Preterm Labor

Author
Michael G Ross, MD, MPH Professor of Obstetrics and Gynecology, University of
California, Los Angeles, David Geffen School of Medicine; Professor, Department of
Community Health Sciences, Fielding School of Public Health at University of California
at Los Angeles

Practice Essentials

Preterm labor is defined as the presence of uterine contractions of sufficient frequency and
intensity to effect progressive effacement and dilation of the cervix prior to term gestation.
Occurring at 20-37 weeks’ gestation, preterm labor precedes almost half of preterm births and is
the leading cause of neonatal mortality in the United States.

Risk of preterm labor

The exact mechanisms of preterm labor are largely unknown but are believed to include the
following:
 Decidual hemorrhage such as abruption and mechanical factors such as uterine overdistention
from multiple gestation or polyhydramnios
 Cervical incompetence (eg, trauma, cone biopsy)
 Uterine distortion (eg, müllerian duct abnormalities, fibroid uterus)
 Cervical inflammation as a result of, for example, bacterial vaginosis (BV) or trichomonas
 Maternal inflammation/fever (eg, urinary tract infection)
 Hormonal changes (eg, mediated by maternal or fetal stress)
 Uteroplacental insufficiency (eg, hypertension, insulin-dependent diabetes, drug abuse,
smoking, alcohol consumption)

Risk assessment during pregnancy

Physical assessment
The integrity of the cervix and the extent of any prior injury to the cervix may be assessed by
speculum and digital examination. The presence of asymptomatic bacteriuria, sexually
transmitted disease (STD), and symptomatic BV may be investigated

History
A history of prior preterm deliveries places the patient in the high-risk category. Of the
predictors of preterm birth, past obstetric history may be one of the strongest predictors of
recurrent preterm birth.
Cervical length
A short cervical length in the early or late second trimester has been associated with a markedly
increased risk of preterm labor and delivery. In a study, a cervical length of 25 mm or less at 28
weeks had a 49% sensitivity for prediction of preterm delivery at less than 35 weeks. [1]

Laboratory tests
In patients with a history of midtrimester loss, laboratory tests for risk assessment include the
following:
 Rapid plasma reagin test
 Gonorrheal and chlamydial screening
 Vaginal pH/wet smear/whiff test
 Anticardiolipin antibody (eg, anticardiolipin immunoglobulin [Ig] G and IgM, anti-beta2
microglobulin)
 Lupus anticoagulant antibody
 Activated partial thromboplastin time
 One-hour glucose challenge test
In addition, one should consider TORCH (toxoplasmosis, other infections, rubella,
cytomegalovirus infection, herpes simplex), immunoglobulin G, and immunoglobulin M
screening whenever the historical or clinical suspicion is present.

Diagnosis
Contractions of sufficient frequency and intensity to effect progressive effacement and dilation
of the cervix at 24-37 weeks’ gestation are indicative of active preterm labor. If the diagnosis of
preterm labor is suspected, but not confirmed, it may be prudent to first obtain a vaginal fetal
fibronectin (FFN) sample before pelvic cervical examination. If the diagnosis remains in doubt
after the exam, the FFN specimen can be sent to the lab for analysis.

Management

Progesterone
Studies support the use of progesterone supplementation to reduce preterm birth in patients at
high risk for recurrent preterm delivery.
Tocolytic agents
Criteria that indicate consideration of tocolytic therapy include more than 6 contractions per hour
resulting in a demonstrated cervical change or presumed prior cervical change (transvaginal
cervical length < 25 mm, >50% cervical effacement, or cervical dilation ≥20 mm). If
contractions are present without cervical change, management options include continued
observation or therapeutic sleep for the patient (eg, morphine sulphate 10-15 mg subcutaneous).
The most common tocolytic agents used to treat preterm labor include the following:
 Magnesium sulfate (MgSO4): Widely used as the primary tocolytic agent because it has
similar efficacy to terbutaline (one of the previous agents of choice), with far better tolerance
 Indomethacin: An appropriate first-line tocolytic for early preterm labor (< 30 wk) or preterm
labor associated with polyhydramnios
 Nifedipine: Despite its unlabeled status, several randomized studies have found nifedipine to
be associated with a more frequent successful prolongation of pregnancy than other tocolytics

Overview
Preterm labor is defined as the presence of uterine contractions of sufficient frequency and
intensity to effect progressive effacement and dilation of the cervix prior to term gestation
(between 20 and 37 wk). Preterm labor precedes almost half of preterm births and preterm birth
occurs in approximately 12% of pregnancies and is the leading cause of neonatal mortality in the
United States. [2, 3] In addition, preterm birth accounts for 70% of neonatal morbidity, mortality,
and health care dollars spent on the neonate, largely due to the 2% of American women
delivering very premature infants (< 32 wk). [2, 3]
Despite the current use of material, effort, and money in perinatal medical technology, neonatal
mortality rates for newborns born in the United States (5 per 1,000 babies) may rank as low as
32nd among the 33 industrialized nations, superior only to Latvia. [4]
Successful reduction of perinatal morbidity and mortality associated with prematurity may
require the implementation of effective risk identification and behavioral modification programs
for the prevention of preterm labor; these in turn require both an improved understanding of the
psychosocial risk factors, etiology, and mechanisms of preterm labor and programs for accurate
identification of pregnant women at risk for premature labor and delivery. In fact, recent
evidence suggests that early identification of at-risk gravidas with timely referral for
subspecialized obstetrical care may help identify women at risk for preterm labor and delivery
and decrease the extreme prematurity (< 32 wk) rate, thereby reducing the morbidity, mortality,
and expense associated with prematurity. [5]

Goals of management

Goals of obstetric patient management of preterm labor should include (1) early identification of
risk factors associated with preterm birth, (2) timely diagnosis of preterm labor, (3) identifying
the etiology of preterm labor, (4) evaluating fetal well-being, (5) providing prophylactic
pharmacologic therapy to prolong gestation and reduce the incidence of respiratory distress
syndrome (RDS) and intra-amniotic infection (IAI), (6) initiating tocolytic therapy when
indicated, and (7) establishing a plan of maternal and fetal surveillance with patient/provider
education to improve neonatal outcome.

isk of Preterm Labor

The exact mechanism(s) of preterm labor is largely unknown but is believed to include decidual
hemorrhage, (eg, abruption, mechanical factors such as uterine overdistension from multiple
gestation or polyhydramnios), cervical incompetence (eg, trauma, cone biopsy), uterine
distortion (eg, müllerian duct abnormalities, fibroid uterus), cervical inflammation (eg, resulting
from bacterial vaginosis [BV], trichomonas), maternal inflammation/fever (eg, urinary tract
infection), hormonal changes (eg, mediated by maternal or fetal stress), and uteroplacental
insufficiency (eg, hypertension, insulin-dependent diabetes, drug abuse, smoking, alcohol
consumption). [2, 3]
Although prediction of preterm delivery remains inexact, a variety of maternal and obstetric
characteristics are known to increase the risk, presumably via one of these mechanisms. Finally,
the fetus plays a role in the initiation of labor. In a simplistic sense, the fetus recognizes a hostile
intrauterine environment and precipitates labor by premature activation of a fetal-placental
parturition pathway.
Risk factors for preterm birth include demographic characteristics, behavioral factors, and
aspects of obstetric history such as previous preterm birth. Demographic factors for preterm
labor include nonwhite race, extremes of maternal age (< 17 y or >35 y), low socioeconomic
status, and low prepregnancy weight. Preterm labor and birth can be associated with stressful life
situations (eg, domestic violence; close family death; insecurity over food, home, or partner;
work and home environment) either indirectly by associated risk behaviors or directly by
mechanisms not completely understood. Many risk factors may manifest in the same gravida.
Methods used for predicting preterm birth include home uterine activity monitoring (HUAM),
assessments of salivary estriol, fetal fibronectin (FFN), the presence of BV, and cervical length
assessment.
 While hospital tocodynamometry has been effective for monitoring uterine contractions to
evaluate preterm labor, HUAM has not been proven valuable in detecting or preventing
preterm birth and is not currently recommended for use.
 The proposed use of salivary estriol measurements in detecting preterm labor was based on
the belief that the adrenal gland production of dehydroepiandrosterone increases before the
onset of labor, which results in an increase of maternal estriol. Unfortunately, maternal estriol
levels show diurnal variation, peaking at night, and are suppressed by betamethasone
administration, thereby decreasing the predictive value of salivary estriol in the detection of
preterm delivery risk.
 FFN is a basement membrane protein that helps bind placental membranes to the decidua.
While a negative FFN is helpful in predicting women who are not destined to deliver preterm,
a positive FFN has limited value in predicting women who will deliver preterm.
 Nevertheless, FFN has a predictive value in identifying patients who will or will not deliver
within the subsequent 1-2 weeks.
 While the presence of BV has been associated with the risk of preterm delivery, prospective
treatment trials eradicating asymptomatic BV failed to reduce the risk of preterm delivery.
 Longer term prediction of the risk of preterm delivery is achieved by cervical length
measurements. A short cervical length in the early or late second trimester has been
associated with a markedly increased risk of preterm labor and delivery (see discussion on
cervical length). The prediction of preterm delivery may potentially be improved by
combining FFN testing with measurements of cervical length.

Preconceptual evaluation

While the risk for preterm birth in nulliparous patients is hard to determine, past obstetric
experience and personal behavior may provide significant insight into future pregnancy outcome
in multiparous women. Identifying at-risk patients preconceptually may allow additional
treatment options. Women who seek birth control have a 30% chance of becoming pregnant in
the next 2 years, suggesting that these women represent one potential opportunity for
intervention. The presence of the following risk factors should be addressed prior to pregnancy.

Cervical trauma

The most common etiologies for cervical injury are elective abortion, surgeries to treat cervical
dysplasia, and injury occurring at delivery. A single uncomplicated elective abortion at less than
10 weeks’ gestation does not increase the risk of midtrimester loss or preterm birth unless the
cervix has been forcibly dilated to more than 10 mm at the time of the abortion. However,
patients with a history of multiple first-trimester elective terminations or one or more second-
trimester elective abortions may be at increased risk for preterm delivery. Cervical dilatation
with laminaria or cervical ripening agents, such as misoprostol, appears to be less traumatizing to
the cervix than mechanical dilation.
Cervical dysplasia should be treated appropriately whenever diagnosed. However the incidence
of preterm birth and cervical incompetence may be increased 200-300% after preconceptual
surgical treatment (eg, cold knife cone, cryoconization, laser cone, LEEP) of cervical
intraepithelial neoplasia (CIN). The risk of subsequent preterm delivery may be proportional to
the amount of cervical tissue removed during surgery. Surprisingly, the ease of performing LEEP
for relatively minor abnormalities may have paradoxically led to more cervical injury than was
observed with the relatively more invasive cone biopsy.

Assessment of Risk During Pregnancy

Physical Assessment Guidelines to Establish Risk

Assessment during the first prenatal exam should include the patient's obstetric history, infection
risk, and the presence of cervical or uterine abnormalities. If an evaluation for antiphospholipid
syndrome is included, it should include anticardiolipin (eg, anticardiolipin IgG and IgM and anti-
beta2 microglobulin) and lupus anticoagulant antibodies.
Previous preterm deliveries, including autopsy reports and medical records, if appropriate and
available, should be reviewed. Social stressors (including housing and food availability), social
support in the family, financial stability, domestic violence, drug abuse involving the patient or
her family, and death or serious illness in a close family member should be assessed.
The integrity of the cervix and the extent of any prior injury to the cervix may be assessed by
speculum and digital examination. The presence of asymptomatic bacteriuria, STD, and
symptomatic BV may be investigated.
In some patients, formal cervical length assessment may be of use in risk assessment.
Cervical length during prenatal care, particularly at 24-28 weeks’ gestation, has been
demonstrated to be the most sensitive prenatal predictor of preterm birth between both high- and
low-risk women. In a mixed high- and low-risk population of singleton pregnancies, transvaginal
ultrasound-measured cervical length at 24 weeks was highly correlated with the risk of
spontaneous preterm delivery before 35 weeks. [1] The relative risk of preterm delivery among
women with a cervix 25 mm or shorter at 24 weeks was 6.2. Furthermore, at 28 weeks, a short
cervix (≤25 mm) was associated with a 9.6 relative risk of preterm delivery. Cervical length 25
mm or shorter at 28 weeks had a 49% sensitivity for prediction of preterm delivery at less than
35 weeks, a value markedly greater than that of cervical funneling.
Among high-risk women with a history of one or more spontaneous preterm births (excluding
those with multiple gestation, uterine anomalies, and prior cervical surgeries), 20% of patients
demonstrated a cervical length shorter than 25 mm by transvaginal ultrasonography at 22-25
weeks. [9] Among these patients with a short cervix and one previous preterm birth, 37.5%
delivered at less than 35 weeks. In contrast, patients with a cervical length longer than 25 mm
had a preterm rate (< 35 wk) of only 10.6%. Cervical length has similarly been demonstrated as
the optimal predictor of preterm delivery in low-risk women. In an assessment of low-risk
women, short cervical length at 24-28 weeks was detected in 8.5% of women. [10] These patients
demonstrated a relative risk of 6.9 for preterm delivery at less than 35 weeks. As compared with
fetal fibronectin or Bishop score, cervical length demonstrated the greatest sensitivity (39%),
with a specificity of 92.5% and a negative predictive value of 98%.
Whereas cervical length assessment by digital exam is a semi subjective measurement, a recent
study has demonstrated the value of an objective cervico-portio length measurement using
Cerivlenz, an intravaginal measuring device. [11] These manually obtained cervical length
measurements appear to be reproducible, accurate, and predictive of a short cervical length by
transvaginal ultrasonography. Therefore, Cerivlenz may represent a low-cost, objective screening
tool to identify at-risk patients for preterm delivery.
In addition to the 24-28 week assessment, evidence shows the value of early midtrimester
cervical length measurement. Studies of Owen et al from the Maternal Fetal Medicine Units
Network [12] demonstrate the value of cervical length measurements between 16 weeks and 23
weeks and 6 days. Serial transvaginal ultrasonographic cervical length measurements in a high-
risk population demonstrated that a cervix shorter than 25 mm resulted in a relative risk of 4.5
for spontaneous preterm birth at less than 35 weeks, with a 69% sensitivity, 80% specificity,
55% positive predictive value, and 88% negative predictive value. As the NIH Maternal Fetal
Medicine Units Network is initiating a study of progesterone treatment for patients with a short
cervix in the early midtrimester, a program of routine cervical length screening may soon be
justified.

Management of Preterm Labor

Preterm labor may be difficult to diagnose and a potential exists for overtreatment of uterine
irritability. Tocolytic agents, while generally safe in appropriate dosages with proper clinical
monitoring, have potential morbidity and should only be used after consideration of the risks and
benefits of such use. Neonatal morbidity and mortality are greatly affected by gestational age,
especially when the pregnancy is less than 28 weeks’ gestation. Tocolysis should be used with
caution when the fetus is previable because the expected prolongation of the pregnancy is
limited, and the neonate has a minimal chance of survival at less than 23 weeks. The likelihood
of survival is further reduced in the presence of significant medical complications, such as intra-
amniotic infection (IAI) at these ages.
On the other hand, the risk of neonatal mortality and morbidity is low after 34 completed weeks
of gestation; although a trial of acute tocolysis may be initiated, aggressive tocolytic therapy is
generally not recommended beyond 34 weeks, due to potential maternal complications. Between
24 and 33 weeks’ gestation, benefits of tocolytic therapy are generally accepted to outweigh the
risk of maternal and/or fetal complications and these agents should be initiated provided no
contraindications exist. Although aggressive tocolysis is not typically used beyond 34 weeks’
gestation, clinicians are advised not to deliver patients at this gestation without indication
because of a higher risk of neonatal morbidity in infants born at 34-36 weeks’ gestation
compared with deliveries at 37-40 weeks’ gestation.

Tocolytic agents have not proven to be efficacious in preventing preterm birth or reducing
neonatal mortality or morbidity. The primary purpose of tocolytic therapy today is to delay
delivery for 48 hours to allow the maximum benefit of glucocorticoids to decrease the incidence
of RDS. While tocolytics can be successful for 48 hours when membranes are intact, some
clinical studies suggest that the effectiveness of tocolytics is only slightly better than bedrest and
hydration, both of which have fewer adverse effects than tocolytic therapy.
A 2016 clinical study [20] suggested a benefit of late preterm (34 0/7 to 36 6/7 weeks) steroids in
women with singleton pregnancies at imminent risk of preterm delivery within 7 days, though
tocolysis should not be used in order to delay delivery. The benefits were primarily a reduction
in respiratory complications, though there was a marked increase in neonatal hypoglycemia in
the treatment cohort. The American Congress of Obstetricians and Gynecologists
(ACOG) issued a practice advisory (Practice Advisory: Antenatal Corticosteroid Administration
in the Late Preterm Period, 2016) [21] that indicated that “administration of betamethasone may
be considered in women with a singleton pregnancy between 34 0/7 and 36 6/7 weeks gestation
at imminent risk of preterm birth within 7 days.”

Tocolytic Agents
The most common tocolytic agents used for the treatment of preterm labor are magnesium
sulfate (MgSO4), indomethacin, and nifedipine. In the past, beta-mimetic agents, such as
terbutaline or ritodrine, were the agents of choice, but in recent years their use has been
significantly curtailed due to maternal and fetal side effects, such as maternal tachycardia,
hyperglycemia, and palpitations The use of these agents can lead to pulmonary edema,
myocardial ischemia, and cardiac arrhythmia.
In February 2011, the US Food and Drug Administration (FDA) required the addition of a new
Black Box Warning and contraindication to the terbutaline prescribing information to warn about
the risk of use for preterm labor. The decision was based on reports of death and serious adverse
reactions, including tachycardia, transient hyperglycemia, hypokalemia, arrhythmias, pulmonary
edema, and myocardial ischemia following prolonged administration of oral or injectable
terbutaline to pregnant women. The FDA concluded that the risk of serious adverse events
outweighs any potential benefit to pregnant women receiving prolonged treatment with
terbutaline injection (>48-72 h) or acute or prolonged treatment with oral terbutaline.
The tocolytic agents currently used to treat preterm labor appear to be equally efficacious in
delaying delivery for at least 48 hours. While MgSO4 is associated with more maternal toxicity,
indomethacin is associated with more fetal and neonatal toxicity.
Haas et al analyzed randomized controlled trials of tocolysis to determine the optimal first-line
tocolytic agent for treatment of premature labor. Fifty-eight studies satisfied the inclusion
criteria. A random-effects meta-analysis showed that all tocolytic agents were superior to
placebo or control groups at delaying delivery both for at least 48 hours (53% for placebo
compared with 75-93% for tocolytics) and 7 days (39% for placebo compared with 61-78% for
tocolytics). No statistically significant differences were found for the other outcomes, including
the neonatal outcomes of respiratory distress and neonatal survival. The decision model
demonstrated that prostaglandin inhibitors provided the best combination of tolerance and
delayed delivery. [29]

Magnesium sulfate

Magnesium sulfate is widely used as the primary tocolytic agent because it has similar efficacy
to terbutaline with far better tolerance. Common maternal side effects include flushing, nausea,
headache, drowsiness, and blurred vision. The mother should be monitored for toxic effects, such
as respiratory depression or even cardiac arrest, that can occur at supratherapeutic levels. In
addition, magnesium sulfate readily crosses the placenta and may lead to respiratory and motor
depression of the neonate.
Although magnesium sulfate is approved to prevent seizures in preeclampsia and for control of
seizures in eclampsia, its use for preterm labor is off-label. In 2013, the FDA issued a safety alert
warning not to exceed 5-7 days of continuous IV magnesium sulfate when the agent is used for
preterm labor. [24, 25, 26] Longer treatment duration may lead to hypocalcemia in the developing
fetus and result in neonates with skeletal abnormalities related to osteopenia. Hypermagnesemia
causes hypocalcemia as a result of a decrease in the secretion of parathyroid hormone. [26]
Several observational studies have reported an association of antenatal treatment with
magnesium sulfate for preterm labor or preeclampsia with a decreased risk of cerebral palsy in
low birth weight or preterm infants.[30, 31, 32] While the use of magnesium sulfate for the
prevention of cerebral palsy in preterm infants has been recently suggested, it has yet to receive
universal acceptance.
Antenatal magnesium sulfate should be considered for use in women at high risk of delivery
before 34 weeks' gestation, mainly in those with premature rupture of membranes, active labor,
and planned delivery within 24 hours. Loading and maintenance doses, and the duration of the
treatment specifically for neuroprotection should not normally exceed 6 g, 1-2 g/h, and 24 hours,
respectively.

The use of magnesium sulfate usually requires baseline maternal laboratory evaluation, including
CBC count and serum creatinine level, urine output greater than 30 mL/h, normal vital signs, and
appropriate maternal mentation. The initial recommended loading dose is 4-6 g IV over 20
minutes, followed by a maintenance dose of 1-4 g/h depending on urine output and persistence of
uterine contractions.
Maintenance of magnesium sulfate therapy requires careful assessment of maternal mentation,
visual symptoms, DTRs, and cardiac rate with discontinuation whenever evidence of toxicity
exists. Urine output should be carefully monitored and ideally maintained at greater than 50
mL/h. Limiting intravenous intake to prevent pulmonary edema may be prudent. Oral intake can
be maintained at the discretion of the provider. Serum magnesium levels may be obtained 1 hour
after the loading dose and then every 6 hours and the maintenance dosage should be titrated to
maintain a serum level of 4-8 mg/dL.
Since the primary therapeutic goal of tocolysis is to delay preterm delivery within 48 hours from
the initiation of steroid prophylaxis, little evidence suggests that extended MgSO4 therapy is
beneficial. The authors recommend discontinuing magnesium sulfate therapy after 48 hours in
most patients unless the gestational age is less than 28 weeks when a gain of an additional 3-4
days may significantly reduce neonatal morbidity and mortality. Due to the risk of toxicity,
consulting an MFM specialist may be beneficial if magnesium sulfate is to be continued for more
than 72 hours. Since no clinical evidence suggests that oral beta-mimetics, subcutaneous
terbutaline pump, or oral magnesium compounds are effective in delaying preterm birth,
alternative tocolysis is not currently recommended after the discontinuation of IV MgSO4
therapy.
When acute mild toxicity exists in the presence of normal urine output, magnesium sulfate
should be temporarily discontinued until the serum magnesium level and DTRs return to normal.
If the toxicity symptoms are life threatening, administering 1 g of calcium gluconate by slow
intravenous push and strongly considering not reinstituting magnesium sulfate despite the return
to normal levels is recommended.

Indomethacin

Indomethacin is an appropriate first-line tocolytic for the pregnant patient in early preterm labor
(< 30 wk) or preterm labor associated with polyhydramnios. A more significant inflammatory
response in the membranes and decidua is observed at gestational ages less than 30 weeks
compared with 30-36 weeks. Indomethacin reduces prostaglandin synthesis from decidual
macrophages. The fetal renal effects of indomethacin may be beneficial to reduce
polyhydramnios.
Prostaglandin synthetase inhibitors, such as indomethacin, have been shown to have efficacy
similar to that of terbutaline but are associated with infrequent maternal side effects. However,
these agents readily cross the placenta and can cause oligohydramnios due to a decrease in fetal
renal blood flow if used for more than 48 hours. The administration of indomethacin is often
limited to 48 hours, and baseline labs, including CBC count and liver function tests (LFTs),
should be ordered prior to initiation of therapy.
During treatment, urine output, maternal temperature, and amniotic fluid index (AFI) should be
evaluated periodically. The initial recommended dose is 100 mg PR followed by 50 mg PO every
6 hours for 8 doses. If oligohydramnios occurs, the amniotic fluid usually reaccumulates when
the indomethacin is stopped, but persistent fetal anuria, renal microcystic lesions, and neonatal
death have been reported. Indomethacin can also cause premature closure or constriction of the
ductus arteriosus. Since this effect is more common after 32 weeks' gestation, indomethacin
therapy is not usually recommended after 32 weeks.

Nifedipine

Nifedipine, a calcium channel blocker, is commonly used to treat high blood pressure and heart
disease because of its ability to inhibit contractility in smooth muscle cells by reducing calcium
influx into cells. Consequently, nifedipine has emerged as an effective and safe alternative
tocolytic agent for the management of preterm labor. Despite its unlabeled status, several
randomized studies have shown that the use of nifedipine in comparison with other tocolytics is
associated with a more frequent successful prolongation of pregnancy, resulting in significantly
fewer admissions of newborns to the neonatal intensive care unit, and may be associated with a
lower incidence of RDS, necrotizing enterocolitis, and intraventricular hemorrhage.
A systemic review by Conde-Aqudelo found that nifedipine was associated with significantly
fewer maternal adverse events than β2 -adrenergic-receptor agonists and magnesium sulfate for
tocolysis in women with preterm labor. [33]
A recommended initial dosage of nifedipine is 20 mg orally, followed by 20 mg orally after 30
minutes. If contractions persist, therapy can be continued with 20 mg orally every 3-8 hours for
48-72 hours with a maximum dose of 160 mg/d. After 72 hours, if maintenance is still required,
long-acting nifedipine 30-60 mg daily can be used.
Contraindications of nifedipine therapy include allergy to nifedipine, hypotension, hepatic
dysfunction, concurrent use of beta-mimetics or MgSO4, transdermal nitrates, or other
antihypertensive medication. Other commonly reported side effects of nifedipine are maternal
tachycardia, palpitations, flushing, headaches, dizziness, and nausea. Continuous monitoring of
the fetal heart rate is recommended as long as the patient has contractions; the patient's pulse and
blood pressure should be carefully monitored. Pregnant women with liver disease should not be
prescribed nifedipine.

Follow-up Care
A true episode of preterm labor becomes a powerful risk factor for recurrent preterm birth, in
addition to other risk factors present prior to the current episode. The prior risk factor may have
been modified; for example, infection may have been identified and treated or behavioral risk
factors may have been modified. Little evidence indicates that prophylactic oral beta-mimetic,
subcutaneous beta-mimetics, or oral magnesium gluconate reduce the incidence of recurrent
preterm birth and therefore should not be prescribed.
Frequent contact, face-to-face or by telephone, with a knowledgeable provider appears to be as
effective as home uterine activity monitoring (HUAM) or continued pharmacological therapy.
Direct contact with the patient is supplemented by education and phone access to a
knowledgeable, consistent provider. Some unique situations exist in which HUAM is still felt to
be beneficial, including patients who are paraplegic and unable to appreciate any muscular
contractions.
The goal of follow-up therapy is to maximally reduce recurrence risk and to speed the access to
subspecialty care if preterm labor should recur.

Inpatient

Once the episode of preterm labor has been arrested, a gradual return to limited activity should
be encouraged prior to hospital discharge. The following factors may influence the decision to
discharge the patient:
 Cervical dilation
 Fetal presentation
 Number of fetuses
 Gestational age
 Access to the hospital
 Social support at home (transportation at all times, telephone)
 The ability to maintain limited activity and pelvic rest
 Good patient compliance
If the patient was referred to a subspecialty care facility, the local obstetrical and pediatric
providers should be comfortable with home management. If labor should recur, they may have to
manage the rapid delivery of premature infant.
The patient should be informed regarding the signs and symptoms of recurrent preterm labor.
The critical signs of recurrent preterm labor include contractions greater than 4 per hour,
rhythmic back or thigh pain, increasing pelvic pressure, unusual discharge, vaginal
spotting/bleeding, or rupture of membranes.

Outpatient

The provider should have increased contact with the patient, and the patient should be directed to
a specific individual to report symptoms of preterm labor or complications. The contact may be
via a combination of telephone contacts and office visits. When genital tract infection may have
played a role in the preterm labor; a repeat culture may be recommended 2-4 weeks after
discharge.
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