1

Preterm premature rupture of membranes (PPROM) is a

leading contributor to preterm birth as well as maternal and
perinatal morbidity and mortality. In the United States in
2010, 11.9% of all births were preterm, and PPROM com-
plicates about one third of all preterm births. This translates
to about 120,000 births per year in the United States being
complicated by PPROM.
1
Unfortunately, PPROM is a con-
dition that all obstetricians will encounter, which necessi-
tates a skill set to accurately diagnose, treat, and manage
patients affected by this condition.
A pregnancy complicated by PPROM elevates the risk of
intrauterine infection, cord compression, and placental abrup-
tion. However, it is important to recognize that the most com-
mon outcome of PPROM is delivery within 1 week. Therefore,
appropriate diagnosis and management of these patients at
presentation is of the utmost importance to minimize the risk
of complications for both the mother and the fetus. The goal
of this article is to address the gap between present practice,
which often is based on anecdotal experience, and more
optimal, evidence-based treatment.
Prediction and Prevention
The risk factors for PPROM are similar to those for preterm
birth. Commonly, PPROM is associated with intra-amniotic
infection. Other risk factors include low socioeconomic status,
body mass index less than 19.8 kg/m
2
, maternal connective
tissue disorders, cigarette smoking, previous conization of
the cervix, cerclage placement, maternal pulmonary disease,
and uterine overdistention.
2
Higher risk of PPROM is also
associated with a history of PPROM or preterm birth, cervical
length less than 25 mm in the second trimester, and symp-
tomatic contractions. However, in the majority of cases,
PPROM occurs in women without any risk factors, making
prevention difficult.
Attempts to reduce the risk of PPROM by changing known
modifiable risk factors have not proved successful.
3
The best
available tool for prevention of PPROM is weekly IM pro-
gesterone for women with a history of preterm birth. There
is no role for routine screening and treatment of bacterial
vaginosis or routine supplementation of antioxidants such
as vitamins C or E.
Diagnosis
Rupture of membranes is first suspected by patient his-
tory and confirmed by physical examination. The traditional
approach is sterile speculum examination to visualize amni-
otic fluid leaking from the cervix or a pool in the vagina. The
fluid is then collected on a sterile swab and applied to nitrazine
pH paper, which turns from yellow to blue in the presence
of amniotic fluid (90%97% sensitivity). The pH of nor-
mal vaginal secretions is 4.5 to 6.0, whereas amniotic fluid
usually has a pH of 7.1 to 7.3. The fluid is then applied to
a slide and examined under the microscope after drying for
10 minutes for crystallization or ferning (98% sensitivity
in labor, 51% sensitivity in no labor). Ferning is observed
Preterm Premature Rupture of Membranes
Sara Mazzoni, MD, MPH, and Elaine Stickrath, MD
Learning objectives: After participating in this CME activity, the obstetrician/gynecologist should be better able to:
1. Identify patients at risk for preterm premature rupture of membranes (PPROM).
2. Accurately diagnose PPROM.
3. Appropriately manage a patient with PPROM.
Lippincott Continuing Medical Education Institute, Inc., is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical
education for physicians.
Lippincott Continuing Medical Education Institute, Inc., designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits. Physicians should
only claim credit commensurate with the extent of their participation in the activity.
To earn CME credit, you must read the CME article and complete the quiz and evaluation on the enclosed answer form, answering at least seven of the 10 quiz questions
correctly. This activity expires on January 14, 2014.
A BIWEEKLY PUBLICATION FOR CONTINUING MEDICAL
EDUCATION IN OBSTETRICS AND GYNECOLOGY
POSTGRADUATE
OBSTETRICS & GYNECOLOGY
POSTGRADUATE
OBSTETRICS & GYNECOLOGY
Dr. Mazzoni is Assistant Professor, and Dr. Stickrath is Instructor, Department of
Obstetrics and Gynecology, Denver Health Medical Center, University of Colorado,
777 Bannock St, MC 0660, Denver, CO 80204; E-mail: elaine.stickrath@dhha.org.
All faculty and staff in a position to control the content of this CME activity, and
their spouses/partners (if any) have disclosed that they have no financial relation-
ships with, or financial interests in, any commercial organizations pertaining to
this educational activity.
VOLUME 33 NUMBER 1
January 15, 2013
PGOv33n1.indd 1 1/16/13 1:10 AM
Postgraduate Obstetrics & Gynecology January 15, 2013
2
less often in previable PPROM, as infre-
quently as 70% of confirmed cases of
PPROM before 22 weeks.
4
Oligohydramnios
observed on ultra sonography may be helpful
but is not diagnostic.
PPROM can be confirmed by injecting
indigo carmine (1 mL in 9 mL of sterile nor-
mal saline) into the uterine cavity transab-
dominally, with passage of blue fluid in the
vagina seen on a tampon. A more recent tool
has been approved by the FDA for diagnosis
of rupture of membranes. This test detects
placenta-specific alpha microglobulin-1 with
a reported 99% sensitivity and 100% specifi-
city for diagnosis of rupture of membranes.
5

Digital examinations increase the risk of
infection and add little to the diagnosis, and
as such should be avoided unless the patient
is in active labor.
General Management
Management of PPROM varies by gesta-
tional age. Gestational age at delivery is the
most important predictor of neonatal sur-
vival, survival without major morbidity,
and long-term neurodevelopmental out-
comes.
6
Planned delivery before 34 weeks
has not been shown to reduce infectious
morbidity. Neurodevelopmental benefits of
expectant management beyond 34 weeks
also have not been demonstrated, and the
risk of infection likely outweighs any ben-
efit of continuing the pregnancy beyond
that time. Therefore, delivery is recom-
mended after 33 completed weeks gesta-
tion (unless there is evidence of intrauterine
infection or fetal compromise), and expect-
ant management should be attempted until
that time. Delivery may be considered at 32
to 33 completed weeks gestation if fetal
pulmonary maturity can be documented.
2

The goals of expectant management are to
increase latency while decreasing the com-
plications of prematurity. Antibiotics, corti-
costeroids, and magnesium are the main-
stays of treatment.
In general, patients with PPROM are encour-
aged to comply with modified bed rest and
complete pelvic rest. Patients should be
assessed for evidence of infection, placental
abruption, cord compression, fetal well-being,
and labor. There is no consensus regarding
the frequency or content of this assessment.
2

Data are also lacking with regard to whether
care should occur in the hospital or at home,
7

although most patients with PPROM are
admitted to the hospital, given that latency
to delivery can be brief, and complications
may occur suddenly.
The cause of PPROM is multifactorial
and remains elusive. However, polymicro-
bial infection likely plays a large role. The
causative organism(s) is unknown, so opti-
mal antibiotic treatment is also unknown,
but it should be broad spectrum to cover a
range of gram-positive and -negative,
aerobic, and anaerobic bacteria.
8,9
Although
the most obvious intent of antibiotic thera-
py is to prevent infectious morbidity, it has
also been proven efficacious in reducing
many other complications of PPROM.
Broad-spectrum antibiotic treatment dur-
ing expectant management of PPROM
before 34 weeks results in prolonged latency
(delivery 7 days, 46% vs 26%) and less
frequent occurrence of amnionitis (21% vs
31%), newborn sepsis (11% vs 17%), respi-
ratory distress syndrome (38% vs 46%), and
intraventricular hemorrhage (13% vs 18%).
9

It does not change the rate of cesarean
delivery, postpartum endometritis, necrotiz-
ing enterocolitis, stillbirth, or survival to
EDITORS
William Schlaff, MD
Professor and Chair,
Department of Obstetrics
and Gynecology, Thomas
Jefferson Medical College,
Philadelphia, Pennsylvania
Lorraine Dugoff, MD
Associate Professor, Sections
of Maternal Fetal Medicine
and Reproductive Genetics,
Department of Obstetrics
and Gynecology, University
of Pennsylvania School of
Medicine, Philadelphia,
Pennsylvania
FOUNDING EDITORS
Edward E. Wallach, MD
Roger D. Kempers, MD
ASSOCIATE EDITORS
Susan A. Davidson, MD
Aurora, Colorado
Nancy D. Gaba, MD
Washington, DC
Elizabeth S. Ginsburg, MD
Boston, Massachusetts
Jennifer Goedken, MD
Atlanta, Georgia
Veronica Gomez-Lobo, MD
Washington, District of Columbia
Nancy Hueppchen, MD
Baltimore, Maryland
Bradley S. Hurst, MD
Charlotte, North Carolina
Christine Isaacs, MD
Richmond, Virginia
Peter G. McGovern, MD
Newark, New Jersey
Francis S. Nuthalapaty, MD
Greenville, South Carolina
William D. Petok, PhD
Baltimore, Maryland
Robert K. Zurawin, MD
Houston, Texas
The continuing education activity in Postgraduate Obstetrics & Gynecology is intended for obstetricians, gynecologists, and other
health care professionals with an interest in the diagnosis and treatment of obstetric and gynecological conditions.
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PGOv33n1.indd 2 1/16/13 1:10 AM
January 15, 2013 Postgraduate Obstetrics & Gynecology
3
discharge. Current American College of Obstetricians and
Gynecologists (ACOG) guidelines recommend a 7-day
course of parenteral and oral therapy consisting of 48 hours
of IV ampicillin and erythromycin followed by 5 days of
amoxicillin and erythromycin for expectant management
of PPROM before 33 completed weeks gestation. It is
important to remember that this prophylactic antibiotic
regimen is unlikely to eradicate intrauterine infection com-
pletely. Clinically evident intra-amniotic infection occurs
in 13% to 60% of patients, and postpartum endometritis
occurs in 2% to 13% of patients with PPROM, even when
treated with latency antibiotics.
It has been demonstrated clearly that administration of
corticosteroids in patients with PPROM improves neonatal
outcomes without increasing the risk of neonatal or mater-
nal infection.
10
Prematurity is the most significant compli-
cation of PPROM and, as such, optimizing the premature
infant remains the goal. Antenatal corticosteroids reduce
the risk of neonatal death, respiratory distress syndrome,
intraventricular hemorrhage, and necrotizing enterocolitis.
The initial recommendation by the National Institutes of
Health Consensus Conference in 1994, supported by
ACOG, recommended corticosteroids for PPROM only up
to 30 to 32 weeks gestation due to theoretical concern of
infection. However, on the basis of currently available evi-
dence, some experts recommend their use up to 33 com-
pleted weeks gestation.
2
At this time, there are no data on
the use of a rescue course of corticosteroids in the setting of
PPROM, and this treatment is not recommended outside of
a research protocol.
The use of magnesium sulfate for neuroprotection has been
well established by randomized clinical trials.
11
Magnesium
sulfate has been shown to reduce the risk of cerebral palsy
among children who survive early preterm birth without
increasing life-threatening events to the mother. The trials
of magnesium sulfate did not stratify for pregnancies com-
plicated by PPROM, but because PPROM precedes a large
number of preterm deliveries, a high proportion of women
with PPROM were included. Expectant management of
PPROM should include magnesium sulfate for patients
at risk of imminent delivery between 24 and 32 weeks
gestation.
6
Additional Management Considerations
Specific recommendations for or against tocolysis cannot
be made on the basis of available data.
2
A Cochrane review
reported that tocolysis increased maternal chorioamnionitis
without significant benefit to the neonate; however, in the
included the studies antibiotics and corticosteroids were not
administered consistently, and both of these drug classes are
now known to improve neonatal outcomes.
12
The authors
concluded that there is insufficient evidence to support
tocolytic therapy in the setting of PPROM. Amnioinfusion,
with the aim of restoring amniotic fluid volume in patients
with PPROM has been evaluated, and although data are
encouraging, there remains insufficient evidence to recom-
mend routine use in clinical practice.
13
The clinician might encounter PPROM in a patient
with known herpes simplex virus (HSV) infection. Optimal
management in this situation is unclear.
14
On the basis of
the low risk of vertical transmission in the setting of
recurrent active HSV, standard expectant management
until 34 weeks gestation is recommended, in addition to
oral acyclovir therapy. The usual indications for cesarean
delivery apply (eg, active lesions or prodromal symp-
toms) when delivery is ultimately indicated. Management
of PPROM in the setting of primary HSV infection is
even less clear, and there are inadequate data to help guide
the clinician.
Women with PPROM should be screened for group B
streptococcal (GBS) colonization at the time of presenta-
tion.
15
Antibiotics for latency should be started per stand-
ard expectant management. If the regimen for latency
includes ampicillin (given 2 g IV 1, then 1 g IV every
6 hours for at least 48 hours), then it is adequate prophy-
laxis for GBS as well. If not, adequate GBS prophylaxis
should also be administered if the patient is entering
labor or for up to 48 hours, when the results of the GBS
culture are available. If the patient is GBS-positive, intra-
partum prophylaxis should be administered at the onset
of labor. If the patient is GBS-negative, GBS prophylaxis
is not indicated for labor. A negative GBS culture is valid
for 5 weeks. If a patient with PPROM has had a negative
GBS screen more than 5 weeks previously, she should be
rescreened and the appropriate intrapartum prophylaxis
administered if indicated at the onset of labor.
PPROM before viability presents a complex dilemma
for the provider and patient. Options include immediate
delivery or expectant management, although there is no
consensus on the ideal method of expectant management.
It might be reasonable to offer an initial period of inpa-
tient observation, followed by home bed rest, with
readmission to the hospital when viability is reached for
the administration of antibiotics and corticosteroids. The
neonatal risks associated with prolonging pregnancy after
previable PPROM remain extremely high. A study of
previable PPROM between 14 and 24 weeks with 2 years
of follow-up documented an overall 17% survival rate,
with only 50% of surviving neonates (or 10% overall)
demonstrating development at 2 years of age.
16
Summary
PPROM continues to be a complication of pregnancy
with significant clinical sequelae for both mother and
fetus. As a contributor to approximately one third of pre-
term births, it is, unfortunately, a fairly common condition.
Each year, nearly 120,000 births are affected by PPROM
in the United States. This requires clinicians to be aware
of patients at risk of PPROM, have the skills to diagnose
PPROM accurately, and be able to manage patients at
various stages of pregnancy. Although there is currently
no way to prevent PPROM, appropriate management of
patients with this condition gives mothers and infants the
best outcome possible.
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Postgraduate Obstetrics & Gynecology January 15, 2013
4
REFERENCES
1. Martin JA, Hamilton BE, Ventura SJ, et al. National Vital Statistics Reports,
Births: Final Data 2010, Volume 61, Number 01. Washington, DC: US
Department of Health and Human Services, Centers for Disease Control and
Prevention; 2011.
2. American College of Obstetricians and Gynecologists Committee on
Practice Bulletins. ACOG Practice Bulletin No. 80: premature rupture of
membranes. Clinical management guidelines for obstetrician-gynecologists.
2007, reaffirmed 2012. Obstet Gynecol. 2007;109(4):1007-1019.
3. Waters TP, Mercer B. Preterm PPROM: prediction, prevention, principles.
Clin Obstet Gynecol. 2011;54(2):307-312.
4. Sugibayashi S, Aeby T, Kim D, et al. Amniotic fluid arborization in the
diagnosis of previable preterm premature rupture of membranes. J Reprod
Med. 2012;57(3-4):136-140.
5. Mariona FG, Cabero L. Are we ready for a new look at the diagnosis of
premature rupture of membranes? J Matern Fetal Neonatal Med.
2012;25(4):403-407.
6. Clark EAS, Varner M. Impact of preterm PROM and its complications on
long-term infant outcomes. Clin Obstet Gynecol. 2011;54(2):358-369.
7. Abou El Senoun G, Dowswell T, Mousa HA. Planned home versus hospital
care for preterm prelabour rupture of the membranes (PPROM) prior to 37
weeks gestation. Cochrane Database Syst Rev. 2010;(4):CD008053.
8. Singh K, Mercer B. Antibiotics after preterm premature rupture of the mem-
branes. Clin Obstet Gynecol. 2011;54(2):344-350.
9. Mercer B. Antibiotics in the management of PROM and preterm labor.
Obstet Gynecol Clin N Am. 2012;39(1):65-76.
10. Vidaeff AC, Ramin SM. Antenatal corticosteroids after preterm premature
rupture of membranes. Clin Obstet Gynecol. 2011;54(2):337-343.
11. Rouse DJ. Magnesium sulfate for neuroprotection. Am J Obstet Gynecol.
2011;205(4):296-297.
12. Mackeen AD, Seibel-Seamon J, Grimes-Dennis J, et al. Tocolytics for
preterm premature rupture of membranes. Cochrane Database Syst Rev.
2011;(10):CD007062.
13. Hofmeyr GJ, Essilfie-Appiah G, Lawrie TA. Amnioinfusion for preterm
premature rupture of membranes. Cochrane Database Syst Rev. 2011;(12):
CD000942.
14. Ehsanipoor RM, Major CA. Herpes simplex and HIV infections and pre-
term PROM. Clin Obstet Gynecol. 2011;54(2):330-336.
15. Verani JR, McGee L, Schrag SJ; Division of Bacterial Diseases, National
Center for Immunization and Respiratory Diseases, Centers for Disease
Control and Prevention. Prevention of perinatal group B streptococcal
diseaserevised guidelines from CDC, 2010. MMWR Recomm Rep.
2010;59(RR-10):1-36.
16. Pristauz G, Bauer M, Maurer-Fellbaum U, et al. Neonatal outcome and two-
year follow-up after expectant management of second trimester rupture of
membranes. Int J Gynaecol Obstet. 2008;101(3):264-268.
Practice Pearls
Accurate diagnosis of PPROM at the time of presenta-
tion is critical, as the most likely outcome is delivery
within 1 week.
Administration of a single course of corticosteroids
before 32 weeks is recommended, and it may also
be beneficial between 32 and 33 completed weeks
gestation.
A 48-hour course of IV ampicillin and erythromycin,
followed by 5 days of oral amoxicillin and erythro-
mycin, is recommended to prolong pregnancy during
expectant management.
Magnesium sulfate should be administered to patients
at risk of imminent delivery between 24 and 32 weeks
gestation.
Expectant management is recommended until 34
weeks gestation.
At 34 weeks gestation or beyond, induction of labor
is recommended, usually via oxytocin infusion.
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PGOv33n1.indd 4 1/16/13 1:10 AM
January 15, 2013 Postgraduate Obstetrics & Gynecology
5
1. Which one of the following is the most accurate method of
diagnosing ruptured membranes?
A. Rely on the patients history alone
B. Check the amniotic fluid with ultrasonography
C. Perform an examination to check for fluid passing
from the cervix, fluid pH, and ferning on microscopic
examination
D. Perform an amnio dye test by instilling indigo carmine
into the amniotic fluid
2. The pH of amniotic fluid is
A. 4.04.4
B. 4.56.0
C. 6.06.5
D. 7.17.3
3. When a patient is first diagnosed with PPROM, the clinician
should
A. check her cervix every 2 hours for labor, so that the pedi-
atrics team has as much advance notice as possible
B. avoid digital cervical examination to reduce the risk of
infection
C. send the patient home if she is not in active labor
D. induce labor regardless of gestational age
4. Which one of the following patients with confirmed PPROM
would meet criteria for expectant management?
A. 28 weeks pregnant with fundal tenderness and fetal
tachycardia
B. 35 weeks pregnant with category 1 fetal heart rate and
no evidence of infection
C. 33 weeks pregnant with nonreassuring fetal status on
nonstress test
D. None of the above
5. A 33-year-old G1 at 31 weeks and 3 days of gestation
presents to the labor and delivery unit reporting a gush of
clear fluid. She denies contractions, abdominal pain, vagi-
nal bleeding, or fevers and reports good fetal movement.
She has had an otherwise uncomplicated pregnancy. You
perform an examination and confirm PPROM. Which of the
following would not be a part of this patients care?
A. Assessment for active labor; if not in active labor, do
not monitor the fetus
B. Confirmation of gestational age
C. Administration of corticosteroids
D. Antibiotic administration to prolong latency
6. You are seeing a 30-year-old G2P0101 at 18 weeks gesta-
tion for prenatal care. She has had a pregnancy complicated
by a previous preterm delivery at 33 weeks, tobacco use,
and chronic hypertension. Which of the following is/are risk
factors for PPROM?
A. Previous preterm birth
B. Chronic hypertension
C. Tobacco use
D. Previous preterm birth and tobacco use
7. Which one of the following statements regarding infection
associated with PPROM is false?
A. Antibiotics administered at the time of diagnosis do not
improve latency or outcomes.
B. Intra-amniotic infection is common in women affected
by PPROM, with incidence ranging from 13% to 60%
of pregnancies.
C. Ampicillin and erythromycin given for latency also pro-
vide adequate GBS prophylaxis.
D. Administration of corticosteroids does not increase the
risk of infection in the setting of PPROM, particularly in
women at less than 32 weeks gestation.
8. During her routine clinic visit, a 17-year-old G1P0 at 27 weeks
gestation reports loss of fluid 2 days previously. You per-
form a speculum examination and do not observe any pool-
ing of fluid or amniotic fluid coming from the cervical canal.
Ultrasonography reveals oligohydramnios. You suspect PPROM
because of the patients history and oligohydramnios but
are not sure because of the negative physical examination.
Which one of the following could be used for definitive diag-
nosis of PPROM?
A. Give indigo carmine IV to the mother and monitor for
blue vaginal discharge
B. Recheck the examination at a later time
C. Instill indigo carmine at a 1:9 ratio with normal saline
into the uterine cavity transabdominally and monitor for
vaginal passage of blue fluid
D. Instill methylene blue at a 1:9 ratio with normal saline
transabdominally and monitor for vaginal passage of
blue fluid
To earn CME credit, you must read the CME article and complete the quiz and evaluation on the enclosed answer form, answering at least
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CME Quiz: Volume 33, Number 1
PGOv33n1.indd 5 1/16/13 1:10 AM
Postgraduate Obstetrics & Gynecology January 15, 2013
6
9. Which of the following patients with confirmed PPROM would
require GBS prophylaxis?
A. A patient at 35 weeks gestation undergoing induction
of labor with unknown GBS status
B. A patient at 34 weeks gestation undergoing induction
of labor who had a negative GBS culture at the time of
admission
C. A patient at 34 weeks who has previously received
latency antibiotics now undergoing induction of labor.
She had a positive GBS culture at 28 weeks.
D. All of the above
E. A and C
10. Which of the following statements describes why appropri-
ate management of patients with PPROM is important?
A. Maternal health is at risk, including the risk of sepsis
from intra-amniotic infection.
B. Fetal health is at risk both from infection and from
complications of prematurity.
C. The most likely outcome after PPROM is delivery
within 1 week, making accurate diagnosis and initial
management critically important.
D. All of the above
PGOv33n1.indd 6 1/16/13 1:10 AM