J. Perinat. Med. 2015; aop

Tanja Nikolova*, Oleg Bayev, Natasha Nikolova and Gian Carlo Di Renzo

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 Abstract 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,

Paper Presentation Information: Preliminary findings of this investigation were presented at the World Congress of Perinatal Medicine in Moscow, Russia in June 2013 by Professor Oleg Bayev, MD. *Corresponding author: Tanja Nikolova, MD, Pirinska 106 a, 2000 Shtip, Republic of Macedonia, Tel.: +389 70 222 820, E-mail: [email protected]; and University Clinic of Obstetrics and Gynecology, Skopje, Republic of Macedonia Oleg Bayev: Research Center of Obstetrics, Gynecology and Perinatology of the Ministry of Healthcare and Social Development of the Russian Federation, Moscow, Russia Natasha Nikolova: University Clinic of Obstetrics and Gynecology, Skopje, Republic of Macedonia Gian Carlo Di Renzo: Department of Obstetrics and Gynecology, University of Perugia, Perugia, Italy

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. Keywords: Cervical length (CL); fetal fibronectin (fFN); PartoSure Test; placental alpha microglobulin-1 (PAMG-1); preterm birth; preterm delivery; preterm labor (PTL); QuikCheck; transvaginal ultrasound (TVU). DOI 10.1515/jpm-2014-0300 Received September 7, 2014. Accepted November 25, 2014.

Introduction Preterm birth occurs in approximately 6%−10% of pregnancies worldwide [1]. Additionally, 28% of neonatal deaths not related to malformations are due to preterm birth [2]. A 2006 report from the Institute of Medicine estimated the annual cost of preterm birth in the US to be $26.2 billion or more than $51,000 per premature infant [3]. A single unnecessary admission of a patient suspected of having preterm labor (PTL) but who does not actually have the condition costs $20,300 USD on average [4]. An accurate test that aids in the diagnosis of true PTL in women presenting to hospitals with signs and symptoms suggestive of the condition would, therefore, be very useful toward reducing unnecessary admissions and/ or evaluations. It follows that a test with a high negative predictive value (NPV) and a high positive predictive value (PPV) would offer the greatest advantage.

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2      Nikolova et al., Prediction of imminent spontaneous preterm delivery in patients with threatened preterm labor

Placental alpha microglobulin-1 (PAMG-1) is a protein found in high concentrations in amniotic fluid but in very low concentrations in background levels of cervicovaginal discharge. In recent years, the medical community has increasingly accepted the widespread use of detecting PAMG-1 to aid the provider in confirming or ruling out rupture of the fetal membranes (ROM) [5–7]. The test used is commercially marketed as the AmniSure® ROM Test, manufactured by AmniSure International, LLC (Boston, MA, USA), a wholly owned subsidiary of QIAGEN N.V. (NASD: QGEN). In one of the original investigations of PAMG-1 for the detection of ROM, Lee et  al. noted that in 20 out of 23 cases where the AmniSure ROM Test was positive and standard clinical assessment (i.e., nitrazine, ferning and pooling) was negative, the patient was ultimately determined to have been ruptured upon retrospective analysis of their clinical course [8]. It was later reported that for all of the preterm patients in this group who showed signs and symptoms of labor, delivery followed within 7  days [9]. In 2012, the clinical value of a positive AmniSure ROM Test in the patient presenting with signs and symptoms of PTL but without membrane rupture was investigated by this same group. The results demonstrated that the AmniSure ROM Test was highly predictive of delivery for these patients within 48 h, 7 days and 14 days, providing both a high NPV and PPV to the clinician [10]. Several additional studies have corroborated these findings [11, 12]. In the patient group on whom the above tests are performed, clinically detectable membrane rupture is excluded, as this condition, if present, confirms imminent delivery and dictates a different course of management. It has been demonstrated that the AmniSure ROM Test can detect PAMG-1 in patients presenting with signs and symptoms of ROM when all other traditional methods are unable to identify a clinical marker for the condition. The likelihoods of adverse outcomes associated with these sub-clinical ruptures have been demonstrated to not be statistically different from the adverse outcomes associated with gross or clinically detectable ruptures [13]. The proposed explanation for this phenomenon is that PAMG-1 is released through micro-perforations of the amniotic membranes so that more copious amounts of fluid cannot pass through [13]. The major difference, however, between the patients presenting with signs of PTL and those just described above is the presence, or absence, of membrane rupture signs or complaints. Given that the complaints of ROM are typically rooted in an overt episode of suspicious fluid leakage, it is hypothesized that the resulting concentration of PAMG-1 in the vagina of the patient without such

overt complaints or signs of ROM will be lower than the current sensitivity threshold of the AmniSure ROM Test. Accordingly, a device that is more sensitive in its detection of PAMG-1 will presumably be able to detect more patients at risk for imminent delivery than its predecessor in patients presenting to labor and delivery units with signs, symptoms, or complaints suggestive of PTL who have no clinical evidence of membrane rupture. Such a device has been developed – the PartoSure™ Test, manufactured by QIAGEN (Boston, MA, USA) – and in a multicenter, multinational pilot clinical trial, Nikolova et al. reported that the PartoSure test provided 97.4% and 93.6% NPVs and 78.3% and 87.0% PPVs at   ≤  7 and   ≤  14 days, respectively. The PartoSure test provided 90.0% and 80.0% sensitivities and 93.8% and 96.1% specificities at   ≤  7 and   ≤  14 days, respectively [14]. For the present investigation, we intended to further evaluate the PartoSure test in a larger symptomatic population as well as compare it with standard tests [e.g., cervical length (CL) measurement by transvaginal ultrasound (TVU) and fetal fibronectin (fFN) testing] for assessing the risk of imminent spontaneous preterm delivery in patients with threatened PTL. Additionally, we sought to determine the extent to which the predictive value, both negative and positive, of a CL measurement by TVU can be enhanced by the results of either of the biomarker tests.

Methods A prospective observational study was performed involving 219 consecutively recruited patients with singleton pregnancies between 200/7 and 366/7 weeks of gestation presenting with self-reported signs, symptoms, or complaints suggestive of PTL including uterine contractions, with or without pain, intermittent lower abdominal pain, and pelvic pressure. Patients were recruited between June 2012 and February 2014. The recruited patients had clinically intact amniotic membranes as determined by speculum examination [and minimal cervical dilatation ( ≤ 3 cm)]. Patients were recruited at the University Clinic of Obstetrics and Gynecology (Skopje, Republic of Macedonia) and the Research Center of Obstetrics, Gynecology and Perinatology of the Ministry of Healthcare of the Russian Federation (Moscow, Russia). The institutional review boards at both the Skopje, Macedonia and Moscow, Russia sites approved this investigation and written informed consents were collected from all recruited patients. Patients with overt rupture of fetal membranes, advanced cervical dilatation, suspected placenta previa, cervical cerclage in place, or who were under the age of 18 were not included. Overt rupture of fetal membranes was diagnosed as fluid was seen leaking from the cervical os during the sterile speculum examination; these patients were not offered enrollment. For all patients recruited into the trial, a full clinical examination was conducted by the attending physician. This included collection of the PartoSure Test sample, sterile speculum examination, TVU, and digital examination. The PartoSure Test sample was taken

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Nikolova et al., Prediction of imminent spontaneous preterm delivery in patients with threatened preterm labor      3

before the cervical examination. Parameters recorded at presentation included CL, cervical dilatation, contraction frequency, membrane status, cervical effacement, patient history, and PartoSure result. In a sub-group of patients who were consecutively recruited upon presentation and for whom use of the test was applicable based on the manufacturer’s recommendations, the QuikCheck fFN Test was performed. Specific testing procedures were performed for each of the CL measurement by TVU (CL), PartoSure (PAMG-1), and QuikCheck (fFN).

PartoSure Test (PAMG-1) The PartoSure Test was performed according to the manufacturer’s instructions. A sterile flocked vaginal swab was inserted into the vaginal cavity for 30  s without the use of a speculum examination and before TVU. The swab was then inserted into a vial with solvent for 30 s and agitated by rotating between the thumb and forefinger. After removing the swab from the vial, a test strip was inserted into the sample to allow migration along the membrane through capillary action. The result was interpreted once two lines were visible, or after 5 min elapsed as soon as the the test strip was inserted into the sample vial. The results were reported by the presence of two lines (positive for PAMG-1) or one line (negative for PAMG-1). The attending physician was not aware of the PartoSure Test results while making decisions about the care of the patient.

Cervical length measurement by TVU (CL) Cervical length was determined using TVU. The cutoff value for a positive result was 25 mm. In other words, we considered a patient with a CL of 25  mm or greater not be at risk for imminent spontaneous delivery within 2, 7, or 14 days (i.e., a negative result) and we considered a patient with a CL of < 25 mm to be at risk for imminent spontaneous delivery within 2, 7, or 14 days (i.e., a positive result).

QuikCheck fFN Test (fFN) The QuikCheck fFN Test was performed according to the manufacturer’s instructions. During speculum examination, and prior to TVU, a sterile polyester vaginal swab was lightly rotated across the posterior fornix of the vagina for 10 s. The swab was then inserted into the buffer-filled test tube provided with the test kit for 10 s. After removing the swab from the vial, the QuikCheck test strip was inserted into the sample. After exactly 10 min, the results were reported by the presence of two lines (positive for fFN) or one line (negative for fFN). Following delivery, the test-to-spontaneous-delivery interval was documented and the physical parameters of the newborn were assessed and recorded. Time to delivery was defined as the interval between the time and date when the results of the test were interpreted and the time and date of spontaneous delivery. Sensitivity (SN) value, specificity (SP) value, NPV and PPV for CL testing by TVU, fFN testing by QuikCheck, and PAMG-1 testing by PartoSure in predicting time to spontaneous preterm delivery (within 7 and 14 days) were calculated at the conclusion of the trial. Some 95% confidence intervals were calculated using the Clopper-Pearson

procedure. Two different methods of analysis were applied to the data. For comparison of the SN and SP values between the different diagnostic methods, McNemar’s exact test was applied to each 2 × 2 table. Only paired results were used in the analysis; for example, for the comparison of SN and SP between PartoSure and fFN, only patient cases that had both PartoSure and fFN results were used in the analysis. Marginal generalized linear models were used to make use of all available data and to enable comparison of accuracy measures PPV and NPV where simple statistical methods (e.g., McNemar’s exact test) were not appropriate. A P-value < 0.05 was considered significant. Additionally, the SN, SP, NPV, and PPV values for the prediction of imminent spontaneous preterm delivery within 7 days of presentation for each biomarker test (i.e., PartoSure and fFN) were calculated for two separate patient groups: (1) those with a short cervix ( < 25 mm) and (2) those without a short cervix (  ≥  25 mm).

Results In total, 219 patients were recruited for this trial. Of these, sixteen were excluded from the final analysis: one lacked cervical assessment data; six did not meet the age requirement; eight underwent indicated deliveries; and one was lost to follow up. Thus, 203 patients were included in the final analysis, 80% (163/203) of whom were recruited at the University Clinic of Obstetrics and Gynecology (Skopje, Republic of Macedonia) and 20% (40/203) of whom were recruited at the Research Center of Obstetrics, Gynecology and Perinatology of the Ministry of Healthcare of the Russian Federation (Moscow, Russia). All 203 patients had a PartoSure Test and CL measurement performed. Some 66 (33%) had an fFN test performed. The median age was 27 years (range: 18–43 years), and the median gestational age at presentation was 32.0 weeks (range: 20.5–36.6 weeks). No multiple gestations were included in the trial. Some 35 patients (17%) delivered within 7  days of presentation and 48 patients delivered within 14 days of presentation (24%). The PartoSure Test was positive in 18% (37/203) of patients tested, while CL was positive ( < 25 mm) in 33% (66/203) of patients tested. For the 66 patients (33%) who received an fFN test, the test was positive in 32% (21/66) of patients tested. Figure 1 shows the comparative performances of PartoSure, fFN, and CL for the prediction of imminent spontaneous preterm delivery within 7  days along with the corresponding upper and lower bounds of the 95% confidence interval; Tables 1 and 2 present this information in tabular form along with the performance for predicting time to delivery within 14  days of presentation. 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%,

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4      Nikolova et al., Prediction of imminent spontaneous preterm delivery in patients with threatened preterm labor

PartoSure

96% 87%

80%

60%

89%

57% 50%

50% 40% 29% 30%

30% 20% 10% 0% SN

SP

PPV

Metric

PartoSure/PAMG-1

fFN

CL ( < 25 mm)

63% (30/48) (47.4%−76.1%) 96% (148/155) (90.9%−98.2%) 89% (148/166) (83.4%−93.5%) 81% (30/37) (64.8%−92.0%)

42% (8/19) (20.3%−66.5%) 72% (34/47) (57.4%−84.4%) 76% (34/45) (60.5%−87.1%) 38% (8/21) (18.1%−61.6%)

54% (26/48) (39.2%−68.6%) 74% (115/155) (66.6%−80.9%) 84% (115/137) (76.7%−89.7%) 39% (26/66) (27.6%−52.2%)

SN (95% CIa) SP (95% CIa) NPV (95% CIa) PPV (95% CIa)

72% 73% 76%

80% 70%

Table 2 Test performance for prediction of imminent spontaneous preterm delivery within 14 days.

CL ( 35

Del   ≤  7 days (#)

Del   ≤  7 days (% range total)

Range total

% Total population

3 6 11 10 4 1

100 55 21 17 8 3

3 11 52 59 48 30

1 5 26 29 24 15

CL = Cervical length measurement by TVU; n = 203.

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6      Nikolova et al., Prediction of imminent spontaneous preterm delivery in patients with threatened preterm labor

100% 100%

35% 29%

% Delivered ≤7 days

80%

30%

26% 24%

70% 60%

25%

55%

20%

50%

15% 15%

40% 30%

10%

10%

21% 17%

5%

20%

5%

8%

1%

3%

0% 10-15

15-20

% Total population

90%

20-25

25-30

30-35

> 35

0% N=203

Cervical length (mm) Figure 4 Stratification of cervical length measurement in the prediction of imminent spontaneous delivery in women symptomatic of preterm labor.

range, the proportion of patients within each range that delivered within 7 days of presentation is presented. For patients with a CL between 10 and 15 mm (1% of the study population), 100% delivered within 7 days. For patients with CL between 15 and 20 mm (5% of the study population), 55% delivered within 7 days. For patients with a CL between 20 and 25 mm (26% of the study population), 21% delivered within 7 days. For patients with a CL between 25 and 30 mm (29% of the study population), 17% delivered within 7 days. For patients with a CL between 30 and 35 mm (24% of the study population), 8% delivered within 7 days. Lastly, for patients with a CL > 35 mm (15% of the study population), only 3% delivered within 7 days. Figure 4 represents this information in graphical form.

Discussion Hospital admissions for patients who are not in true PTL often result in the unnecessary use of potentially harmful therapies including tocolytics, corticosteroids, and antibiotics. Each unnecessary admission can cost up to $20,300 USD [4]. Although the results of observational studies have suggested that knowledge of fFN presence or CL may help reduce unnecessary admissions and use of resources, these findings have not been further confirmed by randomized trials [15–17]. While these tests have high reported NPVs, the PPV of each alone is poor and the use of any one test to exclusively direct management in the setting of acute symptoms has not been recommended [18]. A recent and updated meta-analysis reported that fFN is of limited accuracy in the prediction of imminent spontaneous delivery in symptomatic patients. Additionally, it

was found – as was expected – that higher CL cutoffs were associated with greater SN but decreasing SP in predicting delivery within 7  days [19]. Regarding the combined use of fFN and CL for the prediction of imminent spontaneous delivery within 7 days, Boots et al. reported that the number of studies with data amenable for comparison is small and that several of the studies selected for comparison in a recent systematic review on the topic did not present the results from women who underwent both the tests [20]. A further limitation found by Boots et  al. was that most of the outcomes reported were for deliveries > 7 days after testing. Our preliminary report on the efficacy of the PartoSure (PAMG-1) test revealed a very high SN and SP values. In the present investigation, we sought to expand upon those findings by providing additional cases to evaluate the performance of this test. Additionally, we sought to provide a comparison between PartoSure and currently employed standards (i.e., fFN and CL with a cutoff of 25 mm) for the prediction of imminent spontaneous delivery within 7 days in symptomatic patients. In accordance with our preliminary report on the diagnostic accuracy of PartoSure, our present report reinforces a high NPV (96%) and PPV (76%). In accordance with the previous reports on the diagnostic accuracy of fFN and CL, our study showed that while fFN and CL have high NPVs (87% and 89%, fFN and CL respectively), they have poor PPVs (29% and 30%, fFN and CL, respectively). That the PartoSure test was found to be statistically superior to fFN and CL with respect to SP and PPV (P < 0.01) provides evidence toward being able to significantly enhance current practice to ultimately reduce the unnecessary administration of potentially harmful therapeutics to patients, as well as

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Nikolova et al., Prediction of imminent spontaneous preterm delivery in patients with threatened preterm labor      7

reduce the economic burden associated with unnecessary hospital admissions. In certain settings, measurement of CL by TVU is used as an initial test to assess the risk of imminent spontaneous preterm delivery in symptomatic patients. Then, based on the results of this initial screen, a biomarker test such as fFN may be used. Accordingly, in the present investigation we sought to examine the diagnostic accuracy of both PAMG-1 detection by PartoSure and fFN detection by QuikCheck in two sub-segments of the study population: (1) those with a short cervix, defined as CL < 25 mm and (2) those without a short cervix, defined as CL   ≥  25 mm. Interestingly, the predictive values of a positive PAMG-1 test and a positive fFN test for the prediction of imminent spontaneous preterm delivery within 7 days of presentation in both groups remained relatively stable (see PPVs for PAMG-1 and fFN in Tables 3 and 4). However, it was much more likely to get a positive result by either test in the short cervix group or in the group without a short cervix (30% vs. 12%, groups 1 and 2 respectively, for PAMG-1; 45% vs. 26%, groups 1 and 2 respectively, for fFN). Most interestingly, in the   ≥  25  mm CL group, a negative PartoSure test had a predictive value of 98%, while a negative fFN had a predictive value of 91%. Comparably, CL alone had a NPV of 89%, thus suggesting that a negative PartoSure test in patients without a short cervix (  ≥  25 mm) appears to strongly suggest that the patient will not deliver within 7 days. Conversely, a positive PartoSure test in this patient group remains highly predictive (PPV of 76%) of imminent spontaneous preterm delivery within 7  days and, therefore, a positive PartoSure test result in patients without a short cervix should be considered as a significant risk factor for imminent spontaneous delivery. It is well understood that lower CL cutoffs are associated with a greater SP for the prediction of imminent delivery. Conversely, the higher the cutoff, the lesser specific the test becomes. In an effort to identify whether there is a specific CL range in which a biomarker test would be most applicable (i.e., CL cutoffs that are least predictive of imminent delivery), we stratified CL measurement for the prediction of imminent spontaneous preterm delivery within 7  days for the 203 patients included in the final analysis. In accordance with previous investigations, we found that 100% of patients with a CL < 15 mm (1% of study population) delivered within 7 days and 3% of patients with a CL > 35 mm (15% of study population) delivered within 7 days. However, patients with CL measurements between these two cutoffs had varying rates of delivery within 7 days (see Table 5). For example, 19% of patients with a CL between 20 and 30 mm delivered within 7 days of testing.

Thus because CL is least accurate as a predictor of imminent spontaneous delivery when between 15 and 35 mm, we propose that the PartoSure test be used in these patients; this is particularly relevant in settings where CL by TVU is utilized as an initial screen. In settings where CL by TVU is not utilized as an initial screen, PartoSure is the single most accurate test when compared to fFN and CL for the prediction of imminent spontaneous delivery in patients presenting with signs, symptoms, or complaints suggestive of PTL. Therefore, in these settings, we suggest that PartoSure be considered as a first-line test for any patient presenting with threatened PTL between gestational ages 200/7 and 366/7 , who has intact amniotic membranes and cervical dilatation   ≤  3 cm. Given the predictive power for preterm delivery of PAMG-1 detection by PartoSure in the symptomatic patient population, future research should begin to investigate how well this test predicts preterm birth in the asymptomatic population, including both high risk patients as well as low risk patients. In addition, and perhaps more urgently, future research should focus on whether PartoSure can decrease unnecessary triage costs associated with the evaluation of PTL. Sources of financial support: NeitherAmniSure® International LLC (a QIAGEN® Company) nor Hologic® Inc. provided funding for the trial. PartoSure and QuikCheck fFN test kits were obtained free of charge. The investigators do not have any financial relationship with either company.

References [1] ACOG Practice Bulletin. Assessment of risk factors for preterm birth. Clinical management guidelines for obstetriciangynecologists. Number 31, October 2001. (Replaces Technical Bulletin number 206, June 1995; Committee Opinion number 172, May 1996; Committee Opinion number 187, September 1997; Committee Opinion number 198, February 1998; and Committee Opinion number 251, January 2001). Obstet Gynecol. 2001;98:709−16. [2] ACOG Practice Bulletin. Management of preterm labor. Number 43, May 2003. Int J Gynaecol Obstet. 2003;82:127−35. [3] Institute of Medicine. Preterm birth: causes, consequences, and prevention. Washington, DC: National Academies Press; 2007. [4] Lucovnik M, Chambliss LR, Garfield RE. Costs of unnecessary admissions and treatments for “threatened preterm labor”. Am J Obstet Gynecol. 2013;209:217.e1−3. [5] Di Renzo GC, CaberoRoura L, Facchinetti F, the EAPM-Study Group on “Preterm Birth”. Guidelines for the management of spontaneous preterm labor: identification of spontaneous preterm labor, diagnosis of preterm premature rupture of membranes, and preventive tools for preterm birth. J Matern Fetal Neonatal Med. 2011;24:659−67.

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8      Nikolova et al., Prediction of imminent spontaneous preterm delivery in patients with threatened preterm labor [6] Duff, P. Preterm Premature Rupture of Membranes. In: UpToDate, Basow DS (Ed), UpToDate, Waltham, MA, 2012. [7] Güngördük K, Asicioglu O, Besimoglu B, Güngördük OC, Yildirm G, Ark C, et al. Labor induction in term premature rupture of membranes: comparison between oxytocin and dinoprostone followed 6 hours later by oxytocin. Am J Obstet Gynecol. 2012;206:60.e1–8. [8] Lee SE, Park JS, Norwitz ER, Kim KW, Park HS, Jun JK. Measurement of placental a-microglobulin-1 in cervicovaginal discharge to diagnose rupture of membranes. Obstet Gynecol. 2007;109:634–40. [9] Lee SM, Lee J, Seong HS, Lee SE, Park JS, Romero R, et al. The clinical significance of a positive Amnisure test TM in women with term labor with intact membranes. J Matern Fetal Neonatal Med. 2009;22:305–10. [10] Lee MS, Romero R, Park JW, Kim SM, Park CW, Korzeniewski S, et al. The clinical significance of a positive Amnisuretest(™) in women with preterm labor. J Matern Fetal Neonatal Med. 2012;25:1690−8. [11] Sukchaya K, Phupong V. A comparative study of positive rate of placental alpha-microglobulin-1 test in pre-term pregnant women with and without uterine contraction. J Obstet Gynaecol. 2013;33:566−8. [12] Ehsanipoor RM, Swank M, Jwa SC, Wing DA, Tarabulsi G, Blakemore K. Placental alpha-microglobulin-1 in vaginal secretions as a predictor of preterm birth in women with evidence of preterm labor. Society of Gynecological Investigation. T-079. Mar 27 2014. [13] Lee SM, Yoon BH, Park CW, Kim SM, Park JW. Intra-amniotic inflammation in patients with a positive Amnisure test in preterm labor and intact membranes. Am J Obstet Gynecol. 2011;204:S209.

[14] Nikolova T, Bayev O, Nikolova N, Di Renzo GC. Evaluation of a novel placental alpha microglobulin-1 (PAMG-1) test to predict spontaneous preterm delivery. J Perinat Med. 2013;13:1−5. [15] Plaut MM, Smith W, Kennedy K. Fetal fibronectin: the impact of a rapid test on the treatment of women with preterm labor symptoms. Am J Obstet Gynecol. 2003;188:1588−93; discussion 1593−5. [16] Grobman WA, Welshman EE, Calhoun EA. Does fetal fibronectin use in the diagnosis of preterm labor affect physician behavior and health care costs? A randomized trial. Am J Obstet Gynecol. 2004;191:235−40. [17] Ness A, Visintine J, Ricci E, Berghella V. Does knowledge of cervical length and fetal fibronectin affect management of women with threatened preterm labor? A randomized trial. Am J Obstet Gynecol. 2007;197:426.e1−7. [18] ACOG Practice Bulletin. Management of preterm labor. Obstet Gynecol. 2012;119:1308–17. [19] Boots AB, Sanchez-Ramos L, Bowers DM, Kaunitz AM, Zamora J, Schlattmann P. The short-term prediction of preterm birth: a systematic review and diagnostic metaanalysis. Am J Obstet Gynecol. 2014;210:54.e1−10. [20] DeFranco EA, Lewis DF, Odibo AO. Improving the screening accuracy for preterm labor: is the combination of fetal fibronectin and cervical length in symptomatic patients a useful predictor of preterm birth? A systematic review. Am J Obstet Gynecol. 2013;208:233.e1−6.

The authors stated that there are no conflicts of interest regarding the publication of this article.

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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.

PartoSure is a bedside test for the prediction of time-to-spontaneous preterm delivery by the detection of placental alpha microglobulin-1 (PAMG-1). T...
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