1

Preterm delivery, defined as delivery occurring between

20 to 37 completed weeks of gestation, is one of the most
pressing problems facing obstetricians worldwide. Reports
of the incidence of preterm delivery vary somewhat by the
population studied and by the methods of investigation and
ascertainment employed. Recent data from the United
States March of Dimes initiative suggests a risk of preterm
delivery of approximately 11.5%.
1
This is based on a large
multicenter evaluation of well-dated pregnancies and rep-
resents a reasonable estimate of the incidence of preterm
delivery in the United States. Based on these data, there are
approximately 467,000 preterm deliveries in the United
States per year.
1
Although there are many possible etiolo-
gies for a preterm delivery, idiopathic premature labor
(i.e., preterm labor that begins without an identifiable eti-
ology such as spontaneous rupture of the amniotic mem-
branes) is one of the most common and most vexing,
accounting for approximately 50% of preterm deliveries.
Preterm delivery is an important issue from a societal
view not only because of its high incidence, but because of
the significant associated morbidity and mortality. In fact,
preterm delivery is the most common cause of perinatal
death in nonanomalous newborns.
1,2
Further, it has been
well-documented that both morbidity and mortality
increase with decreased in gestational age at delivery. Even
at gestational ages when the survival rate is relatively sat-
isfactory (i.e., greater than 30 weeks), significant morbidi-
ty can still develop in infants delivered prematurely. For
example, Robertson et al.
3
reported that at 30 weeks gesta-
tion, the risk of respiratory distress syndrome is approxi-
mately 50%; necrotizing enterocolitis, 11%; and intraven-
tricular hemorrhage, 5%. Thus, preterm delivery is a major
cause of morbidity and mortality in the United States.
Because of the frequency of preterm labor as well as
the neonatal complications that can arise should a
preterm birth occur, a great deal of investigative effort has
surrounded the prevention and treatment of idiopathic
preterm labor. Among the most common modalities for
dealing with idiopathic preterm labor is the use of phar-
macological agents designed to arrest preterm labor once
it has begun (tocolysis). The ultimate goal of tocolysis
is the prevention of perinatal deaths and major neonatal
morbidities due to prematurity. However, an intermediate
goal has become delay of delivery for 24 to 48 hours
the time necessary to administer and receive maximal
benefit from antenatal corticosteroids, which have been
documented to improve perinatal outcome.
4,5
Despite the
evaluation of multiple candidates in past decades, there
are still many unanswered questions regarding the rela-
tive efficacy and safety of these agents.
Methodological Considerations of
Studies of Tocolytics
The search for the ideal tocolytic has been complicated
by several factors. The first problem is how best to define
preterm labor. Classically, preterm labor is defined as doc-
umented uterine contractions at 20 to 37 weeks gestation
with either ruptured or intact membranes, accompanied
by documented cervical change. This definition, used in
many studies of preterm labor, undoubtedly results in the
Tocolytic Agents
George A. Macones, M.D., MSCE
Learning Objectives: After reading this issue, the participant should be able to:
1. Explain the incidence and importance of preterm birth.
2. Describe data on efficacy and safety of agents for treatment of patients with acute tocolysis.
3. Explain efficacy data on use of oral beta-agonist therapy for maintenance tocolysis.
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.
A BIWEEKLY PUBLICATION FOR CONTINUING MEDICAL
EDUCATION IN OBSTETRICS AND GYNECOLOGY
POSTGRADUATE
OBSTETRICS & GYNECOLOGY
POSTGRADUATE
OBSTETRICS & GYNECOLOGY
Dr. Macones is Associate Professor of Obstetrics and Gynecology, and
Epidemiology; and Director, Division of Maternal-Fetal Medicine, University
of Pennsylvania, 2000 Courtyard Building, 3400 Spruce Street, Philadelphia,
PA 19104; E-mail: gmacones@obgyn.upenn.edu.
Dr. Macones has disclosed that he has no significant relationships with or
financial interests in any commercial organizations pertaining to this educa-
tional activity.
Wolters Kluwer Health has identified and resolved all faculty conflicts of inter-
est regarding this educational activity.
VOLUME 25 NUMBER 11
June 1, 2005
507946_PGO11_sw 8/8/05 2:36 PM Page 1
Postgraduate Obstetrics & Gynecology June 1, 2005
2
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inclusion of many women who do not have
preterm labor (e.g., those with minimal
cervical change). In fact, in trials of beta-
agonists for preterm labor, up to 50% of
patients treated with placebo actually
delivered at term.
6
This diagnostic mis-
classification, in effect, lowers the statisti-
cal power of the efficacy studies, thereby
biasing the results towards the null (i.e., no
effect). Clearly, a future challenge in peri-
natal medicine is to better define preterm
labor, perhaps with biochemical markers.
A second important consideration when
evaluating the studies of tocolysis is the
primary endpoint for these trials. Although
it may seem apparent that the ultimate goal
of tocolysis is to reduce death and morbid-
ity from prematurity, few studies have had
the statistical power for the evaluation of
such uncommon outcomes. Instead, most
trials use delivery delay as the primary end-
point. Although it is generally believed that
even short delivery delays with tocolysis
are beneficial (because of corticosteroid
use), this hypothesis is largely untested by
virtue of the fact that virtually no tocolytic
has been studied in combination with corti-
costeroid use.
Beta-Mimetics
Mechanism of Action
Beta-mimetics such as ritodrine, terbu-
taline, and isoxsuprine have been commonly
used parenteral tocolytics in the United States
and worldwide during the past three decades.
7
Beta-mimetics are structurally related to cate-
cholamines. Importantly, there are two types
of beta-receptors (beta-1 and beta-2) to which
these agents bind. Beta-1 receptors are locat-
ed in the small intestine, heart, and adipose tis-
sue. Their stimulation leads to increased car-
diac automaticity, positive chronotropic and
inotropic effects, and elevated free fatty acids.
The beta-2 receptors are located in the smooth
muscle of the uterus, blood vessels, and bron-
chioles. Accordingly, their stimulation leads to
uterine relaxation, vasodilatation, and bron-
chodilation. Activation of these receptors
leads to an elevation in cyclic adenosine
monophosphate (cAMP), mediated through
adenylate cyclase. In turn, increased levels of
cAMP prevent myosin light chain kinase
(MLCK) activity through decreased phospho-
rylation and inhibition of release of stored
intracellular calcium. As MLCK phosphory-
lation is the key step in the actinmyosin inter-
action, it is thought that uterine contractions
are thus inhibited. Although the tocolytics of
this class commonly in use are beta-2 selec-
tive, they do retain some beta-1 activity, which
accounts for their side-effect profile. An ideal
beta-agonist tocolytic would be completely
beta-2 selective; however, no such agent
exists. Thus, the benefit of uterine relaxation is
often accompanied by side effects attributable
to beta-1 activity.
Efficacy
Many randomized, placebo-controlled
studies have been performed evaluating the
efficacy of the beta-mimetics as acute
tocolytics. Overall, these placebo-controlled
studies demonstrate that beta-mimetics are
effective in the delay of delivery for 24 to 48
hours. This is borne out by a meta-analysis.
8
Sixteen placebo-controlled trials using beta-
mimetics for the acute treatment of preterm
labor were included in this analysis. The
analysis revealed a statistically significant
reduction in delivery in less than 48 hours
with beta-agonists. No advantage was
demonstrated for treatment with beta-ago-
nists over placebo for: (1) reduction in risk
of preterm delivery; (2) frequency of birth
weight less than 2500 g; (3) frequency of
neonatal respiratory distress syndrome; or
EDITORS
William Schlaff, M.D.*
University of Colorado
Aurora, Colorado
George Macones, M.D.,
MSCE*
University of Pennsylvania
Philadelphia, Pennsylvania
FOUNDING EDITORS
Edward E. Wallach, M.D.
Roger D. Kempers, M.D.
EDITORIAL BOARD
Jonathan S. Berek, M.D.
David Geffen School of Medicine
at UCLA
Los Angeles, California
Daniel L. Clarke-
Pearson, M.D.
Duke University Medical Center
Durham, North Carolina
Harold Fox, M.D.
Johns Hopkins University School
of Medicine
Baltimore, Maryland
Charles B. Hammond, M.D.
Duke University Medical
Center
Durham, North Carolina
Timothy R.B. Johnson, M.D.
University of Michigan Medical
School
Ann Arbor, Michigan
Jack Ludmir, M.D.
Pennsylvania Hospital
Philadelphia, Pennsylvania
Kamran S. Moghissi, M.D.
Wayne State University School
of Medicine
Detroit, Michigan
Jennifer R. Niebyl, M.D.
University of Iowa
Iowa City, Iowa
Antonio Pellicer, M.D., Ph.D.
Associate Editor, Spanish Edition
University of Valencia (Ob/Gyn)
Valencia, Spain
John T. Repke, M.D.
Penn State College of
Medicine Milton S. Hershey
Medical Center
Hershey, Pennsylvania
Nikos Vlahos, M.D.
Johns Hopkins University
School of Medicine
Baltimore, Maryland
*Dr. Schlaff has disclosed that he receives
research support from Organon; Pfizer,
Inc.; and Berlex and that he is a consultant
for Takeda Pharmaceuticals North America,
Inc. Dr. Macones has disclosed that he has
no significant relationships with or financial
interests in any commercial organizations
pertaining to this educational activity.
507946_PGO11_sw 8/8/05 2:36 PM Page 2
(4) frequency of perinatal death. Although one must ques-
tion whether these agents should be used in light of these
results, it is important to remember that few trials employed
concomitant use of corticosteroids. Current thinking asserts
that the primary benefit of tocolysis is to allow for the
administration of corticosteroids.
Safety
Maternal side effects with the treatment of beta-mimet-
ics are common. Those that are less life threatening but
bothersome enough to require discontinuation of therapy
occasionally include emesis, fever, headaches, and
tremulousness. Cardiovascular complications such as
tachycardia, arrhythmias, and ischemia are common.
Metabolic disorders also may be encountered such as
glucose intolerance, hypokalemia, and sodium retention.
The most frequently reported major complication is pul-
monary edema, occurring in as many as 5% of patients.
9
The etiology of pulmonary edema is not clear and is prob-
ably related to a number of factors, including decreased col-
loid oncotic pressure, increased permeability of the pul-
monary vasculature, and inappropriate use of intravenous
fluids. The beta-agonists decrease the release of antidiuret-
ic hormone, resulting in a decrease in renal function that
can produce water retention, further increasing the risk of
pulmonary edema.
10
It is theorized that patients at increased
risk include women with multiple gestations, hypertension,
anemia, treatment extending greater than 24 hours, and
infection.
11
Complications in the neonate have mainly been limited to
hypoglycemia (secondary to fetal hyperglycemia and
hyperinsulinemia) and ileus. However, there are conflicting
reports regarding the incidence of periventricular and intra-
ventricular hemorrhage among infants exposed to beta-
adrenergic tocolysis. In a large retrospective study, patients
delivering between 25 and 36 weeks, the authors conclud-
ed that the use of beta-mimetic tocolysis was significantly
associated with an increase in the incidence of periventric-
ular and intraventricular hemorrhage.
12
Other reports, with
fewer subjects, have demonstrated no association.
13,14
Magnesium Sulfate
Mechanism of Action
Long familiar to obstetricians secondary to its use for
seizure prophylaxis in preeclampsia, magnesium sulfate
has gained popularity as a tocolytic due to its ease of
administration and relatively low risk of significant side
effects. It is now used as the first line agent of choice for
patients with preterm labor at many medical centers. Its
mechanism of action still remains unclear, but it is thought
to exert its action at two possible sites.
15,16
Magnesium has
been shown to decrease acetylcholine release at motor end
plates at the neuromuscular junction and to block nerve
transmission by preventing calcium entry. Magnesium
also acts as a calcium antagonist, both at the intra- and
extracellular levels. Hypocalcemia is produced through
suppression of the parathyroid and prevention of renal
reabsorption of calcium at the renal tubules. Elevated
magnesium levels also compete with cellular calcium
binding sites, resulting in a decrease of adenosine triphos-
phate levels. This renders the cell unable to bind calcium,
and therefore, unable to activate the actin and myosin
complex to initiate uterine contraction.
Efficacy
As with other tocolytic agents, there are few randomized
controlled studies of magnesium sulfate, and these in gen-
eral have enrolled few patients. The first United States
study of magnesium sulfate, by Steer and Petrie in 1977,
was a comparison to alcohol prompted by the investigators
observation that preeclamptic women being treated with
magnesium sulfate for seizure prophylaxis often demon-
strated a slowing of uterine contractions.
17
This study
claimed magnesium sulfate to be the superior tocolytic but
only if used early in the treatment of preterm labor.
Tocolysis was achieved in 96% of patients with cervical
dilation of 1 cm or less but only in 25% if dilation was 2 to
5 cm. The efficacy of magnesium was compared with no
tocolytic therapy in the 1990 study by Cox et al.
18
No sig-
nificant difference was documented between the two
groups in terms of gestational age at delivery, birth weight,
neonatal morbidity, or perinatal mortality. This study has
been faulted for its limitation of dosages of magnesium sul-
fate administered, as it has been shown that magnesium
serum levels do not necessarily correlate with tocolytic
effect.
19
Studies have also been performed comparing mag-
nesium sulfate to the beta-mimetics; these have generally
shown equivalent efficacy in achieving 2 to 3 days of tocol-
ysis with decreased serious maternal side effects. Macones
et al.
20
examined the available evidence regarding the effi-
cacy of magnesium sulfate for acute tocolysis compared
with placebo and beta-agonist agents in their meta-analysis.
In a review of the eight randomized controlled trials of
magnesium sulfate for tocolysis, which met their criteria for
inclusion, there was no significant difference between mag-
nesium and placebo for any of the measured outcomes for
delay in delivery (presumably because of the low number of
patients enrolled). Comparing magnesium sulfate to rito-
drine or beta-agonists did not demonstrate any differences
between the agents in achieving clinically significant tocol-
ysis. A difference did exist between magnesium sulfate and
the beta-agonists in the frequency of medication discontin-
uation secondary to side effects (more common with the
beta-agonists), but the overall rate of major adverse effects
was equitable.
Safety
Magnesium is excreted by the kidney, and unlike patients
being treated for preeclampsia, patients with preterm labor
generally have normal renal function. Magnesium toxicity
with the treatment of preterm labor is therefore rare; serum
levels are usually documented between 4 and 9 mg/dL. Those
side effects most commonly encountered with magnesium
sulfate include flushing, nausea and vomiting, headache, gen-
eralized muscle weakness, diplopia, and shortness of breath.
Patellar reflexes disappear with plasma levels of 9 to 13
June 1, 2005 Postgraduate Obstetrics & Gynecology
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Postgraduate Obstetrics & Gynecology June 1, 2005
4
mg/dL, respiratory depression occurs at 14 mg/dL. Toxic lev-
els are treated with 1 g of calcium gluconate administered
intravenously, with rapid reversal of symptoms.
Pulmonary edema, occurring in approximately 2% of
patients, is the most serious associated drug effect with
magnesium sulfate.
21
It generally responds well to dis-
continuing magnesium sulfate and treatment with diuret-
ics.
6
Although the etiology is uncertain, increased intra-
venous fluids, decreased oncotic pressure, increased pul-
monary capillary permeability, and infection have all
been assigned possible etiologic roles.
22
The use of intravenous magnesium sulfate therapy appears
to involve little fetal/neonatal risk. Radiographic bone
changes have been described in neonates of patients receiving
long-term intravenous magnesium sulfate infusion. These
include radiographic bony abnormalities, rachitic changes of
the calvaria and long bones, abnormal fetal bone mineraliza-
tion, and parietal bone thinning.
23,24
Although these changes
disappear rapidly after birth, long-term therapy with magne-
sium sulfate should not be considered harmless.
Recent studies have also shown a possible benefit of
magnesium in reducing the risk of cerebral palsy and intra-
ventricular hemorrhage in premature neonates, separate
from its tocolytic benefits. Nelson and Grether, in a case-
control study, followed neonates born to women who had
received magnesium sulfate for treatment of either preterm
labor or preeclampsia.
25
At 3 to 7 years after birth, the inci-
dence of cerebral palsy was documented to be 7.1% in
magnesium-exposed children versus 36% in the controls.
DiRenzo et al.
26
reported a decreased incidence of intra-
ventricular hemorrhage and improved survival in prema-
ture neonates (less than 30 weeks gestation) if exposed to
magnesium sulfate and aminophylline antepartum.
Indomethacin
Mechanism of action
Prostaglandins are known to be important mediators in
myometrial contractility. Term labor has been determined to
be associated with increased concentrations of arachidonic
acid and prostaglandins E2 and F2 alpha. Prostaglandins
enhance myometrial gap junction formation and increase
intracellular free calcium levels, thereby increasing the acti-
vation of MLCK and frequency of uterine contractions.
Prostaglandins are frequently used for induction of abortion
and cervical ripening or induction of labor. Therefore,
prostaglandin synthetase inhibitors appear to be natural can-
didates for tocolysis. The focus thus far has been on the non-
steroidal anti-inflammatory drug indomethacin.
Efficacy
Numerous articles on the efficacy of indomethacin have
been published since first reported by Zuckerman and col-
leagues in 1974.
27
As with other studies of other tocolyt-
ics, most of these have lacked adequate sample size, uni-
form diagnosis of preterm labor, and adequate blinding or
control groups. Niebyl et al.
28
and Zuckerman et al.
29,30
reported randomized, double-blinded, placebo-controlled
studies. Both studies suggested that indomethacin is more
effective than placebo in delaying delivery for 48 hours.
However, there was no documentable difference in terms
of neonatal outcome, gestational age at delivery, or birth
weight. It has been thought that inadequate sample size
may be attributable for this finding.
Indomethacin may also be the tocolytic of choice for
patients with polyhydramnios and resultant preterm
labor. A decrease in fetal urine production mediated by
the release of the normal prostaglandin-mediated block
of antidiuretic hormone in the fetus, disturbances in
autoregulation of renal blood flow, and increased fetal
breathing and swallowing are thought to lead to the
decrease in amniotic fluid volume experienced by
women undergoing treatment with indomethacin at usual
doses given for preterm labor. Because these patients are
often treated for longer than the usual 2 to 3 day course,
close fetal surveillance is necessary.
Safety
Treatment with indomethacin is remarkable for the rela-
tive infrequency of serious maternal side effects. Gastro-
intestinal disorders such as heartburn, nausea, vomiting,
and peptic ulcer disease can be encountered, although seri-
ous complications are uncommon when indomethacin is
used for a short course. Thrombocytopenia and increased
bleeding time have also been documented.
31
Acute renal
failure, especially when indomethacin is administered with
other nephrotoxic drugs, also can complicate treatment.
32
Hypertensive women have been noted to suffer acute eleva-
tions in blood pressures. Therefore, aspirin-induced asth-
ma, kidney or liver disease, coagulation disorders, poorly
controlled hypertension, and active peptic ulcer disease are
all thought to be maternal contraindications to treatment.
10
In contrast, neonatal side effects from treatment with
indomethacin are a focus of concern. Worrisome side effects
include oligohydramnios, constriction of the ductus arterio-
sus, and neonatal pulmonary hypertension. As stated above,
oligohydramnios is a consequence of decreased fetal urine
output, which usually resolves rapidly with the cessation of
treatment. Ductal constriction occurs secondary to the inhi-
bition of prostacyclin and prostaglandin E2 formation, which
are responsible for the maintenance of ductal patency.
Moise
33
noted in Doppler echocardiography studies that the
risk of ductal constriction rises rapidly after 32 weeks gesta-
tion. Ductal constriction can lead to cardiac failure with
hydrops, or pulmonary hypertension and persistent fetal cir-
culation in the newborn period. It also may lead to decreased
ability of the ductus to constrict in response to oxygen at
birth, leading to a paradoxically increased risk for patent duc-
tus arteriosus. For these reasons, treatment with
indomethacin should be limited to gestations less than 32
weeks and without evidence of oligohydramnios. Ultrasound
should be performed after 48 hours of therapy to exclude
oligohydramnios, and ductal flow/evidence of tricuspid
regurgitation should be analyzed after 3 days of therapy.
Continuation of therapy beyond 48 to 72 hours has become
rare; if such therapy is deemed necessary, amniotic fluid vol-
ume should be checked twice weekly and Doppler studies
507946_PGO11_sw 8/8/05 2:36 PM Page 4
performed at least weekly. Therapy should be discontinued if
oligohydramnios or ductal constriction is encountered.
34
Recently, concerns have arisen over other possible neona-
tal complications resulting from use of indomethacin at
more premature gestational ages.
35
In this retrospective
cohort study, infants antenatally exposed to indomethacin
prior to 30 weeks gestation demonstrated poorer renal func-
tion, a higher rate of necrotizing enterocolitis, and more
cases of intracranial hemorrhage grade II to IV and patent
ductus arteriosus compared with infants who have not been
exposed to indomethacin. Major et al.,
36
in their analysis of
the effect of indomethacin on the incidence of necrotizing
enterocolitis among low-birth-weight infants, also obtained
concerning results. Neonates born to patients in preterm
labor who received indomethacin tocolysis were compared
with preterm neonates whose mothers did not receive
indomethacin. The incidence of necrotizing enterocolitis in
neonates delivered within 24 to 48 hours of treatment with
indomethacin was significantly higher than that in non-
indomethacin-treated infants. Future prospective trials may
determine whether these risks are outweighed by the effi-
cacy of indomethacin as a tocolytic agent. However, neither
of these studies is conclusive because of some methodolog-
ical considerations. Specifically, in both of these studies,
patients with worse or refractory (failing conventional
therapy) preterm labor are those most likely to be treated
with indomethacin. Thus, it is unclear whether the observed
increases in necrotizing enterocolitis and intraventricular
hemorrhage are due to indomethacin exposure or to some
other underlying reason for more serious preterm labor,
such as an intra-amniotic infection.
Oral Tocolytics for Maintenance Therapy
Although they are commonly used, there is currently no
support in the literature for routine use of oral tocolytics
(most commonly beta-mimetics) after parenteral treatment of
preterm labor. A recent meta-analysis of the four randomized
trials of oral beta-agonist maintenance therapy revealed no
benefit in terms of reducing the incidence of preterm deliv-
ery, increasing the interval to delivery, or reducing the inci-
dence of recurrent preterm labor.
37
Importantly, long-term
beta-agonist use is increasingly associated with maternal glu-
cose intolerance, as well as with the more mild side effects
listed above.
38
These findings also may be confounded by the
issues of tachyphylaxis, subtherapeutic blood levels when
compared with parenteral therapy, and inaccurate diagnosis
of preterm labor. For these reasons, physicians must weigh
the risks of oral beta-mimetics against the uncertain benefits.
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24. Lamm CI, Norton KI, Murphy RJ, et al. Congenital rickets associated with
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tion of magnesium sulfate and aminophylline reduces intraventricular hemor-
rhage in very preterm neonates. Am J Obstet Gynecol 2005;192:433438.
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by indomethacin. Obstet Gynecol 1974;44:787792.
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June 1, 2005 Postgraduate Obstetrics & Gynecology
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Postgraduate Obstetrics & Gynecology June 1, 2005
6
Attention CME Participants
Effective immediately, please fill in the answer boxes on your answer form completely using a blue or black pen.
DO NOT use a check or X mark in the boxes. Thank you.
1. The most common cause of preterm birth in the United States is
A. preterm rupture of membranes
B. spontaneous preterm labor
C. preeclampsia
D. nonreassuring fetal status
2. An important limitation of most prior studies of tocolysis is
A. improper endpoint
B. lack of proper randomization
C. lack of blinding
D. all of the above
3. Beta-1 receptors are located in all of the following except
A. heart
B. small intestine
C. uterus
D. adipose tissue
4. Meta-analysis of the placebo-controlled clinical trials of beta-
agonists in patients with preterm labor suggests that treatment
A. reduces major neonatal complications
B. reduces major maternal complications
C. increases the proportion women of remaining undeliv-
ered after 48 hours
D. none of the above
5. Which one of the following cardiovascular complications
has been reported in association with beta-agonist treat-
ment in pregnancy?
A. Arrhythmia
B. Myocardial ischemia
C. Hypertension
D. Pulmonary edema
6. Magnesium sulfate is excreted by the
A. kidney
B. liver
C. A and B
D. None of the above
7. At what magnesium level does respiratory depression occur?
A. 23 mg/dL
B. 49 mg/dL
C. 913 mg/dL
D. Greater than 14 mg/dL
8. Which one of the following is not a maternal complication
associated with indomethacin use?
A. Gastrointestinal bleeding
B. Thrombocytosis
C. Renal failure
D. Hypertension
9. Which of the following is a potential a neonatal complication
with indomethacin use?
A. Oligohydramnios
B. Ductal constriction
C. Pulmonary hypertension
D. All of the above
10. Which one of the following is a benefit of maintenance oral
tocolysis?
A. Improved latency (time to delivery)
B. Improved neonatal outcome
C. Reduced rate of preterm delivery
D. None of the above
To earn CME credit, you must read the CME article and complete the quiz on the enclosed answer form, answering at least seven of the
10 quiz questions correctly. Select the best answer and use a blue or black pen to completely fill in the corresponding box on the
enclosed answer form. Please indicate any name and address changes directly on the answer form. If your name and address do not appear
on the answer form, please print that information in the blank space at the top left of the page. Make a photocopy of the completed answer form
for your own files and mail the original answer form in the enclosed postage-paid business reply envelope. Your answer form must be
received by Wolters Kluwer Health by May 31, 2006. Participants will receive CME certificates bi-annually, one for the January through June
period and one for the July through December period. For more information, call (800) 787-8981.
Wolters Kluwer Health is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical
education for physicians.
Please do not use the answer forms and business reply envelopes that you may have on hand from previous issues of
Postgraduate Obstetrics & Gynecology.
Wolters Kluwer Health designates this educational activity for a maximum of 1.5 category 1 credits toward the AMAs Physicians
Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity.
CME QUIZ: Volume 25, Number 11
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