The new cut-off values for the sFlt-1/PlGF ratio adjusted by the gestational age at clinical presentation can be used to rule out PE at obstetric triage and to predict imminent delivery with better accuracy than the cutpoint currently accepted.

ObjectiveA high ratio of soluble fms‐like tyrosine kinase‐1 (sFlt‐1) to placental growth factor (PlGF) has been linked to pre‐eclampsia (PE). We evaluated the sFlt‐1/PlGF ratio as a predictive marker for early‐onset PE in women at risk of PE.MethodsThis prospective, Spanish, multicenter study included pregnant women with a risk factor for PE, including intrauterine growth restriction, PE, eclampsia or hemolysis, elevated liver enzymes and low platelet count syndrome in previous pregnancy, pregestational diabetes or abnormal uterine artery Doppler. The primary objective was to show that the sFlt‐1/PlGF ratio at 20, 24 and 28 weeks' gestation was predictive of early‐onset PE (< 34 + 0 weeks). Serum sFlt‐1 and PlGF were measured at 20, 24 and 28 weeks. Multivariate logistic regression was used to develop a predictive model.ResultsA total of 819 women were enrolled, of which 729 were suitable for analysis. Of these, 78 (10.7%) women developed PE (24 early onset and 54 late onset). Median sFlt‐1/PlGF ratio at 20, 24 and 28 weeks was 6.3 (interquartile range (IQR), 4.1–9.3), 4.0 (IQR, 2.6–6.3) and 3.3 (IQR, 2.0–5.9), respectively, for women who did not develop PE (controls); 14.5 (IQR, 5.5–43.7), 18.4 (IQR, 8.2–57.9) and 51.9 (IQR, 11.5–145.6) for women with early‐onset PE; and 6.7 (IQR, 4.6–9.9), 4.7 (IQR, 2.8–7.2) and 6.0 (IQR, 3.8–10.5) for women with late‐onset PE. Compared with early‐onset PE, the sFlt‐1/PlGF ratio was significantly lower in controls (P < 0.001 at each timepoint) and in women with chronic hypertension (P < 0.001 at each timepoint), gestational hypertension (P < 0.001 at each timepoint) and late‐onset PE (P < 0.001 at each timepoint). A prediction model for early‐onset PE was developed, which included the sFlt‐1/PlGF ratio plus mean arterial pressure, being parous and previous PE, with areas under the receiver–operating characteristics curves of 0.86 (95% CI, 0.77–0.95), 0.91 (95% CI, 0.85–0.97) and 0.93 (95% CI, 0.86–0.99) at 20, 24 and 28 weeks, respectively, and was superior to models using the sFlt‐1/PlGF ratio alone or uterine artery mean pulsatility index.ConclusionsThe sFlt‐1/PlGF ratio can improve prediction of early‐onset PE for women at risk of this condition. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

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<b><i>Objective:</i></b> Establish reference ranges for the Elecsys® soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) immunoassay ratio in twin pregnancies. <b><i>Methods:</i></b> Data analyzed were from 3 prospective studies: Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia (PE) (PROGNOSIS), Study of Early-onset PE in Spain (STEPS), and a multicenter case-control study. Median, 5th, and 95th percentiles for sFlt-1, PlGF, and the sFlt-1/PlGF ratios were determined for normal twin pregnancies for 7 gestational windows and compared with the previous data for singleton pregnancies. <b><i>Results:</i></b> The reference range analysis included 269 women with normal twin pregnancies. Before 29 weeks’ gestation, median, 5th, and 95th percentiles for sFlt-1/PlGF ratios did not differ between twin and singleton pregnancies. From 29 weeks’ gestation to delivery, median, 5th, and 95th percentiles for sFlt-1/PlGF ratios were substantially higher in twin versus singleton pregnancies. sFlt-1 values were higher in women with twin pregnancies across all gestational windows. PlGF values were similar or higher in twin versus singleton pregnancies; PlGF concentrations increased from 10 weeks + 0 days to 28 weeks + 6 days’ gestation. <b><i>Conclusions:</i></b> Reference ranges for the sFlt-1/PlGF ratio are similar in women with twin and singleton pregnancies until 29 weeks’ gestation but appear higher in twin pregnancies thereafter.

BackgroundThe management of potential pre-eclamptic patients using the soluble FMS-like tyrosine kinase 1 (sFlt-1)/ placental growth factor (PlGF) ratio is characterised by frequent false-positive results.MethodsA retrospective cohort study was conducted to identify and validate cut-off values, obtained using a machine learning model, for the sFlt-1/PlGF ratio and NT-proBNP that would be predictive of the absence or presence of early-onset pre-eclampsia (PE) in singleton pregnancies presenting at 24 to 33 + 6 weeks of gestation.ResultsFor the development cohort, we defined two sFlt-1/PlGF ratio cut-off values of 23 and 45 to rule out and rule in early-onset PE at any time between 24 and 33 + 6 weeks of gestation. Using an sFlt-1/PlGF ratio cut-off value of 23, the negative predictive value (NPV) for the development of early-onset PE was 100% (95% confidence interval [CI]: 99.5–100). The positive predictive value (PPV) of an sFlt-1/PlGF ratio >45 for a diagnosis of early-onset PE was 49.5% (95% CI: 45.8–55.6). When an NT-proBNP value >174 was combined with an sFlt-1/PlGF ratio >45, the PPV was 86% (95% CI: 79.2–92.6). In the validation cohort, the negative and positive values were very similar to those found for the development cohort.ConclusionsAn sFlt-1/PlGF ratio <23 rules out early-onset PE between 24 and 33 + 6 weeks of gestation at any time, with an NPV of 100%. An sFlt-1/PlGF ratio >45 with an NT-proBNP value >174 significantly enhances the probability of developing early-onset PE.

The addition of NT-proBNP assessment improves the short-term prediction of delivery as a result of PE compared with sFlt-1/PlGF ratio alone, when the sFlt-1/PlGF ratio is > 38. This finding should be considered in future research on the assessment of short-term risk of delivery as a result of PE. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Low vitamin D status in women with suspected late-onset PE increases the risk of imminent development of the disease.

Between 24 and 34 weeks of gestation, no subsequent determination was needed to completely rule out early-onset preeclampsia when the first sFlt-1/PlGF ratio determination was 38 or lower in singleton pregnancies with signs or symptoms of this syndrome. These findings, if confirmed, will reduce costs and facilitate the implementation of the sFlt-1/PlGF ratio in women with clinical suspicion of preeclampsia in the third trimester.