Premature Rupture of Membranes (PROM)

What is PROM?
Premature rupture of membranes (PROM) refers to a rupture of membranes (ROM) beyond 37 weeks' gestation at least 1 Hr prior to the onset of labor. Preterm premature rupture of membranes (PPROM) is ROM prior to 37 weeks' gestation. Prolonged ROM is any ROM that persists for more than 24 hours and prior to the onset of labor.

 Incidence :
7-12% in Indian studies 70% term pregnancies 30% preterm

High risk factors

Infection ( Chlamydia trachomatis, Neisseria gonorrhoeae, Group B Streptococci) Smoking >3 cups of coffee per day in 1st trimester Repetitive stress due to uterine activity tissue fatigue Vaginal bleeding ( First / Second trimester) Physiological changes in membranes Previous PROM (recurrence 20%) Low socio-economic status Short cervix ( <2.5cm) Positive fibronectin However, often PROM cannot be predicted

Why PROM needs to be detected accurately?

PROM may cause severe complications that need relevant counteractions and monitoring Premature birth of the baby and associated problems Cord compression/prolapse Respiratory distress syndrome (RDS)/ Pulmonary hypoplasia Intraventricular hemorrhage (IVH) & Cerebral palsy Neonatal infections with PPROM: 5%, Congenital abnormalities Sepsis Mortality

 Maternal problems: Acute chorioamnionitis- Prolonged PROM (>24 h): incidence of chorionamniotis (3-15%) Premature placental separation (6%) Postpartum endometritis Oligohydramnios causes problems for the pregnancy and labor When PROM occurs preterm the risks are higher!

 Early and accurate diagnosis of PROM - Obstetric interventions designed to optimize perinatal outcome and minimize serious complications. Conversely, a false-positive diagnosis of PPROM may lead to unnecessary obstetric interventions, including hospitalization, administration of antibiotics and corticosteroids, and even induction of labor.

Diagnosis
The minimally invasive , gold standard for the diagnosis of ROM - to document 3 clinical signs on sterile speculum examination: visual pooling of clear fluid in the posterior fornix of the vagina or leakage of fluid from the cervical os; an alkaline pH of the cervicovaginal discharge, which is typically demonstrated by seeing whether the discharge turns yellow nitrazine paper to blue (nitrazine test); and/or microscopic ferning of the cervicovaginal discharge on drying. Evidence of diminished amniotic fluid volume (by ultrasound) alone cannot confirm the diagnosis.

 An amnio-dye test (tampon test) may be recommended if conventional tests for preterm PROM are equivocal and if the pregnancy is remote from term. This test involves amniocentesis and instillation of dye into the amniotic cavity. Indigo carmine is preferred because of the association between methylene blue dye and fetal methemoglobinemia. 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. The amnio-dye test is an invasive procedure with inherent risks - bleeding (placental abruption), infection, iatrogenic PROM, and miscarriage.

 Biochemical tests are based primarily on the identification in the cervicovaginal discharge of one or more biochemical markers that are present in the setting of ROM, but absent in women with intact membranes. Markers - alpha-fetoprotein (AFP), fetal fibronectin (fFN), insulinlike growth factor binding protein 1 (IGFBP-1), prolactin, beta-subunit of human chorionic gonadotropin (-hCG), creatinine, urea, lactate, and placental alpha-microglobulin 1 (PAMG-1).

Principle of the Actim PROM test

Detecting a specific
protein, IGFBP-1 IGFBP1 = insulin-like growth factor binding protein-1 A protein produced by the decidual cells. Exists in large amounts in amniotic fluid. Rupture in the fetal membranes causes amniotic fluid with IGFBP-1 to leak into the vagina.

 Different phosphorylation forms of IGFBP-1 Five differently phosphorylated forms: Highly phosphorylated forms are located in decidual cells and in whole blood. Less phopshorylated forms in amniotic fluid. Actim PROM detects these less and non-phosphorylated IGFBP-1 forms.

Actim PROM test result is not affected by whole blood contamination

The concentration of IGFBP-1 in amniotic fluid is 1001000 times higher than in maternal blood. -> Even a very small amount of amniotic fluid will be detected by the Actim PROM test.

The detection limit of the test has been set to 25 g/l in

the extracted sample. -> The cut off has been optimized to a level where blood contamination is highly unlikely to affect the test result.

Actim PROM does not detect the highly phosphorylated

form of IGFBP-1 that is predominant form of IGFBP-1 in blood.

Actim PROM Technical specifications

Biochemical marker IGFBP-1 (Less and non-phoshphorylated forms)

Sample type Sampling time

Processing time

Swab from posterior fornix (no speculum needed) 10-15 seconds

10-15 seconds

Reading time

5 minutes or less

Suitable gestational ages All GA weeks where measuring PROM is reasonable (Concentrations at peak after about week 13) Interference None

Management of PROM (ACOG guidelines)

Preterm (<30-32 wk) Expectant management No digital exams Bed rest o Antibiotics for Infection o Corticosteroids : For fetal lung maturation (Inj.Betamethasone 12mg 2 doses 24hrs apart) o Tocolytics : To postpone the delivery for corticosteroids to act Inutero transfer to tertiary care centre o Labor induction, when needed

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Expectant management should not be adopted in the following circumstances: Leukocytosis >16000 with neutrophilia & CRP > 0.9 mg/dl and no bacteria in amniotic fluid Gram stain Severe oligohydramnios with the largest pocket of fluid <2 cms in diameter Variable decelerations and poor variability in the FHR tracing Cervical length by USG <1.5 cm with funneling Breech presentation or transverse lie Cervical dilatation >5 cm and effacement >80%

Monitoring for signs of infection (Chorioamnionitis) Fever(>37 C or 100.4 F ) and 2 or more of o Maternal pulse > 100 bpm o Fetal heart rate > 160 bpm o Uterine tenderness o Foul smelling vaginal discharge o Leukocytosis >15000 o C-reactive protein >2.7 mg/dl NO other site of infection.

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Conditions making women with PPROM at high risk for infection Receiving immunosuppresant drugs Infected with HIV Heart valve prosthesis Rheumatic heart disease Sickle cell disease Insulin dependant diabetes Multiple pelvic examinations following PPROM

Near term (32-34 wk) Corticosteroids for pulmonary maturity Antibiotics for infection o Labor induction when needed Consider transfer to a facility with adequate neonatal clinical services (NICU) Term (>35 wk) Expectant management labor induction (usual procedure)