• Information
  1. Definitions
  2. Pathogenesis
  3. Patients At High Risk
  4. Diagnosis
  5. Prognosis After PROM
  6. Management

A. Definitions

1. PROM means rupture of membranes (ROM) prior to onset of labor
2. Preterm PROM occurs with preterm labor (that is, prior to 37 weeks' gestation)
3. Prolonged PROM: ROM >48 hours prior to delivery
4. PROM occurs in ~10% of term pregnancies

B. Pathogenesis

1. PROM usually attributed to generalized weakness in fetal membranes
2. Weakness appears to be due to uterine contractions and repeated stretching
3. Focal defects have been observed in fetal membranes from PROM patients
   1. Altered fetal membrane morphology has been localized near breakpoints
   2. This is characterized by marked swelling and disruption of collagen networks
   3. Both collagen synthetic and degradative abnormalities have been associated with PROM
4. Connective tissue disorders are associated with increased risk of PROM
   1. Ehlers-Danlos syndrome is classical disorder of connective tissue
   2. Over 70% of patients with Ehlers-Danlos were involved in PROM deliveries in one series
   3. Nutritional defieincies, particularly of Vitamin C, also a risk factor
   4. Reduced collagen cross-linking appears to be major problem
5. Infection and PROM [2]
   1. Likely that a significant proportion of these cases due to asymptomatic infection
   2. Colonization of placental membranes with bacteria likely increases preterm risk
   3. These infections stimulate prostaglandins, which induce myometrial contractions
   4. Infections stimulate metalloproteases, which can degrade placental membranes
   5. Elevated levels of inflammatory mediators such as IL-6 found in amniotic fluid
   6. Elevated levels of calgranulin B and a fragment of IGF-1 found in intra-amniotic infection [8]
6. Increased collagen degradation
   1. Appears to be key to most cases of PROM
   2. Increased activity of matrix metalloproteinases (MMPs)
   3. Decreased activity of tissue inhibitors of MMPs (TIMPs)
   4. Infection and inflammation increase MMPs and decrease TIMPs
   5. Progesterone and estradiol suppress matrix remodelling, decrease MMP, increase TIMP
   6. Therefore, hormonal deficiencies may be involved in PROM risk
   7. Increased apoptosis of fetal membrane cells has also been implicated

C. Patients At High Risk

1. Previous history of PROM
2. Preterm Labor
3. Smoking
4. Acute Cervical Infection
   1. Gonorrhea
   2. ? Chlamydia
   3. ? Mycoplasma
5. Subclinical Chorioamnionitis
6. Indigent Population
7. Treatment for Cervical Intraepithelial Neoplasia (CIN) [7]
   1. Loop electroexcision (LEEP) increases risk of preterm delivery + PROM by 1.9X
   2. Laser conization increases risk of preterm delivery + PROM by 2.7X
   3. Laser ablation has no increased risk of PROM

D. Diagnosis

1. Sterile Speculum Examination
2. Nitrizine Test (Amniotic Fluid is pH 8-8.5 and turns nitrizine blue)
3. Fern Test - amniotic fluid onto slide, air dry, forms fern pattern due to crystals
4. Indigo Carmine Injeciton to amniotic cavity (to assess for leakage)
5. Cervical and Urine Culture
   1. Gonorrhea, chlamydia, Group B Streptococcus (GBS)
   2. New PCR test for GBS yields results in 30-45 minutes versus 36 hours for culture [3]
6. Complete Blood Count (WBC with manual differential)
7. Ultrasound to determine amniotic fluid volume

E. Prognosis After PROM

1. Term pregnancies with PROM
   1. 70% of women begin labor within 24 hours
   2. 95% of women begin labor within 72 hours
2. Preterm pregnancies with PROM
   1. Latecy period from ROM to delivery decreases inversely with advancing gestation
   2. For PROM at 20-26 weeks' gestation, mean latency period is 12 days
   3. For PROM at 32-34 weeks' gestation, mean latency period is 4 days
3. Intrauterine infection is the most severe consequence of PROM
4. Chorioamnionitis carries 4.0X increased risk of cerebral palsy in term and near term [6]

F. Management

1. Goals of management of PROM
   1. Minimize risk of intrauterine infections
   2. Minizime incidence of cesarean delivery
2. Options for treatment of patients with PROM
   1. Expectant management with careful monitoring
   2. Induction of labor
   3. Main concerns are maternal/fetal infection and fetal maturation status
   4. Usually observe patients on regular hospital unit until endpoint is reached
   5. Routine administration of prophylactic antibiotics is not beneficial; may be harmful [4,5]
3. Usual Endpoints
   1. Chorioramnionitis
   2. Preterm Labor
   3. Term Labor
4. Send LS/PG Ratio Analysis
   1. PG produced only in mature lungs
   2. LS/PG >2 implies mature lungs (95% confidence infant will NOT develop RDS)
   3. Can also sent an amniostat to measure PG
   4. Determination of maturation status of lungs will aide in decision making
5. Treatment of Infection
   1. Infection of fetal membranes is called Chorioamnionitis
   2. Extremely hazardous to fetus and mother
   3. Commonly caused by Group B Streptococcus
   4. Requires delivering baby, removing placenta
   5. Treat with Ampicillin, Gentamicin, and Clindamycin (anaerobic coverage)
   6. Antibiotics should only be given to women with probable or clear infection [4]
6. Delivery
   1. Preterm Vertex usually has good delivery
   2. Preterm Labor without chorioamnionitis - may use tocolytics to block labor
   3. Breech or <2200gm is indication for Cesarian Section --> risk of head entrapment

References

1. Parry S and Strauss JF III. 1998. NEJM. 338(10):663
2. Goldenberg RL, Hauth JC, Andrews WW. 2000. NEJM. 342(20):1500
3. Bergeron MG, Ke D, Menard C, et al. 2000. NEJM. 343(3):175
4. Kenyon SL, Taylor DJ, Tarnow-Mordi W. 2001. Lancet. 357(9261):989
5. Kenyon SL, Taylor DJ, Tarnow-Mordi W. 2001. Lancet. 357(9261):979
6. Wu YW, Escobar GJ, Grether JK, et al. 2003. JAMA. 290(20):2677
7. Sadler L, Saftlas A, Wang W, et al. 2004. JAMA. 291(17):2100
8. Gravett MG, Novy MJ, Rosenfeld RG, et al. 2004. JAMA. 292(4):462