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Could a better method for ruling out preeclampsia in the short term be on the way?
Using one brand of serum immunoassays measuring soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) in maternal serum, a ratio of 38 or lower appears to rule out preeclampsia among women suspected of having the disorder, with a negative predictive value of 99.3%, according to a report published online Jan. 6 in the New England Journal of Medicine.
A reliable predictor of preeclampsia is needed because women with suggestive signs or symptoms usually must be hospitalized until the disorder can be ruled out, which can take days or weeks. Circulating maternal levels of sFlt-1 are increased and those of PlGF are decreased in preeclampsia, and assessing the ratio of these two biomarkers may serve as a better risk predictor than measuring either one alone, according to Dr. Harald Zeisler of the Medical University of Vienna and his associates.
They performed a 3-year industry-sponsored prospective observational study at 30 sites in 14 countries involving women with singleton pregnancies with suspected preeclampsia.
In the first phase, involving 500 women suspected of having preeclampsia, the investigators established that a ratio cut-off point of 38 reliably distinguished the 79.8% of women who did not develop preeclampsia within 1 week from the 20.2% who did develop the condition. The second phase, involving 550 additional women suspected of having preeclampsia, validated that a ratio of 38 or lower reliably distinguished the 82.2% of women who did not develop preeclampsia from the 17.8% who did develop the condition.
In the validation cohort, the median sFlt:PlGF ratio was 87.8 in women who developed preeclampsia within 1 week and 59.4 among those who developed preeclampsia within 4 weeks. In contrast, these ratios were 8.0 and 6.3, respectively, in women who did not develop preeclampsia. The negative predictive value of an sFlt:PlGF ratio of 38 or lower was 99.3% in this cohort, while the positive predictive value – a diagnosis of preeclampsia, eclampsia, or the HELLP syndrome within 4 weeks – was 36.7% (N Engl J Med 2016 Jan 6;374:13-22. doi: 10.1056/NEJMoa1414838.).
Adding the sFlt:PlGF ratio to proteinuria and blood pressure assessments will likely help clinicians decide whether hospitalization or outpatient monitoring is the better course for such patients, the investigators wrote.
“In clinical practice, a very high negative predictive value is crucial in the evaluation of a patient with suspected preeclampsia, since failure to detect imminent disease could have devastating consequences for the fetus or the mother,” Dr. Zeisler and his associates wrote.
They noted that 38 is the optimal cutoff point only for the specific immunoassays used in this study – Elecsys, manufactured by Roche Diagnostics. Other brands of assays may have different ratio cutoffs. The findings of this observational study must also be confirmed in randomized trials to establish whether use of this ratio in clinical practice could reduce unnecessary hospitalizations and costs.
This study was funded by Roche Diagnostics, maker of the Elecsys sFlt-1 and PlGF immunoassays assessed in the study. The manufacturer also designed the study, analyzed the data, and funded a medical writer to provide assistance to the authors. Dr. Zeisler reported receiving lecture fees from Ferring and Roche Diagnostics, and his associates reported numerous ties to Roche and other industry sources.
A test that could help clinicians decide which women with suspected preeclampsia can be followed safely as outpatients versus which should be admitted to the hospital would be very beneficial. But some features of this study require careful consideration before its findings can be translated into clinical practice.
 |
Dr. Ellen W. Seely |
The assays were used only in women who had suspected preeclampsia at 24-37 weeks of gestation. It will not perform as well in unselected populations in the real world, where the likelihood of preeclampsia is low, nor in women at earlier or later weeks of gestation.
Moreover, the study participants were mostly white, and levels of these biomarkers may differ by racial or ethnic background. More than 25% were obese before pregnancy, and this study did not account for any potential variations in the relevant biomarkers related to patient weight. And the study involved only singleton pregnancies, so the results cannot be applied to women with multiple gestations, who are at the highest risk for preeclampsia.
Dr. Ellen W. Seely and Dr. Caren G. Solomon are in the division of endocrinology, diabetes, and hypertension at Brigham and Women’s Hospital, Boston. They reported having no relevant financial disclosures. These remarks are adapted from an editorial accompanying Dr. Zeisler’s report (New Engl. J. Med. 2016 Jan 6. doi: 10.1056/NEJMe1515223).
A test that could help clinicians decide which women with suspected preeclampsia can be followed safely as outpatients versus which should be admitted to the hospital would be very beneficial. But some features of this study require careful consideration before its findings can be translated into clinical practice.
|
Dr. Ellen W. Seely |
The assays were used only in women who had suspected preeclampsia at 24-37 weeks of gestation. It will not perform as well in unselected populations in the real world, where the likelihood of preeclampsia is low, nor in women at earlier or later weeks of gestation.
Moreover, the study participants were mostly white, and levels of these biomarkers may differ by racial or ethnic background. More than 25% were obese before pregnancy, and this study did not account for any potential variations in the relevant biomarkers related to patient weight. And the study involved only singleton pregnancies, so the results cannot be applied to women with multiple gestations, who are at the highest risk for preeclampsia.
Dr. Ellen W. Seely and Dr. Caren G. Solomon are in the division of endocrinology, diabetes, and hypertension at Brigham and Women’s Hospital, Boston. They reported having no relevant financial disclosures. These remarks are adapted from an editorial accompanying Dr. Zeisler’s report (New Engl. J. Med. 2016 Jan 6. doi: 10.1056/NEJMe1515223).
A test that could help clinicians decide which women with suspected preeclampsia can be followed safely as outpatients versus which should be admitted to the hospital would be very beneficial. But some features of this study require careful consideration before its findings can be translated into clinical practice.
|
Dr. Ellen W. Seely |
The assays were used only in women who had suspected preeclampsia at 24-37 weeks of gestation. It will not perform as well in unselected populations in the real world, where the likelihood of preeclampsia is low, nor in women at earlier or later weeks of gestation.
Moreover, the study participants were mostly white, and levels of these biomarkers may differ by racial or ethnic background. More than 25% were obese before pregnancy, and this study did not account for any potential variations in the relevant biomarkers related to patient weight. And the study involved only singleton pregnancies, so the results cannot be applied to women with multiple gestations, who are at the highest risk for preeclampsia.
Dr. Ellen W. Seely and Dr. Caren G. Solomon are in the division of endocrinology, diabetes, and hypertension at Brigham and Women’s Hospital, Boston. They reported having no relevant financial disclosures. These remarks are adapted from an editorial accompanying Dr. Zeisler’s report (New Engl. J. Med. 2016 Jan 6. doi: 10.1056/NEJMe1515223).
Could a better method for ruling out preeclampsia in the short term be on the way?
Using one brand of serum immunoassays measuring soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) in maternal serum, a ratio of 38 or lower appears to rule out preeclampsia among women suspected of having the disorder, with a negative predictive value of 99.3%, according to a report published online Jan. 6 in the New England Journal of Medicine.
A reliable predictor of preeclampsia is needed because women with suggestive signs or symptoms usually must be hospitalized until the disorder can be ruled out, which can take days or weeks. Circulating maternal levels of sFlt-1 are increased and those of PlGF are decreased in preeclampsia, and assessing the ratio of these two biomarkers may serve as a better risk predictor than measuring either one alone, according to Dr. Harald Zeisler of the Medical University of Vienna and his associates.
They performed a 3-year industry-sponsored prospective observational study at 30 sites in 14 countries involving women with singleton pregnancies with suspected preeclampsia.
In the first phase, involving 500 women suspected of having preeclampsia, the investigators established that a ratio cut-off point of 38 reliably distinguished the 79.8% of women who did not develop preeclampsia within 1 week from the 20.2% who did develop the condition. The second phase, involving 550 additional women suspected of having preeclampsia, validated that a ratio of 38 or lower reliably distinguished the 82.2% of women who did not develop preeclampsia from the 17.8% who did develop the condition.
In the validation cohort, the median sFlt:PlGF ratio was 87.8 in women who developed preeclampsia within 1 week and 59.4 among those who developed preeclampsia within 4 weeks. In contrast, these ratios were 8.0 and 6.3, respectively, in women who did not develop preeclampsia. The negative predictive value of an sFlt:PlGF ratio of 38 or lower was 99.3% in this cohort, while the positive predictive value – a diagnosis of preeclampsia, eclampsia, or the HELLP syndrome within 4 weeks – was 36.7% (N Engl J Med 2016 Jan 6;374:13-22. doi: 10.1056/NEJMoa1414838.).
Adding the sFlt:PlGF ratio to proteinuria and blood pressure assessments will likely help clinicians decide whether hospitalization or outpatient monitoring is the better course for such patients, the investigators wrote.
“In clinical practice, a very high negative predictive value is crucial in the evaluation of a patient with suspected preeclampsia, since failure to detect imminent disease could have devastating consequences for the fetus or the mother,” Dr. Zeisler and his associates wrote.
They noted that 38 is the optimal cutoff point only for the specific immunoassays used in this study – Elecsys, manufactured by Roche Diagnostics. Other brands of assays may have different ratio cutoffs. The findings of this observational study must also be confirmed in randomized trials to establish whether use of this ratio in clinical practice could reduce unnecessary hospitalizations and costs.
This study was funded by Roche Diagnostics, maker of the Elecsys sFlt-1 and PlGF immunoassays assessed in the study. The manufacturer also designed the study, analyzed the data, and funded a medical writer to provide assistance to the authors. Dr. Zeisler reported receiving lecture fees from Ferring and Roche Diagnostics, and his associates reported numerous ties to Roche and other industry sources.
Could a better method for ruling out preeclampsia in the short term be on the way?
Using one brand of serum immunoassays measuring soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) in maternal serum, a ratio of 38 or lower appears to rule out preeclampsia among women suspected of having the disorder, with a negative predictive value of 99.3%, according to a report published online Jan. 6 in the New England Journal of Medicine.
A reliable predictor of preeclampsia is needed because women with suggestive signs or symptoms usually must be hospitalized until the disorder can be ruled out, which can take days or weeks. Circulating maternal levels of sFlt-1 are increased and those of PlGF are decreased in preeclampsia, and assessing the ratio of these two biomarkers may serve as a better risk predictor than measuring either one alone, according to Dr. Harald Zeisler of the Medical University of Vienna and his associates.
They performed a 3-year industry-sponsored prospective observational study at 30 sites in 14 countries involving women with singleton pregnancies with suspected preeclampsia.
In the first phase, involving 500 women suspected of having preeclampsia, the investigators established that a ratio cut-off point of 38 reliably distinguished the 79.8% of women who did not develop preeclampsia within 1 week from the 20.2% who did develop the condition. The second phase, involving 550 additional women suspected of having preeclampsia, validated that a ratio of 38 or lower reliably distinguished the 82.2% of women who did not develop preeclampsia from the 17.8% who did develop the condition.
In the validation cohort, the median sFlt:PlGF ratio was 87.8 in women who developed preeclampsia within 1 week and 59.4 among those who developed preeclampsia within 4 weeks. In contrast, these ratios were 8.0 and 6.3, respectively, in women who did not develop preeclampsia. The negative predictive value of an sFlt:PlGF ratio of 38 or lower was 99.3% in this cohort, while the positive predictive value – a diagnosis of preeclampsia, eclampsia, or the HELLP syndrome within 4 weeks – was 36.7% (N Engl J Med 2016 Jan 6;374:13-22. doi: 10.1056/NEJMoa1414838.).
Adding the sFlt:PlGF ratio to proteinuria and blood pressure assessments will likely help clinicians decide whether hospitalization or outpatient monitoring is the better course for such patients, the investigators wrote.
“In clinical practice, a very high negative predictive value is crucial in the evaluation of a patient with suspected preeclampsia, since failure to detect imminent disease could have devastating consequences for the fetus or the mother,” Dr. Zeisler and his associates wrote.
They noted that 38 is the optimal cutoff point only for the specific immunoassays used in this study – Elecsys, manufactured by Roche Diagnostics. Other brands of assays may have different ratio cutoffs. The findings of this observational study must also be confirmed in randomized trials to establish whether use of this ratio in clinical practice could reduce unnecessary hospitalizations and costs.
This study was funded by Roche Diagnostics, maker of the Elecsys sFlt-1 and PlGF immunoassays assessed in the study. The manufacturer also designed the study, analyzed the data, and funded a medical writer to provide assistance to the authors. Dr. Zeisler reported receiving lecture fees from Ferring and Roche Diagnostics, and his associates reported numerous ties to Roche and other industry sources.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
