Development of a Third Trimester Contingent Prognostic Prediction Scheme for Suspected Early-Onset Pre-Eclampsia.

INTRODUCTION: Short-term prediction of pre-eclampsia (PE) using soluble FMS-like tyrosine kinase-1 (sFlt-1)/ placental growth factor (PlGF) ratio has high false-positive rate. Therefore, we developed a prognostic prediction tool that predicts early-onset PE leading to delivery within 1 week on pregnancies with an sFlt-1/PlGF ratio above 38 and compared it with an analogous model based on sFlt-1/PlGF ratio and with the 655 sFlt-1/PlGF ratio cutoff. METHODS: Cohort study of 363 singleton pregnancies with clinical suspicion of PE before 34 weeks of gestation, allowing repeated assessments (522). 213 samples with an sFlt-1/PlGF ratio above 38 were assessed to construct and identify the best-fit linear mixed model. N-terminal pro-B-type natriuretic peptide (NT-proBNP), sFlt-1 MoM, PlGF MoM, and sFlt-1/PlGF ratio combined with gestational age (GA) were assessed. RESULTS: None of the pregnancies with an sFlt-1/PlGF ratio of 38 or below developed early-onset PE (309 samples from 240 pregnancies). Conversely, 47 women of 213 assessments (22.1%) with an sFlt-1/PlGF ratio above 38 developed the assessed outcome. The selected model included sFlt-1 MoM, NT-proBNP, and GA. Differences in area under the curve were observed between the selected model and the GA + sFlt-1/PlGF model (p = 0.04). At an sFlt-1/PlGF ratio cutoff of 655, detection rate was 31.9% (15/47), while the selected model detection was 55.3% (26/47) (p = 0.008). DISCUSSION: Considering repeated assessments, the sFlt-1/PlGF ratio of 38 or below adequately ruled out early-onset PE, leading to delivery within 1 week. However, when sFlt-1/PlGF ratio is above 38, the prediction tool derived from linear mixed model based on GA, NT-proBNP, and sFlt-1 MoM, provided a better prognosis prediction than the sFlt-1/PlGF ratio.

A new model for screening for early-onset preeclampsia.

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 11.0-13.6 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 = 161), while of early-onset preeclampsia was 0.2% (n = 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% false-positive rate (area under the curve, 0.96, 95% confidence interval, 0.94-0.98). 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.

A more accurate prediction to rule in and rule out pre-eclampsia using the sFlt-1/PlGF ratio and NT-proBNP as biomarkers.

Background The 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. Methods A 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. Results For 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. Conclusions An 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.

Use of the sFlt-1/PlGF ratio to rule out preeclampsia requiring delivery in women with suspected disease. Is the evidence reproducible?

BACKGROUND: Soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) ratio has been proven to predict preeclampsia occurrence. METHODS: Blood samples from 195 pregnant women with suspected preeclampsia were obtained at obstetric triage admission or from the high-risk pregnancy outpatient office. Serum PlGF and sFlt-1 were measured by an electrochemiluminescence immunoassay (ECLIA) on the immunoanalyser Cobas e601 (Roche Diagnostics) and the corresponding ratio was calculated. Final outcomes were reviewed by an independent obstetrician. Only the first determination was considered. RESULTS: A sFlt-1/PlGF ratio of 38 or lower ruled out the need for pregnancy termination due to preeclampsia in the subsequent week with a negative predictive value (NPV) of 99.1% (sensitivity 97.1% and specificity 67.5%). None of the 76 pregnancies with first determination of an sFlt-1/PlGF ratio of 38 or lower between 24 and 34 weeks of gestation delivered due to early-onset preeclampsia. Positive likelihood ratio (PLR) of an sFlt-1/PlGF ratio above 38 for prediction of pregnancy termination due to preeclampsia within 4 weeks is analogous to published evidence. CONCLUSIONS: 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.

Robotic Transperitoneal Infrarenal Para-Aortic Lymphadenectomy With Double Docking: Technique, Learning Curve, and Perioperative Outcomes.

Para-aortic lymphadenectomy (PAL) is a challenging procedure performed by minimally invasive surgery in very few centers, owing to its intrinsic technical complexity. We describe and assess the feasibility and learning curve of robotic double-docking transperitoneal infrarenal PAL combined with oncological pelvic surgery. Fifty patients who underwent this procedure using the Da Vinci S surgical system between March 2010 and May 2013 were included. The mean operating time for PAL surgery was 76 minutes (range, 32-150 minutes), and the mean number of lymph nodes per patient was 11.8 (range, 1-44). There were no conversions to laparotomy or laparoscopy. The mean length of hospital stay was 2 days (range, 1-25 days). Statistically significant decreases were noted for mean table rotation time (17 ± 6.8 minutes vs 13 ± 3.6 minutes; p = .02) and mean PAL operating time (85.4 ± 25.8 minutes vs 69.8 ± 24.6 minutes; p = .04) when comparing the first 20 patients and the last 30 patients. The number of nodes was similar in the first 20 patients and last 30 patients. The double-docking transperitoneal infrarenal PAL technique combined with oncological pelvic surgery is feasible, with minimal morbidity and a short learning curve.