Angiogenic Factors and the Risk of Adverse Outcomes in Women With Suspected Preeclampsia

Abstract

Background An imbalance in circulating angiogenic factors plays a central role in the pathogenesis of preeclampsia. Methods and Results We prospectively studied 616 women who were evaluated for suspected preeclampsia. We measured plasma levels of antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt1) and proangiogenic placental growth factor (PlGF) at presentation, and examined for an association between sFlt1/PlGF ratio and subsequent adverse maternal and perinatal outcomes within 2 weeks. The median [25th–75th centile] sFlt1/PlGF ratio at presentation was elevated in participants who experienced any adverse outcome compared to those who did not (47.0 [15.5–112.2] versus 10.8 [4.1–28.6], p<0.0001). Among those presenting <34 weeks (N=167), the results were more striking (226.6 [50.4–547.3] versus 4.5 [2.0–13.5], p<0.0001), and the risk was markedly elevated when the highest sFlt1/PlGF ratio tertile was compared to the lowest (OR 47.8, 95% CI 14.6–156.6). Among participants presenting at <34 weeks, the addition of sFlt1/PlGF ratio to hypertension and proteinuria significantly improved the prediction for subsequent adverse outcomes (AUC=0.93 for hypertension, proteinuria, and sFlt1/PlGF versus AUC=0.84 for hypertension and proteinuria alone; P=0.001). Delivery occurred within two weeks of presentation in 86.0% of women with sFlt1/PlGF ratio ≥ 85 compared with 15.8% of women with sFlt1/PlGF ratio <85 (HR 15.2, 95% CI 8.0–28.7). Conclusions In women with suspected preeclampsia presenting at <34 weeks, circulating sFlt1/PlGF ratio predicts adverse outcomes occurring within two weeks. The accuracy of this test is substantially better than current approaches and may be useful in risk stratification and management. Additional studies are warranted to validate these findings.

Differential Diagnosis of Preeclampsia

“…7 Apart from being a test to diagnose preeclampsia, recent research has shown that the sFlt-1/PlGF ratio is also strongly associated with subsequent maternal and perinatal adverse outcomes. 8 In women presenting at <34 weeks of gestation, the sFlt-1/PlGF ratio performs better than other currently available clinical signs and laboratory tests, like BP, and serum concentrations of creatinine, uric acid, and ALT in the prediction of adverse outcomes. 8 Furthermore, the sFlt-1/PlGF has been found to discriminate well between patients with preexisting hypertension or gestational hypertension and patients with superimposed preeclampsia.…”

“…4,5 Compared with normal pregnancies, the serum concentration of the antiangiogenic soluble Fms-like tyrosine kinase 1 (sFlt-1) is markedly increased, whereas that of placental growth factor (PlGF) is decreased in preeclampsia. 4,[6][7][8][9][10] Because of the reciprocal changes of these markers, the ratio of sFlt-1/PlGF appears to be a superior marker of (early onset) preeclampsia compared with the individual values of these markers. 7,11 In the 3 complicated pregnancies of this grand round, we used the sFlt-1/PlGF ratio as a biomarker to differentiate among superimposed preeclampsia, activation of the underlying disease, or the combined occurrence of these 2 conditions.…”

New Developments in the Pathogenesis of Preeclampsia

“…We found that the plasma sFlt1/PlGF ratio on presentation predicts adverse maternal and perinatal outcomes (occurring within two weeks) in the preterm setting. This simple, quantitative, rapid test outperformed the standard battery of clinical diagnostic measures including blood pressure, proteinuria, uric acid, and other laboratory assays 57 . Importantly, sFlt1 and/or PlGF levels at presentation were strongly associated with the remaining duration of pregnancy 53,[57][58][59][60] .…”

“…This simple, quantitative, rapid test outperformed the standard battery of clinical diagnostic measures including blood pressure, proteinuria, uric acid, and other laboratory assays 57 . Importantly, sFlt1 and/or PlGF levels at presentation were strongly associated with the remaining duration of pregnancy 53,[57][58][59][60] . We also recently evaluated the role of sEng measurements and found that it has comparable performance to sFlt1/PlGF ratio 61 .…”

Obstetric Nephrology

“…The sFlt/PlGF ratio distinguishes preeclampsia (or SIPE) from either GH or CHTN, especially before 34 weeks of GA (29). Very high ratios before 34 weeks of GA in women with suspected preeclampsia predict the occurrence of adverse maternal or perinatal outcomes within a 2-week horizon and are associated with imminent delivery, whether for maternal or fetal indications (29,30). In this sense, one might imagine that such risk stratification could aid in more efficient clinical resource allocation among hypertensive gravidas, although it seems unlikely in the absence of compelling, well designed, and adequately powered prospective trials, that discrimination would be adequate to allow some women to be discharged, whereas others remain in hospital, based on these tests alone.…”