Identification of potential early biomarkers of preeclampsia.

INTRODUCTION: It is thought that poor placental perfusion caused by inadequate remodelling of the maternal spiral arteries leads to preeclampsia (PE). To identify novel signalling pathways that contribute to PE pathogenesis and to create prerequisites for the non-invasive diagnosis of PE before clinical manifestations of the disease, this study aimed to evaluate miRNA expression levels in the placenta and blood plasma of pregnant women. METHODS: miRNA deep sequencing followed by real-time quantitative RT-PCR was applied to compare miRNA expression profiles in the placenta and blood plasma from women with early- and late-onset PE relative to the control group. RESULTS: A more than two-fold decrease in miR-532-5p, -423-5p, -127-3p, -539-5p, -519a-3p, and -629-5p and let-7c-5p expression levels was observed in the placenta, while a more than two-fold increase in miR-423-5p, 519a-3p, and -629-5p and let-7c-5p was observed in the blood plasma of pregnant women with PE. The above-listed miRNAs are associated with PE for the first time in this study, except for miR-519a-3p, whose role in PE has already been postulated. Using a logistic regression, plasma samples were classified into the early-onset PE group (probability p = 0.01, 80% specificity, 87.5% sensitivity and 87.5% precision) and showed increased miR-423-5p expression levels that were confirmed by the 9.8-fold up-regulation (р = 0.0002498) of miR-423-5p expression observed in the blood plasma at 11-13 GW by RT-PCR in a group of pregnant women manifesting severe PE clinical signs at 28-33 GW. CONCLUSIONS: miR-423-5p may be considered a potential candidate for the early diagnosis of PE during the targeted management of high-risk pregnancies.

Comparison of a novel test for placental alpha microglobulin-1 with fetal fibronectin and cervical length measurement for the prediction of imminent spontaneous preterm delivery in patients with threatened preterm labor.

OBJECTIVE: PartoSure is a bedside test for the prediction of time-to-spontaneous preterm delivery by the detection of placental alpha microglobulin-1 (PAMG-1). The objectives of this study were to further determine the test's efficacy in predicting delivery within 7 or 14 days from testing, and to compare it with fetal fibronectin (fFN) and cervical length (CL) measurement by transvaginal ultrasound. STUDY DESIGN: The study population consisted of 203 consecutively recruited women with singleton pregnancies between 200/7 and 366/7 weeks of gestation with symptoms of preterm labor, clinically intact membranes, and cervical dilatation of ≤3 cm. PartoSure and CL were performed on all patients and the test-to-spontaneous-delivery interval was calculated. In a sub-segment of patients, the QuikCheck fFN test was used. RESULTS: The sensitivities for PartoSure (n=203), fFN (n=66), and CL (n=203) for predicting imminent spontaneous preterm delivery within 7 days were 80%, 50%, and 57%, respectively. The specificities were 95%, 72%, and 73% for PartoSure, fFN and CL, respectively. The NPVs were 96%, 87%, and 89% for PartoSure, fFN and CL, respectively. The PPVs were 76%, 29%, and 30% for PartoSure, fFN and CL, respectively. CONCLUSION: PAMG-1 detection by PartoSure is the single best predictor of imminent spontaneous delivery within 7 days compared to fFN and CL. In settings where CL is used as an initial screen, PartoSure has the greatest clinical utility in patients with CL between 15 and 35 mm. In situations where CL is not an initial screen, PartoSure is the most accurate test compared to fFN and CL.

Evaluation of a novel placental alpha microglobulin-1 (PAMG-1) test to predict spontaneous preterm delivery.

OBJECTIVE: The PartoSure time-to-delivery (TTD) test (AmniSure International, Boston, MA, USA) is a newly available bedside test for the prediction of time to spontaneous preterm delivery via the detection of placental alpha microglobulin-1. The objective of this study was to determine the efficacy of the test in predicting imminent delivery in 7 or 14 days from the time of testing. METHODS: The study population consisted of 101 consecutively recruited pregnant women with singleton pregnancies between 20+0 and 36+6 weeks of gestation with symptoms of preterm labor, clinically intact amniotic membranes, and minimal cervical dilatation (≤3 cm). The PartoSure TTD test was performed on these patients and the test-to-spontaneous-delivery interval was calculated. RESULTS: The PartoSure TTD test predicted spontaneous preterm delivery within 7 days with 90.0% sensitivity, 93.8% specificity, 97.4% negative predictive value (NPV), and 78.3% positive predictive value (PPV). The test predicted spontaneous preterm delivery within 14 days with 80% sensitivity, 96.1% specificity, 93.6% NPV, and 87.0% PPV. CONCLUSION: A positive PartoSure TTD test in patients presenting with symptoms of preterm labor, intact membranes, and minimal cervical dilatation (≤3 cm) indicated spontaneous preterm delivery will occur within 7 days with a high degree of accuracy. A negative result indicated that spontaneous preterm delivery within 14 days is highly unlikely.