decide which women can be followed safely on an outpatient basis would be of great benefit."
But Loralei Thornburg,MD,of the University of Rochester Medical Center in New York,pointed out that the test "may help with avoiding hospitalization by 'ruling out' some women,allowing physicians to focus evaluation and management on a higher risk group of women,we do not know if that would actually result in improved outcomes or cost savings for those women," she wrote in an email to MedPage Today.
Thornburg added that because authors chose at-risk women with symptoms,the use of this test in a lower risk cohort would need to be validated before use in the more general population.
"In a population of lower risk women,or those with less or more vague symptoms,where the prevalence would be expected to be much lower (more like the 2%-5% seen in the general population) the [positive predictive value] and [negative predictive value] may not be as good," she said.
Verlohren said that a randomized trial to see if the test reduces unnecessary hospital admissions and interventions in patients with suspected preeclampsia is currently underway at Oxford University in England.
Rosser agreed that such a randomized trial is needed in order to prove the effectiveness of this test,but even being able to predict which women do not have preeclampsia would still improve care for all patients,allowing for appropriate and timely intervention.