Diagnosis of preterm labor and overview of preterm birth

Author:
Charles J Lockwood, MD, MHCM
Section Editor:
Susan M Ramin, MD
Deputy Editor:
Vanessa A Barss, MD, FACOG

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jan 2017. | This topic last updated: Feb 17, 2017.

INTRODUCTION Identifying women with preterm contractions who will actually deliver preterm is
an inexact process, even though preterm labor is one of the most common reasons for hospitalization
of pregnant women. Accurate identification of women truly in preterm labor allows appropriate
application of interventions that can improve neonatal outcome: antenatal corticosteroid therapy,
group B streptococcal infection prophylaxis, magnesium sulfate for neuroprotection, and transfer to a
facility with an appropriate level nursery (if necessary). On the other hand, accurate triage of women
not actually in preterm labor can avoid performance of unnecessary interventions and associated
costs for the 20 to 50 percent of patients with suspected preterm labor who will go on to deliver at term
without tocolytic therapy [1].

This topic will describe our approach to the diagnostic evaluation of women who present with possible
preterm labor and provide an overview of issues related to preterm birth. Treatment of preterm labor is
discussed separately. (See "Inhibition of acute preterm labor".)

PRETERM LABOR

Pathogenesis The pathophysiology of preterm labor involves four primary pathogenic processes
that result in a final common pathway ending in spontaneous preterm labor and delivery:

Activation of the maternal or fetal hypothalamic-pituitary-adrenal axis associated with either

maternal anxiety and depression or fetal stress
Infection
Decidual hemorrhage
Pathological uterine distention

These processes and the pathophysiology of normal labor are discussed in detail separately.
(See "Pathogenesis of spontaneous preterm birth" and "Physiology of parturition".)

Clinical findings The clinical findings of true labor (ie, contractions plus cervical change) are the
same whether labor occurs preterm or at term. The following are early signs and symptoms of labor;
however, they are non-specific and can be present for several hours in women who do not exhibit
cervical change:

Menstrual-like cramping
Mild, irregular contractions
 Low back ache
Pressure sensation in the vagina
Vaginal discharge of mucus, which may be clear, pink, or slightly bloody (ie, mucus plug, bloody
show)

Uterine contractions are the sine qua non of labor, but mild irregular contractions are a normal finding
at all stages of pregnancy, thereby adding to the challenge of distinguishing true labor (contractions
that result in cervical change) from false labor (contractions that do not result in cervical change, ie,
Braxton Hicks contractions). True labor is more likely when an increasing frequency of contractions is
accompanied by increasing intensity and duration of contractions as an increase in the frequency of
contractions alone may occur transiently, especially at night and with increasing gestational age.
Although many investigators have tried, no one has been able to identify a threshold contraction
frequency that effectively identifies women who will progress to true labor. Only 13 percent of women
presenting at <34 weeks of gestation with explicit contraction criteria for preterm labor deliver within
one week [2].

Cervical changes on physical examination that precede or accompany true labor include dilation,
effacement, softening, and movement to a more anterior position. A short or a dilated cervix may be
the first clinical manifestation of a parturition process triggered by subclinical inflammation [3]. The rate
of cervical change distinguishes cervical ripening, which occurs over days to weeks, from true labor, in
which cervical change occurs over minutes to hours.

Diagnostic evaluation

History and initial examinations Our initial evaluation of women with suspected preterm labor
includes:

Review of the patient's past and present obstetrical and medical history, and assessment of
gestational age.
Evaluation of signs and symptoms of preterm labor (see 'Clinical findings' above) and risk
factors for preterm birth (table 1).
Maternal vital signs (temperature, blood pressure, heart rate, respiratory rate).
Review of the fetal heart rate pattern. (See "Intrapartum fetal heart rate assessment".)
Assessment of contraction frequency, duration, and intensity. (See "Management of normal
labor and delivery", section on 'Uterine contractions'.)
Examination of the uterus to assess firmness, tenderness, fetal size, and fetal position.

Speculum examination We perform a speculum examination using a wet non-lubricated

speculum. Lubricants may interfere with tests on vaginal samples. The goals of this examination are
to:

Estimate cervical dilation. Cervical dilation >3 cm supports the diagnosis of preterm labor.
Assess the presence and amount of uterine bleeding. Bleeding from abruptio placenta or
placenta previa can trigger preterm labor. (See "Placental abruption: Clinical features and
diagnosis" and "Clinical features, diagnosis, and course of placenta previa".)
 Evaluate fetal membrane status (intact or ruptured) by standard methods. Preterm premature
rupture of membranes (PPROM) often precedes or occurs during preterm labor. Diagnosis and
management of PPROM are reviewed separately. (See "Preterm premature (prelabor) rupture of
membranes".)
Obtain a cervicovaginal fluid specimen in case fetal fibronectin (fFN) testing is desired after
transabdominal ultrasound examination. "Blind" sampling is acceptable if a speculum
examination cannot be performed. In one method, the posterior vaginal wall is depressed with an
unlubricated, gloved finger and then the polyester swab is slowly passed along the finger toward
the posterior fornix until resistance is felt [4]. In another method, the labia are held apart and then
the swab is blindly inserted into the vagina and directed slowly toward the posterior fornix until
meeting resistance [5]. The swab is rotated in the posterior fornix for 10 seconds. In both
methods, it is important to stop at the first sign of resistance to avoid rupturing exposed
membranes, if present. (See 'Fetal fibronectin for selected patients' below.)

Cervical examination In most patients, cervical dilation and effacement are assessed by digital
examination after speculum examination and after placenta previa and rupture of membranes have
been excluded by history and physical, laboratory, and ultrasound examinations, as appropriate. A
digital examination should be performed sooner if the information is urgently needed to care for the
patient (eg, abnormal fetal heart rate, probable advanced phase of active labor) and placenta previa is
unlikely. As discussed above, cervical dilation >3 cm supports the diagnosis of preterm labor and
inhibition of acute preterm labor is less likely to be successful as the cervix dilates beyond 3 cm.

When assessing cervical dilation and effacement in the second trimester, it is important to distinguish
between patients whose membranes have hour-glassed (prolapsed) through a mildly dilated and
effaced cervix (suggestive of cervical insufficiency) and those who are in active labor with advanced
cervical dilation and effacement. Transvaginal ultrasound assessment of the cervical length in the
second trimester can be used to make the diagnosis of cervical insufficiency in women with risk
factors. Only a digital cervical examination is needed in patients with advanced cervical dilation.
(See "Cervical insufficiency", section on 'Physical examination reveals a dilated cervix and visible
membranes before 24 weeks' and "Transvaginal cervical cerclage", section on 'Replacement of
prolapsed membranes'.)

Laboratory evaluation

Overview We order the following laboratory tests:

Rectovaginal group B streptococcal culture if not done within the previous five weeks; antibiotic
prophylaxis depends on the results. (See "Neonatal group B streptococcal disease: Prevention",
section on 'Approach to threatened preterm delivery'.)
Urine culture, since asymptomatic bacteriuria is associated with an increased risk of preterm
labor and birth. (See "Urinary tract infections and asymptomatic bacteriuria in pregnancy".)
Drug testing in patients with risk factors for substance abuse, given the link between cocaine
use and placental abruption. (See "Overview of substance misuse in pregnant women".)
 Fetal fibronectin (fFN) in women <34 weeks of gestation with cervical dilation <3 cm and
cervical length 20 to 30 mm on transvaginal ultrasound examination. (See 'Cervical length 20 to
30 mm' below.)

Fetal fibronectin for selected patients Fetal fibronectin (fFN) is an extracellular matrix protein
present at the decidual-chorionic interface. Disruption of this interface due to subclinical infection or
inflammation, abruption or uterine contractions releases fFN into cervicovaginal secretions, which is
the basis for its use as a marker for predicting spontaneous preterm birth [6].

Measurement of fFN is performed to distinguish women in true preterm labor from those with false
labor. Theoretically, accurate identification of women in true preterm labor provides an opportunity for
interventions that can improve neonatal outcome (eg, antenatal corticosteroid therapy, group B
streptococcal infection prophylaxis, magnesium sulfate for neuroprotection, transfer to a facility with an
appropriate level nursery, if necessary). It should also avoid unnecessary intervention and associated
costs for the 20 to 50 percent who will go on to deliver at term without tocolytic therapy [1]. However,
fFN results alone are not useful. In a 2016 systematic review of six randomized clinical trials in which a
total of 546 women with threatened preterm labor were randomly assigned to management with
reported or concealed fetal fibronectin results, clinician knowledge of fFN results did not significantly
reduce rates of maternal hospitalization, use of tocolytics, use of antenatal corticosteroids, or preterm
birth, but increased hospitalization costs [7].

The review excluded studies in which management involved use of both fFN and sonographic cervical
length, which is our approach. We obtain fFN selectively, limiting its use to women with cervical length
20 to 30 mm. (See 'Cervical length 20 to 30 mm' below.)

Qualitative fFN Qualitative fFN results are reported as positive or negative. A positive fFN test
refers to a fFN concentration 50 ng/mL in cervicovaginal fluid between 220/7ths and 346/7ths weeks of
gestation in women with intact membranes, cervical dilation <3 cm, and no gross vaginal bleeding. A
positive fFN result correlates with an increased risk of preterm delivery within seven days.

In women with signs and symptoms of preterm labor, a 2013 systematic review of five randomized
trials and 15 diagnostic test accuracy studies evaluating cervicovaginal fFN for predicting preterm birth
reported the following pooled estimates [8]:

Delivery within 7 to 10 days of testing: sensitivity and specificity 76.7 and 82.7 percent,
respectively
Delivery <34 weeks of gestation: sensitivity and specificity 69.1 and 84.4 percent, respectively
Delivery <37 weeks of gestation: sensitivity and specificity 60.8 and 82.3 percent, respectively

Positive and negative predictive values depend on the prevalence of preterm birth in the population. In
a systematic review in which the prevalence of preterm birth within seven days of sampling varied
from 2 to 30 percent among the included studies, the overall pretest probability of delivery within
seven days of testing was 7.7 percent, and based on positive or negative fFN results, the post-test
probabilities were 25.9 and 2.4 percent, respectively [9].

False-positive results can occur due to ejaculate from coitus within the previous 24 hours, a grossly
bloody specimen, or digital cervical examination [10-12]. Digital cervical examination can also cause a
false positive result [10]. Theoretically, transvaginal ultrasound examination may cause a false positive
result, but in one study all 25 women with a negative baseline fFN test had a second negative fFN test
post-ultrasound [13]. Administration of intravaginal substances, such as lubricants, medications, or
douching may interfere with the assay [14].

Quantitative fFN Quantitative measurement of fFN appears to improve predictive value compared
with use of the qualitative test using a 50 ng/mL threshold [15-17]. In symptomatic women, the positive
predictive values of fFN thresholds of 10, 50, 200, and 500 ng/mL for preterm birth within 14 days
were 11, 20, 37, and 46 percent, respectively, in one prospective blinded study [15]. For preterm birth
<34 weeks of gestation, positive predictive values for the same thresholds were 19, 32, 61, and 75
percent, respectively. Instrumentation for quantitative measurement of fFN is not commercially
available in the United States.

The combination of quantitative fFN testing and cervical length measurement increases predictive
value [18]. An algorithm combining quantitative fFN and cervical length, demographic information, and
obstetric history (previous spontaneous preterm birth/preterm premature rupture of membranes) has
been incorporated into an App (QUiPP) for prediction of spontaneous preterm birth in Europe [19,20].

Other tests Like fFN, placental -microglobulin-1 (PAMG-1) [21,22]or phosphorylated insulin-like
growth factor binding protein 1 (pIGFBP-1) [23] in vaginal or cervical secretions suggests disruption of
the fetal membranes (ROM or labor) and are potential markers of an increased risk of preterm birth.
However, the utility of these tests has not been validated in either large or randomized clinical trials.

Diagnosis We make the diagnosis of preterm labor based upon clinical criteria of regular painful
uterine contractions accompanied by cervical change (dilation and/or effacement). Vaginal
bleeding and/or ruptured membranes in this setting increase diagnostic certainty [24]. Because the
clinical findings of early labor are poorly predictive of the diagnosis, over-diagnosis is common until
labor is well established.

Specific clinical criteria that have been used for selecting subjects in research settings include
persistent uterine contractions (4 every 20 minutes or 8 every 60 minutes) with documented cervical
change or cervical effacement 80 percent or cervical dilation >2 cm. These criteria were chosen
because women who do not meet these criteria are often ultimately diagnosed with false labor and go
on to have a late preterm or term delivery [25].

Triage singleton pregnancies

34 weeks of gestation The 34th week of gestation is the threshold at which perinatal morbidity
and mortality are too low to justify the potential maternal and fetal complications and costs associated
with inhibition of preterm labor, which only results in short term delay in delivery. (See "Inhibition of
acute preterm labor", section on 'Lower and upper gestational age limits'.)

Furthermore, we generally do not administer antenatal corticosteroids after 34 weeks of gestation

because of the low risk of severe respiratory morbidity at this gestational age and the theoretic
potential for long-term harm following late exposure. The risks and benefits of steroid use after 34
weeks is discussed in detail separately. (See "Antenatal corticosteroid therapy for reduction of
neonatal morbidity and mortality from preterm delivery", section on 'After 34 weeks'.)
Therefore, women in preterm labor 34 weeks are admitted for delivery. After an observation period of
four to six hours, women without progressive cervical dilation and effacement are discharged to home,
as long as fetal well-being is confirmed (eg, reactive nonstress test) and obstetrical complications
associated with preterm labor, such as abruptio placenta, chorioamnionitis, and preterm rupture of
membranes, have been excluded. We arrange follow-up in one to two weeks and give the patient
instructions to call if she experiences additional signs or symptoms of preterm labor, or has other
pregnancy concerns (eg, bleeding, rupture of membranes, decreased fetal activity). (See "Patient
education: Preterm labor (Beyond the Basics)".)

<34 weeks of gestation In women <34 weeks with uterine contractions, cervical dilation 3 cm
supports the diagnosis of preterm labor; further diagnostic evaluation with sonographic measurement
of cervical length or laboratory assessment of fetal fibronectin does not enhance diagnostic accuracy.
Treatment of preterm labor is initiated. (See 'Treatment of women <34 weeks with suspected preterm
labor' below.)

The diagnosis of preterm labor is less clear in women with contractions, cervical dilation <3 cm, and
intact membranes. Our approach is based upon clinical experience and available data that the
frequency of preterm birth is low in symptomatic women <34 weeks with cervical length >30 mm
[24,26-28], unless abruption is the cause of their symptoms; the frequency of preterm birth is
increased but still relatively low in symptomatic women with cervical length 20 to 30 mm; and the
frequency of preterm birth is high in symptomatic women with cervical length <20 mm (algorithm 1)
[2,24,26,29,30].

Ultrasound fetal fibronectin examination Measurement of cervical length is useful for

supporting or excluding the diagnosis of preterm labor when the diagnosis is unclear. A short cervix
before 32 weeks of gestation is predictive of preterm birth in all populations, while a long cervix has a
high negative predictive value for preterm birth. (See "Second-trimester evaluation of cervical length
for prediction of spontaneous preterm birth in singleton gestations".)

We also perform an obstetrical ultrasound examination to look for fetal, placental, and maternal
structural abnormalities; confirm the fetal presentation; assess amniotic fluid volume; and estimate
fetal weight. This information can be useful for counseling the patient about the potential causes and
outcomes of preterm birth and determining the best route of delivery, if required.

Cervical length 20 to 30 mm Symptomatic women with cervical dilation <3 cm and cervical length
20 to 30 mm are at increased risk of preterm birth compared with women with longer cervical lengths,
but most of these women do not deliver preterm. Therefore, for this subgroup of women, we send a
cervicovaginal sample for fFN testing (see 'Fetal fibronectin for selected patients' above). We believe
that selective testing helps reduce diagnostic uncertainty and, in turn, unnecessary intervention, by
identifying the significant proportion of patients in this group who are at low (<5 percent) risk of
preterm delivery within seven days [31]. Since the test is expensive, reducing the number of women
tested by one-third is advantageous [32,33].

If the fFN test is positive, we begin interventions to reduce morbidity associated with preterm birth
(see 'Treatment of women <34 weeks with suspected preterm labor' below). If the fFN test is negative,
we discharge the patient after 6 to 12 hours of observation, given its high negative predictive value (98
to 100 percent for delivery within 7 or 14 days [34]) [8].

Use of sonographic cervical length and fFN determinations to differentiate true labor from false labor in
preterm symptomatic women are supported by the American College of Obstetricians and
Gynecologists [35] and Society for Maternal-Fetal Medicine [36], although high quality evidence of
efficacy is not available.

Cervical length <20 mm Symptomatic women with cervical length <20 mm are at high risk (>25
percent) of delivery within seven days; the addition of fFN testing does not significantly improve the
predictive value of cervical length measurement alone [31-33,37,38]. Therefore, we do not send their
cervicovaginal samples to the laboratory for fFN testing and we begin interventions to reduce
morbidity associated with preterm birth. (See 'Treatment of women <34 weeks with suspected preterm
labor' below.)

Cervical length >30 mm Symptomatic women with cervical length >30 mm are at low risk (<5
percent) of delivery within seven days, regardless of fFN result; the addition of fFN testing does not
significantly improve the predictive value of cervical length measurement alone [31,32,37,38].
Therefore, we do not send their cervicovaginal samples to the laboratory for fFN testing.

After an observation period of four to six hours, women without progressive cervical dilation and
effacement are discharged to home, as long as fetal well-being is confirmed (eg, reactive nonstress
test) and obstetrical complications associated with preterm labor, such as abruptio placenta,
chorioamnionitis, and preterm rupture of membranes, have been excluded. We arrange follow-up in
one to two weeks and give the patient instructions to call if she experiences additional signs or
symptoms of preterm labor, or has other pregnancy concerns (eg, bleeding, rupture of membranes,
decreased fetal activity). (See "Patient education: Preterm labor (Beyond the Basics)".)

Triage twin pregnancies The prediction of preterm birth based on cervical length measurement is
somewhat different for twin pregnancies, which necessitates some changes in triage criteria. The
optimal cervical length threshold appears to be higher due to the higher baseline risk for preterm birth
in twins compared with singletons; however, less data are available for establishing appropriate
thresholds [39,40].

34 weeks of gestation Triage is the same as for singletons. (See '34 weeks of
gestation' above.)

<34 weeks of gestation For women <34 weeks with uterine contractions, cervical dilation 3 cm
supports the diagnosis of preterm labor; further diagnostic evaluation with sonographic measurement
of cervical length or laboratory assessment of fetal fibronectin does not enhance diagnostic accuracy.
Treatment of preterm labor is initiated. (See 'Treatment of women <34 weeks with suspected preterm
labor' below.)

The diagnosis of preterm labor is less clear in women with contractions, cervical dilation <3 cm, and
intact membranes, so a transvaginal ultrasound measurement of cervical length is obtained.
 Women with cervical length >35 mm and no change over six hours are at low risk for preterm
delivery, and can be discharged home after a four- to six-hour period of observation, as long as
fetal well-being is confirmed, maternal status is stable, and there are no additional maternal
concerns.
Women with cervical length <25 mm are at high risk of preterm delivery, and thus we begin
interventions to reduce morbidity associated with preterm birth. (See 'Treatment of women <34
weeks with suspected preterm labor' below.)
Women with cervical length 25 to 35 mm on transvaginal ultrasound examination undergo fetal
fibronectin testing. If the test is positive, we begin interventions to reduce morbidity associated
with preterm birth (see 'Treatment of women <34 weeks with suspected preterm labor' below). If
the test is negative, we discharge the patient after a 6- to 12-hour period of observation.

Treatment of women <34 weeks with suspected preterm labor We hospitalize women
diagnosed with preterm labor <34 weeks of gestation and initiate the following treatments, in general
agreement with recommendations from the American College of Obstetricians and Gynecologists [41]:

A course of betamethasone to reduce neonatal morbidity and mortality associated with preterm
birth. A single rescue course of antenatal steroids is indicated for pregnancies <34 weeks of
gestation that are at risk of preterm delivery within the next seven days and had a course of
antenatal corticosteroids at least seven days previously [41]. (See "Antenatal corticosteroid
therapy for reduction of neonatal morbidity and mortality from preterm delivery".)
Tocolytic drugs for up to 48 hours to delay delivery so that betamethasone given to the mother
can achieve its maximum fetal effect. Inhibition of acute preterm labor and management of
pregnancies after successful inhibition are reviewed separately. (See "Inhibition of acute preterm
labor" and "Management of pregnant women after inhibition of acute preterm labor".)
Antibiotics for GBS chemoprophylaxis. (See "Neonatal group B streptococcal disease:
Prevention", section on 'Approach to threatened preterm delivery'.)
Magnesium sulfate for pregnancies at 24 to 32 weeks of gestation. In utero exposure to
magnesium sulfate provides neuroprotection against cerebral palsy and other types of severe
motor dysfunction in offspring born preterm. (See "Neuroprotective effects of in utero exposure to
magnesium sulfate".)

Antibiotic therapy has no role in the treatment of acute preterm labor in the absence of a documented
infection or GBS prophylaxis [42]. (See "Inhibition of acute preterm labor", section on 'Antibiotic
therapy'.)

Progesterone supplementation has no role in the treatment of acute preterm labor.

(See "Progesterone supplementation to reduce the risk of spontaneous preterm birth", section on
'Threatened preterm labor'.)

Outcome Tocolytic therapy is more effective than placebo for delaying delivery for 48 hours in
randomized trials; however, even when tocolytic therapy is not administered, about 50 percent of
women diagnosed with preterm labor deliver at term [43]. (See "Inhibition of acute preterm labor",
section on 'Efficacy'.)
Whether a history of suspected preterm labor is associated with adverse neonatal outcome in women
who go on to deliver at term is controversial. These women may have underlying pathology, such as
subclinical intra-amniotic inflammation, that may adversely affect fetal growth or development even
though they go on to have a term birth [44-46].

OVERVIEW OF PRETERM BIRTH Preterm birth refers to a delivery that occurs before 37 weeks of
gestation. It may or may not be preceded by preterm labor. Although term pregnancy has been
defined as 370/7ths to 416/7ths weeks of gestation, the period 370/7ths to 386/7ths weeks is considered "early
term" because neonates born in this gestational age range have higher neonatal morbidity and
mortality than infants born at "full term" from 390/7ths to 406/7ths weeks [47,48].

Classification Preterm births are described by gestational age, birth weight, and initiating factor.

Gestational age criteria:

World Health Organization [49]:
Moderate to late preterm: 32 to <37 weeks
Very preterm: 28 to <32 weeks
Extremely preterm: <28 weeks
Centers for Disease Control and Prevention [50]
Preterm: <37 weeks
Late preterm: 34 to 36 weeks
Early preterm: <34 weeks
Birth weight criteria [51]:
Low birth weight (LBW): <2500 grams
Very low birth weight (VLBW): <1500 grams
Extremely low birth weight (ELBW): <1000 grams
Initiating factor: spontaneous or iatrogenic (ie, indicated, provider-initiated)
Spontaneous: 70 to 80 percent, due to preterm labor (40 to 50 percent) or preterm
premature rupture of membranes (20 to 30 percent).
Provider-initiated: 20 to 30 percent, due maternal or fetal issues (eg, preeclampsia,
placenta previa, abruptio placenta, fetal growth restriction, multiple gestation). Complications
of pregnancy can lead to both spontaneous and provider-initiated preterm births.

Prevalence Few countries are able to provide reliable national preterm birth prevalence data.
Worldwide, the preterm birth rate is estimated to be about 11 percent (range 5 percent [parts of
Europe] to 18 percent [parts of Africa]), and about 15 million children are born preterm each year
(range 12 to 18 million) [52,53]. Of these preterm births, 84 percent occurred at 32 to 36 weeks, 10
percent occurred at 28 to <32 weeks, and 5 percent occurred at <28 weeks.

In the United States in 2013, 11.4 percent of births were <37 weeks (8 percent at 34 to 36 weeks and
3.4 percent <34 weeks [1.9 percent <32 weeks]) [54].

An increase in multiple gestations due to assisted reproductive technology is one reason for the
increasing prevalence of preterm birth in some countries. (See "Pregnancy outcome after assisted
reproductive technology", section on 'Proportion of singleton and multiple gestation'.)
Epidemiology Preterm birth rates in the United States are highest among women <20 and >35
years of age and among non-Hispanic black mothers, followed by American Indian or Alaskan
Natives, Hispanics, non-Hispanic whites, and Asian or Pacific Islanders [55]. Racial/ethnic disparities
in preterm birth rates may reflect biological (genetic) differences and/or variations in socioeconomic,
lifestyle, and cultural factors; access to medical care; and environmental/occupational exposures.

Risk factors When trying to assess the probability of preterm labor, it can be helpful to assess the
presence or absence of clinical risk factors. Numerous risk factors for spontaneous preterm birth have
been reported (table 1). Causal associations between most of these risk factors and preterm birth
have been difficult to prove because (1) many preterm births occur among women with no risk factors,
(2) some obstetrical complications resulting in preterm birth require cofactors to exert their effect,
making the chain of causality difficult to document, and (3) an adequate animal model for study of
preterm birth does not exist. Risk factors for preterm birth are discussed in detail separately.
(See "Preterm birth: Risk factors and interventions for risk reduction".)

Significance

Child Preterm birth is the leading direct cause of neonatal death (death in the first 28 days of life),
and is responsible for 27 percent of neonatal deaths worldwide [52,56]. The risk of neonatal mortality
decreases as gestational age at birth increases, but the relationship is nonlinear (figure 1). The risk of
neonatal mortality is also significantly impacted by the cause of preterm birth. In a prospective
population-based cohort study, live born neonates <34 weeks of gestation delivered because of
suspected growth restriction had two- to threefold higher mortality than those born after preterm labor
[57]. Preterm birth is the second most common cause of death (after pneumonia) in children younger
than five years. (See "Perinatal mortality", section on 'Causes of infant death'.)

Preterm birth is also a major determinant of short- and long-term morbidity in infants and children. The
burden of preterm birth includes neonatal morbidity and long-term sequelae, including
neurodevelopmental deficits (eg, cerebral palsy, impaired learning, visual disorders) and an increased
risk of a spectrum of diseases in adulthood [58]. (See "Short-term complications of the preterm
infant" and "Long-term complications of the preterm infant".)

Maternal Women who have had a spontaneous preterm birth are at risk for recurrent preterm birth.
(See "Preterm birth: Risk factors and interventions for risk reduction", section on 'History of
spontaneous preterm birth'.)

Spontaneous preterm birth has been associated with an increased risk of maternal cardiovascular
morbidity and mortality years after the delivery. In a 2015 systematic review and meta-analysis of 10
cohort studies, women who had a spontaneous preterm delivery were at higher risk for the following
cardiovascular events when compared with women who delivered at term and followed for 12 to 35
years postpartum [59]:

Fatal and nonfatal ischemic heart disease (hazard ratio [HR] 1.38, 95% CI 1.22-1.57)
Fatal and nonfatal stroke (HR 1.71, 95% CI 1.53-1.91)
Fatal and nonfatal overall cardiovascular disease (HR 2.01, 95% CI: 1.52-2.65)
It is unclear why spontaneous preterm delivery appears to be a marker for later cardiovascular
disease or whether women who delivered preterm should be identified by primary care providers and
encouraged to optimize modifiable risk factors for cardiovascular disease more than women without
this history. (See "Overview of primary prevention of coronary heart disease and stroke".)

Prevention Interventions with proven efficacy for prevention of preterm birth include [60,61]:

Smoking cessation. (See "Cigarette smoking: Impact on pregnancy and the neonate".)
Progesterone supplementation in asymptomatic women with previous spontaneous preterm
birth or in asymptomatic women with no history of spontaneous preterm birth but a short cervix
(ie, 20 mm) in the current pregnancy. (See "Progesterone supplementation to reduce the risk of
spontaneous preterm birth".)
Reduction of multiple gestation by limiting the number of embryo transfers in women undergoing
assisted reproductive technology (see "Strategies to control the rate of high order multiple
gestation") or multifetal pregnancy reduction. (See "Multifetal pregnancy reduction and selective
termination".)
Avoidance of induction of labor and scheduled cesarean delivery in the absence of medical
indications. (See "Induction of labor", section on 'Elective or marginally indicated induction at
term' and "Cesarean delivery: Preoperative issues", section on 'Indications and
contraindications'.)
Cerclage in women with previous spontaneous preterm birth and a short cervix in current
pregnancy. (See "Cervical insufficiency".)

INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The
Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at
the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have
about a given condition. These articles are best for patients who want a general overview and who
prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and
are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-
mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Preterm labor (The Basics)" and "Patient education: How
to tell when labor starts (The Basics)")
Beyond the Basics topics (see "Patient education: Preterm labor (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Preterm labor

Early signs and symptoms of labor are non-specific and include: menstrual-like cramping; mild,
irregular contractions; low back ache; pressure sensation in the vagina; vaginal discharge of
 mucus, which may be clear, pink, or slightly bloody (ie, mucus plug, bloody show). (See 'Clinical
findings' above.)
The diagnosis of preterm labor is based on clinical criteria of regular painful uterine contractions
accompanied by cervical dilation and/or effacement. (See 'Diagnosis' above.)
Thirty-four to 35 weeks of gestation is the threshold at which perinatal morbidity and mortality
are too low to justify the potential maternal and fetal complications and costs associated with
inhibition of preterm labor, which only results in short-term delay in delivery. (See '34 weeks of
gestation' above.)
For pregnancies 34 weeks of gestation, women without progressive cervical dilation and
effacement after an observation period of four to six hours can be discharged to home, as long as
fetal well-being is confirmed (eg, reactive nonstress test) and obstetrical complications associated
with preterm labor, such as abruptio placenta, chorioamnionitis, and preterm rupture of
membranes, have been excluded. Women in preterm labor are admitted for delivery. (See '34
weeks of gestation' above.)
For pregnancies <34 weeks of gestation and cervical dilation <3 cm, transvaginal ultrasound
measurement of cervical length and laboratory analysis of cervicovaginal fetal fibronectin level
help to support or exclude the diagnosis of preterm labor, as described in the algorithm (algorithm
1). (See '<34 weeks of gestation' above.)
For pregnancies <34 weeks and cervical dilation 3 cm, we administer tocolytic drugs for up to
48 hours, antibiotics for group B streptococcal chemoprophylaxis (when appropriate), and
antenatal betamethasone. Magnesium sulfate is administered for neuroprotection to pregnancies
at 24 to 32 weeks of gestation. (See 'Treatment of women <34 weeks with suspected preterm
labor' above.)

Preterm birth

Obstetricians classify preterm births as early (<34 week) or late (34 to 36 weeks) and
spontaneous or initiated by a clinician for medical or obstetrical indications. Seventy to 80 percent
of preterm births are spontaneous and due to preterm labor (40 to 50 percent) or preterm
premature rupture of membranes (20 to 30 percent). (See 'Classification' above.)
In the United States, 11.4 percent of births were <37 weeks (8 percent at 34 to 36 weeks and
3.4 percent <34 weeks [1.9 percent <32 weeks]) in 2013. (See 'Prevalence' above.)
Preterm birth rates in the United States are highest among women <20 and >35 years of age
and among non-Hispanic black mothers. Numerous risk factors for spontaneous preterm birth
have been reported (table 1). (See 'Epidemiology' above and 'Risk factors' above.)
Preterm birth is the leading direct cause of neonatal death (death in the first 28 days of life), and
is responsible for 27 percent of neonatal deaths worldwide. The risk of neonatal mortality
decreases as gestational age at birth increases, but the relationship is nonlinear (figure 1).
Preterm birth is also a major determinant of short- and long-term morbidity.
(See 'Significance' above.)
Spontaneous preterm birth has been associated with an increased risk of maternal
cardiovascular morbidity and mortality years after the delivery. It is unclear why spontaneous
preterm delivery is a marker for later cardiovascular disease or whether women who delivered
preterm should be identified by primary care providers and encouraged to optimize modifiable
 risk factors for cardiovascular disease more than women without this history.
(See 'Maternal' above.)
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REFERENCES

1. Haas DM, Imperiale TF, Kirkpatrick PR, et al. Tocolytic therapy: a meta-analysis and decision
analysis. Obstet Gynecol 2009; 113:585.
2. Sotiriadis A, Papatheodorou S, Kavvadias A, Makrydimas G. Transvaginal cervical length
measurement for prediction of preterm birth in women with threatened preterm labor: a meta-analysis.
Ultrasound Obstet Gynecol 2010; 35:54.
3. Iams JD, Cebrik D, Lynch C, et al. The rate of cervical change and the phenotype of spontaneous
preterm birth. Am J Obstet Gynecol 2011; 205:130.e1.
4. Stafford IP, Garite TJ, Dildy GA, et al. A comparison of speculum and nonspeculum collection of
cervicovaginal specimens for fetal fibronectin testing. Am J Obstet Gynecol 2008; 199:131.e1.
5. Roman AS, Koklanaris N, Paidas MJ, et al. "Blind" vaginal fetal fibronectin as a predictor of
spontaneous preterm delivery. Obstet Gynecol 2005; 105:285.
6. Feinberg RF, Kliman HJ, Lockwood CJ. Is oncofetal fibronectin a trophoblast glue for human
implantation? Am J Pathol 1991; 138:537.
7. Berghella V, Saccone G. Fetal fibronectin testing for prevention of preterm birth in singleton
pregnancies with threatened preterm labor: a systematic review and metaanalysis of randomized
controlled trials. Am J Obstet Gynecol 2016; 215:431.
8. Deshpande SN, van Asselt AD, Tomini F, et al. Rapid fetal fibronectin testing to predict preterm birth
in women with symptoms of premature labour: a systematic review and cost analysis. Health Technol
Assess 2013; 17:1.
9. Sanchez-Ramos L, Delke I, Zamora J, Kaunitz AM. Fetal fibronectin as a short-term predictor of
preterm birth in symptomatic patients: a meta-analysis. Obstet Gynecol 2009; 114:631.
10. McKenna DS, Chung K, Iams JD. Effect of digital cervical examination on the expression of fetal
fibronectin. J Reprod Med 1999; 44:796.
11. McLaren JS, Hezelgrave NL, Ayubi H, et al. Prediction of spontaneous preterm birth using quantitative
fetal fibronectin after recent sexual intercourse. Am J Obstet Gynecol 2015; 212:89.e1.
12. Shimoya K, Hashimoto K, Shimizu T, et al. Cervical fluid oncofetal fibronectin as a predictor of early
ectopic pregnancy. Is it affected by blood contamination? J Reprod Med 2002; 47:640.
13. Ben-Haroush A, Poran E, Yogev Y, Glezerman M. Vaginal fetal fibronectin evaluation before and
immediately after ultrasonographic vaginal cervical length measurements in symptomatic women at
risk of preterm birth: a pilot study. J Matern Fetal Neonatal Med 2010; 23:854.
14. http://www.ffntest.com/pdfs/rapid_ffn_product_insert_lettersize.pdf (Accessed on May 04, 2015).
15. Abbott DS, Radford SK, Seed PT, et al. Evaluation of a quantitative fetal fibronectin test for
spontaneous preterm birth in symptomatic women. Am J Obstet Gynecol 2013; 208:122.e1.
16. Kuhrt K, Unwin C, Hezelgrave N, et al. Endocervical and high vaginal quantitative fetal fibronectin in
predicting preterm birth. J Matern Fetal Neonatal Med 2014; 27:1576.
17. Kuhrt K, Hezelgrave N, Foster C, et al. Development and validation of a tool incorporating quantitative
fetal fibronectin to predict spontaneous preterm birth in symptomatic women. Ultrasound Obstet
Gynecol 2016; 47:210.
18. Bruijn MM, Kamphuis EI, Hoesli IM, et al. The predictive value of quantitative fibronectin testing
in combination with cervical length measurement in symptomatic women. Am J Obstet Gynecol 2016;
215:793.e1.
19. Kuhrt K, Smout E, Hezelgrave N, et al. Development and validation of a tool incorporating cervical
length and quantitative fetal fibronectin to predict spontaneous preterm birth in asymptomatic high-risk
women. Ultrasound Obstet Gynecol 2016; 47:104.
20. www.QUiPP.org.
21. Ehsanipoor RM, Swank ML, Jwa SC, et al. Placental -Microglobulin-1 in Vaginal Secretions of
Women with Evidence of Preterm Labor. Am J Perinatol 2016; 33:208.
22. Nikolova T, Bayev O, Nikolova N, Di Renzo GC. Comparison of a novel test for placental alpha
microglobulin-1 with fetal fibronectin and cervical length measurement for the prediction of imminent
spontaneous preterm delivery in patients with threatened preterm labor. J Perinat Med 2015; 43:395.
23. Ting HS, Chin PS, Yeo GS, Kwek K. Comparison of bedside test kits for prediction of preterm delivery:
phosphorylated insulin-like growth factor binding protein-1 (pIGFBP-1) test and fetal fibronectin test.
Ann Acad Med Singapore 2007; 36:399.
24. Iams JD. Prediction and early detection of preterm labor. Obstet Gynecol 2003; 101:402.
25. Chao TT, Bloom SL, Mitchell JS, et al. The diagnosis and natural history of false preterm labor. Obstet
Gynecol 2011; 118:1301.
26. Tsoi E, Fuchs IB, Rane S, et al. Sonographic measurement of cervical length in threatened preterm
labor in singleton pregnancies with intact membranes. Ultrasound Obstet Gynecol 2005; 25:353.
27. Ness A, Visintine J, Ricci E, Berghella V. Does knowledge of cervical length and fetal fibronectin affect
management of women with threatened preterm labor? A randomized trial. Am J Obstet Gynecol
2007; 197:426.e1.
28. Murakawa H, Utumi T, Hasegawa I, et al. Evaluation of threatened preterm delivery by transvaginal
ultrasonographic measurement of cervical length. Obstet Gynecol 1993; 82:829.
29. Tsoi E, Akmal S, Rane S, et al. Ultrasound assessment of cervical length in threatened preterm labor.
Ultrasound Obstet Gynecol 2003; 21:552.
30. Melamed N, Hiersch L, Domniz N, et al. Predictive value of cervical length in women with threatened
preterm labor. Obstet Gynecol 2013; 122:1279.
31. van Baaren GJ, Vis JY, Wilms FF, et al. Predictive value of cervical length measurement and
fibronectin testing in threatened preterm labor. Obstet Gynecol 2014; 123:1185.
32. Schmitz T, Maillard F, Bessard-Bacquaert S, et al. Selective use of fetal fibronectin detection after
cervical length measurement to predict spontaneous preterm delivery in women with preterm labor.
Am J Obstet Gynecol 2006; 194:138.
33. Audibert F, Fortin S, Delvin E, et al. Contingent use of fetal fibronectin testing and cervical length
measurement in women with preterm labour. J Obstet Gynaecol Can 2010; 32:307.
34. Foster C, Shennan AH. Fetal fibronectin as a biomarker of preterm labor: a review of the literature and
advances in its clinical use. Biomark Med 2014; 8:471.
35. Committee on Practice BulletinsObstetrics, The American College of Obstetricians and
Gynecologists. Practice bulletin no. 130: prediction and prevention of preterm birth. Obstet Gynecol
2012; 120:964.
36. Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org, McIntosh J,
Feltovich H, et al. The role of routine cervical length screening in selected high- and low-risk women
for preterm birth prevention. Am J Obstet Gynecol 2016; 215:B2.
37. Gomez R, Romero R, Medina L, et al. Cervicovaginal fibronectin improves the prediction of preterm
delivery based on sonographic cervical length in patients with preterm uterine contractions and intact
membranes. Am J Obstet Gynecol 2005; 192:350.
38. Hincz P, Wilczynski J, Kozarzewski M, Szaflik K. Two-step test: the combined use of fetal fibronectin
and sonographic examination of the uterine cervix for prediction of preterm delivery in symptomatic
patients. Acta Obstet Gynecol Scand 2002; 81:58.
39. Fox NS, Saltzman DH, Fishman A, et al. Gestational age at cervical length and fetal fibronectin
assessment and the incidence of spontaneous preterm birth in twins. J Ultrasound Med 2015; 34:977.
40. Melamed N, Hiersch L, Gabbay-Benziv R, et al. Predictive value of cervical length in women with twin
pregnancy presenting with threatened preterm labor. Ultrasound Obstet Gynecol 2015; 46:73.
41. American College of Obstetricians and Gynecologists Committee on Practice BulletinsObstetrics.
Practice Bulletin No. 171: Management of Preterm Labor. Obstet Gynecol 2016; 128:e155.
42. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 120: Use of
prophylactic antibiotics in labor and delivery. Obstet Gynecol 2011; 117:1472.
43. Hackney DN, Olson-Chen C, Thornburg LL. What do we know about the natural outcomes of preterm
labour? A systematic review and meta-analysis of women without tocolysis in preterm labour. Paediatr
Perinat Epidemiol 2013; 27:452.
44. Paules C, Pueyo V, Mart E, et al. Threatened preterm labor is a risk factor for impaired cognitive
development in early childhood. Am J Obstet Gynecol 2016.
45. Romero R, Erez O, Maymon E, Pacora P. Is an episode of suspected preterm labor that subsequently
leads to a term delivery benign? Am J Obstet Gynecol 2017; 157:89.
46. Campbell MK, Cartier S, Xie B, et al. Determinants of small for gestational age birth at term. Paediatr
Perinat Epidemiol 2012; 26:525.
47. Spong CY. Defining "term" pregnancy: recommendations from the Defining "Term" Pregnancy
Workgroup. JAMA 2013; 309:2445.
48. ACOG Committee Opinion No 579: Definition of term pregnancy. Obstet Gynecol 2013; 122:1139.
49. World Health Organization (WHO) fact sheet on preterm birth
http://www.who.int/mediacentre/factsheets/fs363/en/ (Accessed on April 22, 2015).
50. http://www.cdc.gov/mmwr/preview/mmwrhtml/su6203a22.htm (Accessed on June 18, 2015).
51. World Health Organization. Guidelines on optimal feeding of low birth-weight infants in low-and
middle-income countries. 2011.
52. WHO, March of Dimes, Partnership for Maternal, Newborn & Child Health, Save the Children. Born
too soon: the global action report on preterm birth.
www.who.int/maternal_child_adolescent/documents/born_too_soon/en/ (Accessed on May 04, 2012).
53. Blencowe H, Cousens S, Oestergaard MZ, et al. National, regional, and worldwide estimates of
preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic
analysis and implications. Lancet 2012; 379:2162.
54. Martin JA, Hamilton BE, Osterman MJ, et al. Births: final data for 2013. Natl Vital Stat Rep 2015; 64:1.
55. www.cdc.gov/nchs/vitalstats.htm (Accessed on April 19, 2012).
56. Lawn JE, Gravett MG, Nunes TM, et al. Global report on preterm birth and stillbirth (1 of 7): definitions,
description of the burden and opportunities to improve data. BMC Pregnancy Childbirth 2010; 10
Suppl 1:S1.
57. Delorme P, Goffinet F, Ancel PY, et al. Cause of Preterm Birth as a Prognostic Factor for Mortality.
Obstet Gynecol 2016; 127:40.
58. Mwaniki MK, Atieno M, Lawn JE, Newton CR. Long-term neurodevelopmental outcomes after
intrauterine and neonatal insults: a systematic review. Lancet 2012; 379:445.
59. Heida KY, Velthuis BK, Oudijk MA, et al. Cardiovascular disease risk in women with a history of
spontaneous preterm delivery: A systematic review and meta-analysis. Eur J Prev Cardiol 2016;
23:253.
60. Chang HH, Larson J, Blencowe H, et al. Preventing preterm births: analysis of trends and potential
reductions with interventions in 39 countries with very high human development index. Lancet 2013;
381:223.
61. Shapiro-Mendoza CK, Barfield WD, Henderson Z, et al. CDC Grand Rounds: Public Health Strategies
to Prevent Preterm Birth. MMWR Morb Mortal Wkly Rep 2016; 65:826.

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