Preterm prelabor rupture of membranes: Clinical

manifestations and diagnosis

Author: Patrick Duff, MD
Section Editor: Charles J Lockwood, MD, MHCM
Deputy Editor: Vanessa A Barss, MD, FACOG

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Feb 2024. | This topic last updated: Jan 16, 2024.

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.

The epidemiology, pathogenesis, clinical manifestations, diagnosis, and clinical course

of PROM at approximately 23 to 37 weeks of gestation will be discussed here.
Management of PROM at 23 to 37 weeks, as well as PROM before and after this
gestational age range, are reviewed separately:
● (See "Preterm prelabor rupture of membranes: Management and outcome".)
● (See "Prelabor rupture of membranes before and at the limit of viability".)
● (See "Prelabor rupture of membranes at term: Management".)

PREVALENCE

Approximately 3 percent of pregnancies <37 weeks are complicated by PPROM. By

gestational age, approximately 0.5 percent of PROM occurs at <27 weeks, 1 percent
occurs at 27 to 34 weeks, and 1 percent occurs at 34 to 37 weeks [1-3].
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 [4]. 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 [5].
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. (See "Spontaneous preterm birth: Pathogenesis".)

RISK FACTORS

A variety of risk factors predispose to development of PPROM. These risk factors are
similar to those for preterm labor ( table 1) (see "Spontaneous preterm birth:
Overview of risk factors and prognosis"). However, many patients have no obvious
identifiable risk factor.

A history of PPROM in a previous pregnancy, genital tract infection, antepartum

bleeding, and cigarette smoking have a particularly strong association with PPROM
and are discussed below [6].
● 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 [7]. (See "Bacterial vaginosis: Clinical manifestations and diagnosis".)
 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. (See "Spontaneous preterm birth:
Pathogenesis" and "Spontaneous preterm birth: Overview of risk factors and
prognosis".)
● 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 (13.5 versus 4.1 percent, relative risk [RR] 3.3, 95% CI
2.1-5.2) [8]. Moreover, in the subsequent pregnancy, patients with a history of
PPROM leading to preterm birth were at high risk of PPROM and preterm birth
before 28 weeks (1.8 versus 0.13 percent in patients with no history of preterm
birth due to PPROM, RR 13.5, 95% CI 23.0-80.3). Others have reported recurrence
rates as high as 32 percent [9].
● 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 [6,11,12].

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. (See 'Pathogenesis' above and "Spontaneous preterm birth:
Pathogenesis", section on '#3 Decidual hemorrhage'.)
● Cigarette smoking – The risk of PPROM among smokers is increased two- to
fourfold compared with nonsmokers. The risk persists even after adjustment for
known confounders. The mechanism for the association is unclear. (See
"Cigarette and tobacco products in pregnancy: Impact on pregnancy and the
neonate".)

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 PPROM.

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 (ie, time from PPROM to delivery) [13-15].

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). (See "Assessment of amniotic
fluid volume", section on 'Semiquantitative techniques'.)

In a prospective study of 290 singleton pregnancies with PPROM at 24 to 34 weeks of

gestation, 67 percent had an AFI <5 cm, and 47 percent had an MVP <2 cm [16].

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. (See 'Laboratory tests' below.)

DIAGNOSTIC EVALUATION AND DIAGNOSIS

Our approach — We base the diagnosis of PPROM primarily on characteristic

findings on both history and physical examination: a pregnant patient presents with a
history of leaking fluid, and on sterile speculum examination, pooling of amniotic fluid
in the posterior vaginal vault is observed. Pooling is the gold standard for diagnosis. If
pooling is not observed, asking the patient to press on their fundus, cough, and bear
down can enhance flow of amniotic fluid from the cervical os and confirm the
diagnosis.

If pooling is still not seen, the author performs an ultrasound examination to assess
amniotic fluid volume. In the author's practice, in a patient with a characteristic
history of leaking fluid:
● Oligohydramnios (defined by an amniotic fluid index [AFI] ≤5 cm, maximum
vertical pocket [MVP] <2 cm, or subjective impression) is presumptive evidence of
PROM, so no additional diagnostic testing is performed.
● If the amniotic fluid volume is low normal (defined as an AFI 6 or 7 cm or by
subjective impression) or normal (eg, by an AFI >7 cm or subjective impression),
the author orders one of the commercial tests for detecting amniotic fluid (see
 'Commercial tests' below) and uses the result to confirm or exclude the diagnosis
of PROM.
● If the amniotic fluid volume is high (defined by an AFI >24 cm, MVP ≥8 cm, or
subjective impression), this finding almost always excludes the diagnosis of
PPROM. The patient is discharged home if not in labor and given instructions to
call if leaking recurs. (See "Polyhydramnios: Etiology, diagnosis, and management
in singleton gestations".)

Access to ultrasound is readily available to most clinicians and the examination also
provides information about fetal status. The author no longer performs nitrazine
paper or fern tests, primarily because of the possibility of false-positive results that
could lead to inappropriate clinical decisions. Moreover, some facilities no longer
permit clinicians to perform these tests because of quality assurance and compliance
issues. (See 'Nitrazine and fern tests' below.)

Laboratory tests

Commercial tests — The author bases the choice of commercial test on cost and the
ease of performance in an individual hospital laboratory. Several tests for diagnosis of
PROM are now commercially available. A 2013 meta-analysis of prospective
observational or cohort studies investigating insulin-like growth factor binding
protein 1 (IGFBP-1 [Actim PROM]) and placental alpha microglobulin-1 protein assay
(PAMG-1 [AmniSure]) for diagnosis of rupture of membranes concluded PAMG-1
(AmniSure) was more accurate than IGFBP-1 (Actim PROM) for diagnosis of rupture of
membranes in all patient populations (eg, known rupture status, uncertain rupture
status) [17]. A subsequent randomized trial reported similar findings [18].

Health care providers using these tests should be aware of their limitations, which are
listed in the manufacturer's instructions, and use them as one component of the
overall clinical assessment for PPROM (eg, history, speculum examination, ultrasound
findings) [19]. There are no data to indicate that the performance of these tests varies
across pregnancy.

PAMG-1 (AmniSure) — AmniSure is a rapid slide test that uses

immunochromatography to detect trace amounts of placental alpha microglobulin-1
protein in vaginal fluid. Placental alpha microglobulin-1 is released from decidual
cells. The test is not affected by semen or trace amounts of blood.

The test is designed to be performed by the provider at the point of care using a
commercially available kit but can be performed in the hospital laboratory if clinician
credentialing is a concern. A sterile swab is inserted into the vagina for one minute,
then placed into a vial containing a solvent for one minute, and then an AmniSure test
strip is dipped into the vial. The test result is revealed by the presence of one or two
lines within the next 5 to 10 minutes (one visible line means a negative result for
amniotic fluid, two visible lines is a positive result, and no visible lines is an invalid
result).

In large studies, sensitivity ranged from 94.4 to 98.9 percent, and specificity ranged
from 87.5 to 100 percent [20-24]. In one study, the authors hypothesized that false-
positive results in three patients might have been due to a small leak that sealed over
[21].

IGFBP-1 (Actim PROM) — IGFBP-1, also called placental protein 12 (PP12), is

secreted by decidual and placental cells and has a very high concentration in amniotic
fluid compared with other bodily fluids. An easy-to-use immunochromatography
dipstick method (eg, Actim PROM) is available in some countries for use at the
bedside to detect IGFBP-1 in vaginal secretions but can be performed in the hospital
laboratory if clinician credentialing is a concern. A positive test is denoted by the
presence of two blue lines on the dipstick. The test is not affected by the presence of
bacteria in vaginal secretions, urine, semen, or small amounts of blood.

Sensitivity ranges from 95 to 100 percent, specificity ranges from 93 to 98 percent,

and positive predictive value approaches 98 percent [23,25-28]. The test is most
accurate when performed as soon as possible after PROM.

Placental protein 12 and alpha-fetoprotein (ROM Plus) — A combination

monoclonal/polyclonal antibody test for diagnosis of PPROM detects two protein
markers found in amniotic fluid: PP12 (also called IGFBP-1) and alpha-fetoprotein
(AFP). The test is performed by placing the ROM Plus test swab in the vagina for 15
seconds, placing the swab in a diluent, and then placing a sample of the diluent on a
special test strip, which develops a line if the proteins are present. Trace amounts of
blood do not affect the test.

A multicenter prospective observational study that compared the accuracy of this

point-of-care test with conventional clinical assessment (speculum examination plus
both fern and nitrazine tests) for diagnosis of rupture of membranes in 285 patients
at 15 to 42 weeks of gestation found that the immunoassay had higher sensitivity (99
versus 85 percent) and lower specificity (91 versus 98 percent) [29]. A limitation of this
study was that confirmation of PROM was based on review of the medical records
following delivery.

Nitrazine and fern tests

● Nitrazine – Nitrazine paper is used to test the pH of vaginal fluid. Nitrazine (or
phenaphthazine) is a pH indicator dye that indicates pH in the 4.5 to 7.5 range.
Amniotic fluid usually has a pH range of 7.0 to 7.3, which is different from the
normal vaginal pH of 3.8 to 4.2 and usually different from the pH of urine, which
is typically <6.0 but may be higher ( picture 1) [30].

False-negative and false-positive nitrazine test results occur in up to 5 percent of

cases [31,32]. False-negative test results can occur when leaking is intermittent or
the amniotic fluid is diluted by other vaginal fluids. False-positive results can be
due to the presence of alkaline fluids in the vagina, such as blood, seminal fluid,
or soap. In addition, the pH of urine can be elevated to near 8 if infected with
Proteus species.
● Fern – Dried amniotic fluid shows an arborization (ferning) pattern when viewed
under a microscope. Fluid from the posterior vaginal fornix is swabbed onto a
glass slide and allowed to dry for at least 10 minutes. Amniotic fluid produces a
delicate ferning pattern, in contrast to the thick and wide arborization pattern of
dried cervical mucus ( picture 2 and picture 3).

Well-estrogenized cervical mucus or a fingerprint on the microscope slide may

cause a false-positive fern test; false negatives can be due to inadequate amniotic
fluid on the swab or heavy contamination with vaginal discharge or blood.

Home tests — In the United Kingdom, an absorbent pad (AmnioSense) that changes
color at pH >5.2 is used as a panty liner and marketed to pregnant people. Vaginal
flora (eg, Candida albicans) may cause false-positive results [33].

The manufacturer cites sensitivity and specificity of 95.8 and 87 percent, respectively,
compared with standard clinical diagnosis [34]. In a study of 139 pregnant people, the
sensitivity and specificity of this device for diagnosis of membrane rupture were 98
and 65 percent, respectively (95% CI 91-100 and 54-75, respectively) [33].

Other
● Instillation of dye (tampon test) – This invasive test has been replaced by
commercial noninvasive tests. It can be challenging to perform when amniotic
fluid volume is severely reduced, and can cause rupture of membranes if the
membranes are intact. (See 'Commercial tests' above.)

In the past, clinicians performed the "tampon test" in problematic cases. Under
ultrasound guidance, 1 mL of indigo carmine dye in 9 mL of sterile saline was
injected transabdominally into the amniotic fluid, and a tampon was placed in the
vagina. Twenty minutes later, the tampon was removed and examined for blue
staining, which indicated leakage of amniotic fluid. It should be noted that
maternal urine will also stain blue and should not be mistaken for amniotic fluid.

Indigo carmine dye is no longer readily available in the United States. Possible
alternatives to indigo carmine include sodium fluorescein and
phenolsulfonphthalein (where available) [35].

DIFFERENTIAL DIAGNOSIS

Other causes of vaginal/perineal wetness include urinary incontinence, excessive

vaginal discharge (normal or related to infection), cervical mucus, and perspiration.
These entities can be distinguished by differences in their characteristics.
● Characteristics of amniotic fluid:

• The appearance of amniotic fluid (clear or pale yellow) can be similar to that of
urine, but amniotic fluid is odorless (in the absence of infection).

• Amniotic fluid leakage is continuous or intermittent, whereas bladder leakage

should cease after the bladder is emptied and kept at low volume.
 • Amniotic fluid usually has a pH range of 7.0 to 7.3, which is different from the
normal vaginal pH of 3.8 to 4.2 and usually different from the pH of urine,
which is typically <6.0 but may be higher ( picture 1) [30].

• Amniotic fluid and urine have different chemical compositions (urine has
higher creatinine and urea levels [36]), but such testing is rarely indicated.
● Characteristics of vaginal discharge:

• Vaginal discharge may be clear or yellow, similar to amniotic fluid and urine,
but it is generally thick, not watery, and has distinct findings ( table 2) that
distinguish it from these other substances.
● Perspiration may result in perineal wetness, but it is not accompanied by pooling
in the vagina.
● Cervical mucus is clear and has a high pH (7) like amniotic fluid, but no more than
a small amount pools in the vagina and leakage is self-limited. It has a thick and
wide arborization pattern ( picture 2 and picture 3) in contrast to the delicate
ferning pattern of amniotic fluid. (See 'Nitrazine and fern tests' above.)
● A reduction of amniotic fluid volume on ultrasound is a nonspecific finding
related to many etiologies, including PPROM, but these etiologies (eg,
abnormality of the fetal kidney/urinary tract, fetal growth restriction) are not
associated with leaking and have other fetal findings. (See "Assessment of
amniotic fluid volume".)

CLINICAL COURSE

Cessation of fluid leakage is rare, except in patients with PPROM related to

amniocentesis. Sealing of membranes is associated with a more favorable prognosis
[37]. (See "Diagnostic amniocentesis", section on 'Leakage of amniotic fluid'.)

The duration of the latency period (ie, time from PROM to delivery) inversely
correlates with gestational age at membrane rupture and is shorter in cases with
residual oligohydramnios [38]. Nevertheless, the majority of pregnancies with PPROM
deliver within one week of membrane rupture. In a randomized trial of 239 group B
streptococcus-negative patients with PPROM at 24 to 32 weeks managed expectantly
with prophylactic antibiotics, the median time to delivery was 6.1 days; the cumulative
delivery rate was 27 percent within 48 hours, 56 percent within 7 days, 76 percent
within 14 days, and 86 percent within 21 days [39,40]. Among the minority of patients
who did not deliver within this timeframe, one had a latency period of 59 days.

In the absence of spontaneous labor, delivery timing depends on occurrence of

complications that would prompt delivery or gestational age ≥34 weeks. Antepartum
management and timing of delivery are discussed in detail separately. (See "Preterm
prelabor rupture of membranes: Management and outcome", section on 'Timing of
delivery'.)

COMPLICATIONS

The fetus and neonate are at greater risk of PPROM-related morbidity and mortality
than the mother ( table 3).
● Chorioamnionitis – Chorioamnionitis has been reported in up to 60 percent of
cases and is a common reason for induction or initiation of spontaneous labor
[41]. Clinical chorioamnionitis is increased twofold in cases with residual
oligohydramnios [38]. (See "Clinical chorioamnionitis".)
● Abruption – Placental abruption occurs in 2 to 5 percent of pregnancies
complicated by PPROM [42-45]. The risk is increased seven- to ninefold in PPROM
pregnancies complicated by intrauterine infection or oligohydramnios [43,44].
Placental abruption may be the precipitating event for, or a consequence of,
PPROM. (See "Acute placental abruption: Pathophysiology, clinical features,
diagnosis, and consequences", section on 'Pathophysiology'.)
● Other – Fetal malpresentation is common, given the preterm gestational age and
the frequent occurrence of reduced amniotic fluid volume. Noncephalic
presentation may increase the risk of cord prolapse, abruption, infection, and
fetal demise [46].

The risk of cord prolapse is especially high (11 percent in one study [47]) in the
setting of both noncephalic fetal presentation and PPROM. (See "Umbilical cord
 prolapse" and "Acute placental abruption: Pathophysiology, clinical features,
diagnosis, and consequences".)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and

regions around the world are provided separately. (See "Society guideline links:
Prelabor rupture of membranes".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond
the Basics." The Basics patient education pieces are written in plain language, at the
5th to 6th grade reading level, and they answer the four or five key questions a patient
might have about a given condition. These articles are best for patients who want a
general overview and who prefer short, easy-to-read materials. Beyond the Basics
patient education pieces are longer, more sophisticated, and more detailed. These
articles are written at the 10th to 12th grade reading level and are best for patients
who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage
you to print or e-mail these topics to your patients. (You can also locate patient
education articles on a variety of subjects by searching on "patient info" and the
keyword(s) of interest.)
● Basics topics (see "Patient education: Preterm prelabor rupture of membranes
(The Basics)")

SUMMARY AND RECOMMENDATIONS

● Terminology and epidemiology – Preterm prelabor rupture of membranes
(PPROM) refers to rupture of fetal membranes prior to onset of labor in
pregnancies <37+0 weeks. It occurs in 3 percent of pregnancies. PPROM is the
 most common identifiable cause of preterm birth and responsible for one-third of
such births. (See 'Introduction' above and 'Prevalence' above.)
● Risk factors – Genital tract infection, a history of PPROM in a previous pregnancy,
antepartum bleeding, and cigarette smoking have a particularly strong
association with PPROM. PPROM in a previous pregnancy is associated with at
least a threefold increase in risk of PPROM in the subsequent pregnancy. Other
important risk factors include polyhydramnios and abdominal trauma. (See 'Risk
factors' above.)
● Diagnosis – The diagnosis of PPROM is clinical, based on visualization of amniotic
fluid coming out of the cervical canal/pooling in the posterior vaginal fornix of a
patient who presents with a history of leaking fluid. In the absence of pooling, we
suggest an ultrasound examination as the next step in the diagnostic evaluation
( algorithm 1). In a patient with a characteristic history of leaking fluid (see 'Our
approach' above):

• In the absence of another obvious cause such as fetal urinary tract obstruction,
oligohydramnios is presumptive evidence of PROM, so no additional diagnostic
testing is performed.

• If the amniotic fluid index (AFI) is low normal or normal, the author orders one
of the commercial tests for detecting amniotic fluid in the vagina and uses the
result to confirm or exclude the diagnosis of PROM. (See 'Commercial tests'
above.)

Checking pH and arborization ("nitrazine and fern") on a sample from the

posterior vaginal fornix is an acceptable alternative. However, these tests can
be misleading in the setting of bleeding, highly estrogenized cervical mucus,
and a urinary tract infection due to Proteus species. (See 'Nitrazine and fern
tests' above.)

• If the AFI is high (polyhydramnios), this finding almost always excludes the
diagnosis of PPROM. The patient is discharged home if not in labor and given
instructions to call if leaking recurs.
● Differential diagnosis – Other causes of vaginal/perineal wetness include
urinary incontinence, excessive vaginal discharge (normal or related to infection),
 cervical mucus, and perspiration. These diagnoses can be excluded by history,
physical examination, sonography, and laboratory testing for amniotic fluid. (See
'Differential diagnosis' above.)
● Clinical course

• Cessation of fluid leakage is rare, except in patients with PPROM related to

amniocentesis. Sealing of membranes is associated with a more favorable
prognosis. (See 'Clinical course' above.)

• The duration of the latency period (ie, time from PROM to delivery) inversely
correlates with gestational age at membrane rupture; however, the majority of
pregnancies with PPROM deliver within one week of membrane rupture. In the
absence of spontaneous labor, delivery timing depends on occurrence of
complications that would prompt delivery or gestational age ≥34 weeks. (See
'Clinical course' above.)

• The fetus and neonate are at greater risk of PPROM-related morbidity and
mortality than the mother ( table 3). In the absence of spontaneous labor,
complications that should prompt delivery include chorioamnionitis, placental
abruption, and fetal heart rate abnormalities suggesting cord prolapse or
compromise. (See 'Complications' above.)
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