Meta-analysis of studies on biochemical marker tests for the diagnosis of premature rupture of membranes: comparison of performance indexes

BACKGROUND: Premature rupture of the membranes (PROM) is most commonly diagnosed using physical examination; however, accurate decision making in ambiguous cases is a major challenge in current obstetric practice. As this may influence a woman's subsequent management, a number of tests designed to assist with confirming a diagnosis of PROM are commercially available. This study sought to evaluate the published data for the accuracy of two amniotic fluid-specific biomarker tests for PROM: insulin-like growth factor binding protein-1 (IGFBP-1 - Actim® PROM) and placental alpha microglobulin-1 (PAMG-1 - AmniSure®). METHODS: Main analysis included all PubMed referenced studies related to Actim® PROM and AmniSure® with available data to extract performance rates. To compare accuracy, a comparison of pooled indexes of both rapid tests was performed. Studies in which both tests were used in the same clinical population were also analysed. Membrane status, whether it was known or a suspected rupture, and inclusion or not of women with bleeding, were considered. RESULTS: All the available studies published in PubMed up to April 2013 were reviewed. Data were retrieved from 17 studies; 10 for Actim® PROM (n = 1066), four for AmniSure® (n = 1081) and three studies in which both biomarker tests were compared directly. The pooled analysis found that the specificity and positive predictive value were significantly higher for AmniSure® compared with Actim® PROM. However, when 762 and 1385 women with known or suspected rupture of membranes, respectively, were evaluated, AmniSure® only remained significantly superior in the latter group. Furthermore, when the two tests were compared directly in the same study no statistically significant differences were observed. Remarkably, women with a history or evidence of bleeding were excluded in all four studies for AmniSure®, in two Actim® PROM studies and in two of the three studies reporting on both tests. CONCLUSIONS: No differences were observed in the performance of the two tests in studies where they were used under the same clinical conditions or in women with known membrane status. Although AmniSure® performed better in suspected cases of PROM, this may need further analysis as exclusion of bleeding may not be representative of the real clinical presentation of women with suspected PROM

Inmersión en agua durante el parto: revisión bibliográfica

La investigación en métodos alternativos para el alivio del dolor durante el trabajo de parto está experimentando muchos avances. Entre ellos, la hidroterapia. Su seguridad durante el trabajo de parto y su uso durante el periodo expulsivo es un tema muy debatido actualmente. Esta revisión bibliográfica tiene el objetivo de conocer la evidencia científica disponible sobre los beneficios y posibles complicaciones de la hidroterapia, tanto en los factores obstétricos como neonatales. La búsqueda bibliográfica se ha llevado a cabo en las bases de datos PubMed, Cinahl, Biblioteca Cochrane y Scopus, entre los años 2004 y 2014. Se seleccionaron 30 referencias bibliográficas. En el uso de hidroterapia durante el parto no se han detectado efectos perjudiciales sobre los parámetros obstétricos maternos estudiados, sino que disminuye la percepción del dolor y el uso de analgesia, se realizan menos episiotomías y aumenta la satisfacción del parto. Las repercusiones neonatales en cuanto a morbilidad por realizar un parto en agua es el aspecto más controvertido, en especial las complicaciones por aspiración de agua o rotura de cordón

Evaluation of an improved tool for non-invasive prediction of neonatal respiratory morbidity based on fully automated fetal lung ultrasound analysis

The objective of this study was to evaluate the performance of a new version of quantusFLM®, a software tool for prediction of neonatal respiratory morbidity (NRM) by ultrasound, which incorporates a fully automated fetal lung delineation based on Deep Learning techniques. A set of 790 fetal lung ultrasound images obtained at 24 + 0-38 + 6 weeks' gestation was evaluated. Perinatal outcomes and the occurrence of NRM were recorded. quantusFLM® version 3.0 was applied to all images to automatically delineate the fetal lung and predict NRM risk. The test was compared with the same technology but using a manual delineation of the fetal lung, and with a scenario where only gestational age was available. The software predicted NRM with a sensitivity, specificity, and positive and negative predictive value of 71.0%, 94.7%, 67.9%, and 95.4%, respectively, with an accuracy of 91.5%. The accuracy for predicting NRM obtained with the same texture analysis but using a manual delineation of the lung was 90.3%, and using only gestational age was 75.6%. To sum up, automated and non-invasive software predicted NRM with a performance similar to that reported for tests based on amniotic fluid analysis and much greater than that of gestational age alone

Clinical feasibility of quantitative ultrasound texture analysis: A robustness study using fetal lung ultrasound images

OBJECTIVES: To compare the robustness of several methods based on quantitative ultrasound (US) texture analysis to evaluate its feasibility for extracting features from US images to use as a clinical diagnostic tool. METHODS: We compared, ranked, and validated the robustness of 5 texture-based methods for extracting textural features from US images acquired under different conditions. For comparison and ranking purposes, we used 13,171 non-US images from widely known available databases (OUTEX [University of Oulu, Oulu, Finland] and PHOTEX [Texture Lab, Heriot-Watt University, Edinburgh, Scotland]), which were specifically acquired under different controlled parameters (illumination, resolution, and rotation) from 103 textures. The robustness of those methods with better results from the non-US images was validated by using 666 fetal lung US images acquired from singleton pregnancies. In this study, 2 similarity measurements (correlation and Chebyshev distances) were used to evaluate the repeatability of the features extracted from the same tissue images. RESULTS: Three of the 5 methods (gray-level co-occurrence matrix, local binary patterns, and rotation-invariant local phase quantization) had favorably robust performance when using the non-US database. In fact, these methods showed similarity values close to 0 for the acquisition variations and delineations. Results from the US database confirmed robustness for all of the evaluated methods (gray-level co-occurrence matrix, local binary patterns, and rotation-invariant local phase quantization) when comparing the same texture obtained from different regions of the image (proximal/distal lungs and US machine brand stratification). CONCLUSIONS: Our results confirmed that texture analysis can be robust (high similarity for different condition acquisitions) with potential to be included as a clinical tool

Mid-trimester cervical consistency index and cervical length to predict spontaneous preterm birth in a high-risk population

Background: Short cervical length (CL) has not been shown to be adequate as a single predictor of spontaneous preterm birth (sPTB) in high-risk pregnancies. Objective: The objective of this study was to evaluate the performance of the mid-trimester cervical consistency index (CCI) to predict sPTB in a cohort of high-risk pregnancies and to compare the results with those obtained with the CL. Study Design: Prospective cohort study including high-risk singleton pregnancies between 19 +0 and 24 +6 weeks. The ratio between the anteroposterior diameter of the uterine cervix at maximum compression and at rest was calculated offline to obtain the CCI. Results: Eighty-two high sPTB risk women were included. CCI (%) was significantly reduced in women who delivered <37 +0 weeks compared with those who delivered at term, while CL was not. The area under the curve (AUC) of the CCI to predict sPTB <37 +0 weeks was 0.73 (95% confidence interval [CI], 0.61-0.85), being 0.51 (95% CI, 0.35-0.67), p  = 0.03 for CL. The AUC of the CCI to predict sPTB <34 +0 weeks was 0.68 (95% CI, 0.54-0.82), being 0.49 (95% CI, 0.29-0.69), p  = 0.06 for CL. Conclusion: CCI performed better than sonographic CL to predict sPTB. Due to the limited predictive capacity of these two measurements, other tools are still needed to better identify women at increased risk

Intra-amniotic inflammatory response in subgroups of women with preterm prelabor rupture of the membranes

Background To evaluate the influence of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) on the magnitude of intra-amniotic inflammatory response in preterm prelabor rupture of membranes (PPROM). Methodology/Principal Finding A prospective cohort study was performed in 107 women with PPROM between 23.0 and 36.6 weeks of gestational age. Twenty-six proteins were assayed by multiple immunoassay in amniotic fluid. The policy for PPROM in Czech Republic is active, and 90% of the women were delivered within 96 hours of membrane rupture. Histopathological placental findings were evaluated based on the Salafia classification. Data were analyzed in four subgroups of population according to the presence of MIAC and/or HCA. Results were stratified by gestational age at PPROM (< or ≥34.0 weeks). The rates of MIAC and HCA were 44% and 57%, respectively. Regardless of gestational age at PPROM, intra-amniotic inflammatory response was higher when MIAC and HCA were both present. There were no differences in the intra-amniotic inflammatory response between women with MIAC or HCA alone and women without infection. Conclusion A higher intra-amniotic inflammatory response was identified when both HCA and MIAC were detected

Systemic and local inflammatory response in women with preterm prelabor rupture of membranes

Objective:To evaluate the inflammatory pattern in maternal circulation, amniotic cavity, cervix and vagina from women with preterm prelabor rupture of membranes (PPROM) considering the occurrence of microbial invasion of the amniotic cavity (MIAC). Methodology: A prospective study was performed in 58 women with PPROM before 34+0 weeks of gestational age. Twenty-six proteins were analyzed by a multiple immunoassay in samples of amniotic fluid, serum, cervix and vagina. Association of an inflammatory response in the invasive and non-invasive samples with MIAC was investigated. Results: The rate of MIAC was 36.2% (21/58). Both amniotic fluid IL-6 and cervical C-reactive protein (CRP) showed to be independent predictors of MIAC. A cut-off level of cervical CRP≥1836 pg/mL showed a detection rate of 75%, false positive rate of 19% and positive and negative predictive values to predict MIAC of 67% and 87%, respectively. There were no independent biomarkers of MIAC either in the serum or vaginal compartment. Conclusion: A cervical inflammatory response mediated by CRP was observed in PPROM women with MIAC. Evaluation of serum or vaginal samples did not add valuable information regarding the outcome evaluated

The predictive value of the cervical consistency index to predict spontaneous preterm birth in asymptomatic twin pregnancies at the second-trimester ultrasound scan: A prospective cohort study

Novel transvaginal ultrasound (TVU) markers have been proposed to improve spontaneous preterm birth (sPTB) prediction. Preliminary results of the cervical consistency index (CCI), uterocervical angle (UCA), and cervical texture (CTx) have been promising in singletons. However, in twin pregnancies, the results have been inconsistent. In this prospective cohort study of asymptomatic twin pregnancies assessed between 18+0-22+0 weeks, we evaluated TVU derived cervical length (CL), CCI, UCA, and the CTx to predict sPTB < 34+0 weeks. All iatrogenic PTB were excluded. In the final cohort of 63 pregnancies, the sPTB rate < 34+0 was 16.3%. The CCI, UCA, and CTx, including the CL was significantly different in the sPTB < 34+0 weeks group. The best area under the receiver operating characteristic curve (AUC) for sPTB < 34+0 weeks was achieved by the CCI 0.82 (95%CI, 0.72-0.93), followed by the UCA with AUC 0.72 (95%CI, 0.57-0.87). A logistic regression model incorporating parity, chorionicity, CCI, and UCA resulted in an AUC of 0.91 with a sensitivity of 55.3% and specificity of 88.1% for predicting sPTB < 34+0. The CCI performed better than other TVU markers to predict sPTB < 34+0 in twin gestations, and the best diagnostic accuracy was achieved by a combination of parity, chorionicity, CCI, and UCA

Vaginal metabolome: towards a minimally invasive diagnosis of microbial invasion of the amniotic cavity in women with preterm labor

Microbial invasion of the amniotic cavity (MIAC) is only identified by amniocentesis, an invasive procedure that limits its clinical translation. Here, we aimed to evaluate whether the vaginal metabolome discriminates the presence/absence of MIAC in women with preterm labor (PTL) and intact membranes. We conducted a case-control study in women with symptoms of PTL below 34 weeks who underwent amniocentesis to discard MIAC. MIAC was defined as amniotic fluid positive for microorganisms identified by specific culture media. The cohort included 16 women with MIAC and 16 control (no MIAC). Both groups were matched for age and gestational age at admission. Vaginal fluid samples were collected shortly after amniocentesis. Metabolic profiles were analyzed by nuclear magnetic resonance (NMR) spectroscopy and compared using multivariate and univariate statistical analyses to identify significant differences between the two groups. The vaginal metabolomics profile of MIAC showed higher concentrations of hypoxanthine, proline, choline and acetylcholine and decreased concentrations of phenylalanine, glutamine, isoleucine, leucine and glycerophosphocholine. In conclusion, metabolic changes in the NMR-based vaginal metabolic profile are able to discriminate the presence/absence of MIAC in women with PTL and intact membranes. These metabolic changes might be indicative of enhanced glycolysis triggered by hypoxia conditions as a consequence of bacterial infection, thus explaining the utilization of alternative energy sources in an attempt to replenish glucose

Mid-trimester prediction of spontaneous preterm birth with automated cervical quantitative ultrasound texture analysis and cervical length: a prospective study

The objective of this study was to evaluate a novel automated test based on ultrasound cervical texture analysis to predict spontaneous Preterm Birth (sPTB) alone and in combination with Cervical Length (CL). General population singleton pregnancies between 18+ 0 and 24 + 6 weeks' gestation were assessed prospectively at two centers. Cervical ultrasound images were evaluated and the occurrence of sPTB before weeks 37 + 0 and 34 + 0 were recorded. CL was measured on-site. The automated texture analysis test was applied ofine to all images. Their performance to predict the occurrence of sPTB before 37 + 0 and 34 + 0 weeks was evaluated separately and in combination on 633 recruited patients. AUC for sPTB prediction before weeks 37 and 34 respectively were as follows: 55.5% and 65.3% for CL, 63.4% and 66.3% for texture analysis, 67.5% and 76.7% when combined. The new test improved detection rates of CL at similar low FPR. Combining the two increased detection rate compared to CL alone from 13.0 to 30.4% for sPTB< 37 and from 14.3 to 42.9% sPTB< 34. Texture analysis of cervical ultrasound improved sPTB detection rate compared to cervical length for similar FPR, and the two combined together increased signifcantly prediction performance. This results should be confrmed in larger cohorts