Premature Rupture of the Fetal Membranes  
Vol.2 No.4 

by Kunle Odunsi M.D., and Paolo Rinaudo, M.D. 
Yale-New Haven Hospital 
 

Editors Note: 
The following information presents an extremely comprehensive summary  
of the pervasive complication of pregnancy, premature rupture of the fetal  
membranes or PROM. Although it is written with many medical terms, I think  
all readers will derive a benefit from its presentation here. 

INTRODUCTION 
Premature rupture of membranes (PROM) constitute one of the most important dilemmas 
in current obstetric practice. The term is applied to leakage of amniotic fluid in the absence 
of labor irrespective of gestational age. PROM before 37 weeks gestation is referred to as 
preterm premature rupture of membranes ( PPROM ). Overall, about 10% of all gestations 
are complicated by PROM. At term, the incidence of PROM varies from 6 to 19%. Nearly 
all women with PPROM will eventually deliver before term, and the majority of these 
women will deliver within one week of rupture regardless of their gestational age at the 
time of membrane rupture. 
MECHINISMS OF PREMATURE RUPTURE OF FETAL MEMBRANES 
The chorioamniotic membranes possess properties which are characteristic of a viscoelastic 
material (3). However, there is evidence to suggest that when the membranes are stressed, 
either by internal pressure due to labor or by infection, they are weakened and have an 
increased susceptibility to premature rupture (3,4). Several studies have shown that both 
the cytoarchitecture of the amniotic membrane and the quality and quantity of membrane 
collagen are altered in the patient with PROM. Specifically, it appears that type 3 collagen 
may be reduced in patients with PROM (5). Additionally, enhanced collagenolytic activity 
has been found in prematurely ruptured amniotic membranes 
  
There is now compelling evidence that infection is a major etiologic factor in a significant 
proportion of preterm labor and preterm premature rupture of fetal membranes. The most 
commonly associated organisms found were those causing bacterial vaginosis, 
Trichomonas vaginalis, mycoplasmae, chlamydia trachomitis, Neisseria gonnorhea 
group B Streptococci. In addition, Bacteroides fragilis, peptostreptococci, and 
Fusobacterium, bacteria commonly isolated from the amniotic fluid in the presence of 
preterm labor, and other common vaginal bacteria including lactobacilli and staphylococcus 
epidermidis may release inflammatory mediators which may cause uterine contractions. 
This leads to cervical change, separation of the chorion from the amnion, and premature 
rupture of the membranes (PROM). 
  
Maternal and fetal " stress" may also lead to the release of stress mediators via the 
hypothalamic-pituitary-adrenal axis leading to enhanced production of placental 
corticotrophin releasing hormone ( CRH ). The latter acts as a paracrine effector, enhancing 
the release of enzymes and compounds which may lead to PPROM. 
  
Other risk factors for PROM include cigarette smoking (7,8,9), vaginal bleeding, 
incompetent cervix and poor nutritional status. Other factors, called not remediable factors, 
include PROM in a previous pregnancy (recurrence rate of 21% ); Ehlers-Danlos 
syndrome, placenta previa, placental abruption, marginal insertion of the umbilical cord, 
battledore placenta, multiple gestation, polyhydramnios, and incompetent cervix. 
  
COMPLICATIONS OF PROM 
The consequences of PROM for the neonate fall into three major overlapping categories. 
The first is the significant neonatal morbidity and mortality associated with prematurity. 
Second are the complications during labor and delivery that increase the risk for neonatal 
resuscitation, and thirdly infection. The morbidity and mortality associated with PROM 
increases with decreasing gestational age. Maternal complications include infection and 
increased risk of cesarean section. 
  
Once membranes rupture, the duration of the latency period varies inversely with the 
gestational age. When PROM occurs between 28 and 34 weeks, 50% are in labor within 24 
hours and 80 - 90"7o within 1 week (IO, I I). Maternal infection is termed chorioarnnionitis 
and fetal infection may occur as septicemia, pneumonia, urinary tract infection, or local 
infections such as omphalitis (infection of the umbelical cord) or conjunctivitis. The 
incidence of chorioamnionitis, in association with PROM varies with the population 
studied. In prolonged rupture of membranes, the incidence is 3 - 15 % and it appears to be 
more common in PPROM with a frequency of 15 to 25% (12,13). Major neonatal 
infections occur in about 5% of all cases of preterm PROM, and in 15 - 20% of those with 
chorioamnionitis (12,13). 
  
The relative contributions of prematurity and perinatal infections to perinatal mortality are 
responsible for most of the controversy surrounding the optimal management of PPROM. 
In most cases, perinatal mortality consequent upon PPROM arises from complications of 
prematurity such as respiratory distress syndrome ( RDS ), intraventricular hemorrhage ( 
IVH ), and necrotizing enterocolitis ( NBC ). Thus, in a 26 week gestation, the relative 
contribution of prematurity to the risks of perinatal morbidity and mortality far outweigh 
any risks from infection, and thus all efforts at prolonging pregnancy would seem 
reasonable. However, in a fetus at 34 weeks, at which point perinatal mortality is not 
substantially different from that for the fetus at term, the relative contribution of infection 
becomes more important. 
  
Umbilical cord prolapse occurs more frequently in PROM with a reported incidence of 
1.5% (14). It has now become clear that cord compression, even without prolapse, is 
more common in PROM because of the accompanying oligohydraumios ( 1 5,1 6). Studies 
of antepartum testing in patients with PPROM suggest a high incidence of antepartum fetal 
distress requiring intervention for fetal heart rate ( FHR ) patterns consistent with umbilical 
cord compression occurring even prior to the onset of labor (17). Vintzileos et al ( 1985 
(1 8) reported a good correlation between the severity of oligohydramnios and the 
frequency of severe variable decelerations, low apgar scores , and perinatal mortality. 
  
The final major complication that may result from PPROM is the fetal deformation 
syndrome. PROM occurring very early in pregnancy can result in growth retardation, 
compression anomalies of the fetal face and limbs, and most importantly, pulmonary 
hypoplasia Sustained adequate amniotic fluid and normal fetal breathing movements are 
necessary for normal lung growth. Itoh and Itoh ( 1988 ) (19) reported that fetuses with 
renal agenesis ( insult before 4 - 6 weeks ) have defects in all three stages of lung 
development whereas fetuses with early oligohydranmios ( insult before 20 weeks ) exhibit 
nearly normal bronchial branching and cartilage development but have histologically 
immature alveoli. 
  
Fetal pulmonary hypoplasia has a 90% mortality rate. The reported incidence in PPROM 
varies between 3% (20,21) and 28% (22). Prenatal diagnosis of pulmonary hypoplasia 
is difficult and there have been unsuccessful attempts to correlate monographic features such 
as fetal thoracic dimension, fetal lung length, and absent fetal breathing movements with 
diagnosis (23,24) 

MAKING THE DIAGNOSIS OF PROM 

The diagnosis of rupture of membranes is based on the logical sequence of history, 
physical examination and investigation. In many instances, it is clear from a history of 
sudden gush of fluid from the vagina and its continuing intermittent trickle. However, most 
fluid might have escaped and fluid may not be present in the vagina making it difficult to 
confirm or refute the diagnosis. Furthermore, fluid may be contaminated with urine, 
cervical mucus, bath water, vaginal discharge, blood or meconium. Because of these 
difficulties, even when fluid is available, differentiation between arymiotic fluid and urine, 
or vaginal secretions is essential. Indeed, Kragt and Keirse ( 1989 ) (1) found that 20% of 
women with preterm gestations who came to a labour and delivery unit with a primary 
complaint of ' aqueous discharge ' did not have ruptured membranes. No one test has been 
found to be completely accurate, and diagnosis still requires an integration of the clinical 
history, physical examination and laboratory testing. Three tests are currently used for 
diagnosis of ROM: Ferning, Nitrazine test, and observation of a pool of fluid (pooling) in 
the vagina. Arborization or " fern-like " pattern occurs in a variety of body fluids when put 
on a glass slide and allowed to dry, because of the presence of proteins and electrolytes. 
Positive "ferning" is considered a sign of ruptured membranes. However, the Nitrazene 
test is probably the most widely used for helping establish the diagnosis of ruptured 
membranes. Nitrazine is an indicator paper with a narrow set point of pH 6.4 - 6.8 where it 
undergoes the characteristic color change to blue in the presence of amniotic fluid. Overall, 
the combination of history, physical examination, nitrazinc testing, and microscopy for fern 
like pattern of an-miotic fluid should lead to the correct diagnosis of up to 90% of cases of 
premature rupture of membranes. The question as to whether or not to perform vaginal 
examination in patients with PROM is a controversial area of practice. The most widely 
held opinion is that a visual speculum examination alone is sufficient to provide most of the 
necessary information required for management. 

  
  
MANAGEMENT OF PRETERM PROM 
The major risks to the baby following PPROM are related to the complications of 
prematurity. The neonatologist and obstetrician should work as a team to ensure that 
optimal care is provided for the mother and fetus. Several studies have shown that small 
changes in gestational age have significant impact on survival especially for neonates 
delivered between 24 and 26 weeks. Morbidity is also dependent on weight and decreases 
with increasing birthweight. 
  
Since the goal of management in PPROM is prolongation of pregnancy, the most 
commonly accepted management scheme for the patient less than 36 weeks is expectant 
management in the hospital which consists of careful observation for signs of infection, 
labor or fetal distress in an effort to gain time for fetal growth and maturation. Although 
most patients comit themselves to delivery by going into labor, some do reach term and the 
timing of delivery must be decided. When the patient reaches 36 or 37 weeks, delivery may 
be accomplished but documented lung maturity may permit a somewhat earlier delivery. 
This expectant approach is complicated by controversies surrounding the efficacy of 
tocolytic agents to stop uterine contractions, prophylactic antibiotics, corticosteroids to 
accelerate fetal lung maturation, and amniocentesis for diagnosis of occult infection and 
fetal lung maturity. In any event, where adequate facilities for intensive perinatal and 
neonatal care is larking, it is prudent to refer the patient to a center where such facilities are 
available. 
  
Documentation of Fetal Well-being in PROM 
PROM is associated with an increased frequency of maternal infection, neonatal infection, 
and fetal distress during preterm and term labor. The main challenge therefore, is how to 
recognize and detect intrauterine infection at its incipient stages. In the United States, 
analysis of arrmiotic fluid obtained by amniocentesis is currently the most widely practiced 
method to determine the presence or absence of bacteria in the amniotic cavity and to 
deten-nine fetal pulmonary maturity. The most common tests for the detection of bacteria are 
Gram stain and cultures for aerobic and anaerobic bacteria including Mycoplasma species. 
In order to improve the efficacy of Gram staining, other markers of infection have been 
examined by different groups such as amniotic fluid white blood cell count, leukocyte 
esterase, and glucose. Although there is currently inadequate evidence on the value of 
amniocentesis in PROM, it would appear that the routine use of transabdominal 
amniocentesis to detect silent intraamniotic infection, is justified. The amniotic fluid is used 
to document pulmonary maturity studies. The demonstration of a lecithin : sphingomyelin ( 
L/S ) ratio greater than 2 from the amniocentesis sample or the presence of a phosphatidyl 
glycerol band in the vaginal pool specimen is usually taken as indication of pulmonary 
maturity. Ultrasonography has become an essential part of the evaluation of patients with PPROM. 
The evaluation includes assessment of dates and size, exclusion of fetal anomalies, and 
determination of fetal behavior. 
  
Antibiotic Therapy in Expectant Management of PPROM 
The use of prophylactic antibiotics in PPROM could reduce maternal and perinatal risks of 
infection and secondly, the interval from PROM to delivery might be prolonged ( since 
occult infection is a probable cause of PPROM and preterm labor ). In a metaanalysis of 
antimicrobial therapy in PPROM , Mercer and Arheat (1995) (25) showed that 
antimicrobial treatment offered significant benefit in pregnancy prolongation and fewer(9) 
women delivered by 24 h with anti microbial therapy ( 13.4 Vs 20.8% ) and at 48 h ( 29.8 
Vs 47.0%). There was also a decrease in chorioamnionitis as well as infectious matemal 
and infant morbidity including sepsis and pneumonia. However, many questions remain to 
be answered including whether or not these findings are applicable to all populations, what 
is the best antibiotic including route and duration of therapy, and whether or not a selective 
approach is feasible reserving antibiotic therapy for a specific group of patients at higher 
risk. Until these issues are addressed, the use of antibiotic prophylaxis in PPROM should 
be individualized and blanket use should not yet be regarded as " standard of care " as it 
may increase iatrogenic morbidity from superinfection due to resistant bacterial species. 
  
Corticosteroids after PPROM 
The benefit of antenatal corticosteroid therapy has been demonstrated in several randomized 
controlled trials. The overall reduction in the odds of neonatal RDS is about 50% (26). 
This beneficial effect on RDS is thought to have a domino effect on other forms of neonatal 
morbidity including a 10% and 80% reduction in the odds of periventricular hemorrhage 
(27) and necrotizing enterocolitis (28) respectively. 
  
In the light of available evidence, corticosteroid therapy should be initiated as soon as 
possible in all cases of PPROM from ?4 to 34 weeks unless immediate delivery is indicated 
for chorioamnionitis, antepartum hemorrhage, cord prolapse or fetal distress. Treatment 
should consist of dexamethasone by intramuscular injection in two doses at 12 hour 
intervals. If the patient remains undelivered after I week, an attempt should be made to 
assess lung maturity and to repeat the corticosteroid regime if necessary.(10) 

Tocolysis in PPROM 
Several prospective randomized controlled trials of tocolytic agents (agents that reduce 
uterine contractions) in patients with PPROM have been conducted (29,30,3 1). Overall, 
there was no difference in pregnancy prolongation beyond 24 hours or any difference in the 
any index of perinatal mortality or morbidity measured. Two randomized trials of 
prophylactic oral tocolytics also failed to show pregnancy prolongation (32,33). These 
data offer no support for suggestions that prophylactic oral tocolysis before the onset of 
uterine contractions is worthwhile. A possible but unproven advantage of tocolysis lie in 
the postponement of labor in order to facilitate in - utero transfer in PPROM. 
  
Previable PROM 
In cases of PROM very early in pregnancy, survival after delivery at or less than 23 weeks 
is limited, and neonatal morbidity and mortality after delivery at 24 to 26 weeks are high. If 
labor or clinical infection is present at initial evaluation of these patients, delivery is 
indicated. For the remainder of patients, there are two options, expectant management or 
termination. It is extremely important that the patient be involved in the decision process. 
On going counselling and psychological support are essential in the management of this 
morbid pregnancy complication. 
  
MANAGEMENT OF PROM AT TERM 
Labor induction or expectant management ? The question as to whether to induce 
labor immediately or not when PROM occurs at term is a vexed issue. @ly reports on the 
widespread practice of immediate induction of labor showed that the policy resulted in high 
cesarean section rates which were thought to be due to the fact that the cervix was unripe in 
many cases. However, a recent careful large randomized controlled trial that included 5041 
_ women with PROM at term (34) showed that induction of labor with intravenous 
oxytocin, induction of labor with vaginal prostagiandin E2 gel, and expectant management 
are all reasonable options for women and their babies if membranes rupture before the start 
of labor at term, since they result in similar rates of neonatal infection and cesarean 
delivery. However, induction of labor with intravenous oxytocin resulted in a lower risk of 
matemal infection and women viewed induction of labor more positively than expectant 
management. 

Prophylactic Antibiotics ? In the recent Centers for Disease Control and Prevention 
recommendations for preventing early onset neonatal group B streptoccocal ( GBS 
disease, prolonged rupture of membrane for more than 18 hours was classified as a risk 
factor for GBS infection and antibiotic chemoprophylaxis with penicillin or ampicillin was 
recommended in this setting. For women who are allergic to penicillin, clindamycin or 
erythromycin would be suitable alternatives. 
  
SUMMARY 
Premature rupture of the fetal membranes is an obstetric enigma and several aspects of 
management of PPROM and PROM at term remain controversial. Although clinical 
judgment, physician experience, and careful individualization of management will often 
come into play, certain principles are widely accepted as being essential. The issues to be 
addressed by the obstetrician caring for the patient presenting with PROM are : Are the 
membranes indeed ruptured ? What is the gestational age ? Should the cervix be examined ? 
Should labor be suppressed ? Should labor be induced ? Should the mother be transported? 
Is there any reason not to administer glueocorticoids ? How and when should delivery be 
accomplished? These questions are best answered based on the best available evidence. 
Future studies are warranted in PROM to identify the optimal methods prolongation of the 
(12)latency interval while avoiding compression defom-iities and pulmonary hypoplasia in cases 
where membrane rupture occur very early in pregnancy as well as the optimal mode of 
surveillance in these pregnancies. 
  
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