PROMComplete for Determination of Rupture of Fetal Membranes

Premature rupture of membranes (PROM) complicates approximately 8 % of pregnancies and is
generally followed by the prompt onset of spontaneous labor and delivery. Preterm PROM
complicates only 2 % of pregnancies but is associated with 40% of preterm deliveries and can
result in significant neonatal morbidity and mortality (ACOG 2007). Intraamniotic infection
has been shown to be commonly associated with preterm PROM, especially at earlier gestational
ages (ACOG 2013). Currently, the diagnosis of PROM is based primarily on the patient's
history and physical examination. The diagnosis of membrane rupture typically is confirmed by
the visualization of amniotic fluid passing from the cervical canal and pooling in the
vagina; a basic pH test of vaginal fluid; or arborization (ferning) of dried vaginal fluid,
which is identified under microscopic evaluation (ACOG 2013).

The classic clinical presentation of PROM is a sudden "gush" of clear or pale yellow fluid
from the vagina. However, many women describe intermittent or constant leaking of small
amounts of fluid or just a sensation of wetness within the vagina or on the perineum (WHEC
2009).

However, the diagnosis of PROM is difficult if there is a slow fluid leak or any bleeding, or
when the classic "gush of fluid "does not occur (Bornstein 2006).

Although ultrasonographically guided transabdominal instillation of indigo carmine dye and
observation for fluid passage transvaginally is designated an "unequivocal" diagnostic method
for confirmation of membrane rupture, this invasive test carries increased maternal and fetal
risk (Mercer 2004). The absence of a non-invasive "gold standard" for the diagnosis of PROM
has led to technically advanced biochemical markers for improved diagnosis (El-Messidi,
2010).

The AmniSure ROM (Rupture of Membranes) test received Food and Drug Administration 510(k)
marketing clearance in 2003. A comparison study of AmniSure versus standard diagnostic
methods for detection of ROM in 203 pregnant women suspected of ROM reported that the
AmniSure test was highly accurate (sensitivity = 98.9 %, specificity = 100 %, and negative
predictive value [NPV] = 99.1 %) in diagnosing ROM (Cousins et al, 2005). Test performance
was calculated by comparing AmniSure results against clinical history, nitrazine and fern
results, presence of pooling, ultrasound (US) evidence of oligohydramnios, and findings from
repeated examinations.

Chen and Dudenhausen (2008) compared 2 rapid strip tests for the detection of amniotic fluid,
based on the detection of insulin-like growth factor-binding protein-1 (IGFBP-1) and of
PAMG-1. Samples of amniotic fluid were taken in 20 pregnant women between 31 3/7 and 41 2/7
gestational weeks at elective cesarean section before delivery of the newborn. These samples
were diluted with 0.9 % saline solution in a dilution series down to concentrations of 1:320.
Immunoassay strip tests were then compared in their ability to detect remaining
concentrations of amniotic fluid. In 5 cases, both test methods showed the same results. In
all remaining 15 cases, the test based on PAMG-1 proved to be superior by detecting amniotic
fluid at least at one descending concentration below the test based on IGFBP-1.

PRO-MComplete proposes an alternative tool for adjuvant diagnosis of PROM by identification
of Insulin-Like Growth Factor Binding Protein1 and Alpha Feto- Protein (AFP). The addition of
AFP is projected to increase the sensitivity and specificity of PRO-MComplete over IGFBP-1
alone.

Inclusion Criteria:

1. Subject has provided verbal and written informed consent to participate in the study.

2. 20-42 weeks of gestation.

3. Subject presents with signs and/or symptoms of premature rupture of membranes.

4. Subject age 18 (years) or older

Exclusion Criteria:

1. Placenta Previa

2. Presenting with vaginal bleeding

3. Intravaginal ultrasound with presence of transducer gel

4. Active labor

5. Imminent delivery

6. Intercourse within 24 hours

7. Cord prolapse