CHAPTER I

Background
Premature rupture of membrane (PROM) is defined as rupture of the amniotic membranes
1,2
prior to 37 weeks of gestation without the onset of uterine contractions. Globally, the
incidence rate of premature rupture of membranes is approximately 8% to 10% in pregnant
women. Epidemiologic data demonstrate an association between colonization of the genital
tract by group B streptococci, Chlamydia trachomatis, Neisseria gonorrhoeae, and the
microorganisms that cause bacterial vaginosis (vaginal anaerobes, Gardnerella vaginalis,
Mobiluncus species, and genital mycoplasmas) and an increased risk of preterm premature
rupture of the membranes. 1,2
PROM is most accurately diagnosed via laboratory evidence of amniotic fluid in the
vaginal vault. 2,4 Management of PROM were based on patient gestational age. The consept in
managing patient with PPROM is an expectative management, while in PROM at term is an
active management. 2,4,5
Expectative management in patients with PPROM include appropriate monitoring of
fetal heart rate and uterine contractions, sign of chorioamnitis. Patients with PPROM should
be cared for expectantly until they have completed 34-37 weeks of gestation. The aim is to
prevent delivery as long as we can while trying to accelerate fetal lung maturity with
corticosteroid as desirable in preterm patients, unless fetal pulmonary maturity is
documented. The combination of birth weight, gestational age, and sex provide the best
estimate of chances of survival and should be considered in individual cases.2,5

1
 CHAPTER II

LITERATURE

DEFINITION
Premature rupture of membrane (PROM) is defined as rupture of the amniotic membranes
prior to 37 weeks of gestation without the onset of uterine contractions. In most cases, this
occurs near term, but when membrane rupture occurs before 37 weeks gestation, it is known
as preterm PROM.1,2

EPIDEMIOLOGY
Globally, the incidence rate of premature rupture of membranes is approximately 8% to 10%
in pregnant women. More than 500,000 babies are born preterm in the US each year,
accounting for 12.5% of all births, and this incidence is increasing. In the UK in 2005, 7.6%
of live births were preterm. In the last decade there has been more than a 50% increase in
preterm births to low-risk European women aged between 20 and 40 years.
A higher proportion of preterm deliveries occur in women of black ethnicity, and this
may in part be related to social disadvantage. Only 1% of all births occur below 32 weeks'
gestation. Rupture of membranes is generally followed by onset of labor within 24 hours.
Ninety percent of patients at term and 50% of preterm patients will begin labor within 24
hours of spontaneous rupture of membranes. For term patients, PROM will generally mark
impending labor and management can be expectant. PPROM often marks the onset of
preterm labor and patients should be managed appropriately for their degree of prematurity.2,3

ETIOLOGY
A number of factors have been associated with PROM including infectious, anatomic, and
pregnancy-related factors. A considerable number of cases, however, are idiopathic.
Trichomonas, bacterial vaginosis, urinary tract infection (UTI), gonorrhea, chlamydia, and
group B strep are among the infectious agents known or suspected to be associated with
PROM. Epidemiologic data demonstrate an association between colonization of the genital
tract by group B streptococci, Chlamydia trachomatis, Neisseria gonorrhoeae, and the
microorganisms that cause bacterial vaginosis (vaginal anaerobes, Gardnerella vaginalis,
Mobiluncus species, and genital mycoplasmas) and an increased risk of preterm premature
rupture of the membranes. 1,2

2
 Women with documented cervical incompetence are also at increased risk for PROM.
Amniocentesis is associated with an increased risk of PROM. This risk may be, in part,
related to the experience of the provider performing the procedure. For this reason, patients
requiring amniocentesis should be referred to providers with considerable experience.
Placental abruption is occasionally associated with PROM and should be considered in the
evaluation of patients with PROM. 2,4

RISK FACTOR
Risk factors of premature rupture of membranes include:
- Infection of the womans genital tract (nonspecific vaginosis, Trichomonas vaginalis,
Mycoplasma hominis, Chlamydia trachomatis, Neisseria gonnorhoe, streptococci of group B
(GBS), other sexually transmittable diseases (STD)
- Premature uterus activity
- Multiple pregnancies
- Vaginal bleeding in current gravidity
- Premature birth in anamnesis
- PROM in past gravidity
- Spontaneous miscarriage in 2nd trimester in anamnesis
- Incompetence of cervix
- Placenta praevia and placentation disorders
- Polyhydramnion
- Inborn development defects of uterus
- Condition after interventions on the cervix (conization, cerclage)
- Coitus
- Low socio-economic status related to bad nutrition
- Cigarette smoking 2,3,5

PATOPHYSIOLOGY
The cause of premature rupture of the fetal membranes is almost certainly multifactorial. It
was traditionally known that rupture of the membranes could be caused by physical stress,
particularly that associated with labor. However, more recent evidence suggests that
membrane rupture is also related to biochemical processes, including disruption of collagen
within the extracellular matrix of the amnion and the chorion and programmed death of cells
in the fetal membranes. It has been proposed that the fetal membranes and the maternal

3
uterine lining (decidua) respond to various stimuli, including membrane stretching and
infection of the reproductive tract, by producing mediators, such as prostaglandins, cytokines,
and protein hormones, that govern the activities of matrix-degrading enzymes. 1,2
Generalized weakness of the membranes has been more difficult to establish when
prematurely ruptured membranes have been compared with membranes that were artificially
ruptured during labor. Membranes that rupture prematurely, however, appear to be focally
defective rather than generally weakened. The area near the rupture site has been described as
a restricted zone of extreme altered morphology that is characterized by marked swelling
and disruption of the fibrillar collagen network within the compact, fibroblast, and spongy
layers. Because this zone does not include the entire rupture site, it may appear before
membrane rupture and represent the initial breakpoint.1

Changes in Collagen Content, Structure and Catabolism

The maintenance of the tensile strength of fetal membranes appears to involve an equilibrium
between the synthesis and the degradation of the components of the extracellular matrix. It
has been proposed that changes in the membranes, including decreased collagen content,
altered collagen structure, and increased collagenolytic activity, are associated with premature
rupture of the membranes. 1

Connective-Tissue Disorders and Nutritional Deficiencies as Risk Factors

Connective-tissue disorders are associated with weakened fetal membranes and an increased
incidence of preterm premature rupture of the membranes. 1
Nutritional deficiencies that predispose women to abnormal collagen structure have
also been associated with an increased risk of preterm premature rupture of the membranes.
Collagen cross-links, which are formed in a series of reactions initiated by lysyl oxidase,
increase the tensile strength of fibrillar collagens. Lysyl oxidase is produced by amniotic
mesenchymal cells, which lay down the collagenous compact layer of the amnion. Lysyl
oxidase is a copper-dependent enzyme, and women with premature rupture of the membranes
have lower copper concentrations in maternal and umbilical-cord serum than women whose
fetal membranes are artificially ruptured during labor. Similarly, women with low serum
concentrations of ascorbic acid, which is required for the formation of the triple helical
structure of collagen, have a higher rate of premature rupture of the membranes than those
with normal serum concentrations. 1

4
 Tobacco smoking, which independently increases the risk of preterm premature
rupture of the membranes, has been associated with decreased serum concentrations of
ascorbic acid. In addition, the cadmium in tobacco has been found to increase the metal-
binding protein metallothionein in trophoblasts, which may result in sequestration of copper.
These data suggest that the decreased availability of copper and ascorbic acid may contribute
to an abnormal structure of fetal-membrane collagen in smokers. Collectively, reduced
collagen cross-linking (possibly due to dietary deficiencies or behavioral activities) may
predispose women to premature membrane rupture. 1

Increased Collagen Degradation

The degradation of collagen is mediated primarily by matrix metalloproteinases, which are
inhibited by specific tissue inhibitors and other protease inhibitors. The matrix
metalloproteinases are a family of enzymes produced by various types of cells that hydrolyze
at least one component of the extracellular matrix. Because of the various substrate
specificities of matrix metalloproteinases, effective catabolism of the many component
molecules in the extracellular matrix requires the concerted actions of several enzymes. The
interstitial collagenases matrix metalloproteinase-1 (MMP-1) and MMP-8 cleave the triple
helix of the fibrillar collagens (types I and III), which are then further degraded by the
gelatinases MMP-2 and MMP-9. These gelatinases also cleave type IV collagen, fibronectin,
and proteoglycans. In human fetal membranes, MMP-1 and MMP-9 messenger RNA and
have been colocalized to amniotic epithelial cells and chorionic trophoblasts. Thus,the
compact (collagenous) layer of the fetal membranes is sandwiched between two layers of
cells that produce matrix metalloproteinases. 1
Tissue inhibitors of metalloproteinases form 1:1 stoichiometric complexes with matrix
metalloproteinases and inhibit their proteolytic activity. Tissue inhibitor of metalloproteinase-
1 (TIMP-1) binds to activated MMP-1, MMP-8, and MMP-9, and TIMP-2 binds to latent and
active forms of MMP-2. The more recently described TIMP-3 and TIMP-4 appear to inhibit
matrix metalloproteinases as efficiently as TIMP-1. Coordinated activities of matrix
metalloproteinases and tissue inhibitors of matrix metalloproteinases are essential to the
process of extracellularmatrix remodeling. 1
The integrity of the fetal membranes remains unaltered throughout most of gestation,
perhaps in part because of a combination of low matrix-metalloproteinase activity and a
relatively higher concentration of TIMP-1. Near the time of delivery, however, the balance
between activated matrix metalloproteinases and their tissue inhibitors shifts toward

5
proteolytic degradation of the extracellular matrix of the fetal membranes. In human amnion
and chorion, MMP-9 activity increases and TIMP-1 concentrations decrease dramatically
with labor. Analyses of membranes collected from women at the time of cesarean delivery
(with and without labor) and after spontaneous labor and delivery suggest that MMP-1
activity increases before labor, MMP-9 and MMP-3 activities increase during labor, and
TIMP-1 concentrations increase after delivery. These changes may reflect a coordinated
progression of events preceding and during parturition, resulting in the controlled degradation
of collagen within the fetal membranes. 1
Premature rupture of the membranes may also be caused by an imbalance between the
activities of matrix metalloproteinases and their tissue inhibitors, leading to inappropriate
degradation of the membranes extracellular matrixes. Collagenase activity is increased in
prematurely ruptured membranes at term. Overall, protease activity is increased in
membranes of women with preterm premature rupture of the membranes, the predominant
activity being that of MMP-9. 1

Clinical Factors Associated with Collagen Degradation and Premature Rupture of the
Membranes :
Infection
The identification of pathologic microorganisms in human vaginal flora soon after membrane
rupture provides support for the concept that bacterial infection may have a role in the
pathogenesis of premature membrane rupture. 1
Intrauterine infection may predispose women to rupture of the fetal membranes
through any of several mechanisms, each of which induces degradation of the extracellular
matrix. Several organisms that are commonly present in the vaginal flora, including group B
streptococci, Staphylococcus aureus, Trichomonas vaginalis, and the microorganisms that
cause bacterial vaginosis, secrete proteases that can degrade collagen and weaken the fetal
membranes. In an in vitro system, proteolysis of the fetal membrane matrix can be inhibited
by the addition of an antibiotic. 1
Bacterial infection and the host inflammatory response also induce prostaglandin
production by the fetal membranes, which is thought to increase the risk of preterm
premature rupture of the membranes by causing uterine irritability and collagen degradation
within the membranes. Certain strains of vaginal bacteria produce phospholipase A, which
releases the prostaglandin precursor arachidonic acid from membrane phospholipids within
the amnion. Furthermore, the immune response to bacterial infection includes the production

6
of cytokines by activated monocytes that increase prostaglandin E production by chorionic
cells. Prostaglandins (specifically prostaglandin E and prostaglandin F) are considered to be
mediators of labor in all mammals, and prostaglandin E diminishes collagen synthesis in fetal
membranes and increases MMP-1 and MMP-3 expression in human fibroblasts. 1
Another component of the host response to infection is the production of
glucocorticoids. In some tissues, including the amnion, glucocorticoids paradoxically
stimulate prostaglandin production. Glucocorticoids produced in response to the stress of
microbial infection facilitate rupture of the fetal membranes. 1
Hormones
Progesterone and estradiol suppress extracellularmatrix remodeling in reproductive tissues.
Both hormones decrease concentrations of MMP-1 and MMP-3 and increase the
concentrations of tissue inhibitors of metalloproteinases in the cervical fibroblasts. Relaxin, a
protein hormone that regulates the remodeling of connective tissues, is produced locally in
the decidua and placenta and reverses the inhibitory effects of estradiol and progesterone by
increasing MMP-3 and MMP-9 activities in fetal membranes. Expression of the relaxin gene
is increased before labor in human fetal membranes at term. Although it is important to
consider the roles of estrogen, progesterone, and relaxin in reproductive processes, their
involvement in the process of fetal-membrane rupture remains to be defined. 1
Programmed Cell Death
Programmed cell death, or apoptosis, has been implicated in the remodeling of various
reproductive tissues, including those of the uterus and cervix. Apoptosis is characterized by
the nuclear DNA fragmentation and catabolism of 28S ribosomal RNA subunits that are
required for protein synthesis. Amniotic epithelial cells undergo apoptotic cell death as labor
approaches. This cell death appears to follow the start of extracellular-matrix degradation,
suggesting that it is consequence and not a cause of catabolism of the extracellular matrix of
the amnion. Human amnion and chorion obtained at term after premature rupture of the
membranes contain many apoptotic cells in areas adjacent to the rupture site and fewer
apoptotic cells in other areas of the membranes. Although apoptotic changes have been
identified in fetal membranes immediately before delivery, the mechanisms regulating
apoptosis and the subsequent effects on the tensile strength of fetal membranes have yet to be
elucidated. 1
Membrane Stretch and Premature Rupture of the Membranes
Uterine overdistention due to both polyhydramnios and multifetal gestation induces
membrane stretch and increases the risk of premature rupture of the membranes. Mechanical

7
stretching of the fetal membranes up-regulates the production of several amniotic factors,
including prostaglandin E and interleukin-8. Stretch also increases MMP-1 activity within the
membranes. 1
Prostaglandin E increases uterine irritability, decreases synthesis of fetal-membrane
collagen, and increases production of MMP-1 and MMP-3 by human fibroblasts. Interleukin-
8, which is produced by amniotic and chorionic cells, is chemotactic for neutrophils and
stimulates collagenase activity. The production of interleukin-8, which is present in low
concentrations in the amniotic fluid during the second trimester but in much higher
concentrations late in gestation, is inhibited by progesterone. 1

Figure1. Patophysiology Mechanism of Premature Rupture of Membrane1

8
DIAGNOSIS
History Taking
Patients with PROM will often report discharge or leaking per vagina. This fluid leak may
be subtle (e.g., increased wetness noted on undergarments or pants) or may be substantial
(e.g., a gush of fluid). A careful history should be obtained to distinguish the causes of
discharge such as cervical infection, physiological mucus production (or loss of the mucus
plug), urinary incontinence, or UTI. Patients may also present with reported urinary
symptoms such as urinary incontinence or urinary frequency. Physiological changes
associated with pregnancy such as relative outflow obstruction and urinary stasis increase the
likelihood of urinary tract infection. For this reason, such urinary symptoms should be
carefully detailed to identify other symptoms consistent with UTI such as urgency, dysuria,
hematuria, abdominal pain, fever chills, nausea, vomiting, or back/costoverterbral angle
pain.2,4
History should include information concerning bleeding per vagina and symptoms
consistent with early or impending labor such as contractions, abdominal pain/cramps, back
pain, or mucus plug loss. In addition to obtaining the history associated with the leakage of
fluid, a brief review of the prenatal course is important. In particular, attention should be paid
to prior infections, previous episodes of contractions or preterm labor, prior episodes of
bleeding or multiple gestation. Review of the gestational dating, estimated date of delivery,
and the data used to calculate these is also critical. 2,4

PHYSICAL EXAMINATION
Vital signs should be documented and should include temperature, pulse, and blood pressure.
Note should be made of patient discomfort or pain. Abdominal examination should include
documentation of fundal height, abdominal tenderness, and fetal position (via Leopolds
maneuvers) Fetal heart rate should be documented including rate and variability. Uterine
contractions should be noted on tocometer.4
The primary concern under such circumstances is to minimize the possibility of
ascending infection. Manual examinations should be minimized. Sterile speculum
examination should be performed and assessment should include testing for common
infectious agents. On sterile speculum examination, note should be made of blood, fluid, or
discharge in the vaginal vault or at the cervical os. Samples should be obtained for gonorrhea,
chlamydia, group B strep, herpes (if characteristic or suspicious lesions are noted), yeast, and
trichomonas/bacterial vaginosis. 2,4

9
LABORATORY EXAMINATION
PROM is most accurately diagnosed via laboratory evidence of amniotic fluid in the vaginal
vault. The two most common tests for rupture of membranes are nitrazine testing and
ferning. A sample of amniotic fluid placed on nitrazine paper will turn the paper blue. 2,4
Litmus paper testing began development at approximately the same time as fetal cell
staining methods. Because of the difference in pH of vaginal secretions (4.5 to 5.5) and
amniotic fluid (7.0 to 7.5), it was rightly assumed that the pH of vaginal secretions would rise
when contaminated by escaping amniotic fluid. The accuracies of nitrazine test is 100%35
and 98.9% in clinically ruptured cases. False positive results from vaginal infections, blood,
semen, alkaline urine or alkaline antiseptics, and false negatives in cases of minimal leakage
from chronic membrane rupture or high leak of the membranes. 2,3,4
A sample of the fluid should also be spread thinly on a microscope slide and allowed
to air dry. The dried sample should show characteristic fern-shaped crystalline pattern on
microscopic examination. Amniotic fluid crystallization, created primarily by the sodium
chloride and protein content, began to dominate cytologic stains, with reported accuracies in
clinically ruptured cases ranging from 73.0% to 98.5%. False positive results were
subsequently attributed to fingerprints, semen, or cervical mucus. 2,3,4
A urine sample should be obtained for urinalysis, culture, and microscopic evaluation.
As noted previously, laboratory studies may include evaluation for gonorrhea, chlamydia,
group B strep, herpes, trichomonas, and bacterial vaginosis. Although gonorrhea, chlamydia,
group B strep, and herpes will not be immediately available, evaluation for yeast,
trichomonas, and bacterial vaginosis can be performed quickly and accurately in the office. A
microscopic examination of discharge/fluid may reveal clue cells (bacterial vaginosis),
flagellated organisms (trichomonas), or fungal elements (yeast). 2,3,4

Ultrasound Assessment Of Amniotic Fluid Volume

In the late 20th century, it was theorized that the sonographic identification of
oligohydramnios would develop after membrane rupture, thereby facilitating diagnosis
and subsequent management.Erdemoglu et al. showed that a reduction in the four-quadrant
AFI below 80 mm did not reliably identify cases of suspected membrane rupture by history
with negative visualization of fluid by speculum examination. The measurement of AFI offers
no advantage over measurement of a single vertical pocket of fluid in cases where ultrasound
is used to evaluate possible membrane rupture. 3,4
Intra-Amniotic Dye Injection

10
By 1970, amniocentesis with injection of dye to confirm amniotic membrane rupture had
become a commonplace procedure; it was thought to be safe and had high patient
acceptability rates. Prior to amniocentesis, intravenous injection of radioisotope was
performed for placental localization, and the amnio-injection was performed under local
anaesthesia. Interestingly, the two reported disadvantages of the procedure at that time were
related to difficulty in diagnosis in the presence of meconium-stained fluid and the possibility
of neonatal skin staining for 48 hours after dye injection. Several types of stains have been
used for amnio-injections, with safety hazards reported only for methylene blue. 3,4
Although ultrasonographically guided transabdominal instillation of indigo carmine
dye (1 mL of dye in 9 mL of sterile normal saline) and observation for fluid passage
transvaginally is designated an unequivocal diagnostic method for confirmation of
membrane rupture,14 this invasive test carries increased maternal and fetal risk. Inherent
risks of intra-amniotic dye injection include trauma, bleeding, infection, and preterm labour.
While strengthening diagnostic certainty, a negative dye test may occur if the membranes
seal after previous amniotic fluid leakage. 3,4

Glucose And Fructose Measurements

During pregnancy, glucose and fructose are present in high concentrations in cervical mucus,
with reported means of 240 mg/100 mL and 30.4 mg/100 mL, respectively. Amniotic fluid
concentrations are noticeably lower, with mean concentrations of 39 mg/100 mL and
3.3mg/100 mL, respectively. Gorodeski et al. showed that low values of glucose and fructose
are found in amniotic fluid aspirated in a true case of membrane rupture. Best results are
obtained with a calculated linear sum of the values (3.32 log glucose + log fructose). 3,4

Modern Methods
Because of the limitations of available testing methods, investigators have sought alternative
markers in vaginal amniotic fluid, such as prolactin, alpha-fetoprotein,-subunit of human
chorionic gonadotropin, fetal fibronectin, diamine oxidase, lactate, creatinine, urea, and
insulin growth factor binding protein-1, previously called placental protein. Interest in
assessment of these markers stems from their high concentrations in amniotic fluid compared
with normal vaginal secretions, but all require special laboratory equipment and training.
Although these markers are useful for patients with intact membranes or unequivocal
membrane rupture, they remain unpopular due to cost, testing complexity, and low test
sensitivities in cases of equivocal rupture. 3,4

11
Placental Alpha-Microglobulin-1
Initially isolated in Moscow in 1975,75 PAMG-1 has undergone recent evaluation for
diagnostic testing in PPROM. This 34kDa placental glycoprotein is abundant in amniotic
fluid (200025 000 ng/mL), with much lower concentrations in maternal blood (525
ng/mL). The protein is present in negligible amounts in cervicovaginal secretions with intact
membranes (0.050.2ng/mL). The 1000- to 10 000-fold difference in concentration between
amniotic fluid and cervicovaginal secretions stimulated interest in a PAMG-1 immunoassay.
The assays minimum detection threshold for PAMG-1 is 5 ng/mL, sufficient for 99%
accuracy with minimal false negatives. PAMG-1 can be detected with as little as 0.25 L of
amniotic fluid in 1 mL of vaginal secretions. In the presence of blood or vaginitis, the
background level of PAMG-1 can occasionally reach a maximum of 3 ng/mL.76 False-
positive results with use of this assay seem very unlikely, although these may appear with
increased use. Further, assay of PAMG-1appears to be reliable over a wide range of
gestational ages (11 to 42 weeks), and proved superior to conventional combined clinical
tests involving visualization of fluid pooling in the posterior fornix, arborization, and
nitrazine testing. 3,4

Non-Invasive Absorbent Pad

Efforts to be able to confirm chorioamniotic membrane rupture with minute amounts of
amniotic fluid have recently led to the development of the absorbent pad, AmnioSense. This
12,4 cm pad has a central strip that changes colour on contact with fluid with a pH > 5.2.
After contact with urine, the strip reverts to its original colour when dry. This is due to the
detachment of conjugate-based nitrazine molecules by the urine ammonium ions. The
AmnioSense pad initially showed 100% sensitivity; overall specificity was 75%. 3,4
In a recent study, Mulhair et al. compared the reliability of the absorbent pad test with
a standard of amniotic fluid pooling in the posterior fornix on speculum examination in
a cohort of 139 women. They found a specificity of 65.0% and a sensitivity of 98.3% for the
AmnioSense pad. The two studies of the absorbent pad currently available15,78 suggest
that a negative AmnioSense result indicates intact membranes in term and preterm gestations
in 99% of cases. A positive result, however, suggests only a 70% chance of ruptured
membranes, and thereby warrants confirmation or further investigations to identify infections.
3,4
It remains unknown whether potential confounding substances such as semen, blood, or
meconium may be distinguished from amniotic fluid by the AmnioSense pad test. As women

12
with negative pad checks are unlikely to have ruptured membranes, this would imply
decreased need for an uncomfortable and intrusive speculum examination. 3,4
The most extensively studied candidate marker is fetal fibronectin, which is present in
the extracellular matrix of fetal membranes and is structurally different from the fibronectin
of adult tissues. The production of fetal fibronectin by human amniotic cells is stimulated
by inflammatory mediators (including interleukin-1 and tumor necrosis factor-) that are
considered important in initiating preterm labor. 1,3,4

TREATMENT
Management of PROM were based on patient gestational age. The consept in managing
patient with PPROM is an expectative management, while in PROM at term is an active
management. 2,4,5
Expectative management in patients with PPROM include appropriate monitoring of
fetal heart rate and uterine contractions, sign of chorioamnitis. Patients with PPROM should
be cared for expectantly until they have completed 34-37 weeks of gestation. The aim is to
prevent delivery as long as we can while trying to accelerate fetal lung maturity with
corticosteroid as desirable in preterm patients, unless fetal pulmonary maturity is
documented. Particular attention should be paid to evaluation and management of possible
infection.Antibiotic prophylaxis is recommended to prevent infection as well to to prolong
latency if there are no contraindications. Some studies include the usage of tocolytic as an
agent to delay delivery by diminishing uterine contraction. 4, 6
Active management in patient with PROM at term is termination of pregnancy, as we
proceed to delivery, usually by induction of labor and also include antibiotic prophylaxis.4,6

Antibiotics
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, such as co-amoxiclav
increased the risk of neonatal necrotising enterocolitis and this antibiotic is best avoided.
Erythromycin or penicillin appears the antibiotic of choice. Erythromycin may be used in
women who are allergic to penicillin.7,8,9,10
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

13
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. 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. 7,8,9,10
Antibiotics are indicated for patients with evidence of infection. Suspected
chorioamnionitis should be treated with an appropriate broad-spectrum regimen such as
ampicillin and gentamicin (e.g., 2 g intravenous ampicillin every 4 hours and 2 mg/kg of
gentamicin loading dose then 1.5 mg/kg every 8 hours). 4,7,8

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. 7,8,11
Current ACOG recommendation
A single course of corticosteroids is recommended for pregnant women 24-34 weeks'
gestation who are at risk of preterm delivery within 7 days.
A single course of antenatal corticosteroids is recommended for women with PROM
before 32 weeks' gestation to reduce the risks of respiratory distress syndrome,
perinatal mortality, and other morbidities.
If pulmonary immaturity is documented, corticosteroid treatment at 32-33 weeks of
completed gestation may be beneficial.
Corticosteroid use before fetal age of viability is not recommended, as sparse data
exists on the efficacy.

14
 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. 7,10,11

Tocolytics
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. 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.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. Twelve to 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.7,8,10
Cervical Sealant and AmnioInfusion
Several investigators have evaluated the use of cervical plugs or membrane sealants in the
management of periviable PROM. Although the exact therapy used in each of these
investigations are different (gelatin sponge, platelets, cryoprecipitate, fibrin) the goal of each
was to repair a defect in the amniotic membrane and allow for reaccumulation of amniotic
fluid. In general, these investigations are limited in size and used other therapies including
cerclage, tocolytics, and/or antibiotics. In addition, 2 of these investigations enrolled patients
with iatrogenic PROM. None offered a control group for comparison of outcomes. The
reported survival for those treated ranged from 30-54%. Absent comparative data that
suggest benefit without significant maternal risks, these treatments should not be incorporated
into routine medical practice.5,13

Transabdominal amniofusion for periviable PROM was evaluated in a trial by Vergani

et al. A total of 18 women with PROM _25 weeks with oligohydramnios were treated with
serial amniofusion and were compared with a historical cohort of 16 untreated patients. The

15
authors reported no adverse events in the amniofusion-treated group, and found a lower
incidence of pulmonary hypoplasia compared with control subjects. Although the findings of
this investigation are interesting, the frequency of pulmonary hypoplasia in the control group
was unusually high and the biologic plausibility of amniofusion without correction of the
membrane rupture is questionable. At present, the benefits of amniofusion for periviable
PROM are unproven and the risks remain undetermined. Additional research is required
before this therapy can be considered for routine clinical use. 5,13

COMPLICATION
1. Pulmonary Hipoplasia
PH is a decrease in the number of lung cells, airways, and alveoli, mainly due in PPROM to
alterations of normal amniotic fluid pressure and egress of lung fluid during the canalicular
stage of lung development (ending at nearly 25 weeks). The gold standard for the diagnosis
of PH is lung weight by autopsy. The incidence of PH resulting from midtrimester PROM
varies from 13 to 28%.The mortality rate in neonates with this condition is 7095%. 13
The main independent reported risk factors for development of PH are:
Early GA at membrane rupture a risk of 5060% was reported when PROM occurs at 20
weeks or less.
Low residual amniotic fluid volume; PH is more common among pregnancies with
maximum pocket < 2 cm or AFI < 5, after controlling for GA at rupture. Incidences of PH
with severe, moderate, and absent to mild oligohydramnios, and 7%, respectively.
Latency.
Tests proposed to identify PH prenatally are ultrasound measurement of amniotic fluid,
fetal breathing movements, fetal chest circumference, lung length, lung volume, Doppler
studies of pulmonary vessels, and O2 tests. In general, the predictive accuracy is poor, and
may be improved by combining tests.3,4,5,7,12,13
2. Contracture / Fetal Deformities
The pattern of fetal restriction deformities occurring subsequent to periviable PROM are
similar to those seen with Potter syndrome, and include abnormal facies (low-set ears,
hypertelorism, receding chin, flattened nose, wrinkled skin), abnormal limb positions, and
flattened hands and feet. The incidence of skeletal deformities after periviable PROM ranges
from 1.5-38%. The overall incidence of deformities was 20.4%, with increasing latency and
severe oligohydramnios identified as significant risk factors. Fortunately, many of these are
easily treated with physiotherapy and do not require surgery.5,12,13

16
PREVENTION
There has been considerable interest in the development of general and specific inhibitors of
matrix metalloproteinases for the treatment of periodontal disease and arthritis and for the
prevention of tumor metastasis. These agents include tetracycline antibiotics, synthetic
matrix-metalloproteinase inhibitors such as batimastat (which selectively chelates the zinc
atom at the active site of the enzymes), and the native inhibitors TIMP-1 and TIMP-2.1
Vitamin C is involved in the synthesis and degradation of collagen and is important
for maintenance of the chorioamniotic membranes. Inadequate availability of ascorbic acid
during pregnancy has been proposed as a risk factor for premature rupture of the
chorioamniotic membranes (PROM). Daily supplementation with 100 mg vitamin C after 20
wk of gestation effectively lessens the incidence of PROM.14

PROGNOSIS
The combination of birthweight, gestational age, and sex provide the best estimate of chances
of survival and should be considered in individual cases.2,5
Fetal death after PROM at or near the limit of viability is common at 31.6%. Although
survival has been reported with membrane rupture as early as 11 weeks gestational age,22 a
significant difference in survival can be found with PROM 22 weeks compared with PROM
occurring 22 weeks. It is important to reiterate that currently available data likely overstate
the survival through exclusion of those not amenable to continued conservative treatment and
those electing pregnancy terminations for persistent fluid leakage, oligohydramnios, or
abnormal ultrasound findings. 5

CASE REPORT

PERSONAL BACKROUND

Name Mrs. P
Age 37 tahun
Occupation Ibu rumah tangga

17
Religion Islam
Race Batak
Address Medan, Belawan
Admittance date 11 September 2012
Time 0918 WIT
Parity G1P0000

HISTORY TAKING

Chief Complain : water discharge from pubic

Further Investigation :

This has been experienced by the patient since 10 September, 2012 at 2300 WIT with 3
times changing of undergarment. The water discharge is clear and odourless. History of
abdominal discomfort was not found. History of bloody show was not found. History of
whitish discharge was found, ordourless, and itchyness . History of trauma/ knocking against
the door during pregnancy was found. History of fever during pregnancy was not found.
Fecal and urine excreation under normal range.

History of previous illness : (-)

History of drug consumption : (-)

HISTORY OF DELIVERY

1. Current pregnancy

HISTORY OF MENSES

Last menstrual period : - -/Desember/2011

Estimated delivery date : - - /September/2012

Menses Cycle : Duration 28 days, Regular, length of cycle 3-4 days, frequency of changing
sanitary napkin 2-3 times a day, Dysmenorhea (-)

PSYCISAL EXAMNINATION

A. PRESENT STATUS

18
 General Condition : Good
Nutritional condition : Good
Contiousness : Compos Mentis
Blood Pressure : 110/70 mmHg
Respiratory rate : 20 x/menit
Pulse : 86 x/menit
Temperature : 36,7C
Anemic : Not found
Icterus : Not found
Cyanosis : Not found
Dyspnoe : Not found
Edema : Not found
Signs of Dehydration : Not found
Physical Deformity : Not found

B. OBSTETRIC STATUS

G1P0000

Antenatal care : Midwife : Twice , Obstetrition : Twice

Inspection : asymmetrical enlargement of

abdomen
Palpation
Leopold I : 3 fingers below xypoideus proc.
(32cm)
Leopold II : right
Leopold III : head
Leopold IV : 4/5
Contraction : not found
a. Frequency per 10 minute :
b. Duration(seconds) :
c. Strength :
Estimated fetal body weight
a. From palpation :-
b. From Johnson Formula :3100 g
Fetal Heart Rate : 148 x/minute, Reguler

C. INTERNAL EXAMINATION
VT- Closed cervix, eff 60%, amnion sac (-), SRM 10 hours, head at Hodge 1, minor
fontanella ??

- Promontorium : not felt

- Linea innominata : felt 2/3

19
 - Pubic arch : >900

- Ischiadica Spine : blunt

- Os sacrum : concave

- Os Coccygeus : concave

Result : adequate hip.

Gloves : bloody mucous (-), Amnion fluid (-)

D. INSPEKULO
Liquid accumulation at the posterior fornix , liquid was cleaned. Result : Liquid flowing
from OUE.
Erosion (-), flour albus (+), lividae (-),
Nitrazin test (+) valsava test (+)

E. DIAGNOSTIC PROCEDURE

USG TAS LABORATORIUM

Single Fetus, Head Presentation, Alive Child Hb :10,69 g/dL
FM (+), FHR (+) 148x/minute regular Ht : 32,7 %
BPD 92 mm Leucocyte : 17,300/mm3
FL 75 mm Thrombocyte : 313.000/mm3
AC 348 mm Blood Glucose Level : 58 mg/dL
AFI 5,3 SGOT : 14
Result : IUP (37-38) weeks+ Head SGPT :8
Presentation + Alive

CONCLUSION

1. Pregency age : 37-38 weeks

2. Fetal position : Head Presentation
3. Hip : Normal
4. High Risk Pregnancy : Found
5. Antepartum bleeding : Not Found
6. Inpartu : Not Found
7. Fetal Condition : Alive
8. Signs of possible uterus rupture : Not Found
9. Membrane rupture : Found
10. Pre-eklampsia : Not Found

20
11. Contraction : Found
12. Complication : Found

CURRENT DIAGNOSIS

Term Premature Rupture of Membrane + Primi Gravida + Intra Uterine Pregnancy (37- 38
weeks) + head presentation + Alive Fetal

PROGNOSIS

Good

DELIVERY PLANNING

Induction with oxytocine

Monitoring of vital sign, contraction, fetal heart rate, progress of labour.
Caesarean section if there is no progress of labour.

THERAPY

IVFD Ringer Lactate 20gtt/menit

Viccillin injection 1,5gram/8hour (skin test)

11 September 2012

First flusk

Time BP HR (x/i) RR (x/i) His DJJ Explanation

(WIT) (mmHg)

0900 130/80 72 24 1x15 144 4gtt

0915 120/70 74 22 2x20 148 8gtt

0930 120/70 72 22 2x20 155 12gtt

0940 130/80 74 22 2x25 160 Oksitosin (-)

21
0950 120/70 72 24 2x25 164 Resusitation

1000 120/70 72 24 3x20 168 Planning : Emergency

C-Sec

Follow up on 11 september 2012 , 10.00 WIT

Chief complain : abdominal discomfort due to labour

Present Status
Sensorium :compos mentis Anemia :-
BP :120/80 mmHg cyanosis :-
HR :88 x/I icteric :-
RR :24 x/I dyspnoe :-
T :36,70C oedem :-

Abdomen : acymmetrically enlarged

Movement :+

His : 2 x 30/10

FHR :172 x/i

VT : cx axial, 2 cm opening , eff (60-70) %,amnion sac (-), SRM 16 hours, greenish,
head at H1,minor fontanella ?

Planning : due to the increased fetal heart rate an emergency C-SEC was planned on
indication of fetal tachycardia.

C-SECTION REPORT

22
 On the 11 9- 2012 C-Sec o/i Fetal Tachycardi
A female child was born with BW: 3100 gr; BL: 48cm; Apgar score 7/8; anus (+)
1. Patient was placed on the surgery table with infuse and cateter placed.
2. Aceptic procedure was done using providone iodine and alcohol 70% on the abdominal
wall and later was covered with steril cloth except the operating site
3. Under spinal anastesia , incision was from the cutis, subcutis until the fascia is seen.
4. Fascia is cut from left to right with anatomical pinset set underneath.
5. The uterus is seen with heck blast placed. .
6. Plika vesikouterina is cut concave until the subendometrium the endometrium is cut blunt
and widend according to the direction of surgical cut. Placenta is seen and is cut.
7. By pulling out the head of fetus, a baby girl with BW : 3100 gr; BL: 49cm; Apgar score
7/8; and anus is born.
8. The umbilical cord is clamped at two sides and cut in between. .
9. By constant pressure to the uterus the plasenta is born.
10. Both end of the uterus is clamped and later the cavum is cleaned from left over blood.
11. Hecting of the uterus is done by overhecting. No bleeding is found.
12. The peritoneum is sewed continuously and later the muscle wall is sewed.
13. Subcutis is sewed using simple method and the fascia is sewed cuticuler.
14. Operation wound is closed with steril gauze and iodine.
15. Post op: patient is stabile.

Therapy :
IVFD RL + Oksitocine 10-10-5-5 20gtt/i
Viccilin SX injection 1,5gr/8hour
Transamin injection 1 amp/8 hour (24hour)
Farmadol drip 1 fls/ 12 hour

Recommendation :

- Monitor vital sign, uterus contraction and signs of bleeding

- Check CBC 2 hours post C-Section
- Mobilization by stage

NEONATE

1. Birth : Single
2. Date of Birth : 11 September 2012 ,time: 1130
3. Birth Condition : Alive
4. APGAR score : 7/8
5. Breating Assistance : Not Found
6. Gender : Female
7. Body Weight (g) : 2750 gram
8. Body length (cm) : 48 cm
9. Congenital Disorder : Not Found
10. Trauma : Not Found

23
 11. Consult : Consult to paediatrics department for
immediate care of the baby.

POST C-SEC MONITORING (STAGE IV)

Time 12.30 13.00 13.30 14.00 14.30

BP (mmHg) 110/70 110/70 110/70 100/70 110/70

HR 76 74 78 78 76
(times/minute)

RR 20 22 22 20 20

(times/minute)

Uterus Strong Strong strong strong strong

Contraction

Hight of Navel level Navel level 1 finger 2 fingers 2 fingers

Fundus below the below the below the
navel navel navel

Bleeding (cc) 0 0 0 0 0

LABORATORIUM RESULTS 2 HOURS POST C-SEC

Date 11 September 2012

24
Hb : 9,8 g/dL
Ht : 34,6%
Leucocyte : 14.300/mm3
Thrombocyte : 264.000/mm3

FOLLOW-UP

12 September 2012 ,08.00 13 September 2012 , 08.00

Chief Painful surgical wound Painful surgical wound

Complain

Sens: Compos Mentis Sens: Compos Mentis

Present BP : 110/70mmHg BP : 120/70mmHg

Status
HR :74x/menit HR :80x/menit

RR : 22x/menit RR : 21x/menit

Temp: 36,8 C Temp: 37,0 C

Anemic :- Anemic :-

cyanosis: - Cyanosis: -

Ikterik : - Ikterik : -

Dypsnoe: - Dypsnoe: -

Oedema: - Oedema: -

25
 Abdomen: soepel, peristaltic + Abdomen: soepel, peristaltic +
normal normal
Localized
Status Hight of fundus: 2 fingers below Hight of fundus: 2 fingers below
navel, strong contraction navel

Bleeding through Vagina: - Bleeding through Vagina: -

Lochia: + Rubra Lochia: + Rubra

Feacal (-) Urine (+) N, Flatus (+) Feacal (+) Urine (+) N, Flatus (+)
Breast Milk (-) Breast Milk (+)

Post C-Sec o/i fetal tachycardy + Post C-Sec o/i fetal tachycardy +
Diagnosa
Confinement Day 1 Confinement Day 2

Ivfd RL + oksitocine 5 iu Amoxicillin tablet 3x500mg

Therapy Viccillin injection sx 1,5 gr/ 8 Asam Mefenamat tablet 3x500mg
Vitamin B Compleks 2x1tablet
hours
Farmadol drip 100 mg/ 12 hours

Planing Mobilization -

14 September 2012 ,08.00

Chief -
Complain

Sens: Compos Mentis

Present BP : 110/70mmHg
Status
HR :74x/menit

RR : 22x/menit

Temp: 37,9 C

Anemic :-

26
 cyanosis: -

Ikterik : -

Dypsnoe: -

Oedem: -

Abdomen: soepel, peristaltic +

normal
Localized
Status Hight of fundus: 2 fingers below
navel

Bleeding through Vagina: -

Lochia: + Rubra

Feacal (+) Urine (+) N, Flatus (+)

Post C-Sec o/i fetal tachycardy +

Diagnosis
Confinement Day 3

Amoxicillin tablet 3x500mg

Therapy Asam Mefenamat tablet 3x500mg
Vitamin B Compleks 2x1tablet

Planing -

27
 CASE ANALYSIS

TEORI KASUS
Premature rupture of membranes (PROM) is This patient is aterm.
a rupture of the membranes before the onset
of labor. KPD full-term pregnancy occurred
about 10-15% and 2-4% of preterm
Etiology
The existence of uterine hypermotility that In this patient was found history of whitish
happened a long time before the rupture of discharge including itchiness , trauma was
membranes. Diseases such as cystitis, also found.
cervicitis, and vaginitis there together with
hipermotilias uterus.
amniotic membrane is too thin (fetal
abnormalities).
Infection (chorioamnionitis or amnionitis).
Other factors that predispose was:
polyhydramnios, smoking, incompetent
cervix.
Artificial premature rupture of membranes
(amniotomy), where amniotic solved too
early.

DIAGNOSIS:
History: a history of water discharge, cloudy Patient came with chief complaint of water
white, clear, yellow-green or brown a little discharge.
or a lot through the vagina, wet feeling in
the perineum. Of history can also be found
to the reduced size of the uterus.

CLINICAL EXAMINATION:

28
With a direct discharge from the genitals.
With inspekulo, see amniotic fluid flowing
out from the cervical canal.
DIAGNOSIS SUPPORT:
Litmus test: red Litmus turns blue when
there is amniotic fluid, this is due to the
alkaline pH amnion (pH 7.1 to 7.4).
From inspekulo fluid was found in the
posterior fornix and was cleaned.
Conclusion: fluid flowing from OUI.valsava
test (+).nitrazin (+) , blood (-), lividae (+),
flour albus (+)

LABORATORY EXAMINATION 11 September 2012

Examination of leukocytes> 15,000 / UL if Hb :10,5 g/dL
there is an infection Ht : 32,6.1 %
Leukocyte : 17.300/mm3
Thrombocyte : 313.000/mm3
POST SC
11 September 2012
Hb :9,8g/dL
Ht : 34,6%
Leukocyte : 14.300/mm3
Thrombocyte : 265.000/mm3

MANAGEMENT
Based on gestational age
Viable For Life (gestational age> 37 weeks,
weight> 2500 g) in the absence of
chorioamnionitis
Good observation for 6 - 12 hours after
rupture of membranes, waiting for signs of
the onset of spontaneous inpartu.
Perform induction of parturition when there
has been no sign of inpartu to prevent the
risk of infection.
Vital signs and pregnancy advances was
monitored. After 2hours and 30 minutes the
patients started having contraction of giving
labour with fetal movement (+), His
2x30/10, fetal heart rate 172x/I, opening of
cervix 2 cm, eff 100%, membrane was not
found, amnion fluid color greenish. With
consideration to fetal tachycardia, the patient
was opted for an emergency C section.

29
Antibiotics showed effective results in ER
prolonging the latency period until delivery Viccillin injection 1,5gram/8jam
and may reduce the number of infections in
patients with KPD. POST C-SEC
Ampicillin 2 g IV every 6 hours + Amoxicillin tablet 3X500mg
Erythromycin 250 mg every 6 hours. After
48 hours, if labor is retained, it can be
replaced with Amoxicillin 250 mg orally per
8 hour

30
 CONCLUSION

A women aged 35 years old came to the Emergency Department of Pringadi Hospital
on the 11 august at 0900 WIT with the chief complaint of watery discharge from her pubic.
This has been experienced from the day before at about 2000 WIT. Abdominal discomfort
due to labour was not felt. History of trauma and whitish discharge was found. Whitish
discharge was odorless and itchy. History of trauma/ knocking against the door during
pregnancy was found.This is her first pregnancy. Last menstrual period : ?/12/2011,
Estimated delivery date: ?/9/2012. Signs of labour is not found.
From inspection there were no abnormalities. From obstetrics finding, the abdomen
was asymmetrically enlarged and during palpation Leopold 1 : 31cm, Leopold II : on the left,
Leopold III : the head and Leopold IV : the head is as low as 4/5, fetal heart rate 140
x/minute, HIS wasnt found. From inspekulo fluid was found in the posterior fornix and was
cleaned. Conclusion: fluid flowing from OUI. Valsava test (+), nitrazin test (+) , blood (-),
lividae (+), flour albus (+). From USG findings : IUP (37-38)week + head presentation+life
baby.
Patient was diagnosed with preterm rupture of membrane + primigravida+ IUP (37-38
week) + head presentation+ life baby and was planned for termination of pregnancy with
oxytocin induction. Vital signs was monitored and pregnancy advances was monitored. After
2 hours and 30 minutes the patients started having labour contraction with fetal movement
(+), His 2x30/10, fetal heart rate 172x/I, opening of cervix 2 cm,eff 80%, membrane was
not found, amnion fluid colour green. With consideration to fetal tachycardia the patient was
opted for an emergency C section. A baby girl was born with BW: 2750 g, BL :48 cm, A/S :
7/8, anus (+). The patient was stabil post operation and was monitored for three days and then
discharged.

31
 PROBLEMS

1. Is the management of this patient correct ?

2. What is a generals practitioners responsibility if presented with such case?

32
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Diseases. N Engl J Med. Feb 2006.
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