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Premature Rupture of Membranes

Author: Allahyar Jazayeri, MD, PhD, FACOG, DACOG, FSMFM; Chief Editor: Carl V
Smith, MD

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%

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and 44%, respectively. Ekin and colleagues concluded that MPV is more efficient than
platelet count for predicting PPROM.[12]
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.

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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 broadspectrum 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.
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]

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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

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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, erythromycinbase 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.

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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]

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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.