Prediction of preterm birth using PAMG-1 test: a single centre experience - preliminary report.

OBJECTIVES: Placental alpha microglobulin-1 (PAMG-1) is a novel biomarker detected in cervicovaginal discharge in patients threatened with preterm birth (PTB). This study aimed to show a single centre experience of assessment of imminent spontaneous PTB risk in patients with symptoms suggesting preterm labour (PTL). MATERIAL AND METHODS: The study group consisted of 46 women with singleton pregnancies between 24 + 0/7 and 33 + 6/7 weeks of gestation who presented with symptoms of threatened PTL, with cervical dilatation of < 3 cm, cervical length (CL) of < 30 mm and clinically intact fetal membranes. CL was measured via transvaginal ultrasound and the PAMG-1 test was performed in all of the objectives. RESULTS: Sensitivity (SN), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) of prediction of PTB within seven days for CL were 100%, 11.11%, 5.88% and 100%, respectively. The PAMG-1 test SN, SP, PPV and NPV of the same endpoint were 50%, 80.56%, 12.5% and 96.67%, respectively. CONCLUSIONS: PAMG-1 is a more accurate predictor of PTB when compared to CL. Routine use of both mentioned tests could allow identification of low-risk patients and reduction of rate of unnecessary hospitalizations and treatments.

Role of cervical length and placental alpha microglobulin-1 to predict preterm birth.

INTRODUCTION: Preterm labor is the leading cause of premature mortality and morbidity. Therefore, to rule-in and rule-out preterm delivery is a very important issue in our clinical practice. OBJECTIVE: The aim of this study was to investigate the value of placental alpha microglobulin-1 (PAMG-1) molecule positivity in cervicovaginal secretions of women who have a CL <25 mm and presenting with preterm labor symptoms to predict spontaneous preterm birth within seven days. MATERIALS AND METHODS: This was a prospective cohort study conducted in Ankara University Department of Obstetrics and Gynecology between August 2017 and February 2019 on the patients who had Preterm labor symptoms, <25 mm transvaginal cervical length (CL), clinically intact membranes. The primary outcome of the study was the power of CL and PAMG-1 positivity on the prediction of preterm birth in seven days. RESULTS: Sensitivity and specificity values of PAMG-1 in our study population to predict spontaneous preterm birth in seven days were calculated 52.94% and 98.84%, respectively, negative predictive value (NPV) and positive predictive value (PPV) were calculated 91.4% and 90%, respectively. When we investigated our data according to different CL cutoffs, sensitivity and NPV for 20 mm cutoff were 88.24% and 96.3% that was better than PAMG-1, but specificity and PPV were 60.47% and 30.61%, respectively, that was more ineffective than PAMG-1. If we calculate the values according to 15 mm and 10 mm CL cutoffs sensitivity values were 58.8% and 23.53%, specificity values were 81.4% and 91.86%, NPV were 90.9% and 85.87%, PPV were 38.46% and 36.36%, respectively. Finally, accuracy value of PAMG-1 to predict spontaneous preterm birth in seven days was 91.26% that was better than other CL cutoffs (20 mm, 15 mm, and 10 mm). CONCLUSION: PAMG-1 molecule with high NPV and PPV (91.4% and 90%) combination will contribute our clinical decision on the population who had preterm labor symptoms and a CL shorter than 25 mm.

Evaluation of placental alpha microglobulin-1(PAMG1) accuracy for prediction of preterm delivery in women with the symptoms of spontaneous preterm labor; a comparison with cervical length and number of contractions.

INTRODUCTION: Since the capacity of tertiary centers is limited, identifying women with the risk of preterm delivery is crucial amongst women who refer to hospitals with threatened preterm labor. OBJECTIVE: The purpose of the present study was to evaluate the accuracy of the placental alpha microglobulin-1 (PAMG-1) test for identifying women who referred to hospitals with signs of spontaneous preterm labor and ultimately delivered within ≤48 h and ≤7 of testing and ≤37 weeks of gestation and its comparison with cervical length of <25 mm and number of contractions. MATERIALS AND METHODS: A prospective observational study was performed on women with the signs of spontaneous preterm labor. Placental alpha microglobulin-1 (PAMG-1) was evaluated in vaginal secretion. Cervical length (CL) and number of contractions were evaluated and recorded. The test to- spontaneous- delivery interval was documented. Sensitivity (SN), specificity (SP), accuracy rate of the PAMG-1, cervical length of <25 mm and number of contractions in prediction of spontaneous preterm delivery within ≤48 h, ≤7 days and preterm delivery (≤37 weeks of gestation) were calculated. RESULTS: One hundred eighty women finished the study. 44 women had positive PAMG-1 test and 58 women had cervical length of <25 mm. Women with a positive PAMG-1 were more likely to deliver within ≤48 h (p < .0001), ≤7 days (p < .0001), and before 37 weeks (p < .0001), compared to the women who had a negative test. For delivery within ≤48 h, ≤7 days and ≤37 weeks, specificity (SP) of the PAMG-1; was statistically higher than cervical length of <25 mm and contractions of 12-17/hr but not contractions of ≥18/hr. PAMG-1 showed a higher accuracy rate than cervical length of <25 mm, contractions of 12-17/hr and contractions of ≥18/hr for deliveries within ≤48 h (78.9, 55.3, 48.9, and 69.44%, respectively) and ≤7 days (76.1, 55.32, 55, and 65.56%, respectively). For deliveries before 37 weeks; the PAMG-1 test showed higher LR + than CL of <25 mm, contractions of 12-17/hr and contractions of ≥18/hr [10.24 (2.57-40.86), 2.01 (1.24-3.23), 1.30 (1.05-1.62), and 5.12 (1.24-21.11), respectively]. PPV for deliveries within ≤48 h and ≤7 days for PAMG-1 was greater than cervical length of <25 mm and number of contractions, however, NPV did not show a significant difference. CONCLUSION: PAMG-1 test showed a higher accuracy rate for prediction of delivery within ≤48 and ≤7 days in comparison with cervical length of <25 mm and number of contractions. Also, PAMG-1 test had a higher positive likelihood ratio for deliveries at ≤37 weeks. PPV for deliveries within ≤48 h and ≤7 days for PAMG-1 was greater than cervical length of <25 mm and number of contractions, however, NPV did not show a significant difference.

The use of PAMG-1 testing in patients with preterm labor, intact membranes and a short sonographic cervix reduces the rate of unnecessary antenatal glucocorticoid administration.

OBJECTIVES: To assess the frequency of antenatal corticosteroid (ACS) administration in cases with shortened cervical length by addition of placental alpha-microglobulin-1 (PAMG-1) testing to sonographic examination. METHODS: Single centre retrospective cohort study. Rate of ACS administration was compared between cases with cervical length between 15 and 25 mm and cases with positive PAMG-1 testing and cervical length between 15 and 25 mm. We evaluated the following outcome parameters: Rate of ACS administration, gestational age at delivery, time to delivery, delivery within seven days, delivery <34 and <37 weeks' gestation, rate of admission to neonatal intensive care unit (NICU). RESULTS: In total, 130 cases were included. "PAMG-1 group" consisted of 68 women, 62 cases built the "historical control group". ACS administration was performed less frequently in the "PAMG-1 cohort" (18 (26%) vs. 46 (74%); p<0.001). The rate of delivery within seven days did not differ (2 (3%) vs. 4 (6.5%); p=0.4239). The rates of delivery <34 weeks' gestation (7 (10%) vs. 9 (15%); p=0.4643) and <37 weeks' gestation (19 (28%) vs. 26 (42%); p=0.0939) did not differ. Time to delivery interval was longer in the PAMG-1 group (61.5 vs. 43 days, p=0.0117). NICU admission occurred more often in the "historical control group" (22 (38%) vs. 28 (60%); p=0.0272). CONCLUSIONS: Addition of biomarker testing can help to avoid unnecessary ACS administrations in women with shortened cervical length.

Current and Emerging Strategies for Prediction and Diagnosis of Prelabour Rupture of the Membranes: A Narrative Review.

Prelabour rupture of membranes (PROM) refers to the disruption of foetal membranes before the onset of labour, resulting in the leakage of amniotic fluid. PROM complicates 3% and 8% of preterm and term pregnancies, respectively. Accurate and timely diagnosis is crucial for effective management to prevent adverse maternal- and foetal-outcomes. The diagnosis of equivocal PROM cases with traditional methods often becomes challenging in current obstetrics practice; therefore, various novel biochemical markers have emerged as promising diagnostic tools. This narrative review is sought to review the published data to understand the current and emerging trends in diagnostic modalities in term and preterm pregnancies complicated with PROM and the potential role of various markers for predicting preterm PROM (pPROM) and chorioamnionitis in women with pPROM.

Comparison of placental α microglobulin-1 protein assay (Amnisure) with speculum examination for the diagnosis of premature preterm rupture of membranes (PPROM): a clinical evaluation.

In this study, we aimed to compare the clinical outcomes of Premature Preterm Rupture of Membranes (PPROM) cases diagnosed by classical speculum examination and by placental alpha microglobulin-1 protein (PAMG-1) assay. The medical records of all patients with singleton pregnancies that were diagnosed with PPROM were retrospectively reviewed. Singleton pregnancies with PPROM diagnosis that was confirmed either by direct visualisation of amniotic fluid leaking through the cervix or by placental alpha microglobulin-1 protein (PAMG-1) assay if no amniotic fluid leakage was documented were included in the study. Demographics, prenatal and postnatal characteristics were reviewed from the medical charts and were recorded. The study included 138 pregnancies with PPROM; 111 patients in clinical speculum examination group and 27 in PAMG-1 assay group. There were no significant differences in maternal and pregnancy characteristics between the clinical speculum examination and PAMG-1 assay groups. Foetal outcomes were comparable between clinical speculum examination and PAMG-1 assay groups. In the clinical speculum examination group, there were nine (8.1%) chorioamnionitis cases, however, there were no chorioamnionitis cases in the PAMG-1 assay group during the latency period (p = .21).Impact statementWhat is already known on this subject? Placental alpha microglobulin-1 protein assay uses immunochromatography method to detect trace amount of placental alpha microglobulin-1 protein in vaginal fluids and has high sensitivity and specificity for ROM diagnosis. However, to the best of our knowledge, the clinical outcome of ROM cases detected by classical speculum examination and by placental alpha microglobulin-1 protein assay has not been compared in the literature previously.What do the results of this study add? Although statistically insignificant, cases diagnosed by PAMG-1 assay had lower risk of chorioamnionitis during latency period.What are the implications of these findings for clinical practice and/or further research? Whether cases diagnosed by PAMG-1 assay represent a milder form of rupture of membranes than cases diagnosed by classical speculum examination group warrants further research.

Diagnosis of rupture of membranes: AmniSure, clinical assessment, and the Food and Drug Administration warning.

BACKGROUND: An accurate diagnosis of rupture of membranes is critical to the rendering of appropriate maternity care in both preterm and term patients. Immunoassays, such as the one detecting placental alpha microglobulin-1 (AmniSure) in cervicovaginal secretions, have replaced the traditional speculum-based assessment in some clinical settings; however, the Food and Drug Administration recently issued a warning regarding the potential risks of using the test in isolation. OBJECTIVE: The study aimed to report the performance of AmniSure as a first-line nurse-administered screening test for rupture of membranes in our teaching county hospital obstetrical triage unit and as part of a clinical protocol to diagnose rupture of membranes. STUDY DESIGN: We conducted a retrospective secondary analysis of 310 randomly selected term and preterm patients with concern for rupture of membranes screened with the AmniSure test. We systematically reviewed medical records to determine membrane status at the time of the AmniSure test. We calculated test characteristics of the AmniSure test used independently and in conjunction with speculum-based assessment. RESULTS: Of 302 women evaluated for retrospective determination of membrane status at 17 to 41 weeks' gestation (median, 36.6 weeks' gestation), 208 (68.9%) were intact and 94 (31.1%) were ruptured at the time of the AmniSure test using a gold standard of retrospective membrane status determined by medical record review. A total of 4 false-negative AmniSure results and 16 false-positive AmniSure results were identified. The AmniSure test used independently had a sensitivity of 95.7%, specificity of 92.3%, positive predictive value of 84.9%, and negative predictive value of 98.0%. A rupture of membranes protocol combining AmniSure and clinical assessment had a sensitivity of 98.2%, specificity of 99.5%, positive predictive value of 100.0%, and negative predictive value of 100.0%. CONCLUSION: The AmniSure has a high sensitivity as a first-line nurse-administered screening test for membrane rupture. Consistent with the Food and Drug Administration warning, the sensitivity, specificity, positive predictive value, and negative predictive value are improved when it is used as part of a clinical protocol and not in isolation. Determination of membrane status remains challenging in a small subset of patients, especially those with an equivocal speculum-based assessment; therefore, engaging women in their care and careful follow-up for identifying persistent or recurrent symptoms are required.

Comparative analysis of Insulin-like growth factor binding protein-1, placental alpha-microglobulin-1, phenol and pH for the diagnosis of preterm premature rupture of membranes between 20 and 36 weeks.

AIM: Preterm premature rupture of membranes (PPROM) is responsible for approximately one-third of premature births worldwide, and although the diagnosis is often straightforward, this condition can still present difficulties. The purpose of this research was to compare the accuracy of several PPROM diagnostic tests. METHODS: A total of 94 pregnant women with clinical suspicion of PPROM who were between 20 and 36 weeks of pregnancy were examined by vaginal speculum, and tests were performed for phenol, pH, insulin-like growth factor binding protein-1 (IGFBP-1) and placental alpha-microglobulin-1 (PAMG-1). All patients were followed up until the diagnosis was fully defined, and a diagnosis of PROM was confirmed by a definitive evolution of the clinical symptoms (visualization of vaginal amniotic fluid or persistence of oligohydramnios). RESULTS: After excluding the cases that could not be definitively diagnosed, a good diagnostic performance of the immunochromatographic tests was observed that was superior to that of the clinical tests. Similar accuracies were observed for IGFBP-1 (98.7%) and PAMG-1 (93.9%). However, while the IGFBP-1 test differed from a vaginal pH ≥7 (88.9%) and the phenol test (85.7%), this did not occur for the PAMG-1 test. The performance of the tests was modified only by the presence of bleeding (with lower specificity rates for pH and phenol), without interference of gestational age or maternal morbidities. CONCLUSION: Immunochromatographic tests are good tools but should be used sparingly in resource-poor settings because they are expensive, and there is no significant difference between PAMG-1 and traditional tests.

[Preterm Birth Screening: What Does Really Make Sense?] / Frühgeburtsscreening: Was ist wirklich sinnvoll?

Preterm Birth Screening: What Does Really Make Sense? Abstract. Spontaneous preterm birth is a syndrome triggered by multiple mechanisms. In view of the pathophysiological heterogeneity of preterm birth, a single biomarker cannot show the required high negative and positive predictive values. From a clinical point of view, anamnesis, sonographic measurement of cervical length, and placental alpha-microglobulin-1 (PAMG-1) testing from cervico-vaginal secretion are established. Further prospective, large-scale longitudinal studies must validate the combined use of new biomarkers.

Prediction of preterm delivery in symptomatic women using PAMG-1, fetal fibronectin and phIGFBP-1 tests: systematic review and meta-analysis.

OBJECTIVE: To assess the accuracy of placental alpha microglobulin-1 (PAMG-1), fetal fibronectin (fFN) and phosphorylated insulin-like growth factor-binding protein-1 (phIGFBP-1) tests in predicting spontaneous preterm birth (sPTB) within 7 days of testing in women with symptoms of preterm labor, through a systematic review and meta-analysis of the literature. The test performance of each biomarker was also assessed according to pretest probability of sPTB ≤ 7 days. METHODS: The Cochrane, MEDLINE, PubMed and ResearchGate bibliographic databases were searched from inception until October 2017. Cohort studies that reported on the predictive accuracy of PAMG-1, fFN and phIGFBP-1 for the prediction of sPTB within 7 days of testing in women with symptoms of preterm labor were included. Summary receiver-operating characteristics (ROC) curves and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and positive (LR+) and negative (LR-) likelihood ratios were generated using indirect methods for the calculation of pooled effect sizes with a bivariate linear mixed model for the logit of sensitivity and specificity, with each diagnostic test as a covariate, as described by the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. RESULTS: Bivariate mixed model pooled sensitivity of PAMG-1, fFN and phIGFBP-1 for the prediction of sPTB ≤ 7 days was 76% (95% CI, 57-89%), 58% (95% CI, 47-68%) and 93% (95% CI, 88-96%), respectively; pooled specificity was 97% (95% CI, 95-98%), 84% (95% CI, 81-87%) and 76% (95% CI, 70-80%) respectively; pooled PPV was 76.3% (95% CI, 69-84%) (P < 0.05), 34.1% (95% CI, 29-39%) and 35.2% (95% CI, 31-40%), respectively; pooled NPV was 96.6% (95% CI, 94-99%), 93.3% (95% CI, 92-95%) and 98.7% (95% CI, 98-99%), respectively; pooled LR+ was 22.51 (95% CI, 15.09-33.60) (P < 0.05), 3.63 (95% CI, 2.93-4.50) and 3.80 (95% CI, 3.11-4.66), respectively; and pooled LR- was 0.24 (95% CI, 0.12-0.48) (P < 0.05), 0.50 (95% CI, 0.39-0.64) and 0.09 (95% CI, 0.05-0.16), respectively. The areas under the ROC curves for PAMG-1, fFN and phIGFBP-1 for sPTB ≤ 7 days were 0.961, 0.874 and 0.801, respectively. CONCLUSIONS: In the prediction of sPTB within 7 days of testing in women with signs and symptoms of preterm labor, the PPV of PAMG-1 was significantly higher than that of phIGFBP-1 or fFN. Other diagnostic accuracy measures did not differ between the three biomarker tests. As prevalence affects the predictive performance of a diagnostic test, use of a highly specific assay for a lower-prevalence syndrome such as sPTB may optimize management. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Combination of three-dimensional ultrasound measurement of foetal adrenal gland enlargement and placental alpha microglobulin-1 for the prediction of the timing of delivery within seven days in women with threatened preterm labour and preterm labour.

The aim of this study was to predict the timing of delivery within seven days in singleton pregnant women with threatened preterm labour and preterm labour by using a three-dimensional (3D) ultrasound measurement of foetal adrenal gland volume enlargement, a foetal zone enlargement and cervicovaginal placental alpha microglobulin-1 (PAMG-1) test. This prospective cohort study included singleton pregnant women at 22-36+6 weeks of gestation who presented with threatened preterm labour and with preterm labour. Transabdominal 3D ultrasound measurement of the whole foetal adrenal gland and of the foetal adrenal zone were performed. Qualitative cervicovaginal PAMG-1 detection was performed at the same time. One hundred and fifty-four pregnant women were included into the study. Eighty-four pregnant women had threatened preterm labour and seventy pregnant women had preterm labour. Twenty-nine pregnant women (18%) delivered within seven days. Use of foetal adrenal gland volume enlargement, foetal zone enlargement and the PAMG-1 test in combination increased sensitivity; if one parameter was positive, the sensitivity, specificity, positive predictive value and negative predictive value were 82.8%, 27.2%, 20.9% and 87.2%, respectively, in the prediction of the timing of delivery within seven days. The combination of foetal adrenal gland enlargement and PAMG-1 increased sensitivity for the prediction of the timing of delivery within seven days in pregnant women presenting with threatened preterm labour and preterm labour. Impact Statement What is already known on this subject? An increased foetal adrenal gland volume is significantly correlated with the risk of preterm birth. What do the results of this study add? The combination of a foetal adrenal gland enlargement and a placental alpha microglobulin-1 increased sensitivity for the prediction of the timing of delivery within seven days in pregnant women presenting with threatened preterm labour and preterm labour. What are the implications of these findings for clinical practice and/or further research? The combination of a foetal adrenal gland enlargement and placental alpha microglobulin-1 may be used for the prediction of the timing of delivery within seven days in pregnant women presenting with threatened preterm labour and with preterm labour.

Predictive performance of PAMG-1 vs fFN test for risk of spontaneous preterm birth in symptomatic women attending an emergency obstetric unit: retrospective cohort study.

OBJECTIVE: To compare the performance of the placental alpha microglobulin-1 (PAMG-1) and fetal fibronectin (fFN) tests for the prediction of spontaneous preterm delivery in patients presenting to an emergency obstetric unit with threatened preterm labor, by conducting a retrospective audit of patient medical records from separate 1-year periods during which either fFN or PAMG-1 was used as the standard-of-care biochemical test. METHODS: This was a retrospective cohort study based on chart review of electronic medical records of women with threatened preterm labor presenting at a level-III maternity hospital over two different periods: (1) the 'baseline' period (year 2012), during which the qualitative fFN test with a cut-off of 50 ng/mL was used as the standard-of-care biochemical test for the risk assessment of preterm delivery, and (2) the 'comparative' period (year 2016), during which the PAMG-1 test with a cut-off of 1 ng/mL was used as the standard-of-care biomarker test. Patients with a singleton pregnancy between 24 + 0 and 34 + 6 weeks' gestation with symptoms of early preterm labor, clinically intact membranes and cervical dilatation < 3 cm, who did not have a medically indicated preterm delivery within 14 days of testing, were selected for chart review and included in the analysis. Key parameters used for the analysis were biochemical test results, time of testing and time of delivery. Positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity, and positive and negative likelihood ratios (LR+ and LR-) for the prediction of spontaneous preterm delivery ≤ 7 and ≤ 14 days of presentation were calculated for the PAMG-1 and fFN tests. RESULTS: Four hundred and twenty patients were identified as having presented with threatened preterm labor during the baseline period, of whom 378 (90.0%) met the eligibility criteria. Of these, 38 (10.1%) were fFN positive and 10 (2.6%) had spontaneous preterm delivery ≤ 7 days of presentation. PPV, NPV, LR+ and LR- of fFN were 7.9%, 97.9%, 3.2 and 0.8, respectively, for spontaneous preterm delivery ≤ 7 days. Four hundred and ten patients were identified as having presented with threatened preterm labor during the comparative period and 367 (89.5%) subjects met the eligibility criteria. Of these, 17 (4.6%) were PAMG-1 positive and 12 (3.3%) had spontaneous preterm delivery ≤ 7 days of presentation. PAMG-1 PPV and NPV were 35.3% and 98.3%, respectively, and LR+ and LR- were 16.1 and 0.5, respectively, for spontaneous preterm delivery ≤ 7 days. CONCLUSIONS: Before switching to PAMG-1, fFN was the standard-of-care test for the risk assessment of spontaneous preterm delivery. This retrospective audit of each test's performance over separate 1-year periods shows that we were more than twice as likely to get a positive fFN test than a positive PAMG-1 test, while the rate of discharging women who ultimately delivered spontaneously within 14 days of testing was not affected. Furthermore, a positive PAMG-1 test was more than four times more reliable than a positive fFN test in predicting imminent spontaneous preterm delivery. The use of a more reliable biomarker that is associated with fewer false-positive results could lead to a reduction in unnecessary admissions, interventions and use of hospital resources. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Combined value of placental alpha microglobulin-1 detection and cervical length via transvaginal ultrasound in the diagnosis of preterm labor in symptomatic patients.

AIM: We aimed to evaluate the combined value of placental alpha microglobulin-1 (PAMG-1) and cervical length (CL) via transvaginal ultrasound for assessing risk of imminent spontaneous preterm delivery in patients presenting with threatened preterm labor (PTL). METHODS: Clinical exam, PAMG-1 test, cardiotocography, and CL measurement via transvaginal ultrasound were performed on all patients meeting inclusion criteria. Ninety-nine patients at 22+0 -36+6 gestational weeks with the symptoms of PTL were included. The interval between sample collection and delivery was measured for each method. RESULTS: Performance metrics were calculated for PAMG-1 test, CL < 25 mm, and contractions ≥ 8/h. The sensitivity, specificity, positive predictive value, and negative predictive value for the PAMG-1 test were 100%, 95%, 75%, 100% and 100%, 98%, 88%, 100% for 7 and 14 days, respectively; the respective values for CL < 25 mm were 83%, 59%, 22%, 96% and 79%, 59%, 24%, 94% for 7 and 14 days; and those for contractions ≥ 8/h were 42%, 38%, 8%, 83% and 43%, 38%, 10%, 80% for 7 and 14 days. Specificity for the PAMG-1 test was statistically significant (P < 0.001) in pairwise comparisons for all other methods. Patients were divided into four groups for analysis of PAMG-1 test performance as follows: CL < 15 mm (100%, 100%, 100%, 100% and 100%, 100%, 100%, 100% for 7 and 14 days, respectively); CL < 25 mm (100%, 94%, 83%, 100% and 100%, 97%, 92%, 100% for 7 and 14 days, respectively); CL of 15-30 mm (100%, 95%, 64%, 100% and 100%, 97%, 82%, 100% for 7 and 14 days, respectively); and CL ≥ 30 mm (100%, 100%, 100%, 100% and 100%, 100%, 100%, 100% for 7 and 14 days, respectively). CONCLUSION: The use of the PAMG-1 test in patients with a CL of 15-30 mm is highly predictive of imminent spontaneous preterm delivery in women presenting with threatened PTL and could save hospital resources.

Comparison of rapid immunoassays for rupture of fetal membranes.

BACKGROUND: Rupture of membranes (ROM) before the onset of uterine contractions, particularly in pregnancies less than 37 weeks gestational age, is a common diagnostic problem in obstetrical practice. Timely detection of ROM is vital to support gestational age-specific interventions to optimize perinatal outcomes and minimize the risk of serious complications such as preterm delivery, fetal distress and maternal/fetal infections. Rapid bedside immunoassay tests designed to detect amniotic fluid proteins in cervicovaginal fluids have emerged as valuable clinical tools to provide timely ROM diagnosis. METHODS: In this prospective observational study, two commercially-available immunoassay tests (ROM Plus®, AmniSure®) were evaluated concurrently in 111 pregnant women who presented with the chief complaint of ROM. Immunoassay results were compared to clinical parameters for determining ROM via comprehensive, retrospective clinical chart review. Diagnostic performance characteristics were calculated including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy. RESULTS: Overall, diagnostic performance characteristics were robust and similar between ROM Plus® and AmniSure®, respectively: sensitivity (96.4 and 89.3%), specificity (98.8 and 100%), PPV (96.4 and 100%), NPV (98.8% and 96.5) and accuracy (98.2 and 97.3%). For term patients (≥37 weeks gestation), the sensitivities were 93.8 and 81.3% and specificities were 97.1 and 100% for ROM Plus® and AmniSure®, respectively. For preterm patients (<37 weeks gestation), both immunoassay tests provided exact concordance with clinical confirmation of ROM resulting in 100% diagnostic accuracy. CONCLUSIONS: Both rapid immunoassay tests provided similarly excellent diagnostic accuracy for the rapid detection of ROM with only two discrepant results for ROM Plus® and three discrepant results for AmniSure® compared to clinical confirmation. The findings from this study recommend these tests for pregnant women presenting with suspected ROM to guide correct clinical management decisions to improve obstetrical and neonatal outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02208011 (1 August 2014).

Accuracy and response time of dual biomarker model of insulin-like growth factor binding protein-1/ alpha fetoprotein (Amnioquick duo+) in comparison to placental alpha-microglobulin-1 test in diagnosis of premature rupture of membranes.

AIM: The aim of this study was to determine accuracy and response time of duo of insulin-like growth factor binding protein-1 (IGFBP-1)/alpha-fetoprotein (Amnioquick duo+) versus placental alpha-microglobulin-1 (PAMG-1) in diagnosing premature rupture of membranes (PROM). METHODS: A multicenter prospective study was conducted among women with features suggestive of PROM between 24 and 42 gestational weeks (GW). PROM was confirmed post-delivery based on presence of any two of these criteria: delivery within 48 h to 7 days, chorioamnionitis, membranes overtly ruptured at delivery, and adverse perinatal outcomes strongly correlated with prolonged PROM. Response time analysis was also done. Outcome measures included specificity, sensitivity, positive predictive value, negative predictive value, accuracy, and response time for both tests. RESULTS: Sensitivity, specificity, and accuracy for Amnioquick duo+ were 97.9%, 97.6%, and 97.9%, which were higher than the levels for PAMG-1, of 95.3%, 90.0%, and 95.7%, respectively (not significant). Accuracy of Amnioquick duo+ versus PAMG-1 in equivocal (pooling = negative) cases was (98.4% vs 96.8%) at ≥34 GW but each was 100.0% at <34 GW (not significant). Overall diagnostic concordance rate of Amnioquick duo+ and PAMG-1 was 97.0% and both have equal positive predictive value (99.5%). Response time analysis showed that the overall response time of PAMG-1 was 4.5% higher than that of Amnioquick duo+. CONCLUSION: This is the largest study to date to reveal that Amnioquick duo+ and PAMG-1 have a comparatively high diagnostic accuracy in identifying women with PROM, with a concordance rate of 97.0%. The diagnostic response time of Amnioquick duo+ appears shorter. In equivocal cases, accuracy of Amnioquick duo+ was equal to that of the PAMG-1.

The accuracy of placental alpha-microglobuline-1 test in diagnosis of premature rupture of the membranes.

BACKGROUND: Premature rupture of membranes (PROM) is a common obstetric issue during pregnancy which might lead to serious fetal or maternal problems. Therefore, an appropriate diagnosis and management of PROM are of significant importance in patients. OBJECTIVE: The aim of this study was to determine the accuracy of placental alpha microglobuline-1 (PAMG-1) test in PROM diagnosis and compare this diagnostic method with other standard tests in diagnosis of PROM. MATERIALS AND METHODS: In this prospective diagnostic accuracy study, patients with symptoms of membrane rupture in 16-39 weeks of gestation were involved. Three tests including Fern, Nitrazine and PAMG-1 were performed at the same time. RESULTS: PROM was confirmed in 86 patients out of 100. The sensitivity and specificity were respectively 81.3% and 100% for Fern test, 93% and 92.8% for Nitrazine test, 98.9% and 92.8% for PAMG-1 test. PAMG-1 test showed higher sensitivity (98.9% with p<0.001) and accuracy (98%) compared with conventional tests. Although PAMG-1showed a lower positive predictive value (PPV) compared to conventional tests such as Fern test (100%), it was shown to be more accurate. CONCLUSION: The accuracy of PAMG-1 test was superior to both Fern and Nitrazine test in PROM diagnosis.

Accuracy and cost-analysis of placental alpha-microglobulin-1 test in the diagnosis of premature rupture of fetal membranes in resource-limited community settings.

AIM: To determine accuracy and costs of placental α-microglobulin-1 (PAMG-1) test compared to standard clinical assessment (SCA) for diagnosing rupture of membranes (ROM). METHODS: A multicenter double-blind study of consecutive women with symptoms and signs of ROM in Nnamdi Azikiwe University Teaching Hospital, Nnewi and University of Nigeria Teaching Hospital, Enugu, both in south-east Nigeria using SCA for ROM and the PAMG-1 test was done. ROM was diagnosed if two out of three methods from SCA (pooling, positive nitrazine test or ferning) were present and confirmed post-delivery based on presence of any two of these clinical criteria: delivery in 48 h to 7 days, evidence of chorioamnionitis, membranes overtly ruptured at delivery and adverse perinatal outcomes strongly correlated with prolonged PROM. A cost-analysis was also done. The outcome measures included sensitivity, specificity, accuracy and costs for the two tests. RESULTS: Accuracy, sensitivity and specificity for the PAMG-1 test were 97.2%, 97.4% and 96.7%, higher than for SCA which were 83.7%, 87.9% and 70.5%, respectively (P < 0.001). Accuracy of SCA was higher at less than 34 weeks than 34 weeks or more (88.3% vs 81.4%) while the PAMG-1 test performed equally at both gestational age categories (96.1% vs 97.7%). In women without pooling, accuracy of the PAMG-1 test was 96.7%, while it was 40.0% with SCA. Analysis showed that the overall cost of SCA was 45% higher than the PAMG-1 test. CONCLUSION: This study confirms that the PAMG-1 test has a consistently high diagnostic accuracy at all gestational ages and with equivocal cases of ROM. The PAMG-1 test appears less costly than SCA.

Premature preterm rupture of the membrane diagnosis in early pregnancy: PAMG-1 and IGFBP-1 detection in amniotic fluid with biochemical tests.

OBJECTIVES: Previable premature rupture of the membranes (pPROM), occurring before 24WG, is associated with a 25% neonatal survival rate. This terrible prognosis may lead to elective pregnancy termination on parents' request. Therefore, certain diagnosis is essential but remains difficult in about 10% of patients. Bed-side biochemical tests developed to help in diagnosis had never been evaluated in early pregnancies. This study aimed to evaluate and compare the in vitro sensitivity, detection limit, reaction time and consistency of AmniSure detecting placental alpha microglobulin-1 (PAMG-1) and actim PROM detecting Insulin Growth Factor Binding Protein-1 (IGFBP-1) in amniotic fluid between 15 and 20weeks of gestation (WG). DESIGN AND METHODS: Samples of amniotic fluid were collected by amniocentesis performed between 15 and 20 completed WG in 55 patients. Dilution series were prepared and both tests were performed twice at each dilution. In vitro sensitivity, detection limit, and reaction time were evaluated and compared in serial dilution. RESULTS: A total of 460 AmniSure and 476 actim PROM tests were performed. Both tests' in vitro sensitivity was 100% at dilution 1:20 and remained up to 90% until dilution 1:80. In vitro sensitivities were not different at any dilution. Detection limit and consistency were similar for both tests at all dilution. Actim PROM reaction time was shorter than AmniSure at all dilutions, except 1:320 (p<0.05). CONCLUSIONS: PAMG-1 and IGFBP-1 can be detected in amniotic fluid between 15 and 20 completed WG, using respectively AmniSure and actim PROM.

Placental alpha-microglobulin-1 in vagina liquid to diagnose premature rupture of membranes / 中国医师进修杂志

Objective To explore the value of placental alpha-microglobulin-1 in vagina liquid to diagnose premature rupture of membranes. Methods A prospective observational study to initial evaluation included both the standard clinical evaluation for rupture of membranes and placental alpha-microglobulin-1 immunoassay. Rupture of membranes was diagnosed if fluid was seen leaking from the cervical os or if two of the following three conditions were present: pooling of fluid, positive nitrazine test, or feming. Rupture of membranes was diagnosed definitively on review of the medical records after delivery. Results Placental alpha-microglobulin-1 immunoassay confirmed rupture of membranes at initial presentation with a sensitivity of 100% (89/89), specificity of 91% (10/11), positive predictive value of 99% (89/90), and negative predictive value of 100% (10/10),false positive rate of 9% (1/11). Placental alpha-nricroglobulin-1 immunoassay was better than the conventional clinical assessment in confirming the diagnosis of rupture ofmembranes (P<0.01). Conclusion Measurement of placental alpha-microglobulin-1 in cervicovaginal secretions is superior to conventional clinical assessment in the diagnosis of rupture of membranes.