PPROM

Vindula JMO (MD/2018/5370)

41st Batch

PPROM
INTRODUCTION
Prelabor rupture of membranes (PROM) refers to fetal membrane rupture before the onset of
uterine contractions. Preterm PROM (PPROM) refers to
PROM before 37+0 weeks of gestation. It is responsible
for, or associated with, approximately one-third of preterm
births and is the single most common identifiable factor
associated with preterm birth.

Spontaneous rupture of membranes prior to onset of

labour at POG <37 wks
2 – 3 % of pregnancies of POG < 37 wks
POG - Latent phase
POG of 32 weeks: approx. 50 % in labour within 24 – 48
hrs.

POG of 26 weeks: approx. 50 % in labour within 1 wk.

PPROM associated with - 1/3 of preterm deliveries

- placental abruption

- Increased NND – due to Prematurity, Sepsis &

Pulmonary Hypoplasia

- Chorioamnionitis

PATHOGENESIS
The pathogenesis of spontaneous membrane rupture is not completely understood. The
strength and integrity of fetal membranes derive from extracellular membrane proteins,
including collagens, fibronectin, and laminin, whereas matrix metalloproteases (MMPs)
decrease membrane strength by increasing collagen degradation. A variety of pathologic events
(eg, subclinical or overt infection, inflammation, mechanical stress, bleeding) can disrupt these
and other homeostatic processes and initiate a cascade of biochemical changes that culminate
in PROM. Although the pathway varies depending on the initiating event (which is not always
identifiable), it is likely that all pathways lead to a final common pathway ending in membrane
rupture.

RISK FACTORS
Usually pathological in origin
- ascending infections (majority subclinical )
vaginal (Chlamydia, Bacterial vaginosis)
UTI
- polyhydramnios
- multiple pregnancies
- recurrent APH
- history of previous PPROM or PTL (ascending infection)

1.Genital tract infection – Genital tract infection is the single most common identifiable risk
factor for PPROM. Three lines of epidemiologic evidence strongly support this association: (1)
patients with PPROM are significantly more likely than those with intact membranes to have
pathogenic microorganisms in the amniotic fluid, (2) patients with PPROM have a significantly
higher rate of histologic chorioamnionitis than those who deliver preterm without PPROM, and
(3) the frequency of PPROM is significantly higher in patients with certain lower genital tract
infections (particularly bacterial vaginosis) than in uninfected patients.

The association between bacterial colonization of the lower genital tract and PPROM is not
surprising. Many of the microorganisms that colonize the lower genital tract have the capacity
to produce phospholipases, which can stimulate the production of prostaglandins and thereby
lead to the onset of uterine contractions. In addition, the host's immune response to bacterial
invasion of the endocervix and/or fetal membranes leads to the production of multiple
inflammatory mediators that can cause localized weakening of the fetal membranes and result
in PPROM [7]. Genetic regulation of the host's immune and inflammatory responses appears to
play a role in susceptibility and response to infections associated with PPROM

2. Previous PPROM – Studies have consistently reported that a history of PPROM is a strong
risk factor for recurrence. As an example, the Preterm Prediction Study, a large prospective
study conducted by the National Institute of Child Health and Human Development (NICHD)
Maternal-Fetal Medicine Units (MFMU) Network, observed that patients with a history of PPROM
leading to preterm birth had a threefold higher frequency of PPROM in a subsequent pregnancy
compared with those with no such history

3. Antepartum bleeding – First trimester vaginal bleeding is associated with a small but
statistically significant increase in the risk of PPROM [10]. Antepartum bleeding in more than
one trimester increases the risk of PPROM three- to sevenfold

The development of PPROM in the setting of bleeding from abruption may be related to the high
decidual concentration of tissue thromboplastin factor (also known as tissue factor III). In
addition to its hemostatic properties, thrombin binds to decidual protease-activated receptors
(PAR1 and 3) that up-regulate the expression of proteases such as matrix metalloproteases,
which, in turn, degrade membranes.

4. Cigarette smoking – The risk of PPROM among smokers is increased two- to fourfold
compared with nonsmokers.

 In addition, polyhydramnios, acute abdominal trauma (eg, from a motor vehicle collision,
accidental fall, or domestic violence), and several polymorphisms of genes related to
infection, inflammation, and collagen degradation have been identified as risk factors
for PPR
CLINICAL FINDINGS
Patient presentation — The classic clinical presentation of PPROM is a sudden "gush" of clear
or pale yellow fluid from the vagina that soaks through clothes. However, many patients
describe only leaking small amounts of fluid either continuously or intermittently, and some just
report a sensation of abnormal wetness of the vagina or perineum.

Physical examination — For patients who are not in active labor, examination of the cervix and
vagina should be performed using a sterile speculum. Digital examination should be avoided
because it may increase the risk of intrauterine infection and thus decrease the latency period

Direct observation of amniotic fluid leaking from the cervical os and pooling in the vaginal
vault is diagnostic of PPROM. If amniotic fluid is not immediately visible, the patient can be

asked to push on their fundus, Valsalva, or cough to provoke leakage of amniotic fluid from the
cervical os.

The cervix may appear dilated and/or effaced, and rarely, prolapse of a fetal part or the umbilical
cord may be observed.

Ultrasonography — Many, if not most, patients have amniotic fluid volume that is less than
expected for gestational age. Criteria for oligohydramnios vary slightly among sonographers but
can be defined as a maximum vertical pocket (MVP, also called single deepest pocket [SDP]) of
amniotic fluid <2 cm or an amniotic fluid index (AFI) ≤5 cm (some use ≤2 cm and <5 cm,
respectively).

Laboratory — Hematology and chemistry tests are normal in the absence of infection or other
complications of pregnancy. Laboratory tests to identify amniotic fluid are described below.

INVESTIGATIONS
DIAGNOSIS
Crucial (Vide PROM) : Interventions & management will depend on diagnosis

The diagnosis of spontaneous rupture of the membranes is made by maternal history

followed by a sterile speculum

examination demonstrating liquor
 MANAGEMENT
 ANTEPARTUM MANAGEMENT

The management of pregnancies complicated by PPROM is based upon consideration of

several factors, which are assessed upon presentation:

●Gestational age

●Presence or absence of maternal/fetal infection

●Presence or absence of labor

●Fetal presentation

●Fetal well-being

●Expectation of fetal lung maturity based on gestational age

●Cervical status (by visual inspection)

●Availability of an appropriate level of neonatal care

The key decision is whether to induce labor (or perform cesarean delivery) or to manage the
pregnancy expectantly.

The early preterm fetus (ie, <34+0 weeks) who is otherwise stable will benefit by prolonging the
time it remains in the uterus if the duration is sufficient to allow a significant reduction in
gestational age-related morbidity.

The late preterm fetus (34+0 to 36+6 weeks) may benefit as well, although there is less
consensus at this gestational age. However, this benefit needs to be balanced with the risks of
PPROM-associated complications and their sequelae in expectantly managed pregnancies:
intrauterine infection, placental abruption, and cord prolapse/compression.

Expeditious delivery of women with PPROM is appropriate in the setting of intrauterine infection,
placental abruption, or nonreassuring fetal testing. In each of these conditions, fetal well-being
can deteriorate rapidly with expectant management, and there are no therapeutic interventions
available other than delivery. For the same reason, an unstable lie with a high risk of cord
prolapse is an indication for delivery rather than expectant management, but the balance
between the risks of cord prolapse and birth of a very or extremely preterm birth also needs to
be considered on a case-by-case basis.

In the absence of complications, there is a consensus that patients with PPROM before 34+0
weeks should be monitored closely and managed expectantly at least until 34+0 weeks of
gestation. We believe that well-dated pregnancies initially managed expectantly should be
delivered at 34+0 weeks of gestation, but continuing expectant management until 37 weeks is
also a reasonable approach. A more detailed discussion of delivery timing is provided below.

Components of expectant management

 Administer antenatal corticosteroids — A course of corticosteroids should be

administered to pregnancies that present with PPROM between 23+0 and 33+6 weeks of
gestation.

A course of corticosteroids can be considered for patients who present with PPROM at 34+0 to
36+6 weeks of gestation who are going to be managed expectantly, have not received a
previous course of steroids, and who are scheduled for delivery in >24 hours and <7 days

Administration of antenatal steroids for pregnancies that present with PPROM in the 22nd week
of gestation is also reasonable if delivery in the next seven days is anticipated and the family
desires aggressive neonatal intervention after thorough consultation with maternal-fetal
medicine and neonatology specialists.

The effect of PPROM on fetal pulmonary maturation is unclear as studies have reported
inconsistent results. This discordancy may be due to failure to adjust for factors that affect
neonatal respiratory function, such as mode of delivery and presence or absence of labor, as
well as gestational age, duration of latency, and comorbidities such as chorioamnionitis.

Fetal exposure to inflammation can induce interleukin (IL)-1 production, which enhances
surfactant protein and lipid synthesis thereby promoting lung maturation; however, adverse
effects on lung development and outcome can also occur

 Screen for infection — The Centers for Disease Control and Prevention (CDC)
recommends screening for STIs (eg, HIV, syphilis, chlamydia, gonorrhea) in the third
trimester in women with risk factors for acquiring an STI

In women with PPROM, we perform this screening, as well as screening for group B
Streptococcus (GBS), on admission since these pregnancies are at high risk of preterm delivery.
Women with positive results are treated as appropriate. In some cases, the prophylactic
antibiotic therapy administered to prolong latency will provide adequate treatment.

Screening women with PPROM for bacterial vaginosis (BV) and Trichomonas vaginalis; however,
screening for these infections is controversial. Testing for BV using Amsel criteria (which
includes pH) is problematic since amniotic fluid in the vagina will interfere with pH-based
diagnosis of these entities; a positive Gram stain is predictive of BV but has low sensitivity. A
commercial test using nucleic acid amplification testing (NAAT; eg, Affirm VPIII or OSOM
BVBlue) is the most sensitive option for diagnosis of BV in this setting.
GBS — Chemoprophylaxis specifically for GBS is indicated if GBS test results are positive or
unknown and delivery is imminent.

For patients being managed expectantly, the intravenous portion of the prophylactic antibiotic
regimen to prolong latency described below (ampicillin 2 grams intravenously every 6 hours for
48 hours) should provide adequate prophylaxis for GBS-colonized women.

As noted below, this regimen of intravenous ampicillin, followed by oral amoxicillin, combined
with a single 1 gram dose of azithromycin, is usually given for seven days. After completion of
this regimen, antibiotics should be discontinued. If the patient's GBS culture is positive, specific
prophylaxis for GBS colonization (eg, penicillin) should be resumed when the patient
subsequently goes into labor.

Fetal monitoring

●Nonstress test and biophysical profile – Some type of fetal surveillance is generally employed
(eg, kick counts, NSTs, biophysical profile [BPP]) to provide the clinician and patient some
assurance of fetal well-being]. At our center, we perform a daily NST. If the NST is not
reassuring, we perform a BPP. However, none of these tests have good sensitivity for predicting
fetal infection, even when performed daily

PPROM does not alter the way the BPP is calculated or interpreted. A low BPP score (0, 2, or 4)
should be managed in standard fashion. The predictive value for infection is low since the low
score may be due to infection or to oligohydramnios and absent fetal breathing related to
PPROM.

●Amniotic fluid volume – Oligohydramnios is associated with an increased risk of umbilical

cord compression and shorter latency, but, as with other tests, the value of this finding alone for
prediction of adverse fetal/neonatal outcome in PPROM is low.

●Fetal growth – Periodic ultrasound evaluation of fetal growth is reasonable as pathologic

processes responsible for PPROM may also interfere with fetal growth. As a general rule,
growth assessments should be performed no more often than every two to three weeks.

●Umbilical artery Doppler – Doppler surveillance is not useful for monitoring fetal status in
PPROM, unless growth restriction (FGR) is also present. In this setting, the key abnormal
umbilical artery Doppler finding would be absent or reversed end-diastolic flow.
Maternal monitoring

Women with PPROM should be monitored for signs of infection; however, there is no consensus
as to the best approach. At a minimum, routine clinical parameters (eg, maternal temperature,
presence of uterine tenderness, frequency of contractions, maternal and fetal heart rate) should
be monitored.

Periodically monitoring white blood cell counts or other markers for inflammation/infection has
not been proven to be useful.

Amniocentesis to obtain amniotic fluid for Gram stain, culture, leukocyte esterase, glucose
concentration, and interleukin-6 (IL-6, where available) is more controversial. We do not routinely
perform amniocentesis to screen for intra-amniotic infection in asymptomatic women. If the
clinical diagnosis of chorioamnionitis is uncertain and we need more information to decide
whether to recommend expectant management, then we perform amniocentesis to rule out
infection. An in-depth discussion of the diagnosis and management of intraamniotic infection
can be found separately.

If there is insufficient amniotic fluid to sample, which occurs in up to 50 percent of patients,

then the diagnosis of chorioamnionitis will have to be based on clinical examination and indirect
testing such as identification of an abnormal peripheral white blood cell count.

Special situations

Women with HSV, HIV, or cerclage — Expectant management of women with PPROM and
genital herpes simplex virus (HSV) or HIV infection is controversial, and opinions about the best
course of action diverge widely.

Meconium-stained fluid — Patients with PPROM and meconium-stained amniotic fluid should be
evaluated for signs of chorioamnionitis. In the absence of these signs, meconium alone is not
an indication for intervention.

Studies of term and preterm PROM patients have generally reported that those with meconium-
stained amniotic fluid have higher rates of both overt and subclinical chorioamnionitis and
positive amniotic fluid cultures. Meconium release predisposes to infection. enhancing the
growth of bacteria and lowering phagocytic capacity of neutrophils.. However, it is also possible
that, in some cases, meconium-like staining is actually pigment associated with decidual
hemorrhage (abruption).

Twin pregnancy — We manage twin pregnancies with PPROM in the same way as singleton
pregnancies with PPROM based on clinical experience and generally accepted practice patterns.
Guidelines : SLCOG
- High vaginal swab (HVS) for microscopy, culture and ABST
- Confirm gestation
- Size of the fetus, lie, presentation
- Daily QH Temperature Chart
- FBC & CRP
- CTG if POG > 28 weeks
- Inform SHO / Registrar
- USS – fetal biometry / fetal anomalies /
AFI / placenta / cord presentation / doppler velocimetry
- Steroids -Women who have PPROM between 24+0 and 33+6 weeks’ gestation
should be offered corticosteroids; steroids can be considered up to 35+6 weeks’
gestation.
- Sterile pads for inspection
-Intravenous magnesium sulphate -women who are in established labour or having a
planned preterm birth within 24 hours, intravenous magnesium sulfate should be
offered between 24+0 and 29+6 weeks of gestation, magnesium sulfate should be
considered when preterm birth is anticipated between 30+0 and 33+6 weeks.

POG 34 – 37 Wks : Management Controversial

Remove cervical cerclage if present

Counsel / Informed choice
Delivery should be strongly considered if > 35 wks
Risk benefit analysis of expectant care :
Psychological & social factors
Risk of maternal DVT / chorioamnionitis
Risk of perinatal infection & morbidity
Risk of respiratory morbidity
If delivery is considered : management similar to PROM at > 37 wks
Risk of CS due to failed IOL
POG < 34 Wks : Expectant Management

- Routine management of PPROM

- CTG : Frequency as indicated by clinical condition
Daily CTG if AFI is low
- Daily QH Temp. chart
- DFMC
- FHS - Thrice daily fetal heart rate auscultation
(Pinnard or Handheld Doppler )
- Antibiotics
Ampicillin iv 2g / 6 hrly x 48 hrs
Erythromycin orally 250 mg / 6 hrly x 1 wk
Amoxycillin orally 500mg / 8 hrly x 5 days after 48 hrs
Change antibiotics depending on C/S report of HVS
Rpt. HVS after 3 days of no antibiotics & treat sos
- Tocolysis (vide PTL guidelines )
- Steroids (vide PTL guidelines )
- FBC Rpt. weekly
- CRP Rpt. twice weekly: poor predictive value for chorioamnionitis
supports a clinical diagnosis
- USS Rpt. weekly (esp AFI)
- HVS Rpt. after 10 days (no antibiotics for 3 days)
- If cervical cerclage present : remove after 48 hrs (steroid course completed )
or if chorioamnionitis + / fetal compromise + / PTL +

Delivery is indicated if:

Any signs of chorioamnionitis (broad spectrum IV antibiotics needed)
Fetal compromise
POG of 37 weeks achieved
Mode of delivery: decided on an individual basis
Continuous CTG monitoring if possible
Major Risks
- Chorioamnionitis
Diagnosis:
- Maternal pyrexia (> 38॰C)
+
at least two of either
- maternal tachycardia > 100 bpm
- fetal tachycardia> 160 bpm
- uterine tenderness
- increased CRP > 3 x upper limit of normal
- offensive vaginal discharge
- Placental abruption
- Preterm delivery
- Cord prolapse
- Operative delivery

If POG < 24 Wks (Pre Viable),

the fetus is at risk of:

- Pulmonary hypoplasia
- Chronic pulmonary morbidity
- Fetal limb shortening / dysplasia
- Extreme prematurity
DELIVERY
o Magnesium sulfate for neuroprotection — Magnesium sulfate is administered prior to
delivery according to standard clinical protocols for fetal neuroprotection
Route of delivery — In the absence of contraindications to labor and vaginal birth, most patients
will deliver by spontaneous or induced vaginal delivery. Cesarean delivery is performed for
standard indications; otherwise, labor is induced.
o Cervical ripening — Once delivery is indicated, we perform a digital cervical examination
to determine whether cervical ripening has occurred naturally. If the cervix is favorable
(Bishop score ≥6) , oxytocin is administered for induction according to standard
protocols.
If the cervix is unfavorable, we administer a prostaglandin (misoprostol) for cervical ripening;
however, the value of a cervical ripening agent in pregnancies with ruptured membranes has not
been established.
Prostaglandin E2 is a reasonable alternative There is no evidence that its use increases the risk
of infection in women with PROM

MANAGEMENT OF THE NEWBORN

OUTCOME
The fetus and neonate are at greater risk for PPROM-related morbidity and mortality than the
mother.
Fetal/neonatal — For the neonate, morbidity and mortality are primarily related to preterm birth;
residual oligohydramnios also plays a role [67]. The type and frequency of prematurity-related
morbidity depend on the gestational age at birth and whether chorioamnionitis is present [68].
Fetal exposure to intrauterine inflammation has been associated with an increased risk of
neurodevelopmental impairment.
Early, severe, prolonged oligohydramnios can be associated with pulmonary hypoplasia, facial
deformation, and orthopedic abnormalities. Such complications are most likely when membrane
rupture occurs at less than 23 weeks of gestation.
Maternal — Approximately one-third of women with PPROM develop potentially serious
infections, such as chorioamnionitis, endometritis, or septicemia. Endometritis is more common
after cesarean than vaginal delivery. The frequency of infection is higher at earlier gestational
ages at PPROM
MANAGEMENT OF FUTURE PREGNANCIES
As discussed above, a history of PPROM is a strong risk factor for recurrence
PPROM may be related to cervical insufficiency in some cases. In future pregnancies,
sonographic measurement of cervical length and placement of a cerclage if cervical length is
≤25 mm before 24 weeks of gestation can reduce the risk of recurrent preterm birth. Daily
vaginal progesterone administration is an alternative approach for patients with a short cervix.
Neither screening for asymptomatic infection with treatment of positive results nor empiric
antibiotic therapy has been proven to prevent PPROM.