|Subject:||AmniSure® ROM (Rupture of Membranes) Test|
|Policy #:||LAB.00029||Current Effective Date:||05/13/2013|
|Status:||New||Last Review Date:||05/09/2013|
This document addresses the AmniSure® test which detects PAMG-1 (placental alpha-1 microglobulin) protein marker of amniotic fluid in vaginal secretions and is intended for use by health care professionals as a point-of-care service to aid in the detection of rupture of membranes (ROM) in pregnant women with signs, symptoms or complaints suggestive of ROM.
Investigational and Not Medically Necessary:
The use of the AmniSure ROM (Rupture of Membranes) test is considered investigational and not medically necessary for all indications, including detection of preterm ROM.
Placental alpha-1 microglobulin (PAMG-1) is being investigated as a marker for the detection of premature rupture of membranes (PROM). PAMG is found in high levels in amniotic fluid and low levels in cervicovaginal discharge when fetal membranes are intact. The AmniSure ROM (Rupture of Membranes) test (Amnisure® International, LLC, Cambridge, MA) is a rapid, non-instrumented, qualitative immunochromatographic test for in-vitro detection of amniotic fluid in the vaginal secretions of pregnant women.
On February 3, 2004 the AmniSure one-step Fetal Membranes Rupture (ROM) test obtained clearance from the U.S. Food and Drug Administration (FDA). This initial clearance was for the in vitro detection of amniotic fluid in vaginal secretions of pregnant women. "AmniSure detects PAMG-1 protein marker of the amniotic fluid in vaginal secretions. The test is for use by health care professionals to aid in the detection of rupture of membranes (ROM) in pregnant women at > 34 weeks gestation when patients report signs, symptoms or complaints suggestive of ROM" (FDA, 2004). The clinical performance of AmniSure was determined by one study involving two sites in which individuals between 34-41 weeks of gestation, without active vaginal bleeding from any source and placenta previa, were evaluated by clinical assessment control and the AmniSure device. The clinical assessment control was considered positive if two out of three tests (nitrazine, ferning, and pooling) were positive. Statistical analysis was available on 159 women with the positive and negative agreements between AmniSure and the control as follows:
Positive agreement = 97.2% (69/71), 95% CI = (90.2%, 99.7%);
Negative agreement = 97.6% (81/83), 95% CI = (91.6%, 99.7%).
The AmniSure Fetal Membranes Rupture Test was found to be similar to the predicate device in intended use (that is, detection of rupture of membranes in pregnant women). According to the original FDA clearance, "The devices differ in technological characteristics; however, the methodology of the AmniSure device is well-established and raises no concerns with safety or effectiveness. Furthermore, the AmniSure device was found to be in greater than 97% agreement with the standard clinical procedures used to detect rupture of membranes. Therefore, a substantial equivalence determination was granted for the AmniSure Fetal Membranes Rupture Test." On January 9, 2009 the FDA cleared indication for use was modified to remove the specification that the device is for use in women at greater than 34 weeks gestation. The updated FDA labeling is as follows: "The Amnisure ROM (rupture of fetal membrane) Test is a rapid, non-instrumented, qualitative immunochromatographic test for the in vitro detection of amniotic fluid in vaginal secretions of pregnant women. Amnisure detects PAMG-1 protein marker of the amniotic fluid in vaginal secretions. The test is for use by health care professionals to aid in the detection of ROM when patients report signs, symptoms or complaints suggestive of ROM." (FDA, 2009)
The evidence basis for this change in FDA labeling was provided as follows:
"Pooled data from the 3 studies for less than 34 weeks gestational age showed:
98% percent agreement with current methods among positive results (95% confidence intervals 91.6% to 99.9%) and 96% agreement with current methods among negative results (95% confidence intervals 86.3 to 98.9).
Pooled data from 3 studies for greater than or equal to 34 weeks showed:
99% percent agreement with current methods among both positive and negative results (95% confidence intervals of 96.76 to 99.84% and 95.42 to 99.95% for positive and negative results, respectively)." (FDA, 2009)
To date, the available published studies that have evaluated the safety and effectiveness of PAMG-1 testing to detect PROM have been limited. In 2005, Cousins conducted a comparative study (n=203) of AmniSure versus standard diagnostic methods for detection of ROM in women suspected of PROM. The AmniSure test was found to have a sensitivity of 98.9%, specificity of 100%, and negative predictive value (NPV) of 99.1% in diagnosing ROM. Test performance was assessed by comparing AmniSure results to clinical history, nitrazine and fern results, presence of pooling, ultrasound evidence of oligohydramnios, and findings from repeated examinations (Cousins, 2005).
A retrospective cohort study examined the frequency and clinical significance of a positive AmniSure test in subjects with preterm labor and intact membranes by sterile speculum examination. A total of 90 subjects with preterm labor and intact membranes underwent AmniSure testing prior to amniocentesis; most participants (n = 64) also underwent fetal fibronectin (fFN) testing. Amniotic fluid (AF) was cultured for aerobic/anaerobic bacteria and genital mycoplasmas and assayed for matrix metalloproteinase-8. Results demonstrated that the prevalence of a positive AmniSure test was 19% (17/90); also subjects with a positive AmniSure test had significantly higher rates of adverse pregnancy and neonatal outcomes (for example, impending preterm delivery, intra-amniotic infection/inflammation, and neonatal morbidity) than those with a negative AmniSure test. A positive test was associated with significantly increased risk of intra-amniotic infection and/or inflammation, delivery within 7, 14, or 28 days and spontaneous preterm birth (at less than 35 weeks), among subjects with a negative fFN test. The authors concluded that a positive AmniSure test in subjects with preterm labor and intact membranes is a risk factor for adverse pregnancy outcome, particularly in those with a negative fFN test. However, it was noted that a positive AmniSure test in subjects without symptoms or signs of ROM should not be taken as an indicator that membranes have ruptured (Lee, 2012). Additional cohort, uncontrolled comparative, and observational studies have demonstrated the accuracy of AmniSure ROM testing, however, no studies have shown how use of this test will impact clinical outcomes, as compared to conventional methods of PROM detection, and further research is needed (Abdelazim, 2012; Birkenmaier, 2012; Lee, 2007; Tagore, 2010).
According to the American Congress of Obstetricians and Gynecologists (ACOG) Practice Bulletin No. 80: Premature Rupture of Membranes, "Most cases of PROM can be diagnosed based on the patient's history and physical examination. Sterile speculum examination allows for visual inspection of fluid and provides an opportunity to assess for cervicitis and umbilical cord or fetal prolapse, cervical dilation and effacement, and to obtain cultures as appropriate…In unusual cases, in which the diagnosis remains unclear after physical examination, ultrasonography may be useful. When the clinical history or physical examination is unclear, membrane rupture can be diagnosed unequivocally with ultrasonographically-guided transabdominal instillation of indigo carmine dye, followed by observation for passage of blue fluid from the vagina." (ACOG, 2007; ACOG reaffirmed this guideline which does not address testing for PAMG-1 with AmniSure - December 2012.)
The Royal College of Obstetricians and Gynecologists (RCOG), Scientific Advisory Committee Guideline on Preterm Prelabor Rupture of Membranes concurs with ACOG that, "The diagnosis of PROM is based primarily on the patient's history and physical examination. Patients often report a sudden gush of fluid or continued leakage of fluid. Sterile speculum examination provides a visual inspection of fluid and an opportunity to inspect for cervicitis and umbilical cord or fetal prolapse, cervical dilation and effacement, and to obtain cultures as appropriate… In unusual cases in which the diagnosis remains unclear after physical examination, ultrasonography may be helpful. Management of ROM hinges on knowledge of gestational age and evaluation of the relative risks of preterm birth versus intrauterine infection, abruptio placentae, and cord accident that could occur with expectant management." (RCOG, 2006)
In 2010, the Health Technology Inquiry Service (HTIS) of the Canadian Agency for Drugs and Technologies in Health (CADTH) conducted a review of AmniSure, in which six controlled clinical trials and one evidence-based guideline were identified regarding the diagnostic accuracy and use of the AmniSure and other similar tests for determining whether PROM has occurred in a pregnancy. CADTH identified no relevant health technology assessments, systematic reviews, meta-analyses, or randomized controlled trials (HTIS, 2010). In 2012, the CADTH conducted a further review and report of AmniSure versus fern testing to assess the rupture of fetal membranes in pregnant women. The CADTH found that AmniSure had high sensitivity and predictive accuracy for rupture of fetal membranes; however, the lack of direct comparison to individual tests and limited statistical reporting prevent drawing conclusions about comparative effectiveness. Performance results suggest that AmniSure may be a useful tool for detecting membrane rupture. The assessment stated that evidence-based guidelines for the use of AmniSure in clinical practice are lacking. The assessment stated that there is a limited quantity of evidence directly comparing AmniSure to conventional clinical methods, which include fern testing as one of the diagnostic criteria, for detecting rupture of fetal membranes (CADTH, 2012).
To summarize, the available evidence regarding the use of the AmniSure ROM test to detect PROM is inadequate to form firm conclusions regarding its safety, efficacy and how this testing will impact clinical outcomes for the pregnant woman and neonatal child, in comparison with established methods of PROM detection. According to a 2012 review article, to date, published studies have been prospective and observational with small sample size. The lack of a noninvasive test "Gold Standard" with which to compare other forms of testing for PROM, such as the AmniSure test, confounds the evidence and emphasizes the need for larger randomized controlled trials before the clinical utility of the AmniSure test of PAMG-1 protein marker in suspected PROM can be established (van der Ham, 2012).
Membrane rupture that occurs before 37 weeks of gestation is referred to as preterm PROM (PPROM). PROM complicates approximately 8% of pregnancies and is generally followed by the prompt onset of spontaneous labor and delivery. Risk factors for PROM include previous preterm birth (especially if the cause was PROM), short cervical length (less than 25 mm) during the second trimester, and preterm labor (PTL) or symptomatic contractions in the current pregnancy. PROM can also occur without any identifiable risk factor. The most significant maternal risk of term PROM is intra-uterine infection, a risk that increases with the duration of membrane rupture. Fetal risks associated with term PROM include umbilical cord compression and ascending infection. PPROM complicates only 2% of pregnancies but is associated with 40% of preterm deliveries and can result in significant neonatal morbidity and mortality. The three causes of neonatal death associated with PPROM are prematurity, sepsis and pulmonary hypoplasia. In the absence of clinical history or confirmatory physical exam, PROM can be definitively diagnosed with ultrasonographically-guided transabdominal instillation of indigo carmine dye, followed by observation for passage of blue fluid from the vagina (RCOG, 2006; ACOG, 2007).
Fern Test: This term refers to microscopic crystallization of amniotic fluid on drying which is used as a measure of possible PROM.
Indigo Carmine Test: This test involves amniocentesis and instillation of dye into the amniotic cavity. Leakage of blue-stained fluid into the vagina within 20 to 30 minutes, as evidenced by staining of a tampon, is regarded as a definitive diagnosis of preterm PROM. This invasive test is currently considered the "Gold Standard" diagnostic for detection of PROM.
Nitrazine Test: This is designed only to confirm an alkaline pH in the cervicovaginal secretions (the pH of the vaginal secretions is generally 4.5–6.0, whereas amniotic fluid usually has a pH of 7.1–7.3), and is the most common test used to diagnose PROM.
Pooling Test: This test involves direct visualization of clear fluid in the posterior fornix of the vagina or leakage of fluid from the cervical os which is considered a diagnostic option for detection of PROM.
Premature Rupture of Membranes (PROM): Rupture of membranes that occurs before the onset of labor.
Preterm Premature Rupture of Membranes (PPROM): Rupture of membranes that occurs before 37 weeks of gestation.
The following codes for treatments and procedures applicable to this document are included below for informational purposes. A draft of future ICD-10 Coding (effective 10/01/2014) related to this document, as it might look today, is included below for your reference. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.
When services are Investigational and Not Medically Necessary:
|84112||Placental alpha microglobulin-1 (PAMG-1), cervicovaginal secretion, qualitative|
|ICD-10 Diagnosis||ICD-10-CM draft codes; effective 10/01/2014:|
Peer Reviewed Publications:
Government Agency, Medical Society, and Other Authoritative Publications:
|Web Sites for Additional Information|
Premature Rupture of Membranes
Rupture of Membranes, Premature
The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.
|New||05/09/2013||Medical Policy & Technology Assessment Committee (MPTAC) review. Initial document development.|