BACKGROUND: Early identification of women with an increased risk for preeclampsia is of utmost importance to minimize adverse perinatal events. Models developed until now (mainly multiparametric algorithms) are thought to be overfitted to the derivation population, which may affect their reliability when applied to other populations. Options allowing adaptation to a variety of populations are needed. OBJECTIVE: The objective of the study was to assess the performance of a first-trimester multivariate Gaussian distribution model including maternal characteristics and biophysical/biochemical parameters for screening of early-onset preeclampsia (delivery <34 weeks of gestation) in a routine care low-risk setting. STUDY DESIGN: Early-onset preeclampsia screening was undertaken in a prospective cohort of singleton pregnancies undergoing routine first-trimester screening (8 weeks 0/7 days to 13 weeks 6/7 days of gestation), mainly using a 2-step scheme, at 2 hospitals from March 2014 to September 2017. A multivariate Gaussian distribution model including maternal characteristics (a priori risk), serum pregnancy-associated plasma protein-A and placental growth factor assessed at 8 weeks 0/7 days to 13 weeks 6/7 days and mean arterial pressure and uterine artery pulsatility index measured at 11.0e13.6 weeks was used.RESULTS: A total of 7908 pregnancies underwent examination, of which 6893 were included in the analysis. Incidence of global preeclampsia was 2.3% (n ¼ 161), while of early-onset preeclampsia was 0.2% (n ¼ 17). The combination of maternal characteristics, biophysical parameters, and placental growth factor showed the best detection rate, which was 59% for a 5% false-positive rate and 94% for a 10% falsepositive rate (area under the curve, 0.96, 95% confidence interval, 0.94e0.98). The addition of placental growth factor to biophysical markers significantly improved the detection rate from 59% to 94%. CONCLUSION: The multivariate Gaussian distribution model including maternal factors, early placental growth factor determination (at 8 weeks 0/7 days to 13 weeks 6/7 days), and biophysical variables (mean arterial pressure and uterine artery pulsatility index) at 11 weeks 0/7 days to 13 weeks 6/7 days is a feasible tool for early-onset preeclampsia screening in the routine care setting. Performance of this model should be compared with predicting models based on regression analysis.

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.

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