9/7/04njm

**Preterm Labor and Preterm Premature Rupture of Membranes**

**1 How to participate**

For more details about how to participate in this C.E.U./C.M.E. program,
see the [Perinatologist
Corner](http://www.ihs.gov/MedicalPrograms/MCH/M/MCHpericrnr.asp#top)
page. Also see specifics there on [Goals, Sponsorship and Credit, and
Disclosure](http://www.ihs.gov/MedicalPrograms/MCH/M/MCHpericrnr.asp#Goals).

**Goals and objectives**

The student will understand the maternal and fetal consequences, methods
and limitations of screening, and understand the management of Preterm
Labor and Preterm Premature Rupture of Membranes

**Objectives**

The objectives for this module are:

-   The student will understand the maternal and fetal consequences of
    Preterm Labor and Preterm Premature Rupture of Membranes

-   The student will understand the methods and limitations of Preterm
    Labor and Preterm Premature Rupture of Membranes

-   The student will understand the management of Preterm Labor and
    Preterm Premature Rupture of Membranes

**Case scenario**

**Case 1**

J.N., a 23 y/o G1P0 at 29 weeks by her dates consistent with a 9 week
ultrasound, presents with an 8 hour history of uterine contractions. Her
pregnancy has been uncomplicated to date. She relates that the
contractions are not very strong, but they are persistent, and are
occurring about every 5-10 minutes. She reports no leakage of fluid, no
bleeding, and no urinary tract symptoms. Fetal movements are good.

a.  How would you work up this problem?

b.  How would you manage this problem?

**2** **Background**

**Case 2**

L. B., a 19 y/o G1P0 at 30 weeks by her dates consistent with an 11 week
ultrasound, presents with a history of continuous leakage of clear fluid
starting approximately 8 hours ago. Her pregnancy has been uncomplicated
to date. She is currently experiencing some very mild irregular uterine
contractions. She reports good fetal movements.

a.  How would you work up this problem?

b.  How would you manage this problem?

**Background**

Preterm labor is a major cause of neonatal morbidity and mortality in
the United States. While infant mortality is decreasing due to
improvements in neonatal intensive care, the incidence of preterm birth,
and of the complications of being born prematurely, are increasing. Over
the last two decades, despite improvements in care, the incidence of
preterm birth has increased from 9.4 to 11.2 per cent. Nevertheless,
survival after 32 weeks gestation has increased to 95 per cent, very
close to survival at term. Complications of prematurity are also low
after 32 weeks, but morbidity, principally long term pulmonary and
neurologic sequelae, remains high in survivors born at less than 28
weeks.

The cause(s) of most preterm births remains unknown and unpreventable.
Approximately two third of preterm births are the result of spontaneous
preterm labor or spontaneous preterm premature rupture of membranes.

Please link the words 'cause(s) of most preterm births remains unknown'
to the text at the very end of this document called **GUIDELINES FOR THE
MANAGEMENT OF PRETERM LABOR**

That text (**GUIDELINES FOR THE MANAGEMENT OF PRETERM LABOR)**

is referenced twice in the document above, so might be best made into a
separate document to link to?

A 2003 literature review found that LEEP appears to be associated with
subsequent preterm birth, even when smoking status is matched. Studies
with adequate sample size are needed to further evaluate the
relationship of LEEP and preterm birth, controlling for potential
confounders, including depth of the tissue sample. This was confirmed in
May 2004 and careful consideration should be given to treatment of CIN
in women of reproductive age, especially when treatment might reasonably
be delayed or targeted to high-risk cases.

Please link the words '2003 literature review' to this

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14672487]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14672487)

Please link the words 'confirmed in May 2004' to this

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15126438]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15126438)

The remainder of cases are due to a variety of causes, but many are due
to unavoidable indicated preterm birth such as those that are the result
of life-threatening placental bleeding, or of maternal disorders such as
early onset severe preeclampsia. Native American women and Mexican
American women tend to have a lower incidence of preterm birth than
Caucasian women depending on their access to health care, while African
American women tend to have a higher incidence. There is now extensive
evidence that infection is an important etiology of preterm labor, but
implications for prevention have not been realized. The role of social
and lifestyle factors is also poorly predictive of who will deliver
preterm. Prior preterm birth remains the most accurate predictor of
recurrent preterm birth.

Please link the words 'Native American women' above to the 'Native
American Article References' section on page 15 of this module

**3 Management**

**Case 3**

E. J. E., a 25 y/o G2P0 at 23 weeks by her dates consistent with a 10
week ultrasound, presents with a history of low back pain and "pressure
down there" for the last 24 hours. This has been accompanied by a
copious clear vaginal discharge that has now become slightly blood
tinged over the last hour. She denies uterine contractions and has no
urinary tract symptoms. She has a history of a "LEEP" procedure for
moderate dysplasia two years ago and an elective termination 10 years
ago.

a.  How would you work up this problem?

b.  How would you manage this problem?

**Management**

Since the etiology of idiopathic preterm labor remains cryptic despite
extensive investigation, management remains suboptimal. A review of the
evidence does reveal what does and what doesn't work well however. But
first, how do you decide if your patient is in true preterm labor (PTL),
or is just experiencing the "premature onset of contractions" ("POOC")?

Should she be admitted, transported, or discharged home?

You also have to decide [how early is too early for your
institution]{.underline}. Most level II and III centers will not
intervene at all at 34, or even 32, weeks, but that may not be true for
your facility. The incidence of any type of infant respiratory distress
syndrome (IRDS) is about one per cent after 36 weeks, but some sort of
transient respiratory assistance, such as supplemental oxygen, and in
rare instances a ventilator, may be necessary in up to 15-20 per cent of
infants born at 34 weeks. Infant nutritional requirements, issues of
thermostability, and available personnel to care for a premature infant
are all important considerations.

Please link the words '[how early is too early for your
institution']{.underline} to the text near the end of this document
called **GUIDELINES FOR THE MANAGEMENT OF PRETERM LABOR**

That text (**GUIDELINES FOR THE MANAGEMENT OF PRETERM LABOR)**

is referenced twice in the document above, so might be best made into a
separate document to link to?

**4 Diagnosis**

**Case 4**

A. L., a 29 y/o G6P1313 at 23 weeks by her dates presents for her first
prenatal visit. She has an obstetric history of having delivered her
first child at 37 weeks, followed by 3 preterm deliveries at 32, 28, and
26 weeks, following spontaneous preterm labor. She also had one early
trimester miscarriage. The infant that delivered at 26 weeks succumbed
to complications of prematurity after a protracted nursery course.

a.  How would you work up this problem?

b.  How would you manage this problem?

**Diagnosis**

[The diagnosis of true preterm labor]{.underline} is not always easy.
The textbook definition of 4 contractions in 20 minutes accompanied by
cervical change is somewhat subjective. Due to normal biologic
variation, some multiparous women walk about significantly dilated
throughout the third trimester, but deliver at term. Likewise some
nulliparous women may efface significantly earlier than usual. Serial
cervical examinations may help you decide on cervical change, but is
hampered by both inter- and intra-observer variability. Bloody show is
almost always a reliable sign of true labor, but is not necessarily
always seen. Preterm premature rupture of membranes (PPROM) should
always be sought, as it may be occult or unnoticed or misinterpreted by
the patient.

A common error when evaluating patients in suspected preterm labor is to
perform a cervical digital exam as your first maneuver. ("Check her
quick! We have to get her out of here!") There are disadvantages to this
approach. If the patient does not appear to be making obvious expulsive
efforts, but is uncomfortable, she probably is remote from delivery, and
you have some time...., so [hold off on that cervical
check!]{.underline} Observing her on the monitor for 30 minutes while
you do other things will allow you to evaluate her contraction pattern
and whether the fetus looks stable. A clean catch urinalysis
occasionally detects an occult urinary tract infection as the etiology
of the uterine activity. If her dating is not certain it is helpful to
get an ultrasound for biometry and an estimated fetal weight. A low
amniotic fluid index (AFI) may be your first clue to occult PPROM.

**5 Speculum exam versus digital exam**

The reason you want to defer the digital exam is so that you can [do a
sterile speculum exam]{.underline}. Be sure to avoid lubricant as it
will confound the tests you want to collect. Most patients will have
sufficient vaginal secretions so that a gentle exam will hopefully not
be too uncomfortable without lubricant. You will usually need a large
speculum with a long blade because of the redundancy of the vaginal
folds in the third trimester. You need to check for ferning to be sure
PPROM isn't part of the diagnosis. Remember, in the case of PPROM, "the
examining finger winds the clock of infection", so defer digital exam if
your suspect ruptured membranes.

Please link the words '"the examining finger winds the clock of
infection", to this

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1407885]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1407885)

**Management of PPROM**

The latency period before birth after PPROM is usually inversely related
to the gestational age. With the most immature fetuses you want to
prolong that as much as possible, so "keep fingers out"! Visual
inspection of the cervix may also help you. If you see a small circle of
membranes or hair surrounded by cervix, you can be sure that the cervix
is at least 4 cm dilated. (It could be 8 cm dilated too, so this would
be the patient you would definitely want to check before transport!) If
the cervix looks closed, it may be 0-3 cm dilated, but delivery will not
be imminent. At this time you also should collect a vaginal and rectal
specimen for group B strep culture, as well as another very helpful
laboratory investigation, a fetal fibronectin. Other PPROM management
tips are here.

# Please link the words '"Other PPROM management tips are here", to the text at the very end of this document called 'GUIDELINES FOR PRETERM PREMATURE RUPTURE OF MEMBRANES'

That text (**GUIDELINES FOR PRETERM PREMATURE RUPTURE OF MEMBRANES')**
is referenced in the module, so might be best made into a separate
document to link to?

**6 Fetal fibronectin**

[Fetal fibronectin]{.underline} is, simplistically, the extracellular
matrix protein that helps attach the fetal chorion to the maternal
decidua. As parturition approaches it is released into the cervix and
vagina through proteolysis. Its clinical utility derives from its
ability to help you triage your patient. The [negative]{.underline}
predictive value of fetal fibronectin (fFN) is over 95 per cent in
almost all published studies involving *symptomatic* women (those having
premature contractions).

Please link to the words 'negative predictive value of fetal
fibronectin'

[[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat1.chapter.26758]{.underline}](http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat1.chapter.26758)

So.... if your patient has a [negative]{.underline} fFN, you can be
reasonably well assured that she will not deliver in the next 7 days,
and probably not before 37 weeks. The positive predictive value of fFN
is poor however. Most studies show that symptomatic women with a
[positive]{.underline} fFN have only a 12-15 per cent chance of
delivering within the next 7 days, so a [positive]{.underline} test is
clinically much less useful, but still may be helpful with the patient's
triage.

The turnaround time for fFN is usually about two hours, a good interval
to watch the patient for cervical change. A caveat with its use is that
a false positive can be produced by blood, lubricant, amniotic fluid, or
semen in the vagina within the last 24 hours. If these conditions can be
ruled out, collect a cervico-vaginal specimen at the time you obtain
your sample for ferning, and *before* you do a digital exam with
lubricant. If PTL is a frequent problem at your institution, you should
certainly consider adding this test to your laboratory's armamentarium.
Unfortunately, fFN is not that helpful to predict preterm delivery in
*asymptomatic* women however. In this situation, a positive fFN has a
positive predictive value for delivery at less than 35 weeks of only 4-5
per cent, not worth your screening women who you feel are high-risk by
their history.

**7 Ultrasound: Cervical length**

Another possibly helpful ancillary investigation, if available at your
institution, is a [transvaginal ultrasonographic cervical
length]{.underline}. It is not an easy sonographic exam however, so if
you don't have access to an experienced sonographer at your facility,
this section may not be pertinent, or you may want to have someone
trained.

Please link the words '[transvaginal ultrasonographic cervical
length]{.underline}' to the **Other Reference Articles: Cervical
Length** section on page 15 of this module

Transvaginal sonography for cervical length is *not* recommended for
[screening]{.underline} asymptomatic women because of its low positive
predictive value in this population. However, it may be a helpful
adjunct for triage of symptomatic women. The median (50^th^ percentile)
cervical length is 3.5 [+]{.underline} 0.8 cm in the third trimester.
The "short cervix", less than the 10^th^ percentile, measures less than
2.5 cm in the late trimester.

Transvaginal sonography also gives you an insight into the condition of
the internal cervical os which you often cannot palpate. Cervical
"funneling" refers to a shortening of the overall cervical length by
prolapse of the amniotic membranes into the upper cervical canal in a
"V" or "U" configuration. Significant "funnels" are 1.5 x 1.5 cm in
their widest dimensions, and their presence increases your level of
suspicion for true PTL rather than just "POOC".

Cervical lengths greater than 3.0 cm have a negative predictive value
for preterm delivery of 89-93 per cent, while cervices shorter than 2.0
cm have a positive predictive value for delivery within the next seven
days of about 15-18 per cent, values similar to those obtained with fFN
determinations. Combining fFN and cervical length enhances the
sensitivity of your predictions. So a woman with minimal cervical change
on exam, a negative fFN, and a cervix \>2.5 cm may be a candidate to go
home. On the other hand, the same woman with unimpressive cervical
change, but who has a positive fFN and a cervix shorter than 2.5 cm,
would be a good candidate for admission or transport, other clinical
variables being equal.

**8 Management**

One quick and easy, but evidence-based and effective, [triage
maneuver]{.underline} that helps you differentiate true PTL from POOC is
a *single* injection of subcutaneous terbutaline 0.25 mg. If the
patient's contractions have significantly diminished or resolved in 2
hours after your intervention, this probably is not true PTL. By that
time you may also have your ancillary studies back to help with the
decision. While terbutaline has some downsides as a tocolytic (see
below), its use here may be a clinically helpful maneuver.

Please link the words '*single* injection of subcutaneous terbutaline
0.25 mg above to this

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10546776]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10546776)

Okay...., so now you've gotten your baseline studies, and you've decided
this is real PTL and you want to try to formally stop the contractions.
What does the evidence show are effective interventions? While often
recommended, [bed rest is not an evidence-based
intervention.]{.underline}

Please link to the words '[bed rest is not an evidence-based
intervention']{.underline} to this

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14974024]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14974024)

There are no randomized controlled trials (RCT) showing a benefit of bed
rest in prolongation of pregnancy, and two studies in twins actually
demonstrated an increase in preterm birth in the groups managed with bed
rest. The medical downsides of bed rest include muscle weakness,
osteoporosis, and thrombophlebitis. The social downsides include loss of
employment, childcare problems, marital discord, and guilt when the
regimen is not adhered to as recommended. Nevertheless, many women
experience fewer contractions at rest, so individualize.

Please link to the words 'two studies in twins' to this

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11279677]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11279677)

[Hydration and sedation]{.underline} are also frequently employed
strategies for this problem. Two RCT of hydration (1000 mL of
intravenous Ringer's lactate) showed no benefit, nor did a trial
employing morphine sulfate. The disadvantage of sedation is mainly fetal
depression, while that of over-vigorous hydration may be pulmonary
edema, especially when combined with aggressive tocolytic therapy.

Please link to the words 'Two RCT of hydration' to this

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12076470]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12076470)

**9 Tocolysis**

[Tocolytics for the treatment of preterm labor]{.underline} have been
extensively studied, but have demonstrated little long term benefit.
Most tocolytic agents will reduce the risk of delivery within the first
48 hours, and there are definite advantages to such delay. Nevertheless,
no tocolytic agent has consistently reduced the perinatal mortality
rate, the incidence of IRDS, or the number of low birth weight infants.
This is true for the beta-mimetics (terbutaline, ritodrine), and the
calcium channel blockers (nifedipine, magnesium sulfate). Maternal
pulmonary edema has been associated with the prolonged use of all these
agents, especially in women carrying twins, those with chorioamnionitis,
and those subjected to enthusiastic hydration. Neonatal neuromuscular
blockade and difficult resuscitation may be associated with excessive
use of magnesium sulfate. Despite this agent having been shown to be
equivalent to placebo for tocolysis in the meta-analysis data, it
inexplicably remains the first-line tocolytic agent in many
institutions! The data is conflicting as to the neuroprotective effect
of magnesium sulfate, with both a lower and a higher incidence of later
cerebral palsy being reported in surviving children. The meta-analysis
data show a neutral effect.

Please link the words 'beta-mimetics (terbutaline, ritodrine' above to
this

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10546776]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10546776)

Please link the words 'magnesium sulfate' above to this

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12519550]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12519550)

Please link the words 'nifedipine' above to this

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8238157]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8238157)

[Nonsteroidal anti-inflammatory agents]{.underline} such as indomethacin
have a better success rate, as measured by lowering the occurrence of
low birth weight and prolonging pregnancy. They suppress myometrial
prostaglandin production, the last step in the labor cascade. Earlier
retrospective reports demonstrated an association of indomethacin with
neonatal necrotizing enterocolitis, intraventricular hemorrhage, patent
ductus arteriosus, and oliguria. These findings were not confirmed when
the RCT employing this agent were subjected to meta-analysis. Likewise,
multivariate analysis showed that these effects were not significantly
associated with the drug when outcomes were corrected for gestational
age, the adverse events being ascribed to immaturity, not to the
therapy. A decision analysis concluded that indomethacin tocolysis would
result in a lower total number of adverse neonatal outcomes compared to
no tocolysis, when restricted to a 48 hour course. Indomethacin is
probably the tocolytic of choice because of best efficacy and fewest
maternal side effects. It may be given as 50 mg orally q6h over 48 hours
with a maximum dose of 400 mg. Greatest benefit and safety is seen when
it is given at less than 32 weeks, and it should not be given if there
is pre-existing oligohydramnios.

Please link the first time the word 'indomethacin' listed above to this

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10430197]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10430197)

Please link the word 'patent ductus arteriosus' listed above to this

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8498410]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8498410)

Please link the word 'oliguria' listed above to this

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2340255]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2340255)

Women between 32-34 weeks, or those with a low AFI, may be more
prudently treated with terbutaline 0.25 mg subcutaneously q4h x 4-6
doses. Indomethacin, being administered orally, is somewhat slow acting,
so despite having the most evidence favoring its use, you may need to
overlap it, or combine it, with another agent initially. Experience with
parenteral nonsteroidal agents, such as ketorolac, or the newer
selective COX-2 inhibitors such as rofecoxib, is promising but limited.
Long-term oral tocolytics of any class really have no place in
contemporary obstetrics. It will usually (but not always!) be futile to
attempt to tocolyse women in active labor who are at greater than 5 cm
cervical dilation, and it will also be risky to attempt to transport
these women. Women with PPROM are usually not candidates for tocolysis,
however tocolysis may be crucial for transport to the site of delivery.

There are thus two important advantages to the use of tocolytic agents.
One is facilitating transport to a level III center for birth, an issue
of great significance in our rural-based Indian Health Service setting.
The other is buying time for the administration of [antenatal
corticosteroids]{.underline}.

Please link the word '[antenatal corticosteroids']{.underline} to page
10 in this module

**10 Corticosteriods**

Corticosteroid therapy has been an important step forward in perinatal
medicine and extensive data support its benefit. Steroids act by
promoting the transcription of the enzymes necessary for production of
the cellular products needed for extrauterine existence, most prominent
of which is pulmonary surfactant. The Oxford Database of Perinatal
Trials convincingly demonstrate that the incidence of IRDS is halved (OR
0.49, CI 0.41-0.60), and that this effect is most marked in infants
under 32 weeks (OR 0.38, CI 0.24-0.60), and applies as well to
pregnancies delivered because of PPROM (OR 0.55, CI 0.40-0.75), as well
as idiopathic preterm labor. The effect is maximum from 24 hours up to 7
days after administration (OR 0.31, CI 0.23-0.42), but is also seen more
than 7 days after dosing (OR 0.69, CI 0.50-0.94). Male and female
fetuses will benefit equally. Repeated courses of steroids are not
recommended because of the association of repeated dosing, especially
more than three courses, with lower birth weight, reduced head
circumference, as well as the later development of childhood attention
deficit disorder.

Please link the first time the word 'Corticosteroid therapy' appears
above to this

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11978304]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11978304)

Besides its pulmonary effects, antenatal corticosteroid administration
is also associated with a reduced incidence of neonatal death (OR 0.59,
CI 0.47-0.75), intraventricular hemorrhage (OR 0.45, CI 0.21-0.97),
necrotizing enterocolitis (OR 0.37, CI 0.17-0.69), and a trend toward
fewer later neurologic abnormalities (OR 0.61, CI 0.34-0.1.08). Their
use is not associated with a higher risk of infection, either maternal
(OR 1.11, CI 0.81-1.51), or neonatal (OR 0.83, CI 0.54-1.26). This lack
of an association with infection was similarly seen in patients with
PPROM. Clearly, the utility of tocolysis is the opportunity it presents
to "get the steroids on board"! Betamethasone and dexamethasone are not
inactivated by placental 11-beta-hydroxylase, and are thus the only
corticosteroids that cross the placenta to the fetus. There seems to be
a slight survival advantage of betamethasone over dexamethasone, making
betamethasone the preferred agent. The dose of betamethasone is 12 mg IM
q24 hours x 2 doses. The dexamethasone dose is 6 mg IM q12 h x 4 doses.
Because of issues with the manufacturer, the pharmacy doesn't always
have betamethasone available, so use what you have. **Of all the things
you do for your patient with PTL, steroids are probably the most
significant!**

**11 Antibiotics**

**What about [antibiotics]{.underline} for the patient in preterm
labor**?

Current investigation has incriminated infection as a likely cause of at
least a subset of "idiopathic" preterm labor. In studies of women with
idiopathic PTL with intact membranes who underwent amniocentesis, 8-12
per cent had positive bacterial cultures. More significantly, various
inflammatory cytokines, most prominently among them, interleukin-6
(IL-6), were elevated in the amniotic fluid of many more of these women,
even if culture negative, and most of them went on to deliver quickly.
However, despite much evidence suggesting occult intrauterine infection
as an important subset of PTL, antibiotic trials have been
disappointing.

Please link the words 'important subset of PTL to this

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12519538]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12519538)

Please link the words 'have been disappointing.

to this section 'Other Reference Articles: Preterm Labor' on page 15 in
this module

Eight RCTs involving erythromycin, ampicillin, and clindamycin, alone or
in various combinations, have shown contradictory results as regards
delay of delivery, and none has demonstrated an increase in birth weight
or a decrease in mortality. This was not true for women experiencing
PPROM.

Please link the words 'Eight RCTs involving' to this section '**Other
Reference Articles: PPROM'** on page 15 in this module

In the setting of PPROM antibiotics have been shown to increase the
latency period before delivery, decrease the incidence of
chorioamnionitis and postpartum endometritis, and to reduce the
incidence of neonatal sepsis.

In the largest study, "ORACLE I", with almost 5,000 women with PPROM
participating, erythromycin 250 mg po qid x 10 days significantly
prolonged the latency interval to delivery, reduced the incidence of
neonatal sepsis, and showed a trend towards improving the incidence of
the composite outcome of neonatal death, neurologic injury, and chronic
lung disease. Treatment of asymptomatic women with bacterial vaginosis,
recommended in the past, has not proven to be beneficial, except in a
subset of African-American women with more than one prior preterm
births. Some studies have shown more preterm births in women treated
with metronidazole, possibly due to a treatment associated release of
proinflammatory bacterial products.

Please link the words 'ORACLE I' to this

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11293640]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11293640)

**So, should antibiotics not be used for PTL with intact membranes**?

They do have a specific role, and that is in the prevention of neonatal
early onset group B streptococcal (GBS) infection. The 2002 CDC
Guidelines suggest that women presenting with PTL or PPROM should have a
vaginal and rectal culture for GBS collected on their initial
assessment. They should then be empirically treated, preferably with
penicillin.

Please link the word '2002 CDC Guidelines' to this

[[http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5111a1.htm]{.underline}](http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5111a1.htm)

The loading dose of aqueous penicillin G is 5.0 million units IV,
followed by 2.5 million units IV q4h for 48 hours, or until the GBS
culture is back. It is best to give penicillin piggy-backed into a fast
flowing IV because, undiluted, it tends to cause a very unpleasant local
burning sensation.

Ampicillin is a second choice because, with its broader spectrum, it may
encourage the emergence of more resistant E.coli, the other leading
neonatal pathogen. Remember to ask for sensitivities on isolates of
patients with a history of penicillin allergy. Up to 20 per cent of GBS
isolates are resistant to clindamycin and erythromycin, so those drugs
unfortunately cannot be recommended empirically.

Women who have had only a minor drug reaction to penicillin (rash,
itching) may be treated with cefazolin 1g IV q8h. Patients with a known
history of anaphylaxis however will require vancomycin 500 mg IV q12h,
unless sensitivies of the organism are known.

If the GBS culture is negative, the antibiotics may be stopped. If the
culture is positive, antibiotics may be continued for 48 hours and then
stopped. If the patient is a carrier and subsequently goes into active
labor after her initial course of tocolytics and steroids, GBS
prophylaxis should be resumed again intrapartum.

For a free case based CEU/CME module on Group B Streptococcal disease in
the perinatal period with Clinical Pearls and Frequently Asked Questions
go Here.

Please link the word 'Here' to this

[[http://www.ihs.gov/MedicalPrograms/MCH/M/DP41.asp#top]{.underline}](http://www.ihs.gov/MedicalPrograms/MCH/M/DP41.asp#top)

Please link the word 'Clinical Pearls and Frequently Asked Questions' to
this

<http://www.ihs.gov/MedicalPrograms/MCH/M/DP46.asp#top>

Joy this next page, page 12, should be 'blinded' to the non-WAN

**12 I.H.S. online resources**

If you are a member of the Indian Health Service or Tribal wide-area
network (W.A.N.), the resources on this page are available to you.

If you are not a member of the Indian Health Service or Tribal wide-area
network, some of the resources on this page will not be available to
you; for additional resources please go to 13 Other Online Resources and
Patient Education

(Please link to the words above 'Other Online Resources and Patient
Education' to page 13 in this module)

**A.C.O.G. / I.H.S. Postgraduate Reference Text 2003**

**A.C.O.G. / I.H.S. Reference Text Online:**

Preterm Premature Rupture of Membranes, Chapter F Scroll down to pp 5 --
7

Preterm Labor, Chapter F Scroll down to pp 8 - 10

Please link to the words above 'Preterm Labor, Chapter F Scroll down to
pp 8 -- 10 to:

[[http://www.ihs.gov/MedicalPrograms/MCH/M/MCHdownloads/Chap_F.pdf]{.underline}](http://www.ihs.gov/MedicalPrograms/MCH/M/MCHdownloads/Chap_F.pdf)

Please link to the words above 'Preterm Premature Rupture of Membranes,
Chapter F Scroll down to pp 5 -- 7 to:

[[http://www.ihs.gov/MedicalPrograms/MCH/M/MCHdownloads/Chap_F.pdf]{.underline}](http://www.ihs.gov/MedicalPrograms/MCH/M/MCHdownloads/Chap_F.pdf)

**UpToDate software**\
\
\[Notes: Click on the link below, and then the Accept button on the
screen that comes up.\]

Inhibition of Preterm Labor, Simhan H, Caritas S. UpToDate software
12.2, 2004.

Please link to the words above 'Inhibition of Preterm Labor' to:

[[http://www.uptodateonline.com/application/topic.asp?file=pregcomp/11591&type=A&selectedTitle=1\~25]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=pregcomp/11591&type=A&selectedTitle=1~25)

Prediction of preterm labor and delivery, Lockwood, C. UpToDate software
12.2, 2004.

Please link to the words above 'Prediction of preterm labor and
delivery' to:

[[http://www.uptodateonline.com/application/topic.asp?file=pregcomp/6957&type=A&selectedTitle=2\~25]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=pregcomp/6957&type=A&selectedTitle=2~25)

Prevention of spontaneous preterm birth, Norwitz, ER, Lockwood, C.
UpToDate software 12.2, 2004.

Please link to the words above 'Prevention of spontaneous preterm birth'
to:

[[http://www.uptodateonline.com/application/topic.asp?file=pregcomp/22936&type=A&selectedTitle=3\~25]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=pregcomp/22936&type=A&selectedTitle=3~25)

Pathogenesis of preterm birth. Lockwood, C. UpToDate software 12.2,
2004.

Please link to the words above 'Pathogenesis of preterm birth' to:

[[http://www.uptodateonline.com/application/topic.asp?file=pregcomp/2457&type=A&selectedTitle=4\~25]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=pregcomp/2457&type=A&selectedTitle=4~25)

Risk factors for preterm labor and delivery. Robinson J, Regan J,
Norwitz, E. UpToDate software 12.2, 2004.

Please link to the words above 'Risk factors for preterm labor and
delivery' to:
[[http://www.uptodateonline.com/application/topic.asp?file=pregcomp/18104&type=A&selectedTitle=5\~25]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=pregcomp/18104&type=A&selectedTitle=5~25)

Antenatal use of corticosteroids in women at risk for preterm delivery.
Lee M, Guinn D. UpToDate software 12.2, 2004.

Please link to the words above 'Antenatal use of corticosteroids in
women at risk for preterm delivery to:
[[http://www.uptodateonline.com/application/topic.asp?file=pregcomp/2842&type=A&selectedTitle=6\~25]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=pregcomp/2842&type=A&selectedTitle=6~25)

Patient information: Preterm labor. Lockwood, C. UpToDate software 12.2,
2004.

Please link to the words above 'Patient information: Preterm labor'
to:[[http://www.uptodateonline.com/application/topic.asp?file=pregnan/6340&type=A&selectedTitle=7\~25]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=pregnan/6340&type=A&selectedTitle=7~25)

**Other Related UpToDate Topics**

Incidence and sociodemographic characteristics of preterm birth,
Berkowitz G. UpToDate software 12.2, 2004.

Please link to the words above 'Incidence and sociodemographic
characteristics of preterm birth to:

[[http://www.uptodateonline.com/application/topic.asp?file=pregcomp/25250&type=A&selectedTitle=11\~25]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=pregcomp/25250&type=A&selectedTitle=11~25)

Intraamniotic infection, Newton ER. UpToDate software 12.2, 2004

Please link to the words above 'Intraamniotic infection' to

[[http://www.uptodateonline.com/application/topic.asp?file=pregcomp/18597&type=A&selectedTitle=12\~25]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=pregcomp/18597&type=A&selectedTitle=12~25)

Prediction of prematurity by transvaginal ultrasound assessment of the
cervix. Johnson JR, Iams JD. UpToDate software 12.2, 2004

Please link to the words above 'Prediction of prematurity by
transvaginal ultrasound assessment of the cervix. to

[[http://www.uptodateonline.com/application/topic.asp?file=antenatl/5245&type=A&selectedTitle=18\~25]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=antenatl/5245&type=A&selectedTitle=18~25)

Smoking and pregnancy. Rodriguez-Thompson D. UpToDate software 12.2,
2004

Please link to the words above 'Smoking and pregnancy' to

[[http://www.uptodateonline.com/application/topic.asp?file=maternal/6664&type=A&selectedTitle=21\~25]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=maternal/6664&type=A&selectedTitle=21~25)

Recommendations for exercise during pregnancy and the postpartum period.
Artal R. UpToDate software 12.2, 2004

Please link to the words above 'Recommendations for exercise during
pregnancy and the postpartum period.' to

[http://www.uptodateonline.com/application/topic.asp?file=antenatl/12055&type=A&selectedTitle=20\~25]{.underline}

Trauma in pregnancy. Kilpatrick, SJ. UpToDate software 12.2, 2004

Please link to the words above 'Trauma in pregnancy' to

[[http://www.uptodateonline.com/application/topic.asp?file=pregcomp/10295&type=A&selectedTitle=23\~25]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=pregcomp/10295&type=A&selectedTitle=23~25)

**Cochrane Library**

Calcium channel blockers for inhibiting preterm labour King JF, Flenady
VJ, Papatsonis DNM, Dekker GA, Carbonne B. (Cochrane Review). In: *The
Cochrane Library,* Issue 3, 2004. Chichester, UK: John Wiley & Sons,
Ltd.

**Reviewers\' conclusions:** When tocolysis is indicated for women in
preterm labour, calcium channel blockers are preferable to other
tocolytic agents compared, mainly betamimetics. Further research should
address the effects of different dosage regimens and formulations of
calcium channel blockers on maternal and neonatal outcomes.

Please link to the words above 'Calcium channel blockers for inhibiting
preterm labour' to
[[http://www.update-software.com/cochrane/abstract.htm]{.underline}](http://www.update-software.com/cochrane/abstract.htm)

Prophylactic corticosteroids for preterm birth Crowley P. (Cochrane
Review). In: *The Cochrane Library,* Issue 3, 2004. Chichester, UK: John
Wiley & Sons, Ltd.

**Reviewers\' conclusions:** Corticosteroids given prior to preterm
birth (as a result of either preterm labour or elective preterm
delivery) are effective in preventing respiratory distress syndrome and
neonatal mortality. However there is not enough evidence to evaluate the
use of repeated doses of corticosteroids in women who remain
undelivered, but who are at continued risk of preterm birth.(This
abstract has been prepared centrally.)

Please link to the words above 'Prophylactic corticosteroids for preterm
birth' to
[[http://www.update-software.com/cochrane/abstract.htm]{.underline}](http://www.update-software.com/cochrane/abstract.htm)

Magnesium sulphate for preventing preterm birth in threatened preterm
labour Crowther CA, Hiller JE, Doyle LW. (Cochrane Review). In: *The
Cochrane Library,* Issue 3, 2004. Chichester, UK: John Wiley & Sons,
Ltd.

**Reviewers\' conclusions:** Magnesium sulphate is ineffective at
delaying birth or preventing preterm birth, and its use is associated
with an increased mortality for the infant. Any further trials should be
of high quality, large enough to assess serious morbidity and mortality,
compare different dose regimens, and provide neurodevelopmental status
of the child.

Please link to the words above 'Magnesium sulphate for preventing
preterm birth in threatened preterm labour to
[[http://www.update-software.com/cochrane/abstract.htm]{.underline}](http://www.update-software.com/cochrane/abstract.htm)

Hydration for treatment of preterm labour Stan C, Boulvain M,
Hirsbrunner-Amagbaly P, Pfister R. (Cochrane Review). In: *The Cochrane
Library,* Issue 3, 2004. Chichester, UK: John Wiley & Sons, Ltd.

**Reviewers\' conclusions:** The data are too few to support the use of
hydration as a specific treatment for women presenting with preterm
labour. The two small studies available do not show any advantage of
hydration compared to bed rest alone. Intravenous hydration does not
seem to be beneficial, even during the period of evaluation soon after
admission, in women with preterm labour. Women with evidence of
dehydration may, however, benefit from the intervention.

Please link to the words above 'Hydration for treatment of preterm
labour'

to
[[http://www.update-software.com/cochrane/abstract.htm]{.underline}](http://www.update-software.com/cochrane/abstract.htm)

Prophylactic antibiotics for inhibiting preterm labour with intact
membranes King J, Flenady V. (Cochrane Review). In: *The Cochrane
Library,* Issue 3, 2004. Chichester, UK: John Wiley & Sons, Ltd.

**Reviewers\' conclusions:** This review fails to demonstrate a clear
overall benefit from prophylactic antibiotic treatment for preterm
labour with intact membranes on neonatal outcomes and raises concerns
about increased neonatal mortality for those who received antibiotics.
This treatment cannot therefore be currently recommended for routine
practice. Further research may be justified (when sensitive markers for
subclinical infection become available) in order to determine if there
is a subgroup of women who could experience benefit from antibiotic
treatment for preterm labour prior to membrane rupture, and to identify
which antibiotic or combination of antibiotics is most effective.

Please link to the words above 'Prophylactic antibiotics for inhibiting
preterm labour with intact membranes' to
[[http://www.update-software.com/cochrane/abstract.htm]{.underline}](http://www.update-software.com/cochrane/abstract.htm)

Magnesium maintenance therapy for preventing preterm birth after
threatened preterm labour Crowther CA, Moore V. (Cochrane Review). In:
*The Cochrane Library,* Issue 3, 2004. Chichester, UK: John Wiley &
Sons, Ltd.

**Reviewers\' conclusions:** There is not enough evidence to show any
difference between magnesium maintenance therapy and either placebo or
no treatment, or alternative therapies (ritodrine or terbutaline) in
preventing preterm birth after an episode of threatened preterm labour.

Please link to the words above 'Magnesium maintenance therapy for
preventing preterm birth after threatened preterm labour' to

[[http://www.update-software.com/cochrane/abstract.htm]{.underline}](http://www.update-software.com/cochrane/abstract.htm)

Maintenance therapy with calcium channel blockers for preventing preterm
birth after threatened preterm labour Gaunekar NN, Crowther CA.
(Cochrane Review). In: *The Cochrane Library,* Issue 3, 2004.
Chichester, UK: John Wiley & Sons, Ltd.

**Reviewers\' conclusions:** The role of maintenance therapy with
calcium channel blockers for preventing preterm birth is not clear. Well
designed randomised trials of sufficient size with relevant outcomes are
required.

Please link to the words above 'Maintenance therapy with calcium channel
blockers for preventing preterm birth after threatened preterm labour to

[[http://www.update-software.com/cochrane/abstract.htm]{.underline}](http://www.update-software.com/cochrane/abstract.htm)

Terbutaline pump maintenance therapy after threatened preterm labor for
preventing preterm birth Nanda K, Cook LA, Gallo MF, Grimes DA.
(Cochrane Review). In: *The Cochrane Library,* Issue 3, 2004.
Chichester, UK: John Wiley & Sons, Ltd.

**Reviewers\' conclusions:** Terbutaline pump maintenance therapy has
not been shown to decrease the risk of preterm birth by prolonging
pregnancy. Furthermore, the lack of information on the safety of the
therapy, as well as its substantial expense, argues against its role in
the management of arrested preterm labor. Future use should only be in
the context of well-conducted, adequately powered randomized controlled
trials.

Please link to the words above 'Terbutaline pump maintenance therapy
after threatened preterm labor for preventing preterm birth to

[[http://www.update-software.com/cochrane/abstract.htm]{.underline}](http://www.update-software.com/cochrane/abstract.htm)

  ----------------------------------------------------------------------------------------------- -------- ------------------------------------------------------------ ----------- -------------- ----------------------------------------------------
  **Cochrane Library Access**                                                                                                                                                                      

  To see the Cochrane Library reference articles above please follow these steps                                                                                                                   

                                                                                                  **A.**   Go directly to the [Cochrane Library sign-in                                            
                                                                                                           page](http://www.update-software.com/clibng/cliblogon.htm)                              
                                                                                                           and press the Enter button.                                                             

                                                                                                                                                                        From the                   
                                                                                                                                                                        I.H.S.                     
                                                                                                                                                                        W.A.N., you                
                                                                                                                                                                        should not                 
                                                                                                                                                                        need to                    
                                                                                                                                                                        enter                      
                                                                                                                                                                        username or                
                                                                                                                                                                        password.                  
                                                                                                                                                                        If you are                 
                                                                                                                                                                        denied                     
                                                                                                                                                                        access, use                
                                                                                                                                                                        one of the                 
                                                                                                                                                                        two options                
                                                                                                                                                                        below:                     

                                                                                                                                                                                    **Option 1** . 
                                                                                                                                                                                    If you already 
                                                                                                                                                                                    have a         
                                                                                                                                                                                    personal IHS   
                                                                                                                                                                                    Cochrane       
                                                                                                                                                                                    username and   
                                                                                                                                                                                    password, then 
                                                                                                                                                                                    enter your     
                                                                                                                                                                                    personal IHS   
                                                                                                                                                                                    Cochrane       
                                                                                                                                                                                    username and   
                                                                                                                                                                                    password       

                                                                                                                                                                                    **Option 2** . 
                                                                                                                                                                                    If you don\'t  
                                                                                                                                                                                    already have a 
                                                                                                                                                                                    personal IHS   
                                                                                                                                                                                    Cochrane       
                                                                                                                                                                                    username and   
                                                                                                                                                                                    password, then 
                                                                                                                                                                                    enter this     
                                                                                                                                                                                    username and   
                                                                                                                                                                                    password       
                                                                                                                                                                                    account        
                                                                                                                                                                                    information:   

                                                                                                                                                                                                   Username: Indian\
                                                                                                                                                                                                   Password: health

                                                                                                                                                                        After                      
                                                                                                                                                                        entering                   
                                                                                                                                                                        the                        
                                                                                                                                                                        username                   
                                                                                                                                                                        and                        
                                                                                                                                                                        password                   
                                                                                                                                                                        above, the                 
                                                                                                                                                                        Cochrane                   
                                                                                                                                                                        library                    
                                                                                                                                                                        software                   
                                                                                                                                                                        will prompt                
                                                                                                                                                                        you to                     
                                                                                                                                                                        develop                    
                                                                                                                                                                        your                       
                                                                                                                                                                        personal                   
                                                                                                                                                                        IHS                        
                                                                                                                                                                        Cochrane                   
                                                                                                                                                                        username                   
                                                                                                                                                                        and                        
                                                                                                                                                                        password.                  

                                                                                                  **B**.   When you reach the Cochrane Library, on the left side of the                            
                                                                                                           page enter \"**Preterm birth, preterm labor, or preterm                                 
                                                                                                           premature rupture of membranes**\" (without the quote marks)                            
                                                                                                           in the Search phrase box, then click on the Search Go                                   
                                                                                                           button.                                                                                 

                                                                                                  **C.**   On the results page that you see next, click on the Complete                            
                                                                                                           Reviews link under The Cochrane Database of Systematic                                  
                                                                                                           Reviews heading The Cochrane Database of Systematic Reviews.                            
                                                                                                           The article titles above should be in the list, in alpha                                
                                                                                                           order.                                                                                  

                                                                                                  **D**.   Then click on Complete Reviews and you will be able to link                             
                                                                                                           to any Complete Reviews you find appropriate                                            

                                                                                                                                                                                                   

  \*Note: If you are using the Internet at home or at another site outside the I.H.S. W.A.N., the                                                                                                  
  Cochrane sign-in page will not give you access without username and password. You can go to the                                                                                                  
  I/T/U Gateway to the Cochrane Library page and use the Password link low on the page to request                                                                                                  
  username and password. If you have never used the Cochrane Library before, here is a brief,                                                                                                      
  simple introduction. [Cochrane Library                                                                                                                                                           
  introduction](http://www.ihs.gov/MedicalPrograms/MCH/M/MCHdownloads/CochraneExplain11002.doc)                                                                                                    
  (.DOC) 108K \| [Cochrane Library                                                                                                                                                                 
  introduction](http://www.ihs.gov/MedicalPrograms/MCH/M/MCHdownloads/CochraneExplain11002.pdf)                                                                                                    
  (.PDF) 372K.                                                                                                                                                                                     
  ----------------------------------------------------------------------------------------------- -------- ------------------------------------------------------------ ----------- -------------- ----------------------------------------------------

**13 Other Online Resources and Patient Education**

**National Guidelines Clearinghouse**

[Many practice guidelines compiled by the Agency for Healthcare Research
and Quality](http://www.guidelines.gov/) . Once at the link above,
search for Preterm Labor and Preterm Premature Rupture of Membranes

Please link to the words above '[Many practice guidelines compiled by
the Agency for Healthcare Research and
Quality](http://www.guidelines.gov/) to
[[http://www.guidelines.gov/]{.underline}](http://www.guidelines.gov/)

**PubMed**\
Once at the PubMed,
[search](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed)
for: Preterm Labor or Preterm Premature Rupture of Membranes and
American Indians

Please link to the words above
'[search](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed)
to

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed)

**Agency for Research Quality and Healthcare**

## Management of Preterm Labor: Summary

### Evidence Report/Technology Assessment: Number 18

# Please link to the words above *'*Management of Preterm Labor

## To [***[http://www.ahrq.gov/clinic/epcsums/pretermsum.htm]{.underline}***](http://www.ahrq.gov/clinic/epcsums/pretermsum.htm)

AHRQ Preterm Labor: Clinical Focus

Please link to the words above 'Preterm Labor: Clinical Focus

## To [***[http://www.ahrq.gov/clinic/tp/pretermtp.htm]{.underline}***](http://www.ahrq.gov/clinic/tp/pretermtp.htm)

Management of Preterm Labor

Evidence Report/Technology Assessment: Number 18

Please link to the words above 'Management of Preterm Labor

To
[[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat1.chapter.26758]{.underline}](http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat1.chapter.26758)

**Conclusions.** Based on the literature reviewed, two biologic markers
(fFN and EVUSD) are found to be quite useful in identifying women in
preterm labor who are at low risk of experiencing a preterm birth.
Although the evidence remains mixed, certain tocolytics-beta- mimetics,
calcium channel blockers, magnesium sulfate, and NSAIDs-appear effective
in prolonging pregnancy when used as first-line agents in arresting
preterm labor, but beta- mimetics in comparison with other tocolytics
seem to present a higher risk of maternal harms. Ethanol is not found to
be an appropriate tocolytic agent. Tocolytics are not useful as
maintenance interventions. Antibiotics for suspected genital tract
infections may be useful. Home uterine activity monitoring was found to
confer no maternal or fetal/neonatal benefits.

The literature concerning the management of preterm labor is flawed in
several ways relating largely to definitions of preterm labor,
appropriate measures of outcomes, and use of survival analysis.
Epidemiologic research as well as additional efficacy and effectiveness
studies of the two biologic markers, selected tocolytics, and
antibiotics are warranted.

This document is in the public domain and may be used and reprinted
without permission except those copyrighted materials noted for which
further reproduction is prohibited without the specific permission of
copyright holders.

**US Preventive Services Task Force (USPSTF)**\
[Guide to clinical preventive
services](http://www.ahrq.gov/clinic/cpsix.htm) . 2nd ed; Baltimore
(MD): Williams & Wilkins; 1996. Screening Ultrasonography in Pregnancy

Please link to the words above 'Screening Ultrasonography in Pregnancy

To
[[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat3.section.10931#14038]{.underline}](http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat3.section.10931#14038)

**CLINICAL INTERVENTION**

Routine ultrasound examination of the fetus in the third trimester is
not recommended, based on multiple trials and meta-analyses showing no
benefit for either the pregnant woman or her fetus **(\"D\"
recommendation).** There is currently insufficient evidence to recommend
for or against a single routine midtrimester ultrasound in low-risk
pregnant women **(\"C\" recommendation).** These recommendations apply
to routine screening ultrasonography and not to diagnostic
ultrasonography for specific clinical indications (e.g., follow-up
evaluation of elevated maternal serum alpha-fetoprotein).

**Patient Education**

**Preterm Labor Websites for patients**

**National Institutes of Health**

Please link to

<http://www.nichd.nih.gov/womenshealth/premature_birth.cfm>

**March of Dimes: PTL**

Please link to

<http://www.marchofdimes.com/pnhec/188_1080.asp>

**March of Dimes: Prematurity**

Please link to

<http://www.marchofdimes.com/prematurity/5505.asp>

**March of Dimes: Fetal Fibronectin (fFN): A Test for Preterm Delivery**

Please link to

<http://www.marchofdimes.com/professionals/681_1149.asp>

**Preterm Premature Rupture of Membranes Websites for patients**

**Children\'s Hospital and Health System**

Please link to

<http://www.chw.org/display/PPF/DocID/3201/router.asp>

**University of North Carolina**

Please link to

<http://www.mombaby.org/level2/pprom.html>

**University of Virginia Health System: Choose title from A -- Z menu**

Please link to

[[http://www.uvahealth.com/]{.underline}](http://www.uvahealth.com/)

**14 A.C.O.G. Resources**

**What is the latest A.C.O.G. statement on this?**

**Management of preterm labor.**

ACOG Practice Bulletin No. 43. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2003; 101:1039-47.

**Summary of Recommendations**

***The following recommendations are based on good and consistent
scientific evidence (Level A):***

-   There are no clear \"first-line\" tocolytic drugs to manage preterm
    labor. Clinical circumstances and physician preferences should
    dictate treatment.

-   Antibiotics do not appear to prolong gestation and should be
    reserved for group B streptococcal prophylaxis in patients in whom
    delivery is imminent.

-   Neither maintenance treatment with tocolytic drugs nor repeated
    acute tocolysis improve perinatal outcome; neither should be
    undertaken as a general practice.

-   Tocolytic drugs may prolong pregnancy for 2-7 days, which may allow
    for administration of steroids to improve fetal lung maturity and
    the consideration of maternal transport to a tertiary care facility.

***The following recommendations are based on limited or inconsistent
scientific evidence (Level B):***

-   Cervical ultrasound examination and fetal fibro-nectin testing have
    good negative predictive value; thus, either approach or both
    combined may be helpful in determining which patients do not need
    tocolysis.

-   Amniocentesis may be used in women in preterm labor to assess fetal
    lung maturity and intraamniotic infection.

-   Bed rest, hydration, and pelvic rest do not appear to improve the
    rate of preterm birth and should not be routinely recommended.

**Non-ACOG members**

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12738177]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12738177)

**ACOG Members**

[[http://www.acog.org/publications/educational_bulletins/pb043.cfm]{.underline}](http://www.acog.org/publications/educational_bulletins/pb043.cfm)

**Assessment of Risk Factors for Preterm Birth.**

ACOG Practice Bulletin No. 31. American College of Obstetricians and
Gynecologists. Obstet Gynecol. 2001 Oct;98(4):709-16.

**Summary of Recommendations**

***The following recommendation is based on good and consistent
scientific evidence (Level A):***

-   There are no current data to support the use of salivary estriol,
    HUAM, or BV screening as strategies to identify or prevent preterm
    birth

***The following recommendations are based on limited or inconsistent
scientific evidence (Level B):***

-   Screening for risk of preterm labor by means other than historic
    risk factors is not beneficial in the general obstetric population.

-   Ultrasonography to determine cervical length, fFN testing, or a
    combination of both may be useful in determining women at high risk
    for preterm labor. However, their clinical usefulness may rest
    primarily with their negative predictive value given the lack of
    proven treatment options to prevent preterm birth.

-   Fetal fibronectin testing may be useful in women with symptoms of
    preterm labor to identify those with negative values and a reduced
    risk of preterm birth, thereby avoiding unnecessary intervention.

**Non-ACOG members**

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11592272]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11592272)

**ACOG Members**

[[http://www.acog.org/publications/educational_bulletins/pb031.cfm]{.underline}](http://www.acog.org/publications/educational_bulletins/pb031.cfm)

**15 Reference Texts and Articles**

If you have been unable to obtain the previous references online, then
try these paper-based materials with online abstract and full text links
when available.

1\. Obstetrics: Normal and Problem Pregnancies, 4th Edition. Gabbe SG,
Neibyl JR, Simpson JL (Eds.) Preterm Birth. Chapter 23. Churchill
Livingstone, New York, 2002. Pages 755-826 (level III).

This reference may be available to you online. If your facility has
access to MD Consult, try enter your username and password at
[MDConsult](http://www.mdconsult.com/) .

Please link the words 'MDConsult' to
[[http://www.mdconsult.com/]{.underline}](http://www.mdconsult.com/)

2 . Williams Obstetrics. Preterm Birth, 21st Edition. Cunningham GF, et
al (Eds.) Section 7 Common Complications of Pregnancy, No. 27, pp. 689 -
728. McGraw-Hill, 2001 (Level III).

**Native American Article References:**

Abel EL, Kruger M, Burd L. Effects of maternal and paternal age on
Caucasian and Native American preterm births and birth weights. Am J
Perinatol. 2002 Jan;19(1):49-54.\
Please link the words 'Effects of maternal and paternal age on Caucasian
and Native American preterm births and birth weights' to

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11857096]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11857096)

Baldwin M, Stevenson Y. A model for providing prenatal health care to
indigenous women living in remote areas. Int J Circumpolar Health. 2001
Nov;60(4):623-31.\
Please link the words 'A model for providing prenatal health care to
indigenous women living in remote areas to

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11768444]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11768444)

Bohn DK. Lifetime and current abuse, pregnancy risks, and outcomes among
Native American women. J Health Care Poor Underserved. 2002
May;13(2):184-98.\
Please link the words 'Lifetime and current abuse, pregnancy risks, and
outcomes among Native American women' to

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12017909]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12017909)

Buck GM, Mahoney MC, Michalek AM, Powell EJ, Shelton JA. Comparison of
Native American births in upstate New York with other race births,
1980-86. Public Health Rep. 1992 Sep-Oct;107(5):569-75

Please link the words 'Comparison of Native American births in upstate
New York with other race births, 1980-86' Pediatrics' to\
[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1410239]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1410239)

Campbell BC, Kimball EH, Helgerson SD, Alexander IL, Goldberg HI. Using
1990 national MCH objectives to assess health status and risk in an
American Indian community. Public Health Rep. 1989
Nov-Dec;104(6):627-31.

Please link the words 'Using 1990 national MCH objectives to assess
health status and risk in an American Indian community'. Pediatrics' to\
[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2511597]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2511597)

Grossman DC, Baldwin LM, Casey S, Nixon B, Hollow W, Hart LG.
Disparities in infant health among American Indians and Alaska natives
in US metropolitan areas. Pediatrics. 2002 Apr;109(4):627-33.

Please link the words 'Disparities in infant health among American
Indians and Alaska natives in US metropolitan areas. Pediatrics' to\
[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11927707]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11927707)

Khoshnood B, Lee KS, Wall S, Hsieh HL, Mittendorf R Short interpregnancy
intervals and the risk of adverse birth outcomes among five
racial/ethnic groups in the United States. Am J Epidemiol. 1998 Oct
15;148(8):798-805.

Please link the words 'Short interpregnancy intervals and the risk of
adverse birth outcomes among five racial/ethnic groups in the United
States' to\
[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9786235]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9786235)

Luo ZC, et al. Risks of adverse pregnancy outcomes among Inuit and North
American Indian women in Quebec, 1985-97. Paediatr Perinat Epidemiol.
2004 Jan;18(1):40-50.\
Please link the words 'Risks of adverse pregnancy outcomes among Inuit
and North American Indian women in Quebec, 1985-97' to

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14738546]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14738546)

Sugarman JR, Brenneman G, LaRoque W, Warren CW, Goldberg HI. The urban
American Indian oversample in the 1988 National Maternal and Infant
Health Survey. Public Health Rep. 1994 Mar-Apr;109(2):243-50.

Please link the words 'The urban American Indian oversample in the 1988
National Maternal and Infant Health Survey' to\
[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8153276]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8153276)

Vanlandingham MJ, Buehler JW, Hogue CJ, Strauss LT. Birthweight-specific
infant mortality for native Americans compared with whites, six states,
1980. Am J Public Health. 1988 May;78(5):499-503.

Please link the words 'Birthweight-specific infant mortality for native
Americans compared with whites, six states, 1980' to\
[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3354730]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3354730)

**Other Reference Articles: Preterm Labor**

Glock JL, Morales WJ. Efficacy and safety of nifedipine versus magnesium
sulfate in the management of preterm labor: a randomized study. Am J
Obstet Gynecol. 1993 Oct;169(4):960-4.

Please link the words 'Efficacy and safety of nifedipine versus
magnesium sulfate in the management of preterm labor: a randomized
study' to

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8238157]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8238157)

Crane JM. Pregnancy outcome after loop electrosurgical excision
procedure: a systematic review. Obstet Gynecol. 2003 Nov;102(5 Pt
1):1058-62.

Please link the words 'Pregnancy outcome after loop electrosurgical
excision procedure: a systematic review' to\
[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14672487]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14672487)

Crowther CA, Hiller JE, Doyle LW. Magnesium sulphate for preventing
preterm birth in threatened preterm labour. Cochrane Database Syst Rev.
2002;(4):CD001060.

Please link the words 'Magnesium sulphate for preventing preterm birth
in threatened preterm labour'. to

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12519550]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12519550)

Gyetvai K, Hannah ME, Hodnett ED, Ohlsson A. Tocolytics for preterm
labor: a systematic review. Obstet Gynecol. 1999 Nov;94(5 Pt 2):869-77.

Please link the words 'Tocolytics for preterm labor: a systematic
review' to

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10546776]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10546776)

Hendricks SK, Smith JR, Moore DE, Brown ZA. Oligohydramnios associated
with prostaglandin synthetase inhibitors in preterm labour. Br J Obstet
Gynaecol. 1990 Apr;97(4):312-6.\
Please link the words 'Oligohydramnios associated with prostaglandin
synthetase inhibitors in preterm labour' to

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2340255]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2340255)

Kenyon SL, Taylor DJ, Tarnow-Mordi W; ORACLE Collaborative Group.
Broad-spectrum antibiotics for spontaneous preterm labour: the ORACLE II
randomised trial. ORACLE Collaborative Group. Lancet. 2001 Mar
31;357(9261):989-94.

Please link the words 'Broad-spectrum antibiotics for spontaneous
preterm labour: the ORACLE II randomised trial' to

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11293641]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11293641)

Lewis DF, et al Effects of digital vaginal examinations on latency
period in preterm premature rupture of membranes. Obstet Gynecol. 1992
Oct;80(4):630-4.

Please link the words 'Effects of digital vaginal examinations on
latency period in preterm premature rupture of membranes to

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1407885]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1407885)

Moise KJ Jr. Effect of advancing gestational age on the frequency of
fetal ductal constriction in association with maternal indomethacin use.
Am J Obstet Gynecol. 1993 May;168(5):1350-3.

Please link the words 'Effect of advancing gestational age on the
frequency of fetal ductal constriction in association with maternal
indomethacin use' to

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8498410]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8498410)

Panter KR, et al. The effect of indomethacin tocolysis in preterm labour
on perinatal outcome: a randomised placebo-controlled trial. Br J Obstet
Gynaecol. 1999 May;106(5):467-73.

Please link the words 'The effect of indomethacin tocolysis in preterm
labour on perinatal outcome: a randomised placebo-controlled trial' to

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10430197]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10430197)

Sadler L, et al Treatment for cervical intraepithelial neoplasia and
risk of preterm delivery. JAMA. 2004 May 5;291(17):2100-6.

Please link the words 'Treatment for cervical intraepithelial neoplasia
and risk of preterm delivery.' to

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15126438]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15126438)

**Other Reference Articles: Corticosteriods**

Committee on Obstetric Practice. ACOG committee opinion: antenatal
corticosteroid therapy for fetal maturation. Obstet Gynecol. 2002
May;99(5 Pt 1):871-3.

Please link the words 'ACOG committee opnion: antenatal corticosteroid
therapy for fetal maturation' to

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11978304]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11978304)

**Other Reference Articles: Cervical Length**

Iams JD, et al The length of the cervix and the risk of spontaneous
premature delivery. National Institute of Child Health and Human
Development Maternal Fetal Medicine Unit Network. N Engl J Med. 1996 Feb
29;334(9):567-72.

Please link the words 'The length of the cervix and the risk of
spontaneous premature delivery' to

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8569824]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8569824)

**Other Reference Articles: Fetal fibronectin**

Leitich H, Kaider A. Fetal fibronectin\--how useful is it in the
prediction of preterm birth? BJOG. 2003 Apr;110 Suppl 20:66-70.

Please link the words 'Fetal fibronectin\--how useful is it in the
prediction of preterm birth?' to

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12763115]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12763115)

**Other Reference Articles: PPROM**

Canavan TP, Simhan HN, Caritis S. An Evidence-Based Approach to the
Evaluation and Treatment of Premature Rupture of Membranes: Part I.
Obstet Gynecol Surv. 2004 Sep;59(9):669-677.\
Please link the words 'An Evidence-Based Approach to the Evaluation and
Treatment of Premature Rupture of Membranes: Part I' to

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15329560]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15329560)

Canavan TP, Simhan HN, Caritis S. An Evidence-Based Approach to the
Evaluation and Treatment of Premature Rupture of Membranes: Part II.
Obstet Gynecol Surv. 2004 Sep;59(9):678-689.

Please link the words 'An Evidence-Based Approach to the Evaluation and
Treatment of Premature Rupture of Membranes: Part II' to\
[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15329561]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15329561)

Kenyon S, Boulvain M, Neilson J. Antibiotics for preterm rupture of
membranes. Cochrane Database Syst Rev. 2003;(2):CD001058.

Please link the words 'Antibiotics for preterm rupture of membranes' to

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12804398]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12804398)

Kenyon S, Taylor DJ, Tarnow-Mordi WO; ORACLE Collaborative Group.
ORACLE\--antibiotics for preterm prelabour rupture of the membranes:
short-term and long-term outcomes. Acta Paediatr Suppl.
2002;91(437):12-5.\
Please link the words 'ORACLE\--antibiotics for preterm prelabour
rupture of the membranes: short-term and long-term outcomes' to

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12200889]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12200889)

Kenyon SL, Taylor DJ, Tarnow-Mordi W; ORACLE Collaborative Group.
Broad-spectrum antibiotics for preterm, prelabour rupture of fetal
membranes: the ORACLE I randomised trial. ORACLE Collaborative Group.
Lancet. 2001 Mar 31;357(9261):979-88

Please link the words 'Broad-spectrum antibiotics for preterm, prelabour
rupture of fetal membranes: the ORACLE I randomised' to

[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11293640]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11293640)

Mercer BM, et al. What we have learned regarding antibiotic therapy for
the reduction of infant morbidity after preterm premature rupture of the
membranes. Semin Perinatol. 2003 Jun;27(3):217-30.

Please link the words 'What we have learned regarding antibiotic therapy
for the reduction of infant morbidity after preterm premature rupture of
the membranes to\
[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12889589]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12889589)

Mercer BM, et al. Antibiotic therapy for reduction of infant morbidity
after preterm premature rupture of the membranes. A randomized
controlled trial. National Institute of Child Health and Human
Development Maternal-Fetal Medicine Units Network. JAMA. 1997 Sep
24;278(12):989-95.

Please link the words 'Antibiotic therapy for reduction of infant
morbidity after preterm premature rupture of the membranes. A randomized
controlled trial' to\
[[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9307346]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9307346)

# 

# Prevention of Perinatal Group B Streptococcal Disease: Revised Guidelines from CDC MMWR August 16, 2002 / 51(RR11);1-22

Please link the words 'Prevention of Perinatal Group B Streptococcal
Disease to

[[http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5111a1.htm]{.underline}](http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5111a1.htm)

**page 16**

Joy this should be in the same format as the previous Posttest(s) e.g.,

<http://www.ihs.gov/MedicalPrograms/MCH/M/SyphPreg15.cfm#top>

**Preterm Labor and Preterm Premature Rupture of Membranes**

**16 Posttest and Evaluation**

To receive credit for this module, please complete the contact
information, posttest, and evaluation form below and send your answers
to Dr. Murphy by selecting the \"send\" button at the end of the
posttest.

Information in all three sections below, Part 1, Part 2 and Part 3 are
required for C.E. credit. Please include as much contact information as
possible. It will only be used if we need to get in touch with you about
your credit.

Do you have any other questions about Preterm Labor and Preterm
Premature Rupture of Membranes ? Please ask [George Gilson,
MD](mailto:gjgilson@anmc.org?Subject=Question about diabetes in pregnancy).\
\
Do you have other questions about pregnancy that you would like to see
the Perinatologist Corner address? We really want to know.

Please contact [Neil Murphy,
MD](mailto:nmurphy@anmc.org?Subject=Questions for the Perinatologist Corner)
with your topics, questions, or issues.

**Part 1: POSTTEST Contact Information**

Top of Form

Contact Information

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**Part 2: POSTTEST Questions**

Bottom of Form

**Case 1**

1\. J.N. is a primigravida at 29 weeks by good dating criteria who has
no known risk factors. She presents to your level I facility with mild
but persistent uterine contractions and no history to suggest PPROM.
What would be the MOST helpful initial diagnostic test for management of
this patient?

a.  complete blood count with differential

b.  dating ultrasound

c.  group B strep culture

d.  fetal fibronectin

2\. After your initial maneuvers you decide J.N. is in true preterm
labor. Moderately uncomfortable uterine contractions are occurring every
5 minutes despite your initial management. Serial digital exams reveal
her cervix to be 1-2 cm dilated, 50 per cent effaced, soft, posterior,
with the vertex at -3 station, and without bloody show on the glove. No
ferning was seen on microscopic exam of the vaginal secretions. The
fetal tracing is reassuring. Because of logistic problems, immediate
transport is not possible at this time.... What is the MOST important
therapeutic agent for her at this time?

a.  intravenous magnesium sulfate

b.  oral indomethacin

c.  subcutaneous terbutaline

d.  intramuscular betamethasone

> **Case 2**

1.  L.B. is a primigravida at 30 weeks by good dating criteria who
    presents with a history suggestive of PPROM and possible early
    labor. She has no allergies. She presents for evaluation to your
    level I facility. What is the MOST important initial diagnostic test
    for management of this patient?

```{=html}
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```
a.  complete blood count and differential

b.  nitrazine test of vaginal fluid

c.  fern test of vaginal fluid

d.  fetal lung maturity testing of vaginal fluid

```{=html}
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```
2.  You confirm that L.B. has experienced PPROM. What is the MOST
    important therapeutic agent for her at this time?

```{=html}
<!-- -->
```
a.  intravenous magnesium sulfate

b.  intravenous penicillin

c.  oral erythromycin

d.  intramuscular betamethasone

**Case 3**

1\. E.J.E. is a nulliparous patient at 23 weeks by good dating criteria
who presents with low back pain, vaginal pressure, and a copious clear
vaginal discharge that has now become blood-tinged. She has a history of
a prior elective termination of pregnancy and a prior cervical loop
excision procedure for dysplasia. Her story is most suspicious for which
of the following diagnoses?

a.  preterm labor

b.  preterm premature rupture of membranes

c.  cervicitis/vaginitis

d.  cervical insufficiency

> 2\. In order to help you confirm your suspicions about the cause of
> Ms. E.J.E.'s problem, which of the following tests would be most
> helpful?

a.  sterile speculum examination

b.  cervical digital examination

c.  fetal fibronectin

d.  transvaginal sonographic cervical length

**Case 4**

1.  A.L. is a 29 y/o multiparous patient at 23 weeks who has had three
    prior preterm births. Which of the following tests would be most
    helpful to decide whether she is at risk of having another preterm
    birth?

```{=html}
<!-- -->
```
a.  wet mount for bacterial vaginosis

b.  fetal fibronectin

c.  transvaginal sonographic cervical length

d.  cervical digital examination

e.  none of the above

```{=html}
<!-- -->
```
2.  A.L. inquires if there is anything she can do to prevent her having
    another preterm birth. Your best choice of possible preventive
    therapy would be which of the following?

```{=html}
<!-- -->
```
a.  bed rest

b.  oral metronidazole

c.  oral terbutaline

d.  intramuscular progesterone

The rest of page 16 should just be like all the other Perinatalogy
Corner posttests

**Part 3: POSTTEST Module Evaluation**

Module Evaluation\
To receive credit you will also need to complete this brief evaluation.
Thanks.\
Title of activity: Perinatologist Corner - \"Preterm Labor and Preterm
Premature Rupture of Membranes\" C.E. module

Goal/purpose of activity: The student will understand the maternal and
fetal consequences, methods, and limitations of screening, and
understand the management of Preterm Labor and Preterm Premature Rupture
of Membranes

It is now   ![](media/image3.wmf)at    ![](media/image4.wmf)MST.\
\
Please indicate your profession by checking one:

![](media/image5.wmf)MD\
![](media/image5.wmf)RN\
![](media/image5.wmf)NP\
![](media/image5.wmf)PA\
![](media/image6.wmf)Other

 If you chose \"Other,\" please list your profession:
![](media/image7.wmf)

The rest of page 16 should just be like all the other posttests

# The following is referenced twice in the document above, so might be best made into a separate document to link to? 

# 

# Please note there is one more set of guidelines that follow called GUIDELINES FOR PRETERM PREMATURE RUPTURE OF MEMBRANES

**GUIDELINES FOR THE MANAGEMENT**

> **OF PRETERM LABOR**

**Definitions:**

A.  Preterm Labor - regular uterine contraction after 20 weeks or before
    37

weeks GA, which occur regularly, leading to progressive cervical change.

Associations with preterm birth:

1.  Preterm premature rupture of membranes (see below)

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1.  Chorioamnionitis

2.  Fetal anomalies

3.  History of prior preterm labor

4.  Multiple gestation

5.  Polyhydraminos

6.  Intrauterine fetal demise

7.  Cervical insufficiency

8.  Uterine anomalies

9.  Placenta previa or abruptio placentae

10. Retained IUD

11. Serious maternal disease (e.g., preeclampsia)

12. Cervical conization or L.E.E.P.

13. Idiopathic

Preterm birth due to:

-   PROM 35% of the time

-   Maternal fetal complications 35%

-   Idiopathic preterm labor 30%

Risks of reccurent preterm birth

First Birth Second Birth Next Birth Preterm

term \-\-\-\-\-\-\-\-\-\-\-\-\-\-- 5%

preterm \-\-\-\-\-\-\-\-\-\-\-\-\-\-- 15%

term preterm 24%

preterm preterm 32%

**Management:**

1.  History of Preterm Labor with preterm delivery

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a.  preconceptual counseling to eliminate risk factors, e.g., stop
    tabacco,

> alcohol, drugs, space pregnancies, good nutrition, normalize
> hypertension,
>
> stabilize maternal medical conditions, anticipate need for increased
> pregnancy
>
> surveillance and possibly prophylactic rest.

b.  early pregnancy care

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b.  excellent dating by exam and early ultrasound

c.  urine culture x1

d.  identify and treat cervical or vaginal infection

e.  preterm labor education by qualified personnel by 20 to 23 weeks GA.

f.  intensive monitoring for signs and symptoms of recurrent preterm
    labor and/or

> asymptomatic cervical change
>
> signs & symptons:
>
> \*increased vaginal discharge

\*blood tinged mucus

\*low backache

\*pelvic pressure

\*menstrual - like cramps

\*intestinal cramping, with or without diarrhea

\*"not feeling right"

\*precocious cervical dilations (1 cm or more)

j.  1\) lives in town: cervical exam 24-26 weeks

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2.  lives outside of town: travel to town at 26 weeks GA, obtain
    cervico-vaginal swab for fetal fibronectin (fFN) (no lubricant, no
    coitus, no bleeding) (excellent negative predictive value-95%, poor
    positive predictive value-15%), perform cervical exam, transvaginal
    ultrasound for cervical length, and ultrasound for dating if not yet
    done.

> \-[Cervix no change]{.underline}, in combination with negative fFN,
> and transvaginal ultrasound cervical length\>2.5 cm- return to
> village, weekly radio monitoring for early signs

and symptoms, transfer to town as needed

\-[Cervix changed,]{.underline} or transvaginal ultrasound cervical
length \<2.5 cm, or fFN positive- to remain in town for routine prenatal
care, refer to Anchorage as needed

2.  If local resources do not permit, consider counseling the patient to
    remain in town regardless of cervical findings. Time of patient
    remaining in town should be based on prior time of preterm birth.

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2.  History of preterm labor with Term Delivery- Same as 1.

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2.  History of preterm labor due to prior maternal or fetal

Complications

a.  Reassess risk of recurrence

> -if prior preterm birth associated with nonrecurring condition, i.e.
> twins, preterm
>
> birth risk probably same as "normal" singleton pregnancy.

b.  Liberally consult ANMC OB-GYN to determine risk of recurrent preterm
    labor and management.

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4.  **Current preterm labor**

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a.  Obtain cervico-vaginal swab for fFN

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a.  Review pregnancy dating

b.  Rule out maternal fetal complications before initiating tocolytic

> therapy

-   obtain NST

-   repeat U/S as needed to check fetal anatomy, size, amniotic fluid

> volume, and placentation; obtain transvaginal ultrasound for cervical
> length

-   monitor maternal status for infections, hypertensive disease,
    bleeding, etc.

-   administer [betamethasone]{.underline} 12 mg IM x2 doses 24 hrs
    apart

-   if GA \<32 weeks and true preterm labor (cx change) and no
    oligohydramnios (AFI \<8.0 or no pocket \>2.0 cm) initiate tocolysis
    with [indomethacin]{.underline} 100 mg po initially, followed by 50
    mg po q6h to a maximum of 400 mg total.

-   If GA 32-34 weeks, bolus with 500 mL lactated Ringer's and then
    initiate tocolysis with [terbutaline]{.underline} 0.25 mg SQ and
    repeat q4h prn not to exceed 4 doses

-   initiate group B strep prophylaxis: [penicillin]{.underline} G 5
    mullion units IV load, then 2.5 million units IV q4h until delivery.
    Because of concerns about the emergence of bacterial resistance,
    penicillin is the preferred drug, but as an alternative,
    [ampicillin]{.underline} 2g IV initially, followed by 1g IV q4h
    until delivery is also acceptable (if not allergic to penicillin)

d.  Liberally consult ANMC OB - GYN consultant re: management or
    transfer

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d.  Although preterm labor is defined as labor prior to 37 weeks, it has
    been the current practice to tocolyze and transfer patients only for
    true preterm labor at \<35 weeks GA. This has been based on nursery
    care, facilities and neonatal outcomes.

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5.  ANMC Practice Guidelines

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a.  Current preterm labor

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a.  Management same as above

-   Preterm labour education while hospitalized

-   Outpatient management if medical compliance assured. Social Service

> Mental Health, and Home Health Care consults may be appropriate.

-   If discharged, the patient should be seen in clinic on a weekly
    basis.

> Symptoms and compliance are re-assessed at each visit and cervical
>
> exam is considered at each encounter.
>
> Preterm labor recommendations are maintained until 35 weeks GA.

-   Patients referred in from outside the Anchorage Service Unit remain
    in

> town until preterm labor is resolved. They should not transfer back to
>
> their Service Unit until their delivery could be safely managed by
> their
>
> Level 1 Nursery, eg., after 36 weeks. The patient should return to the
>
> Service Unit Hospital and not to their village. Notify referring
> provider
>
> prior to patients return to Service Unit.

# The following is referenced in the module above, so might be best made into a separate document to link to? 

# 

Please note there is one more set of guidelines above called GUIDELINES
FOR THE MANAGEMENT OF PRETERM LABOR

# 

# 

# GUIDELINES FOR PRETERM PREMATURE RUPTURE OF MEMBRANES

> **1. Definition:**
>
> Rupture of the membranes prior to 37 weeks gestation and prior to the
> onset of labor.
>
> **NB:**
>
> This is to be distinguished from "[premature rupture of
> membranes"]{.underline} prior to the onset of labor at term, and from
> premature rupture of membranes without labor prior to viability at
> 23-24 weeks, which is most commonly associated with "hour-glassing" of
> the membranes secondary to cervical insufficiency.
>
> a\. Associations with PPROM:
>
> -same as for preterm birth above, current theory is that PPROM is the
> result of occult infection at the choriodecidual interface with
> production of microbial collagenases resulting in membrane rupture.
>
> **2. Management:**

a.  Review pregnancy dating criteria

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a.  Perform sterile speculum examination for fern and nitrazine testing

b.  Refrain from performing a digital examination unless absolutely
    necessary to document advanced labor prior to transport. (Remember
    that if you can visualize a portion of the presenting part, the
    cervix is most likely significantly effaced and at least 4 cm
    dilated, but if it appears "closed" it may be any dilation \<4cm...)
    Digital examination "winds the clock of infection" and significantly
    decreases the latency period for the onset of labor, and increases
    the risk of infection, and is to be avoided in this setting if at
    all possible!

c.  Confirm presentation by Leopold's and/or ultrasound

d.  Perform level I ultrasound to assess GA, EFW, AFI, presentation, and
    anatomy

e.  A sample of vaginal pool amniotic fluid for fetal lung maturity
    testing may be appropriate if the patient is between 34 and 36 weeks
    gestation

f.  Obtain fetal monitor strip and maternal vital signs

g.  Administer [betamethasone]{.underline} 12 mg IM and repeat the dose
    in 24 hours

h.  Administer group B strep prophylaxis with [penicillin]{.underline}
    5.0 MU IV initially and then 2.5 MU IV q6h for 48 hrs (if not
    allergic to penicillin). Administer with a fast flowing IV in order
    to reduce burning sensation during administration.

i.  Tocolysis (see above) may be appropriate to facilitate transport,
    but is otherwise not indicated

j.  Consult with ANMC OB-GYN is advised for further management and
    transport

k.  **At ANMC** PPROM is managed as an in-patient

l.  Daily NST should be carried out

m.  After 48 hours of group B strep prophylaxis with IV
    [penicillin]{.underline}, the latency period has been shown to be
    prolonged by administration of [erythromycin]{.underline} 250 mg po
    q6h for 10 days or until delivery

n.  Maternal temperature and fetal heart rate are monitored q4h, but the
    onset of uterine contractions is the most common sign of incipient
    infection. Overt chorioamnionitis mandates delivery.

o.  Labor may be induced at 34 weeks documented gestation or with mature
    vaginal pool amniotic fluid studies after consultation with the
    Pediatrics service

p.  Patients may be induced with either vaginal or oral
    [misoprostol]{.underline} or IV oxytocin

q.  Group B strep prophylaxis with IV [penicillin]{.underline} should be
    re-instituted in labor

r.  If chorioamnionitis is suspected, [ampicillin]{.underline} 2g q6h
    and [gentamicin]{.underline} 2 mg/kg IV q8h should also be
    administered to cover gram negative pathogens

s.  Patients \<32 weeks should be delivered at a level III nursery
    facility

t.  Patients with **rupture of membranes at term** who are not in labor
    have a better outcome without an increase in their cesarean birth
    rate if induced as soon as they present.