Preterm PROM (PPROM) is a problem affecting all classes of society, though it is more likely to occur in populations of lower socioeconomic status. It complicates one-quarter to one-third of preterm births.1 As such, PROM and PPROM complicate more than 400,000 and 120,000 pregnancies, respectively, in the United States each year.2 Lack of education, poverty, living at high altitude, poor nutritional status of women in this area, and improper utilization of available health resources may be the causes of this high prevalence.3 Nutritional deficiencies that predisposes women to abnormal collagen structure have also been associated with an increased risk of preterm premature rupture of membranes.4
The membranes surrounding the amniotic cavity are composed of the amnion and the chorion, which are closely adherent layers consisting of several cell types, including epithelial cells, mesenchymal cells, and trophoblast cells, embedded in a collagenous matrix. They retain amniotic fluid, secrete substances both into the amniotic fluid and toward the uterus, and guard the fetus against infection ascending the reproductive tract. At term, 8 to 10 percent of pregnant women present with PROM, these women are at increased risk for intrauterine infection when the interval between the membrane rupture and delivery is prolonged (Table 1).
Preterm premature rupture of the membranes occurs in approximately 1 to 3 percent of all pregnancies and is associated with 30 to 40 percent of preterm deliveries.5 Accurate diagnosis is very important in managing a case of PPROM. In management, decision making of whether to continue the pregnancy or to terminate the pregnancy is very crucial and depends on many factors. The clinician 2should decide after thorough evaluation of risks and benefits of both these options.
PPROM is a common cause of perinatal morbidity and mortality in developed as well as underdeveloped countries. There are differences in various studies because of following factors as shown in following table such as:
- Demographic characteristics of the population studied
- Methods used for diagnosis
- Age of pregnancy at the moment of PPROM
- Type of study (retrospective or prospective).
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Demographic variables associated with PPROM were lower maternal age, nulliparity, low socioeconomic class and lack of maternal education which are reported in many studies.7
Preterm PROM is an important cause of perinatal morbidity and mortality, particularly because often times there is some time lapse between rupture of membranes and delivery, risk of perinatal infection increases as delivery gets delayed after PPROM, and there is a risk of umbilical cord compression due to oligohydramnios. Even with conservative management, 50 to 60 percent of women with 3preterm PROM remote from term will deliver within one week of membrane rupture. Amnionitis (13–60%) and clinical abruptio placentae (4–12%) are commonly associated with preterm PROM which adds to maternal and fetal morbidity. In one of the studies conducted in Canada, overall 53 percent of placentas submitted for histopathology after PPROM demonstrated evidence of chorioamnionitis.8 The earlier the PPROM there is more potential for pregnancy prolongation. In 2.8 to 13 percent of patients have spontaneous cessation of fluid leakage.
In babies who survive respiratory distress syndrome (RDS) is the most common serious complication after preterm PROM at any gestation. In babies who survive RDS there is risk of other serious acute morbidities such as necrotizing enterocolitis, intraventricular hemorrhage, and sepsis. There is also a risk of neurological morbidities and cerebral palsy.9 These complications are common with early preterm birth but relatively uncommon nearer term.
It has been observed that perinatal sepsis is two-fold more common after preterm birth after PPROM than preterm labor with intact membranes.
PPROM also affects on hospital costs which increases to almost eight times and longer hospital stay for both mother and infant.10
DEFINITIONS
We need to understand following definitions related to PPROM.
PROM: Prelabor rupture of the membranes is defined as spontaneous membrane rupture that occurs before the onset of labor.
PPROM: When spontaneous membrane rupture occurs before 37 weeks' gestation but after 26 weeks, before the onset of labor, it is referred to as preterm PROM.
Latency: It refers to the time from membrane rupture to delivery.
Conservative management: It is defined as treatment directed at continuing the pregnancy.
Midtrimester PROM: Preterm PROM that occurs at or before 26 weeks' gestation.
As period of viability is decreasing over years and as we know nowadays babies more than 23 weeks can survive with NICU support, following definitions are more appropriate.
Preterm PROM remote from term: Which occurs from viability that is 23 weeks to about 32 weeks' gestation.
Preterm PROM near term: Which occurs approximately 32 to 36 weeks' gestation move in a case of PPROM simultaneous occurence of more than one pathophysiological process.
The importance of this definition is management and outcome differs in each group like in previable PROM occurs, immediate delivery will lead to neonatal death.
Conservative management may lead to previable or periviable birth, but may also lead to extended latency and delivery of a potentially viable infant.
Immediate delivery after preterm PROM remote from term is associated with a high risk of significant perinatal morbidity and mortality that decreases with advancing gestational age at delivery.
As against, preterm PROM near term, immediate delivery of a noninfected and nonasphyxiated infant is associated with a high likelihood of survival and a low risk of severe morbidity.
PATHOPHYSIOLOGY OF PPROM
Over years obstetricians used to correlate PPROM with physical stress but now it is realized that preterm rupture of membranes is multifactorial in nature. However, if we narrate all causes which can be one or move in a case of PPROM. Simultaneous occurrence of more than one pathophysiological process could be responsible for PPROM. Basically it is suggested that membrane rupture is also related to biochemical processes, including disruption of collagen within the extracellular matrix of the amnion and the chorion and programmed death of cells in the fetal membranes which could be stimulated by following causes.
- Infection: Choriodecidual infection or inflammation appears to play an important role in etiology of preterm PROM, especially at early gestational ages.
- Decreased membrane collagen content has been demonstrated in the setting of preterm PROM and with increasing gestational age. In support of this, increases in amniotic fluid matrix metalloproteases as well as decreases in tissue inhibitors of matrix 5metalloproteases have been identified among women with preterm PROM.
- Other factors associated with preterm PROM include lower socioeconomic status, cigarette smoking, sexually transmitted infections, prior cervical conization, prior preterm delivery, prior preterm labor in the current pregnancy, uterine distention (e.g. twins, hydramnios), cervical cerclage, amniocentesis, and vaginal bleeding in pregnancy. Each of these may be associated with preterm PROM through membrane stretch or degradation, local inflammation, or a weakening of maternal resistance to ascending bacterial colonization.Tobacco smoking, which independently increases the risk of preterm PROM, has been associated with decreased serum concentrations of ascorbic acid. Cadmium in tobacco has been found to increase the metal-binding protein metallothionein in trophoblasts, which may result in sequestration of copper.11Smoking and history of previous PPROM were found to be risk factors for PPROM in black population.12The incidence increases four-fold after third trimester PV bleeding.13Though it is said that coitus, cervical examination, parity or exercise are not associated with PPROM, there is evidence that incidence increases four-fold after coitus in third trimester.14
- The ultimate cause of premature membrane rupture is unknown in many cases.
Membranes that rupture prematurely, however, appear to be focally defective rather than generally weakened. The area near the rupture site has been described as a “restricted zone of extreme altered morphology” that is characterized by marked swelling and disruption of the fibrillar collagen network within the compact, fibroblast, and spongy layers.
PREDICTION OF PRETERM PROM
As there is an association of preterm labor and PPROM and as there is risk of infection associated, it is always preferred if we can predict and prevent it.
In the study the investigators found medical complications, work in pregnancy, symptomatic contractions, bacterial vaginosis, and low 6body mass index to be associated with preterm birth due to preterm PROM in nulliparas.
The presence of a short cervix (less than 25 mm by transvaginal ultrasound) was associated with preterm PROM in both nulliparas and multiparas.
A positive fetal fibronectin screen was also associated with preterm PROM in multiparas. Nulliparas with a positive cervicovaginal fetal fibronectin and a short cervix had a 16.7 percent risk of preterm birth due to preterm PROM, whereas multiparas with a prior history, a short cervix, and a positive fetal fibronectin had a 25 percent risk of preterm PROM. Unfortunately despite our developing an ability to identify women at increased risk testing is expensive and inconvenient to the patient for preterm PROM as such and will identify only a small fraction of those ultimately delivering preterm. Because of this, our clinical efforts remain focused on treatment of preterm PROM once it has occurred, rather than its prevention.
DIAGNOSIS
It is more of a clinical diagnosis but many times there is no correlation between history and actual leaking seen on observation.
It is always advisable to do a sterile speculum examination to see for clear fluid coming from cervix rather than per vaginal examination which increases risk of infection and more disruption of membranes. One should also take a sample for culture and sensitivity at the same time. Ruptured membranes is confirmed by direct visualization of fluid draining from cervical os upon Valsalva maneuver or spontaneously or there may be pooling of fluid in posterior fornix. In advanced cases fetal scalp or hair on sterile speculum exam may be visualized.
A secondary investigation would be ultrasonography to see for oligohydramnios.
The presence of nitrazine positive or ferning positive in fluid from vaginal pool of fluid would confirm the diagnosis. One should understand the fallacies of these tests as vaginal pH can be increased by blood or semen contamination, alkaline antiseptics or due to bacterial vaginosis.7
Cervicovaginal fetal fibronectin (fFN) is 100 percent accurate if membranes are ruptured. If negative, fFN rules out ruptured or leaking membranes. False positive tests can occur with heavy bleeding, labor, and recent intercourse.
The tests like ultrasound guided transabdominal amnioinfusion of indigo carmine and observation of dye by per speculum examination is too invasive and not practical as there are more chances of infection.
MANAGEMENT
Survival and outcome in PPROM is correlated with three variables; gestational age at rupture, amount of residual fluid and duration of fluid loss. It is noted that the mortality rate is more than 90 percent when there is PPROM earlier than the midtrimester and when there is significantly reduced amniotic fluid volume.
Standard approach in management is either termination of pregnancy or expectant management to wait for PPROM to stop. It should depend on gestational age, e.g. near term pregnancy and PROM always demands for termination. But in PPROM, decision of delivery or expectant management should depend on individual assessment of maternal, fetal and neonatal complications.
Here ultrasound plays a vital role which will tell us about gestational age, amniotic fluid volume and fetal position and also will give information about polyhydramnios, multiple pregnancies and fetal anomalies. If AFI is less than 5 after 26 weeks in cases of PPROM, there is increased risk of infection and more chances of cesarean section.15
In cases with clinical evidence of advanced labor, chorioamnionitis, fetal distress or abruption placenta it is better to expedite delivery irrespective of gestational age.
It is necessary to start broad spectrum course of antibiotics immediately after culture to avoid further morbidity.
In PPROM between 32 and 36 weeks, it is always advisable to terminate pregnancy as it not only reduces risk of infection but also increases chances of baby survival. Additionally there is risk of cord prolapse or occult cord compression. Cord prolapse risk is more common in a nonvertex presentation.8
Other noninfectious risks with PPROM are placental abruption which increases to 25 percent if there is bleeding after PPROM as against overall risk of 5 percent.
It is necessary to have extensive consultation regarding fetal risk such as possibilities of poor neurological outcome in survivors and maternal risks of bleeding, infection and even death.
There is a risk of pulmonary hypoplasia in PPROM which decreases as gestational age advances. For example, it is 50 percnet if fetus is 20 weeks, 25 percent if it is 22 weeks and less than 10 percent if pregnancy goes beyond 26 weeks.16
There are several other therapies tried in cases of PPROM with variable success. The success has to be yet proved with randomized trials. These therapies include serial amnioinfusions, intracervical tissue sealants and amniopatches.
For patients managed conservatively, daily fetal assessments, daily assessment of fetal activity as appreciated by the patient, assessment of uterine tenderness, temperature, persistent leaking of amniotic fluid associated with purulence or bleeding is required.
Antibiotic administration is a must in all cases of PPROM irrespective of evidence of infection. The NICHD regimen was ampicillin and erythromycin for 48 hours, followed by the same agents orally for 5 days if delivery did not occur. Two large meta-analyses done from studies on PPROM in the last ten years have both shown a benefit in using adjunctive antibiotics with expectant management. A large multicenter study with antibiotics but no steroids or tocolytics also showed a benefit, Another prospective randomized double blinded study looked at patients with PPROM and treated with antibiotics and steroids for all patients showed similar results.
Prophylactic tocolytics after PPROM have not been shown to prolong latency. Similarly, therapeutic tocolysis has not been shown to prolong the latency period. The effect of tocolytics to permit antibiotic administration and corticosteroid administration has not yet been investigated.
Another controversy associated with PPROM is whether we should give steroids in these cases for lung maturity. Lewis demonstrated a significant reduction in RDS almost 18 percent with steroid administration verses 44 percent when steroids were not given. The NICHD Research Study demonstrated a benefit regardless of membrane status. The NICHD Panel recommends steroids in 9patients from 24 to 32 weeks gestation in the absence of infection. It would seem better to adopt a rescue approach rather than a routine administration regimen.
REFERENCES
- Meis JP, Ernest M, Moore ML. Causes of low birth weight births in public and private patients. Am J Obstet Gynecol 1987;156:1165.
- Savitz DA, Blackmore CA, Thorp JM. Epidemiologic characteristics of preterm delivery: Etiologic heterogeneity. Am J Obstet GynecoI 1991;164:467.
- Shehla Noor, Ali Fawwad Nazar. Prevalence of PPROM and its outcome J Ayub Med Coll Abbottabad 2007;19(4):3–6.
- Parry S, Strauss JS. Premature rupture of fetal membranes N Engl J Med 1998;338:663–4.
- PROM ACOG Technical Bulletin. No. 115 April 1988.
- Anthony R. Introduction to PPROM. Obstet Gyne Clinics of North America 1992;19(2):241–7.
- Chen CP, Wang CB. Risk factor for preterm births in upper middle class of Chinese women. Eur J Obstet Gynecol Reprod Biol 1996; 70(1):53–9.
- Smith G, Rafuse C. Prevalence, management and outcome of PPROM in women of Canada, HYPERLINK “http://www.ncbi.nlm.nih.gov/pubmed/16100631” \o “Journal of obstetrics and gynaecology Canada: JOGC = Journal d'obstétrique et gynécologie du Canada: JOGC.” J Obstet Gynaecol Can 2005;27(6):547–53.
- Robert Goldenberg, Dwight J Rouse. Prevention of premature birth, review article N Engl J Med 1998;339:313–4.
- David RD. Risk factor for PROM. Paediatric and Perinatal Epidemiology, 1997;11(Suppl)1:96–106.
- Schectman G, Byrd JC, Gruchow HW. Am J Public Health 1989;79:158–4.
- Hadley CB, Main DM, Gabby SG. Risk factor for PPROM. Am J Perinatol 1990;7(4):374–9.
- Jiwane KA, J OBGY India 1991;41:337.
- Kodkany BS, Telang MA, J OBGY India 1991;41:493.
- Sedigheh Borna, Hajieh Borna, Soghra khazardoosf and Sedigheh Hantoushzadeh, Perinatal outcome in preterm premature rupture of membranes with Amniotic fluid index <5, BMC Pregnancy and Childbirth 2004; 4:15.
- Nimrod C, Varela-Gittings F, Machin G, et al. The effect of very prolonged membrane rupture on fetal development. Am J Obstet Gynecol 1984;148:540.