1. AmniSure®
Rapid, Reliable, Non-Invasive Test for ROM
17Th June

2. (P)PROM is a Major Diagnostic Challenge
Premature Rupture of Membranes (PROM)
9.5% of UK pregnant population in
Increased risk of infection with latency [maternal & neonatal]2
Preterm Premature Rupture of Membranes (pPROM)
3% of pregnant population (NHS)1
18-20% perinatal deaths 3-8
30% of all preterm births 3-8
In light of the challenging financial circumstances surrounding the NHS a highly accurate and quick method of diagnosing (P)PROM is needed.
1. Sanchez-Ramos L et al. ObstetGynecol 2009;114:
2. Schaaf JM et al. BJOG 2011;118:
3. McPheeters ML et al. Am J Obstet Gynecol 2005;192:
4. Ness A et al. Am J Obstet Gynecol 2007;197:426.e1–426.e7
5. Alfirevic Z et al. Ultrasound Obstet Gynecol 2007; 29: 47–50

3. What is AmniSure? Global leading rupture of membrane bedside test.
99% accuracy at all gestations.
Simple vaginal swab test.
Detects PAMG-1, only found in amniotic fluid.
Can be used with/without speculum.

4. CLINICAL EVIDENCE RELEVANT METRICS - AMNISURE® ROM TEST
Over 25 publications supporting very high accuracy.
Only test to maintain same level of accuracy in ‘known’ and ‘unknown’ cases.
Only test to have 100% accuracy with Gold Standard Test – Amnio-Infusion.
Range of publications below – includes lowest and highest accuracy.
Study
Year N SN SP
PPV
NPV
Accuracy
Cousins1
2005
203
98.9%
100.0%
99.1%
99.5%
Park2
2007
183
98.7%
87.5%
98.1%
91.3%
97.3%
Grizzell3
2008 46
Silva4
2009 63
Kwek5
2010
100
92.7%
95.2%
97.0%
Hosli6
2011
199
94.4%
98.6%
96.2%
97.9%
97.5%
Albayrak7
167
94.3%
97.6%
93.9%
95.8%
Dates? Marcellin
2011 80
95.0%
94.8%
Cousins LM, Smok DP, Lovett SM, Poeltler DM. Amnisure placental a microglobulin-1 rapid immunoassay versus standard diagnostic methods for detection of rupture of membranes. Am J Perinatol 2005;22:317–320.
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;109:634–640.
Grizzell et al. Wesley Medical Center | Data found in AmniSure ROM Test Package Insert (FDA Cleared). AmniSure International, LLC. 2011
Silva E, Martinez JC. Diagnosing ROM: a comparison of the gold standard, indigo carmine amnioinfusion, to the rapid immunoassay, the AmniSure ROM test. J Perinat Med 2009; 37(S1):956.
Tagore S, Kwek K. Comparative analysis of insulin-like growth factor binding protein-1 (IGFBP-1), placental alpha microglobulin-1 (PAMG-1) and nitrazine test to diagnose premature rupture of membranes in pregnancy. J Perinat Med 2010; 38: 1-4.
Birkenmaier A, Ries JJ Kuhle J, Burki N, Lapaire N, & Hosli I. Placental a-microglobulin-1 to detect uncertain rupture of membranes in a European cohort of pregnancies. Arch Gynecol Obstet, April 2011
Albayrak M, Ozdemir I, Koc O, Ankarali H, & Oren O. Comparison of the diagnostic efficacy of the two rapid bedside immunoassays and combined clinical conventional diagnosis in prelabour rupture of membranes. European Journal of Obstetrics & Gynecology and Reproductive Biology, June 2011.
Abdelazim IA, Makhlouf HH. Placental alpha microglobulin-1 (AmniSure(®) test) for detection of premature rupture of fetal membranes. Arch Gynecol Obstet Oct 30. [Epub ahead of print]
Marcellin L, Anselem O, Guibourdenche J, De la Calle A, Deput-Rampon C, Cabrol D, Tsatsaris V. Comparison of two bedside tests performed on cervicovaginal fluid to diagnose premature rupture of membranes. J Gynecol Obstet Biol Reprod (Paris) Nov;40(7): Epub 2011 Oct 17..

5. Why is AmniSure much more accurate than comparable tests? – PAMG-1
Placental Alpha Microglobulin-1 is only found in amniotic fluid above 1ng/ml – Simple relationship between a rupture and presence of PAMG-1.
Threshold for PAMG-1 detection, >1 ng/ml
Faint Positive Line
PAMG-1 concentration in amniotic fluid,
2,000-25,000 ng/ml
Hypothetical PAMG-1 concentration in ruptured patient
PAMG-1 Concentration (ng/ml)
Even after miniscule leakages of amniotic fluid, drastic increases of PAMG-1 are found in vaginal discharge

6. Patient Presents With Signs and Symptoms of Premature Rupture of Membranes (PROM)
Patient presents with signs and symptoms of rupture of membranes (PROM)
Complete Speculum Examination
Obvious Leakage – Admit or Discharge Patient
Unsure Following Speculum
Collect and run AmniSure ROM Test sample
Admit patient with clinical judgement
Discharge patient with clinical judgement
Opportunity to administer corticosteroids, ABx, tocolytics and/or transfer patient

7. AMNISURE® ROM TEST (PAMG-1 TEST) PROCEDURE
Step 1: Vaginal swab, 5-7 cm deep,
no speculum required
Step 2: Rotate swab in vial to dilute sample for 1 min
Step 3: Insert test strip into vial and read results after 5 min sharp

8. AMNISURE® ROM TEST (PAMG-1 TEST) READING THE RESULTS
Control Line
Test Line
Faint or broken lines should always be interpreted as a positive result.
If both the control line and test line are visible, the test result is positive.
If only the one control line is visible on the test strip, the test result is negative.
If no lines are visible, the test result is invalid.

9. Current Methods
Currently two methods of diagnosing (P)PROM within NHS Trusts:
Speculum and History
47% of the time clinicians are not fully confident of diagnosis following a speculum1.
30% misdiagnosis rate of these difficult cases.
Alternate Rupture of Membrane Tests
Actim Prom
ROM Plus
AmniSure
1Neil PRL, Wallace EM. Is AmniSure® useful in the management of women with prelabour rupture of the membranes? Australian and New Zealand Journal of Obstetrics and Gynaecology 2010.

10. *Appropriate management hinges on correct diagnosis*
SCOPE OF THE PROBLEM
PROM DIAGNOSIS AND MANAGEMENT
*Appropriate management hinges on correct diagnosis*
25-30%
Estimated percent of pregnancies presenting w/suspicion of p/PROM1
47%
of the time clinicians will be uncertain about the diagnosis based on physical examination alone2
1Nisell H, Hagskog K, Westgren M. Assessment of fetal fibronectin in cervical secretion in cases of equivocal rupture of the membranes at term. Acta Obstet Gynecol Scand Feb;75(2):132-4.
2Neil PRL, Wallace EM. Is AmniSure® useful in the management of women with prelabour rupture of the membranes? Australian and New Zealand Journal of Obstetrics and Gynaecology 2010.
30%
Admitted without a rupture or discharged with a rupture.
1Nisell H, Hagskog K, Westgren M. Assessment of fetal fibronectin in cervical secretion in cases of equivocal rupture of the membranes at term. Acta Obstet Gynecol Scand Feb;75(2):132-4.
2Neil PRL, Wallace EM. Is AmniSure® useful in the management of women with prelabour rupture of the membranes? Australian and New Zealand Journal of Obstetrics and Gynaecology 2010.

11. Speculum Case Study – 4,000 Births
Mid-Size Trust
1,200 Births
Based on NHS Average, a hospital will see 30% SROM cases.
565
Based on Neil and Wallace (2011) study, 47% of the time clinicians will not be totally confident if the mother has ruptured or not from speculum and history alone.
170
Based on the average from accepted business cases, 30% of difficult cases will be misdiagnosed i.e. mother is admitted unnecessarily or discharged incorrectly.
£172,490.50
Average cost of misdiagnosis is £1, – One night admission (£658.00), Medication (£27.85), 4 x 1 hour clinician’s time (£328.80).
Multiply this cost by the number of misdiagnosis equals £172,490.50

12. Current Tests – Actim Prom
Actim Prom detects a protein named IGFBP-1.
IGFBP-1 is not just found in amniotic fluid, it is also found in background vaginal discharge and blood.
Leads to high of number of contra-indications producing false results.
Over 40 publications have been produced analysing IGFBP-1 and PAMG-1 (AmniSure). In 2012 the most recognised (P)PROM publication was produced. A meta-analysis which reviewed all 40 publications – Ramsauer et al

13. Clinical Evidence – Ramsauer et al. 2012
Summary – IGFBP-1 test is acceptable in ‘known’ cases i.e. obvious leakage, but unacceptable in ‘unknown’ cases i.e. when ROM tests are used throughout the NHS.
Conclusion – “Comparison with its performance in women for whom membranes status is known, the performance of the IGFBP-1 test decreases significantly when used on patients for whom membrane status is unknown. In this latter clinically relevant population, the PAMG-1 test has higher accuracy than the IGFBP-1 test”.

14. ROM Plus
Accuracy:
ROM Plus has an FDA cleared specificity of 75% (58% >36 weeks) and a PPV of 85%.
ROM Plus Test 510(k) Substantial Equivalence Determination Decision Summary, K pdf.
FDA Warning:
“The ROM Plus test may report positive results in patients with intact membranes (see specificity in the performance section) and therefore decisions to induce labor should not be based solely on the ROM Plus results”

15. Actim Prom vs. AmniSure Case Study – 4,000 Births
1,200 SROM Cases
565 Difficult Cases – Actim Prom used.
Based on Ramsauer et al – 75.8% Accuracy in ‘Unknown’ i.e. difficult cases
Of 565 Cases Actim Prom would statistically misdiagnose 136 cases.
Total Unnecessary Costs = £137, (136 x £ )
AmniSure
565 Difficult Cases – AmniSure Used
Based on Ramsauer et al – 97.5% accuracy in ‘Unknown’ i.e. Difficult cases.
Of 565 Cases AmniSure would statistically misdiagnose 14 cases.
Total Unnecessary Costs = £14, (14 x £ )
Using AmniSure, as found by more than 60 NHS Trusts, produces significant cost savings – In the case of a 4,000 birth hospital savings would be c£123,787.30

16. Realistic Benefits using AmniSure
Efficiency - A mother visits the hospital with relevant signs and symptoms – first complete speculum, if unsure, use AmniSure – mother can be accurately diagnosed and therefore treated relevantly within 10 minutes of being seen.
Contra-Indications - Only test not contra-indicated by blood, semen, urine and/or infection so can be used in all scenarios. Other tests do not offer the same.
Community Programs – Many busier Trusts allow community midwives to use AmniSure to prevent mothers unnecessarily being on the unit.
Liability – Clinicians can add AmniSure sticker to patient’s notes as evidence of taking necessary precautions.

17. QUESTIONS?