An sFlt-1:PlGF ratio of 38 or lower can be used to predict the short-term absence of preeclampsia in women in whom the syndrome is suspected clinically. (Funded by Roche Diagnostics.).
Preeclampsia is a multisystem disorder in pregnancy. With an incidence of 2% to 5% of all pregnancies, it is a frequent pregnancy-related disease and a major cause of maternal and fetal morbidity and mortality.1 Preeclampsia is defined as the newonset of hypertension (≥140/90 mm Hg on 2 separate occasions ≥4 hours apart) and proteinuria (≥300 mg/24 h). 2 The simplicity of this definition contrasts with the complexity of the disease. The pathophysiology of preeclampsia is not conclusively resolved up to now. Early-onset preeclampsia, defined as the onset before 34 weeks of gestation, comprises the mal implantation of the placenta, insufficient spiral-artery remodeling, prevalently resulting in intrauterine growth restriction and an altered expression of placental proteins such as soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factors (PlGFs).3 In contrast, lateonset preeclampsia, defined as the onset after 34 weeks of gestation, is not necessarily accompanied by placental dysfunction 4 but angiogenic and antiangiogenic factors are also dysregulated, though to a less dramatic extent. 5 We and others have previously shown that the sFlt-1/PlGF ratio is elevated in patients with preeclampsia.6-10 The automated measurement of the sFlt-1/PlGF ratio detects early-onset preeclampsia with a sensitivity of 89% and a specificity of 97% when the single, gestation-wide cutoff of 85 is used. 8 Recently, Rana et al 9 have shown that in patients with signs and symptoms for the disease, an sFlt-1/PlGF ratio ≥85 predicts the occurrence of preeclampsia-related adverse maternal and fetal outcomes, Abstract-To establish gestational phase adapted cutoffs for the use of the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio as a diagnostic tool for preeclampsia in the clinical setting, a multicenter case-control study including a total of 1149 patients was performed. We report normal values of sFlt-1, PlGF, and the sFlt-1/PlGF ratio based on the analysis of a total of 877 patients with uneventful pregnancy outcome. A total of 234 patients with preeclampsia and a matched cohort consisting of 468 patients with normal pregnancy outcome were compared, and sFlt-1 and PlGF were measured on an automated platform. Separate cutoffs for the sFlt-1/PlGF ratio were determined for the early (20+0-33+6 weeks) and the late gestational phase (34+0 weeks-delivery). For each of the 2 gestational phases, 2 independent cutoffs framing an equivocal zone were determined: the first cutoff with focus on high sensitivity, and the second focusing on high specificity. Between 20+0 and 33+6 weeks, the cutoffs at ≤33 and ≥85 resulted in a sensitivity/specificity of 95%/94% and 88%/99.5%, respectively. An sFlt-1/PlGF ratio of ≤33 had the lowest likelihood of a negative test (0.05; 95% confidence interval, 0.02-0.13), whereas values ≥85 had the highest likelihood of a positive test (176; 95% confidence interval, 24.88-1245). After 34+0 weeks, the cutoffs at ≤33 and ≥110 yielded a sensitivity/specificity of 89.6%/73.1% ...
(N Engl J Med. 2016;374:13–22)
Preeclampsia is a serious multisystem disorder affecting up to 5% of pregnancies worldwide. A reliable predictor of preeclampsia would be helpful in allowing health care providers to identify women at risk for developing the disorder. Serum levels of circulating maternal soluble fms-like tyrosine kinase 1 (sFlt-1) are known to be elevated in preeclampsia, while levels of placental growth factor (PlGF) are decreased. A high ratio of sFlt-1 to PlGF indicates an increased risk for preeclampsia and could potentially be a more reliable predictor than either of those factors alone. The authors of this study sought to evaluate the ratio as a predictive tool among women with suspected preeclampsia.
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