PROM

Overview
Premature rupture of membranes (PROM) refers to a patient who is beyond 37 weeks'
gestation and has presented with rupture of membranes (ROM) prior to the onset of labor.
Preterm premature rupture of membranes (PPROM) is ROM prior to 37 weeks' gestation.
Spontaneous preterm rupture of the membranes (SPROM) is ROM after or with the onset of
labor occurring prior to 37 weeks. Prolonged ROM is any ROM that persists for more than 24
hours and prior to the onset of labor.
At term, programmed cell death and activation of catabolic enzymes, such as collagenase
and mechanical forces, result in ruptured membranes. Preterm PROM occurs probably due to the
same mechanisms and premature activation of these pathways. However, early PROM also
appears to be linked to underlying pathologic processes, most likely due to inflammation and/or
infection of the membranes. Clinical factors associated with preterm PROM include low
socioeconomic status, low body mass index, tobacco use, preterm labor history, urinary tract
infection, vaginal bleeding at any time in pregnancy, cerclage, and amniocentesis. [1]
Eighty-five percent of neonatal morbidity and mortality is a result of prematurity. PPROM is
associated with 30-40% of preterm deliveries and is the leading identifiable cause of preterm
delivery. PPROM complicates 3% of all pregnancies and occurs in approximately 150,000
pregnancies yearly in the United States. [2]When PPROM occurs remote from term, significant
risks of morbidity and mortality are present for both the fetus and the mother. Thus, the
physician caring for the pregnant woman whose pregnancy has been complicated with PPROM
plays an important role in management and needs to be familiar with potential complications and
possible interventions to minimize risks and maximize the probability of the desired outcome.
This article focuses on information the physician needs to achieve these goals. [1, 3, 4]
For patient education resources, see the Pregnancy Center and Labor Signs.

Premature Rupture of Membranes (at Term)

Premature rupture of membranes (PROM) at term is rupture of membranes prior to the
onset of labor at or beyond 37 weeks' gestation. PROM occurs in approximately 10% of
pregnancies. Patients with PROM present with leakage of fluid, vaginal discharge, vaginal
bleeding, and pelvic pressure, but they are not having contractions.
ROM is diagnosed by speculum vaginal examination of the cervix and vaginal cavity. Pooling of
fluid in the vagina or leakage of fluid from the cervix, ferning of the dried fluid under
microscopic examination, and alkalinity of the fluid as determined by Nitrazine paper confirm
the diagnosis.
Blood contamination of the Nitrazine paper and ferning of cervical mucus may produce
false-positive results. Pooling of fluid is by far the most accurate for diagnosis of ROM. If all
fluid has leaked out as in early PROM, an ultrasonographic examination may then show absence
of or very low amounts of amniotic fluid in the uterine cavity.
 New evidence suggests that the use of biochemical markers to diagnose ROM in
uncertain cases may be appropriate and cost effective. Echebiri et al reported cost effectiveness
compared to standard methods of diagnoses between 34 and 37 weeks. [5]
Ng et al reported placental alpha-microglobulin-1 levels have a 95.7% sensitivity, 100%
specificity, 100% positive predictive value, and 75% negative predictive value.[6] In select cases
when the diagnoses or ROM is not clear, placental alpha-microglobulin-1 should be used to
provide additional information for appropriate management.
Given the importance of making the correct diagnoses, the associated morbidity with
hospitalization and delivery prior to term in PROM reaching 34 weeks and beyond, and the
potential neonatal morbidity resulting from prematurity in cases of incorrect diagnoses of
PROM, it is mandatory to confirm the diagnosis of PROM with pooling of amniotic fluid with
some evidence of decreased or absence of amniotic fluid in all cases of suspected PROM.
Most patients (90%) enter spontaneous labor within 24 hours when they experience ROM
at term. The major question regarding management of these patients is whether to allow them to
enter labor spontaneously or to induce labor. In large part, the management of these patients
depends on their desires; however, the major maternal risk at this gestational age is intrauterine
infection. The risk of intrauterine infection increases with the duration of ROM. Evidence
supports the idea that induction of labor, as opposed to expectant management, decreases the risk
of chorioamnionitis without increasing the cesarean delivery rate. [7, 8]
Hannah et al studied 5041 women with PROM who were randomly assigned to induction
of labor with intravenous oxytocin or vaginal prostaglandin E2 gel versus expectant management
for as many as 4 days with induction of labor for complications. [9] They concluded that, in
women with PROM, induction of labor and expectant management resulted in similar rates of
cesarean delivery and neonatal infection. However, induction with oxytocin resulted in a lower
risk of maternal infection (endometritis) when compared with expectant management.
Additionally, the women in the study viewed induction of labor more favorably than expectant
management.
Other smaller studies have shown results with higher cesarean and/or operative delivery
rates when the cervix was unfavorable.
At term, infection remains the most serious complication associated with PROM for the mother
and the neonate. The risk of chorioamnionitis with term PROM has been reported to be less than
10% and to increase to 40% after 24 hours of PROM. [10]This points out the importance of
appropriate management strategies for PROM at term.
Since risk of infection at term with ROM is small during the first 24 hours, expectant
management and waiting for spontaneous labor may be considered in selected patients for the
first 12-24 hours if a patient desires expectant management. The use of expectant management
after the first 24 hours is questionable.
Digital vaginal examinations should be avoided until labor is initiated; however, fetal
presentation should be documented to avoid discovering malpresentation of the fetus long after
admission for ROM. All patients with ROM should be asked to come to the hospital to ensure
fetal well being.
The neonatal risks of expectant management of PROM include infection, placental abruption,
fetal distress, fetal restriction deformities and pulmonary hypoplasia, and fetal/neonatal death.
Fetal death does occur in approximately 1% of patients with PROM after viability who have
been expectantly managed [1] and in about 1:1000 term PROM. [11]
The primary determinant of neonatal morbidity and mortality is gestational age at delivery, again
stressing the importance of conservative management when possible. (See the Gestational Age
from Estimated Date of Delivery calculator.)
In general, prognosis is good after 32 weeks' gestation as long as no other complicating factor,
such as congenital malformation or pulmonary hypoplasia, exists.

Premature Preterm Rupture of Membranes

Premature preterm rupture of membranes (PPROM) occurring from 24-37 weeks'
gestation is far more difficult to manage than premature rupture of membranes (PROM) at term.
Several issues need to be considered in formulating a plan of management. Prematurity is the
principal risk to the fetus, while infection morbidity and its complications are the primary
maternal risks. All plans for management of PPROM remote from term should include the
family and the medical team caring for the pregnancy, including the neonatal and maternal
medical team. Remote from term, PPROM should only be cared for in facilities where a NICU is
available and capable of caring for the neonate. Because most PPROM pregnancies deliver
within a week of ROM, transfer of the pregnant mother to a qualified facility is urgent and
should be facilitated immediately upon diagnoses.
The vast majority of women proceed to active labor and deliver soon after PPROM. With
appropriate therapy and conservative management, approximately 50% of all remaining
pregnancies deliver each subsequent week after PPROM. Thus, very few women remain
pregnant more than 3-4 weeks after PPROM. This is important information to give the woman
considering expectant management remote from viability. [1]
Spontaneous sealing of the membranes does occur occasionally (< 10% of all cases), mostly after
PPROM that has occurred subsequent to amniocentesis; however, this is the exception rather
than the rule.
Several areas of controversies exist regarding the best medical approach or management
of PROM remote from term. Expectant management and immediate delivery are potential
options in these patients, and each has its own advantages and disadvantages. With appropriate
care, the maternal risks of expectant management are generally accepted to be minimal and a
clear neonatal advantage exists by reducing risks of prematurity.
Controversies exist as to interventions such as steroids for acceleration of lung maturity,
antibiotics, and tocolytics. See Medical Treatment.
A study by Ekin et al suggested that mean platelet volume (MPV) in the first trimester of
pregnancy can be used to predict the likelihood of PPROM. In a retrospective record review of
318 women with PPROM and 384 controls, the investigators found that, comparing values
between the 7th and 14th weeks of gestation, the MPVs were significantly lower and the platelet
counts significantly higher in patients who had experienced PPROM than in pregnant women
who had not. Using cutoff values of less than or equal to 8.6 fL for MPV and greater than or
equal to 216 x 103/L for platelet count, the study found that these measurements had a
sensitivity and specificity for predicting PPROM of 58% and 65%, respectively, and 62% and
44%, respectively. Ekin and colleagues concluded that MPV is more efficient than platelet count
for predicting PPROM. [12]

Maternal and Fetal Surveillance

After an initial period of continuous monitoring of fetal heart rate and uterine
contractions (24-48 h), if findings are suggestive of reassuring surveillance, then the patient
would be a candidate for expectant management. In general, common practice has been to place
the patient on bed rest on the obstetric floor. However, the the existing data show no benefit to
bed rest for any obstetric condition. Because bed rest in pregnancy is associated with an
increased chance of deep venous thrombosis, prophylaxis to reduce this risk should be instituted.
In addition, fetal monitoring should be performed at least once a day. If evidence of frequent
cord compression is present as determined by moderate-to-severe variables, continuous
monitoring should be reinstituted. Maternal vitals need to be monitored closely. Tachycardia and
fever are both suggestive of chorioamnionitis and require careful evaluation to determine the
presence of intra-amniotic infections, in which case delivery and initiation of broad-spectrum
antibiotics should be promptly facilitated.
Ultrasonographic examination for amniotic fluid index and fetal growth and well being
should be used liberally to ensure appropriateness of continued expectant management. While
oligohydramnios, defined as an amniotic fluid index of less than 2 cm, has been associated with
short latency and chorioamnionitis, it alone is not an indication for delivery when other means of
surveillance are reassuring. White blood cell count is not predictive of outcome and does not
need to be monitored other than to support clinical suspicion of chorioamnionitis.
Digital cervical examinations should be avoided. [13] In a noncephalic presentation, especially
with a dilated cervix, continuous monitoring should be considered to avoid missing the diagnosis
of cord prolapse.
Intra-amniotic infection should invoke prompt delivery. Practitioners should have a low
threshold for diagnosing infection in a patient with PPROM as evidence clearly shows poor
outcome in an infected neonate compared with a similar uninfected neonate.
PPROM in the Second Trimester
Premature preterm rupture of membranes (PPROM) prior to fetal viability is a unique and
relatively rare problem that is often difficult to manage. It occurs in less than 0.4% of all
pregnancies. [14] The major maternal risk is infection, namely chorioamnionitis, which occurs in
about 35%; abruption, which occurs in 19%; and sepsis, which is rare and occurs in less than
1%. [14] The major morbidity in the fetus with midtrimester ROM is lethal pulmonary hypoplasia
from prolonged, severe, early oligohydramnios, which occurs in about 20% of cases. Other
morbidities such as RDS (66%), sepsis (19%), grade III-IV IVH (5%), and contractures (3%)
also occur with high frequency, resulting in intact survival rates of more than 67%. Fetal death is
common and occurs in more than 30%. [14]
Older studies have reported that approximately 50% of all remaining pregnancies deliver
each subsequent week after PPROM. [1] More recent studies have shown better prognosis and
may be more relevant to todays clinical practice. With appropriate therapy and conservative
management, more recent studies have reported less than 40% delivering in a week and more
than 30% remaining pregnant after 5 weeks. This information is probably better suited to be used
in counseling patients regarding early PROM. [15]
The risk of infection increases with the duration of PPROM. Outpatient management of
PPROM prior to viability is appropriate in the well-informed and educated patient. The patient
needs to be informed of warning signs that indicate the need for immediate evaluation. These
signs include fever, abdominal pain, vaginal spotting, foul-smelling discharge, and rapid heart
rate. The woman should monitor her temperature at home at least 3 times daily and report any
elevation beyond 100.4F (38C). Frequent examinations are necessary to ensure maternal
safety. Patients must be educated about the warning signs of intra-amniotic infection, and they
must take their temperature 3 times a day at home. After viability is reached, inpatient
management needs to be considered.
Midtrimester (13-26 wk) PPROM has a poor prognosis, although more recent studies
have reported better outcome. Expectant management may be appropriate in select patients who
are well informed and educated about the risks and the dismal prognosis for the neonate.
Delivery is also appropriate when the mother is concerned about her own risks, especially when
PPROM has occurred prior to 20 weeks' gestation. Incomplete abortion may be the appropriate
term for the condition, as products of conception (the amniotic fluid) have passed the cervical
opening and into the vagina in these cases. Other heroic measures such as amnioinfusion,
tocolysis, and cervical plug to seal the membranes are unproven and should be considered in
research protocols.
Survival varies with gestational age at diagnosis (from 12% when diagnosed at 16-19 wk, to as
much as 60% when diagnosed at 25-26 wk). [16] Until viability, maternal safety should be the
primary concern.

Management of PPROM
The initial evaluation of premature preterm rupture of membranes (PPROM) should include a
sterile speculum examination to document ROM. Cervical cultures including Chlamydia
trachomatis and Neisseria gonorrhoeae and anovaginal cultures for Streptococcus
agalactiae should be obtained. Maternal vital signs should be documented as well as continuous
fetal monitoring initially to establish fetal status. Ultrasonographic documentation of gestational
age, fetal weight, fetal presentation, and amniotic fluid index should be established. Digital
examination should be avoided, but visual inspection of the cervix can accurately estimate
cervical dilatation. Digital examination of the cervix with PPROM has been shown to shorten
latency and increase risk of infections without providing any additional useful clinical
information. [13]
In certain circumstances, immediate delivery of the fetus with PPROM is indicated. These
circumstances include chorioamnionitis, advanced labor, fetal distress, and placental abruption
with nonreassuring fetal surveillance. If fetal lung maturity has been documented by either
amniocentesis or collection of vaginal fluid, delivery should be facilitated. In a noncephalic fetus
with advanced cervical dilatation (more than or equal to 3 cm), the risk of cord prolapse may also
outweigh the benefits of expectant management and delivery should be considered.
If after initial evaluation of the mother and fetus, they are both determined to be clinically stable,
expectant management of PPROM may be considered to improve fetal outcome. The primary
maternal risk with expectant management of PPROM is infection. This includes
chorioamnionitis (13-60%), endometritis (2-13%), sepsis (< 1%), and maternal death (1-2 cases
per 1000). Complications related to the placenta include abruption (4-12%) and retained placenta
or postpartum hemorrhage requiring uterine curettage (12%). [3]
The risks and potential benefits of expectant management should be discussed with the patient
and her family, and informed consent should be obtained. The maternal and fetal status need to
be reevaluated daily, and the safety and potential benefits of expectant management should be
reassessed. If the condition remains stable, the immature fetus may benefit from expectant
management, even if for a short period, to allow administration of steroids and antibiotics. Once
maturity has been reached, the benefit from expectant management of PPROM is unclear and the
risks of infection outweigh any potential benefits.
Amniocentesis can provide information about lung maturity accuracy and correctness of the
diagnoses of PROM and infection. However, in most cases of PPROM, the amount of fluid is
scant; thus, amniocentesis should be performed only by individuals with experience in
performing difficult amniocentesis, and the appropriate risks with potential for fetal
complications and the need for immediate delivery should be discussed with patients before
attempting amniocentesis.
Medical Treatment of PPROM
Antibiotics
The initial step in management of PPROM is informed consent. The patient needs to be given
risks and benefits information and must participate in decision making. Once the decision to
manage a patient expectantly has been made, the institution of broad-spectrum antibiotics should
be considered. Multiple trials have examined the advantages and disadvantages of using
antibiotics and the choice of antibiotics. In most studies, use of antibiotics has been associated
with prolongation of pregnancy and reduction in infant and maternal morbidity. However, a few
studies have reported increased neonatal morbidity with certain types of antibiotics, as discussed
below.
Two of the largest studies that have looked at the efficacy of antibiotic use in PPROM are the
National Institute of Child Health and Human Development - Maternal Fetal Medicine Units
(NICHD-MFMU) study of PROM and the ORACLE trial. In the NICHD study, intravenous
antibiotics were used for 48 hoursampicillin 2 g q6h and erythromycin 250 mg q6h. The
patients were then placed on oral amoxicillin 250 mg q8h and enteric-coated, erythromycin-base
333 mg q8h to complete a 7-day course of antibiotic therapy. In this study, the control group,
compared with the antibiotic group, had a significantly shorter duration of latency. The antibiotic
group was twice as likely to remain undelivered after 7 days. The increased latency continued for
up to 3 weeks after discontinuation of antibiotics. Composite and individual morbidities for the
neonate were lower in the antibiotic group. The incidence of chorioamnionitis and neonatal
sepsis, including group B streptococci sepsis, was decreased. [17]
The ORACLE trial used erythromycin alone, amoxicillin clavulanic acid alone, or amoxicillin
clavulanic acid in combination with erythromycin. Their results were different in that no
significant difference was noted in latency to delivery and neonatal morbidity was not decreased
as defined in their primary outcome (death, chronic lung disease, and major cerebral abnormality
on ultrasonography). Decreased need for supplemental oxygen and positive blood culture results
were apparent. When amoxicillin clavulanic acid was used either alone or in combination with
erythromycin, an increased risk of necrotizing enterocolitis (1.9% vs 0.5%, p=0.001) was
present. [18]
Based on current evidence, 7 days of antibiotics, as proposed by the NICHD-MFMU study of
PROM, should be the antibiotic regimen used in patients with PPROM who are being managed
expectantly. When another antibiotic is being used for other indications, such as a urinary tract
infection, attempts should be made to avoid duplicated therapy. For example, a patient being
treated with a cephalosporin for a urinary tract infection does not need penicillin therapy.
Therapy longer than 7 days should be avoided; it has not been shown to be more effective and
may promote the emergence of resistance organisms.
Revised guidelines from the Centers for Disease Control and Prevention (CDC) recommend that
women with preterm PROM who are not in labor should receive intravenous group B
streptococcus (GBS) coverage for at least the first 48 hours of preterm PROM latency
prophylaxis, until the GBS test results obtained on admission are available. [19] However, GBS
test results should not affect the duration of antibiotic therapy. If the patient completes the full 7-
day course of antibiotic prophylaxis has no evidence of infection or labor, intrapartum GBS
prophylaxis can be managed based on the results of the baseline GBS test at the time of preterm
PROM, unless 5 weeks have passed. This is because a negative GBS test result is considered
valid for 5 weeks. [20, 21]
Antenatal corticosteroid treatment
The use of corticosteroids to accelerate lung maturity should be considered in all patients with
PPROM with a risk of infant prematurity from 24-34 weeks' gestation. The latency period has
been suggested to be too short for the effects of corticosteroids to make a difference in neonatal
morbidity; however, this clearly does not appear to be the case. Most patients with PPROM
remain pregnant at 48 hours and thus will benefit from corticosteroid therapy. The use of steroids
has also been suggested to increase the risk of infection. However, the current evidence does not
support this concern based on individual studies and meta-analyses; no difference (either higher
or lower rates of infections) has been observed with corticosteroid use.
In contrast to these concerns, data indicate that the use of corticosteroids reduces neonatal
morbidity and mortality. The rates of respiratory distress syndrome (RDS), necrotizing
enterocolitis, and intraventricular hemorrhage were all lower when either 12 mg of
betamethasone IM was given twice in a 24-hour interval or dexamethasone 6 mg q12h was given
for 4 doses. [22]
Current ACOG recommendations [23, 2]
A single course of corticosteroids is recommended for pregnant women 24-34 weeks'
gestation who are at risk of preterm delivery within 7 days and as early as 23 weeks if
delivery is imminent.
A single rescue course of antenatal corticosteroids may be considered if the antecedent
treatment was given more than 2 weeks prior, the gestational age is less than 32 6/7 weeks,
and the woman is judged by the clinician to be likely to give birth within the next week.
However, regularly scheduled repeat courses or more than 2 courses are not recommended.
Further research regarding the risks and benefits, optimal dose, and timing of a single
rescue course of steroid treatment is needed.
Tocolytics
The most common cause of labor in the setting of PPROM is underlying chorioamnionitis. The
use of tocolysis in that setting is not justified. No data indicate that administering tocolysis
benefits the neonate. [24] In one study, prophylactic tocolysis was found to briefly prolong
latency. In another study by Jazayeri et al, latency was shorter when magnesium sulfate was
given. [25] The use of tocolysis, unlike corticosteroids and antibiotics, should be considered only
when a clear clinical benefit exists, such as in transport of the mother to a tertiary institution with
a NICU.
Many large clinical studies have evaluated neuroprotective benefits from exposure to magnesium
sulfate in preterm neonates. The studies show a reduction in cerebral palsy in surviving infants
who were exposed to magnesium. None of the individual studies found a benefit with regard to
their primary outcome. However, available evidence suggests that magnesium sulfate given
before anticipated early preterm birth reduces the risk of cerebral palsy in surviving
infants, [26, 27]Physicians electing to use magnesium sulfate for fetal neuroprotection should
develop specific guidelines regarding inclusion criteria, treatment regimens, concurrent tocolysis,
and monitoring in accordance with one of the larger trials. [28]
In these studies, 12-24 hours of exposure was used with either a 4- or 6-g bolus and a
maintenance dose of 1-2 g. These findings should be discussed with patients undergoing
expectant management of PROM. [29]
Note that antenatal administration of magnesium sulfate in preterm children (at risk of being
delivered at 24.0 weeks' gestation) in the setting of chorioamnionitis does not appear to provide
neuroprotection. [30]
The use of tocolysis for 48 hours to administer steroids and allow acceleration of fetal lung
maturity has been proposed and is being used by some obstetricians. No data support the efficacy
of this practice and, as such, when used in this manner, the lack of evidence to support this
practice should be discussed with patients to allow informed consent prior to the use of tocolytics
and the potential complications and side effects.
Summary
PPROM is a common complication of pregnancy occurring in about 3% of all pregnancies. The
obstetrician needs to be familiar with appropriate management of PPROM. High-risk
consultation with a maternal-fetal medicine subspecialist should be considered in all cases to
ensure appropriate current therapy is instituted.
In general, the following guidelines should be followed:
ROM diagnosis needs to be confirmed.
Digital vaginal examinations should be avoided.
Ultrasonography should be performed to confirm gestational age, estimated fetal weight,
presentation, amniotic fluid index, and fetal anatomy if not already fully evaluated.
Antibiotics need to be given based on present evidence. See Medical Treatment.
Corticosteroids should be given to accelerate lung maturity between 24 and 34 weeks.
Informed consent should be obtained for expectant management versus delivery with
careful documentation in the chart.
In PPROM, the rule should be hospitalization after viability in an institution where care for
a premature neonate can be provided.
Maternal health is the primary indicator for the need to deliver. Any evidence of infection
or maternal instability due to complications of PPROM, such as bleeding, requires careful
evaluation and determination of the appropriateness of expectant management.
Fetal monitoring should be performed at least daily until delivery, and fetal well being and
growth should be evaluated periodically with ultrasonography.
After 32 weeks' and certainly after 34 weeks' gestation, the appropriateness of expectant
management of PPROM should be reevaluated individually for each case.
PROM at term should be managed by delivery unless reasons exist to consider waiting for
spontaneous labor. Large enough studies to document neonatal safety of expectant
management of PROM at term do not exist.