Prediction of pre-eclampsia-related complications in women with suspected or confirmed pre-eclampsia: development and internal validation of clinical prediction model.

OBJECTIVE: A model that can predict reliably the risk of pre-eclampsia (PE)-related pregnancy complications does not exist. The aim of this study was to develop and validate internally a clinical prediction model to predict the risk of a composite outcome of PE-related maternal and fetal complications within 7, 14 and 30 days of testing in women with suspected or confirmed PE. METHODS: The data for this study were derived from a prospective, multicenter, observational cohort study on women with a singleton pregnancy and suspected or confirmed PE at 20 to < 37 weeks' gestation. For the development of the prediction model, the possible contribution of clinical and standard laboratory variables, as well as the biomarkers soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and their ratio, in the prediction of a composite outcome of PE-related complications, consisting of maternal and fetal adverse events within 7, 14 and 30 days, was explored using multivariable competing-risks regression analysis. The discriminative ability of the model was assessed using the concordance (c-) statistic. A bootstrap validation procedure with 500 replications was used to correct the estimate of the prediction model performance for optimism and to compute a shrinkage factor for the regression coefficients to correct for overfitting. RESULTS: Among 384 women with suspected or confirmed PE, 96 (25%) had an adverse PE-related outcome at any time after hospital admission. Important predictors of adverse PE-related outcome included sFlt-1/PlGF ratio, gestational age at the time of biomarker measurement and protein-to-creatinine ratio as continuous variables. The c-statistics (corrected for optimism) for developing a PE-related complication within 7, 14 and 30 days were 0.89, 0.88 and 0.87, respectively. There was limited overfitting, as indicated by a shrinkage factor of 0.91. CONCLUSIONS: We propose a simple clinical prediction model with good discriminative performance to predict PE-related complications. Determination of its usefulness in clinical practice awaits further investigation and external validation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Soluble fms-like tyrosine kinase-1 and placental growth factor kinetics during and after pregnancy in women with suspected or confirmed pre-eclampsia.

OBJECTIVES: To assess the evolution of the soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio in women with suspected or confirmed pre-eclampsia (PE), and to investigate the changes in sFlt-1 and PlGF levels in pre-eclamptic women after delivery. METHODS: This was an exploratory study in which secondary analysis was performed on a prospective cohort study that enrolled women with a singleton pregnancy and suspected or confirmed PE from 18 weeks' gestation, carried out between December 2013 and April 2016 at the Department of Obstetrics of the Erasmus Medical Center in Rotterdam. sFlt-1 and PlGF were determined using Roche Diagnostics Elecsys assays in two groups of patients. In the first group, patients with suspected or confirmed PE had sFlt-1 and PlGF levels measured at least twice during their pregnancy. Changes in these biomarkers over the course of pregnancy were compared for patients in this group with a baseline sFlt-1/PlGF ratio of ≤ 38 and for those with a ratio > 38. In the second group, sFlt-1 and PlGF levels of women with PE or HELLP syndrome were measured before and after delivery. For this group, pre- and postpartum sFlt-1 and PlGF levels were compared and half-lives were calculated. RESULTS: Women with suspected or confirmed PE for whom sFlt-1 and PlGF levels were measured at least twice during pregnancy (n = 46) had a median gestational age at inclusion of 26 weeks (range, 18-40 weeks). In 27 of the 30 patients with sFlt-1/PlGF ratio ≤ 38 at baseline, thereby ruling out PE, the sFlt-1/PlGF ratio remained stable for up to 100 days. In the remaining three patients with a ratio ≤ 38 and in most of the 16 patients with a ratio > 38, the ratio increased further. For women diagnosed with PE or HELLP syndrome for whom sFlt-1 and PlGF levels were measured before and after delivery (n = 26), median gestational age at inclusion was 29 weeks (range, 16-37 weeks) and median time between antepartum measurement and delivery was 2 days (range, 1-17 days). In this group, after delivery, sFlt-1 dropped to < 1% of its pre-delivery value, with a half-life of 1.4 ± 0.3 days, while PlGF dropped to ∼30% of its pre-delivery value, with a half-life of 3.7 ± 4.3 days. CONCLUSIONS: Based on this small cohort, up to 10% of pregnant women admitted with suspected or confirmed PE presenting with a sFlt-1/PlGF ratio of ≤ 38 display a rise in sFlt-1/PlGF ratio in subsequent weeks, implying that repeat determination of the sFlt-1/PlGF ratio is required to exclude definitively a diagnosis of PE. Furthermore, the rapid and pronounced decline in sFlt-1 levels after delivery in patients with PE/HELLP syndrome suggests that sFlt-1, in contrast to PlGF, is almost entirely derived from the placenta. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Variation of urinary protein to creatinine ratio during the day in women with suspected pre-eclampsia.

OBJECTIVE: To investigate the stability throughout the day of the protein to creatinine ratio (PCR) in spot urine, to demonstrate whether the PCR is a valid alternative for 24-hour protein investigation in pregnant women. DESIGN: Prospective study. SETTING: Tertiary referral university centre. POPULATION: Women suspected of having pre-eclampsia, admitted to the Erasmus Medical Centre. METHODS: Twenty-four-hour urine collections and simultaneously three single voided 5-ml aliquots were obtained at 8 a.m., 12 a.m. (noon) and 5 p.m. A PCR was measured in each specimen and compared with the 24-hour protein excretion. MAIN OUTCOME MEASURES: The 24-hour proteinuria and PCR measured in spontaneous voids. RESULTS: The PCRs correlated strongly with each other and with the 24-hour protein excretion but did show variation throughout the day (mean coefficient of variation 36%; 95% confidence interval 31-40%). The coefficient of variation was unrelated to the degree of 24-hour proteinuria. Receiver operating characteristics curves to discriminate between values below and greater than or equal to the threshold of 0.3 g protein per 24-hour had an area under the curve of respectively 0.94 (8 a.m.), 0.96 (noon) and 0.97 (5 p.m.). Sensitivities at 8 a.m., noon and 5 p.m. were respectively 89%, 96% and 94%; specificities were 75%, 78% and 78% with the proposed PCR cut-off of 30 mg/mmol (0.26 g/g) (National Institute for Health and Care Excellence guidelines).There is no evidence of a difference between the three measurement times regarding the sensitivities and specificities. CONCLUSION: The PCR determined in spot urine varies throughout the day but is a valid alternative for 24-hour urine collections in pregnant women. It is especially useful to rapidly identify clinically relevant proteinuria.

Meniscal transplantation: still experimental surgery? A review.

INTRODUCTION: The objective of this review is to give a state of affairs of meniscal transplantation, with the accent on preservation and surgical techniques. MATERIALS AND METHODS: All articles were selected by performing a search on the literature by using relevant keywords. The most relevant articles were selected with close attention to the publication date. RESULTS: When a meniscal tear is diagnosed, suture can be an option in the vascular zone, whereas the more frequently affected avascular zone heals poorly. A meniscectomy however is not without consequences, wherefore meniscal transplantation can be seen as a therapeutic option for pain reduction and improvement of function when the meniscus is lost. The meniscal scaffold, allograft and autograft can be currently withheld as possible grafts, where the meniscal scaffolds hold great promise as an alternative to the allograft. Various fixation techniques are therefore developed, where viable, deep frozen as well as cryopreservated allografts seem to give the most promising short term results. The transplantation can be performed using an open as well as an arthroscopic technique, using soft tissue fixation, bone plugs or blocks. De primacy of one technique can't be proven. In general meniscal transplantation can be considered as an acceptable procedure. DISCUSSION: Since the outcomes of different studies are difficult to compare, an attempt should be made to limit new studies to the comparison of one aspect. We can conclude that larger, more comparative randomised controlled long-term studies are necessary to resolve which techniques can give the best long-term results.