The fully automated Sysmex XN-31 hematology analyzer can detect bloodstream form Trypanosoma brucei.

BACKGROUND: For fully automated detection and quantification of Plasmodium parasites, Sysmex developed the XN-31 hemocytometer. This study investigated whether the XN-31 can also detect and quantify bloodstream form trypanosomes (trypomastigotes). METHODS: Axenic cultures of Trypanosoma brucei brucei were used to prepare two dilution series of trypomastigotes in the whole blood of a healthy donor, which were subsequently examined by the XN-31 as well as by microscopic examination of thin and thick blood films. Trypomastigote intactness during the procedures was evaluated by microscopy. RESULTS: The XN-31 hemocytometer detected trypomastigotes with a detection limit of 26 trypomastigotes/µL. Scattergram patterns of Trypanosoma and Plasmodium parasites were clearly distinct, but current interpretation settings do not allow the identification of trypomastigotes yet, and therefore, need future refinement. CONCLUSION: Proof of concept was provided for an automated fluorescent flow cytometry method that can detect and quantify Plasmodium spp., as well as Trypanosoma brucei trypomastigotes.

Interference of bovine hemoglobin-based oxygen carrier-201 (Hemopure) on four hematology analyzers.

INTRODUCTION: Hemoglobin-based oxygen carriers, for example HBOC-201 (Hemopure), are aimed to bridge acute anemia when blood transfusion is not available or refused by the patient. However, since HBOC-201 appears free in plasma, it interferes with laboratory tests. This study presents an overview of HBOC-201 interference on four commonly used hematology analyzers and suggests treatment monitoring possibilities. METHODS: Blood samples were spiked with therapeutic doses of HBOC-201 and nine hematology parameters were measured with the Sysmex XN-20, Siemens Advia 2120i, Abbott Alinity Hq and Abbot Cell Dyn Sapphire hematology analyzers. The results were compared to control samples and the bias was determined. RESULTS: Most parameters, including all cell counts, hematocrit and MCV, showed a non-significant bias compared to control. However, the standard, total hemoglobin (Hb) measurement as well as MCH and MCHC showed poor agreement with control, as HBOC-201 was included in this measurement. Yet, the flow cytometry-based Hb method quantified intracellular Hb in spiked samples, excluding HBOC-201. CONCLUSION: Of all included hematology parameters, only total Hb and the associated MCH and MCHC suffered from interference. In contrast, the flow cytometry-based Hb measurement provided an accurate measure of intracellular Hb. The difference between total Hb and cellular Hb represents the HBOC-201 concentration and can be used to monitor HBOC-201 treatment.

Fast detection and quantification of Plasmodium species infected erythrocytes in a non-endemic region by using the Sysmex XN-31 analyzer.

BACKGROUND: Due to increased travel from endemic countries, malaria occurs more frequently in non-endemic regions. It is a challenge for diagnostic laboratories in non-endemic countries to provide reliable results, as experience of staff is often limited to only a few cases per year. This study evaluated the diagnostic accuracy of the fully automated Sysmex XN-31 malaria analyzer in a routine diagnostic setting in a non-endemic region was evaluated. METHODS: Samples from 112 patients suspected for malaria were examined by the Sysmex XN-31 analyzer to determine the absolute count of malaria-infected red blood cells count (MI-RBC/µL). Microscopic examination of both Quantitative Buffy Coat capillary tubes and thick and thin blood films were used as reference methods. Limits of blank (LoB), detection (LoD) and quantification (LoQ) were investigated using an in vitro Plasmodium falciparum culture. Nine hundred twenty samples of patients with RBC abnormalities were included to determine which RBC abnormalities trigger indeterminate or false positive results. RESULTS: No false positive nor false negative results were obtained for the examined patient samples suspected for malaria. For 3% of samples an indeterminate result by the XN-31 was obtained. The Passing-Bablok regression line for diagnostic accuracy of the parasitaemia was y = 39.75 + 0.7892 × showing a positive bias of about 21% when comparing the MI-RBC results to microscopy. The LoB, LoD and LoQ were calculated to be 4.7, 5.9, and 19.0 infected RBC/µL, respectively. From the 920 abnormal RBC samples collected, 4.6% resulted in a false positive MI-RBC result and almost half of the samples produced indeterminate results. These results were related to increases in nucleated red blood cells, reticulocytes and other abnormal RBC morphologies such as sickle cells. CONCLUSIONS: Based on the results, the XN-31 is a fast and reliable screening method in the detection and quantification of Plasmodium species in patients However, if an abnormal red blood cell morphology is present, the results of the XN-31 should be interpreted with caution as false positive results can be caused by interfering abnormal erythrocytes.

Omeprazole Administration in Preterm Preeclampsia: a Randomized Controlled Trial to Study Its Effect on sFlt-1 (Soluble Fms-Like Tyrosine Kinase-1), PlGF (Placental Growth Factor), and ET-1 (Endothelin-1).

BACKGROUND: Low sFlt-1 (soluble Fms-like tyrosine kinase-1) and ET-1 (endothelin-1) levels have been reported in preeclamptic women using proton pump inhibitors. METHODS: Here, we examined whether the proton pump inhibitor omeprazole could acutely reduce sFlt-1 and ET-1 (measured as CT-proET-1 [C-terminal pro-endothelin-1]), or increase free PlGF (placental growth factor) in 20 women with confirmed preeclampsia. Primary outcome was specified as the difference in sFlt-1, PlGF, or CT-proET-1 after 4 days of omeprazole versus 20 preeclamptic women not receiving omeprazole. RESULTS: Mean maternal age was 30 years, and median gestational age was 30+3 weeks. Baseline sFlt-1 levels were identical in both groups, and the same was true for PlGF or CT-proET-1. After 4 days, sFlt-1 levels remained similar in women not receiving omeprazole compared with women receiving omeprazole, while the levels of PlGF and CT-proET-1 also did not differ between groups. Women receiving omeprazole had a similar prolongation of pregnancy after inclusion compared with those in the nonomeprazole group (median 15 versus 14 days). Except for a higher neonatal intubation rate in the nonomeprazole group (31% versus 4%, P=0.02), there were no differences in maternal/perinatal complications. Finally, making use of the placenta perfusion model, we established that both omeprazole and its S-isomer, esomeprazole, when maternally applied, reached the fetal compartment (fetal-to-maternal ratio's 0.43-0.59), while only esomeprazole inhibited placental sFlt-1 release. CONCLUSIONS: Administration of omeprazole to women with confirmed preeclampsia does not alter their circulating levels of sFlt-1, PlGF, or ET-1, arguing against a role of this drug as a treatment for this syndrome.

Method comparison of three serum free light chain assays on the Roche Cobas 6000 c501 chemistry analyzer.

OBJECTIVES: Free light chains (FLC) are important in the diagnosis, prognosis and monitoring of therapy response of patients with monoclonal gammopathies. In this study, we performed a method comparison of three FLC assays on the Cobas 6000 c501 chemistry analyzer of Roche Diagnostics. METHODS: Samples of 119 patients with various monoclonal gammopathies and 26 control patients were measured with the Freelite (The Binding Site), Diazyme (Diazyme Laboratories) and KLoneus (Trimero Diagnostics) FLC assays. A method comparison was performed and reference intervals of the three assays were validated. RESULTS: The analysis of the Bland-Altman agreement showed bias between the three FLC assays, ranging from -62.7 to 5.1% for κFLC and between -29.2 to 80.5% for λFLC. The Freelite and Diazyme assays have the highest agreement. The concordance of the FLC-ratio ranges from 41 to 75%, with the highest concordance between the Freelite and KLoneus assays. The FLC-ratio in 25 sera from healthy controls were within the reference ranges of the Freelite and KLoneus assays. The FLC-ratio was elevated in all 25 samples tested with the Diazyme assay. CONCLUSIONS: The agreement for the free light chains is highest between the Freelite and the Diazyme assay and fair for the KLoneus assay. However, concordance of the FLC-ratio is highest when the Freelite and KLoneus assays were compared. Our data suggest that concordance for the Diazyme assay could be improved by recalibration. Because of absolute differences between the three methods in individual patients, none of the three FLC assays can be used interchangeably.

Accurate Prediction of Total PlGF (Placental Growth Factor) From Free PlGF and sFlt-1 (Soluble Fms-Like Tyrosine Kinase-1): Evidence for Markedly Elevated PlGF Levels in Women With Acute Fatty Liver of Pregnancy.

[Figure: see text].

The Sysmex XN-L (XN-350) hematology analyzer offers a compact solution for laboratories in niche diagnostics.

INTRODUCTION: In 2015, Sysmex launched a new series of hematology analyzers (XN-L Series) designed to fulfill the needs of niche laboratories in areas such as pediatrics, dialysis, neurology, and oncology while providing a compact solution. In this study, we evaluate the whole blood and body fluid modes of one of these analyzers, the XN-350. METHODS: A total of 300 residual EDTA samples were measured on the XN-350 in whole blood mode and the XN-1000 to evaluate method comparison, flagging sensitivity, repeatability, reproducibility, linearity, carryover, and stability. In addition, 191 samples were obtained and processed in body fluid mode which included, cerebrospinal fluid (CSF), continuous ambulatory peritoneal dialysis (CAPD), ascites, synovial, and pleural fluid to perform method comparison, repeatability, reproducibility, linearity, limit of quantitation, and carryover studies. RESULTS: Strong agreement was shown between the XN-350 and XN-1000 for both whole blood and body fluid modes in results and flagging. Linearity results in both modes on the XN-350 showed a high R2 value (>.99). For WBC, RBC, HGB, and PLT, the carryover results were well within the predetermined criteria of ≤0.5% for whole blood and ≤0.3% for CSF. Repeatability and reproducibility were acceptable for both modes, and there were no significant deviations present in stability for whole blood. In addition, there was high agreement in all body fluid types evaluated. CONCLUSION: The performance of the XN-350 is comparable to the XN-1000 in both whole blood and body fluid modes, making it a reliable alternative to larger analyzers for smaller, niche laboratories.

Development and Validation of Hematocrit Level Measurement in Dried Blood Spots Using Near-Infrared Spectroscopy.

BACKGROUND: Dried blood spots (DBSs) have gained recent popularity as a sampling method for therapeutic drug monitoring. For patients, DBS sampling has several advantages over venous blood sampling. However, technical issues primarily influenced by hematocrit levels, interfere with the implementation of this method in daily clinical practice. The results of concentration measurements of drugs that are influenced by hematocrit should be corrected for hematocrit levels. In this article, we developed a fast, nondestructive, near-infrared (NIR)-based method for measuring the hematocrit in DBSs. METHOD: Using a partial least squares algorithm, an NIR-based quantification method was developed for measuring hematocrit levels of 0.19-0.49 L/L. Residual venous blood of 522 patients was used to build this partial least squares model. The validity of the method was evaluated using 40 patient samples. DBSs were created by adding a small amount (50 µL) of blood on a Whatman filter paper and drying for 24 hours in a desiccator cabinet. The robustness was evaluated by measuring 24 additional samples with a high hemolysis, icterus, and lipemia (HIL) index. The hematocrit values obtained using a Sysmex XN hemocytometry analyzer were used as reference. RESULTS: The difference between hematocrit measurements obtained with NIR spectroscopy and a hemocytometry analyzer was <15% for the 40 samples. The accuracy (≤9%) and precision (≤7%) for all the quality control samples were within the acceptance criteria of <15%. The intraassay and interassay coefficient of variability was ≤3% and ≤6%, respectively, for the different quality control levels. There were no deviations in the measurements for the samples with high HIL indices. The stability of hematocrit in DBS was up to 14 days for all levels. CONCLUSIONS: We developed and validated a hematocrit model using NIR spectroscopy. This nondestructive, accurate, and reproducible method has a short analysis time (51 seconds), and can be used to analyze DBS samples stored for up to 2 weeks in a desiccator cabinet.

A novel haemocytometric COVID-19 prognostic score developed and validated in an observational multicentre European hospital-based study.

COVID-19 induces haemocytometric changes. Complete blood count changes, including new cell activation parameters, from 982 confirmed COVID-19 adult patients from 11 European hospitals were retrospectively analysed for distinctive patterns based on age, gender, clinical severity, symptom duration, and hospital days. The observed haemocytometric patterns formed the basis to develop a multi-haemocytometric-parameter prognostic score to predict, during the first three days after presentation, which patients will recover without ventilation or deteriorate within a two-week timeframe, needing intensive care or with fatal outcome. The prognostic score, with ROC curve AUC at baseline of 0.753 (95% CI 0.723-0.781) increasing to 0.875 (95% CI 0.806-0.926) on day 3, was superior to any individual parameter at distinguishing between clinical severity. Findings were confirmed in a validation cohort. Aim is that the score and haemocytometry results are simultaneously provided by analyser software, enabling wide applicability of the score as haemocytometry is commonly requested in COVID-19 patients.

Method comparison of four clinically available assays for serum free light chain analysis.

Background Serum free light chain (sFLC) measurements are increasingly important in the context of screening for monoclonal gammopathies, prognostic stratification and monitoring of therapy responses. In this study we have performed a method comparison of four sFLC assays that are currently available for routine clinical use. Methods In a retrospective study, sFLC analyses were performed on a cohort that included 139 patients with various monoclonal gammopathies and 54 control sera without an M-protein. Method comparisons of the following four FLC assays were performed: Freelite (Binding Site), N-Latex FLC (Siemens), Seralite (Abingdon Health) and Sebia FLC (Sebia). Results Bland-Altman agreement analysis showed biases varying between -0.1 and 16.2 mg/L for κFLC, -6.0 and 6.8 mg/L for λFLC and -0.04 and 0.38 for the ratio of the involved to uninvolved FLC. Strong agreements were observed for FLC-concentrations below 100 mg/L. The clinical concordance of the κ/λFLC-ratio of the four methods varied between 86% and 92%. Significant quantitative differences were observed between the different methods, mainly in sera with high FLC concentrations. Most assays consistently overestimated FLC concentrations compared to SPE. Conclusions Good overall clinical concordances were observed between the four sFLC assays that were compared in this study. Although good agreements were observed between the FLC assays, significant absolute differences in FLC concentrations in individual patients can be seen, particularly at higher FLC concentrations. Because of inequivalent absolute sFLC values between the methods in individual patients, none of the four sFLC assays can be used interchangeably.

Multicenter evaluation of the cobas m 511 integrated hematology analyzer.

INTRODUCTION: The cobas m 511 integrated hematology analyzer conducts a complete blood count (CBC), white blood cell (WBC) differential, reticulocyte count, and nucleated red blood cell count using automated digital microscopy. This multicenter study validated the analytical performance of the cobas m 511 system. METHODS: Repeatability, reproducibility, carryover, mode-to-mode comparison, cytomorphology, WBC clinical sensitivity, and method comparison were analyzed at four clinical sites using residual whole blood clinical samples (n = 2546) and fresh whole blood from healthy volunteers (n = 480). For WBC clinical sensitivity, the cobas m 511 system automated CBC and WBC differential, system flags, cobas m 511 images, and stained cobas m 511 slides were compared with manual microscopy. Sysmex® XN analyzers were used for interinstrument method comparison. RESULTS: Repeatability and reproducibility results showed low variability. There was no significant sample carryover and no difference between open/closed modes. The overall percentage agreement of morphology assessments with manual microscopy (n = 163 samples) was 95.6% for cobas m 511 images and 95.7% for cobas m 511 slides. The sensitivity and specificity for detecting distributional and/or morphological abnormalities were 94.4% and 74.6% for cobas m 511 automated differential, and 95.9% and 73.3% for cobas m 511 image assessment, compared with a manual 400-cell reference differential (n = 439 samples). Some discordance was seen for monocytes and basophils. Correlations between cobas m 511 and Sysmex XN system data were very good (Pearson's R ≥ 0.95 for most CBC parameters). CONCLUSION: The cobas m 511 system performs robustly in the clinical laboratory and is suitable for routine clinical use.

Ebola Virus Inactivation by Detergents Is Annulled in Serum.

Background: Treatment of blood samples from hemorrhagic fever virus (HFV)-infected patients with 0.1% detergents has been recommended for virus inactivation and subsequent safe laboratory testing. However, data on virus inactivation by this procedure are lacking. Here we show the effect of this procedure on diagnostic test results and infectious Ebola virus (EBOV) titers. Methods: Serum and whole-blood samples were treated with 0.1% or 1% sodium dodecyl sulfate (SDS) or 0.1% Triton X-100 and assayed for clinical chemistry and malaria antigen detection. Infectious EBOV titers were determined in SDS-treated plasma and whole blood from EBOV-infected nonhuman primates (NHPs). Infectious titers of EBOV or herpes simplex virus type 1 (HSV-1) in detergents-treated cell culture medium containing various serum concentrations were determined. Results: Laboratory test results were not affected by 0.1% detergent treatment of blood samples, in contrast with 1% SDS treatment. However, 0.1% detergent treatment did not inactivate EBOV in blood samples from infected NHPs. Experiments with cell culture medium showed that virus inactivation by detergents is annulled at physiological serum concentrations. Conclusions: Treatment of blood samples with 0.1% SDS or Triton X-100 does not inactivate EBOV. Inactivation protocols for HFV should be validated with serum and whole blood.

Angiogenic Markers Predict Pregnancy Complications and Prolongation in Preeclampsia: Continuous Versus Cutoff Values.

To assess the incremental value of a single determination of the serum levels of sFlt-1 (soluble Fms-like tyrosine kinase 1) and PlGF (placental growth factor) or their ratio, without using cutoff values, for the prediction of maternal and fetal/neonatal complications and pregnancy prolongation, 620 women with suspected/confirmed preeclampsia, aged 18 to 48 years, were included in a prospective, multicenter, observational cohort study. Women had singleton pregnancies and a median pregnancy duration of 34 (range, 20-41) weeks. Complications occurred in 118 women and 248 fetuses. The median duration between admission and delivery was 12 days. To predict prolongation, PlGF showed the highest incremental value (R2=0.72) on top of traditional predictors (gestational age at inclusion, diastolic blood pressure, proteinuria, creatinine, uric acid, alanine transaminase, lactate dehydrogenase, and platelets) compared with R2=0.53 for the traditional predictors only. sFlt-1 showed the highest value to discriminate women with and without maternal complications (C-index=0.83 versus 0.72 for the traditional predictors only), and the sFlt-1/PlGF ratio showed the highest value to discriminate fetal/neonatal complications (C-index=0.86 versus 0.78 for the traditional predictors only). Applying previously suggested cutoff values for the sFlt-1/PlGF ratio yielded lower incremental values than applying continuous values. In conclusion, sFlt-1 and PlGF are strong and independent predictors for days until delivery along with maternal and fetal/neonatal complications on top of the traditional criteria. Their use as continuous variables (instead of applying cutoff values for different gestational ages) should now be tested in a prospective manner, making use of an algorithm calculating the risk of an individual woman with suspected/confirmed preeclampsia to develop complications.

Multicenter study to evaluate a new enumeration method for hematopoietic stem cell collection management.

BACKGROUND: CD34 flow cytometry is the gold standard for stem cell enumeration in peripheral blood at the mobilization stage and in the final apheresis product. The new stem cell mode of the Sysmex XN Series analyzer enumerates an immature cell population in the white progenitor and pathological cell (WPC) channel, based on the cell size, internal cellular complexity, and fluorescence intensity. STUDY DESIGN AND METHODS: In this multicenter study we analyzed 147 peripheral blood samples, 22 samples during collection of stem cells, and 45 samples from the apheresis product of 18 healthy allogeneic donors and 84 autologous patients. RESULTS: In this multicenter study we demonstrate that the XN stem cell enumeration method correlates well with viable CD34+ cells determined by flow cytometry during the stem cell mobilization phase to determine apheresis start time, during apheresis for real-time monitoring and adjustment, and for quality control of the final stem cell harvest. CONCLUSION: Our data show that there is an improvement in the correlation of XN stem cells and CD34+ cells in the peripheral blood during stem cell mobilization as well as in stem cell harvests compared to SE or XE Series analyzers. The XN stem cell enumeration method has a number of advantages compared to CD34 flow cytometry: it is fast, simple, reproducible, and less expensive. CE marking for the European market has been obtained, making the stem cell count on the XN analyzer a reportable clinical variable.

Maternal and Neonatal Markers of the Homocysteine Pathway and Fetal Growth: The Generation R Study.

BACKGROUND: Suboptimal dietary intake during pregnancy may have long-term health implications in children. These effects may be mediated by fetal growth. We investigated the associations of early pregnancy and umbilical cord total homocysteine (tHcy), folate, and total and active vitamin B12 concentrations with fetal growth parameters repeatedly measured in pregnancy and at birth. METHODS: This study was performed in 5890 pregnant women, participating in a population-based prospective cohort study. Blood samples were obtained from women in early pregnancy and from the umbilical vein at delivery. Fetal size parameters were repeatedly measured by ultrasound. Information about birth anthropometrics was retrieved from medical records. RESULTS: High early pregnancy maternal tHcy (≥8.31 µmol/L), as compared with low maternal homocysteine (≤5.80 µmol/L), and low early pregnancy maternal folate (≤9.10 nmol/L), as compared with high maternal folate (≥25.81 nmol/L) concentrations, were associated with reduced weight growth patterns throughout pregnancy, resulting in birthweight differences of -102.3 g (95% CI -139.6, -65.0) and -113.0 g (95% CI -159.6, -66.3), respectively. Low umbilical cord folate concentrations (≤15.20 nmol/L) as compared with high umbilical cord folate concentrations (≥28.41 nmol/L) were also associated with a lower birthweight and birth length (P < 0.001). Interestingly, compared with higher umbilical cord vitamin B12 , lower vitamin B12 concentrations were associated with a higher weight, length, and head circumference at birth (P < 0.01). CONCLUSION: Early pregnancy maternal and umbilical cord markers of the homocysteine pathway are significantly associated with fetal growth patterns. These differences arise from mid-pregnancy onwards.

Evaluation of Sysmex XN-1000 High-Sensitive Analysis (hsA) Research Mode for Counting and Differentiating Cells in Cerebrospinal Fluid.

OBJECTIVES: Counting cells in cerebrospinal fluid (CSF) using automated analyzers is generally problematic due to low precision at low cell numbers. To overcome this limitation, Sysmex (Kobe, Japan) developed the high-sensitive analysis (hsA) research mode specifically for counting cells in fluids that contain low cell counts. We evaluated this mode by counting RBCs, WBCs, and differentiated WBCs in CSF samples. METHODS: We analyzed 248 CSF samples using the hsA mode and compared these results with those obtained using the manual counting method. We also evaluated the linearity, detection limits, carryover, and precision of the hsA mode. RESULTS: Using the hsA mode, the lower limit of quantification for RBCs and WBCs was 10 and 2 cells/µL, respectively. Comparing the two methods revealed good agreement with respect to WBCs (y = 1.08x + 0.52), RBCs (y = 1.07x + 0.00), lymphocytes (y = 1.00x + 0.00), neutrophils (y = 1.05x + 0.00), and monocytes (y = 0.88x + 0.07). Regression analysis for samples containing low WBCs (<10 cells/µL) and low RBCs (<50 cells/µL) also had good agreement, although a slight positive bias was found for RBCs. Linearity was good (r(2) ≥ 0.99) for all parameters evaluated. Carryover was negligible and never exceeded 0.04%. CONCLUSIONS: The XN hsA research mode provides reliable cell counts in CSF samples, even in samples containing low numbers of WBCs and RBCs.

The sFlt-1/PlGF ratio associates with prolongation and adverse outcome of pregnancy in women with (suspected) preeclampsia: analysis of a high-risk cohort.

OBJECTIVE: To evaluate the additive value of the sFlt-1/PlGF ratio for diagnosing preeclampsia (PE) and predicting prolongation of pregnancy and adverse outcome in a cohort of women with PE or at high risk of PE. STUDY DESIGN: Patients with suspected or confirmed clinical PE were recruited. At time of inclusion blood for measurement of sFlt-1and PlGF was taken. Values were determined after delivery. A cut-off ratio of ≥85 was defined as a positive test. RESULTS: A total of 107 patients were included. Of the patients, 62 (58%) met the clinical criteria of PE at time of blood sampling. In 10% of these patients (n=6) the ratio was <85 (false negative), whereas in 7% (n=3) of patients without clinical PE the ratio was ≥85 (false positive), resulting in positive and negative predictive values of 95% and 88% respectively. One patient with false positive ratio developed superimposed PE and 2 developed gestational hypertension, and adverse outcome occurred in all three. An adverse pregnancy outcome was only encountered in 1 of the 6 patients with a false negative ratio. Using a binary regression model with adjustment for gestational age <34 weeks, the adverse outcome risk was 11 times increased on the basis of clinical PE, and 30 times on the basis of an elevated ratio (P=0.036). CONCLUSION: The additive value of an increased ratio for diagnosing PE is limited since most patients with clinical PE also have a positive ratio. However, an elevated ratio is superior to the clinical diagnosis of PE for predicting an adverse pregnancy outcome. Furthermore, irrespective of clinical PE, a low ratio is inversely correlated with prolongation of pregnancy.