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Preterm labor: Clinical findings, diagnostic evaluation, and initial treatment

Preterm labor: Clinical findings, diagnostic evaluation, and initial treatment
Author:
Charles J Lockwood, MD, MHCM
Section Editor:
Vincenzo Berghella, MD
Deputy Editor:
Vanessa A Barss, MD, FACOG
Literature review current through: Feb 2022. | This topic last updated: Oct 29, 2021.

INTRODUCTION — Identifying women with preterm contractions who will go on to 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 in true 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 of newborn care (if necessary). Just as important, accurate identification of women not actually in preterm labor avoids unnecessary and sometimes costly interventions in the approximately 50 percent of patients with suspected preterm labor who subsequently deliver at term without tocolytic therapy [1].

This topic will describe the clinical findings and diagnostic evaluation of women who present with signs and symptoms of preterm labor, and initial treatment of women in whom a diagnosis of preterm labor is made. Risk factors, prevention, and tocolytic therapy for preterm labor are discussed separately. (See "Preterm birth: Risk factors, interventions for risk reduction, and maternal prognosis" and "Inhibition of acute preterm labor".)

PATHOGENESIS OF PRETERM LABOR — The pathophysiology of preterm labor involves at least four primary pathogenic processes that result in a final common pathway ending in spontaneous preterm labor and delivery:

Premature activation of the maternal or fetal hypothalamic-pituitary-adrenal axis

Inflammation and infection

Decidual hemorrhage

Pathological uterine distention

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

CLINICAL FINDINGS — The clinical findings that define true labor (ie, regular contractions plus cervical change) are the same whether labor occurs preterm or at term. The following prodromal signs and symptoms may be present for several hours before diagnostic criteria for labor are met:

Menstrual-like cramping

Mild, irregular contractions

Low back ache

Pressure sensation in the vagina or pelvis

Vaginal discharge of mucus, which may be clear, pink, or slightly bloody (ie, mucus plug, bloody show)

Spotting, light bleeding

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 the contractions since an increase in the frequency 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 who meet 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. 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. A short or a dilated cervix may be the first clinical manifestation of impending preterm labor triggered by subclinical inflammation [3].

COMPONENTS OF THE DIAGNOSTIC EVALUATION — In most women, the diagnostic evaluation is performed on the labor unit or a labor triage unit. However, the clinician may elect to evaluate women with very mild, nonspecific symptoms in the office.

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

Review of the patient's past and present obstetric and medical history, including risk factors for preterm birth (table 1). A standardized interview to screen for misuse of substances is part of this review; some examples are shown in the table (table 2). (See "Substance use during pregnancy: Screening and prenatal care", section on 'Screening for substance use'.)

Although many cases appear to be idiopathic, clinicians should consider possible causes of the preterm contractions based on the history and physical examination.

Preterm labor may be triggered by an underlying obstetric complication (eg, abruption) or medical/surgical disorder (eg, appendicitis, bowel obstruction or strangulation, pyelonephritis, acute cholecystitis, pneumonia [4]) that requires specific intervention. These cases may present with additional symptoms and/or symptoms atypical for preterm labor. Sometimes, this requires a high index of suspicion since laboring women have abdominal pain and may have back pain, nausea, vomiting, or diarrhea.

Assessment of gestational age, based on the best estimate from the first ultrasound examination [5]. If prior ultrasound estimation of gestational age is not available, an ultrasound examination for fetal biometry to assist in estimation of gestational age should be performed. (See "Prenatal assessment of gestational age, date of delivery, and fetal weight".)

Evaluation of signs and symptoms of preterm labor. (See 'Clinical findings' above.)

Maternal vital signs (temperature, blood pressure, heart rate, respiratory rate).

Review of the fetal heart rate pattern. (See "Intrapartum fetal heart rate monitoring: Overview".)

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 performed on vaginal specimens). 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 placentae or placenta previa can trigger preterm labor. (See "Placental abruption: Pathophysiology, clinical features, diagnosis, and consequences" and "Placenta previa: Epidemiology, clinical features, diagnosis, morbidity and mortality".)

Evaluate fetal membrane status (intact or ruptured) by standard methods. Preterm prelabor rupture of membranes (PPROM) often precedes or occurs during preterm labor. Diagnosis and management of PPROM are reviewed separately. (See "Preterm prelabor rupture of membranes: Clinical manifestations and diagnosis".)

Use a swab to obtain a cervicovaginal fluid specimen in case fetal fibronectin (fFN) testing is desired after transabdominal ultrasound examination. The swab is rotated in the posterior fornix for 10 seconds.

"Blind" sampling without a speculum is also acceptable. 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 [6]. 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 [7]. 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.)

Digital cervical examination — In most patients, cervical dilation and effacement are assessed by digital examination 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 before speculum examination 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 in the presence of uterine contractions at 20+0 to 36+6 weeks supports the diagnosis of preterm labor; 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 (TVUS) assessment of the cervix can help distinguish between the two entities when the diagnosis is uncertain. (See "Cervical insufficiency", section on 'Physical examination-based cervical insufficiency' and "Transvaginal cervical cerclage", section on 'Replace prolapsed membranes, if present'.)

Transvaginal ultrasound examination — TVUS measurement of cervical length is useful for supporting or excluding the diagnosis of preterm labor when the diagnosis is unclear. A short cervix before 34 weeks of gestation (<30 mm) is predictive of an increased risk for preterm birth in all populations, while a long cervix (≥30 mm) has a high negative predictive value for preterm birth. Knowledge of cervical length in women with threatened preterm labor may improve outcome, particularly avoidance of unnecessary hospitalization and interventions when the cervix is long, but data are limited [8].

The procedure for measurement of cervical length is described separately. (See "Short cervix before 24 weeks: Screening and management in singleton pregnancies".)

Obstetric ultrasound examination — Obstetric ultrasound examination provides other useful information, including presence/absence of fetal, placental, and maternal anatomic abnormalities; confirmation of fetal presentation; assessment of amniotic fluid volume; and estimated fetal weight. This information may be used for counseling the patient about the potential causes and outcomes of preterm birth and determining the best route of delivery.

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 "Early-onset neonatal group B streptococcal disease: Prevention", section on 'Special populations'.)

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".)

fFN in women <34 weeks of gestation with cervical dilation <3 cm and cervical length 20 to 30 mm on TVUS examination. (See 'Cervical length 20 to <30 mm' below.)

Testing for sexually transmitted infections (eg, chlamydia, gonorrhea) depends on the patient’s risk factors for these infections and, if indicated, whether antepartum testing was recently performed. (See "Prenatal care: Second and third trimesters", section on 'Screen for sexually transmitted infections'.)

Fetal fibronectin for selected patients — 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 [9].

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 and sometimes costly intervention for the approximately 50 percent of patients who will subsequently deliver at term without tocolytic therapy [1].

However, fFN results alone are not useful [10,11]. In a systematic review of six randomized trials in which a total of 546 women with threatened preterm labor were randomly assigned to management with reported or concealed fFN results, clinician knowledge of fFN results did not reduce rates of maternal hospitalization (risk ratio [RR] 1.06, 95% CI 0.79-1.43) or preterm birth <34 weeks (RR 1.09, 95% CI 0.54-2.18) [12]. Use of tocolytics and betamethasone, gestational age at delivery, rate of respiratory distress syndrome, and number of days in a neonatal intensive care unit were similar for both groups. Costs were increased in the reported group [10]. It is possible that physicians place greater significance on positive test results than on negative results, resulting in an overall increase in health care utilization [13].

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 22+0 and 34+6 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 systematic review of five randomized trials and 15 diagnostic test accuracy studies evaluating cervicovaginal fFN for predicting preterm birth reported the following pooled estimates [14]:

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 posttest probabilities were 25.9 and 2.4 percent, respectively [15].

False-positive results can occur due to ejaculate from coitus within the previous 24 hours, a grossly bloody specimen, or digital cervical examination [16-18]. Theoretically, TVUS 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 [19]. Administration of intravaginal substances, such as lubricants, medications, or douching may interfere with the assay [20].

Quantitative fFN — Quantitative measurement of fFN appears to improve predictive value compared with use of the qualitative test using a 50 ng/mL threshold [21-23]. 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 [21]. 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 in symptomatic women increases predictive value [24]. An algorithm combining quantitative fFN and cervical length, demographic information, and obstetric history (previous spontaneous preterm birth/preterm prelabor rupture of membranes or suspected preterm labor) has been incorporated into an App (QUiPP) for prediction of spontaneous preterm birth in Europe [25-27].

Other laboratory tests — Like fFN, placental alpha-microglobulin-1 (PAMG-1) [28-30] or phosphorylated insulin-like growth factor binding protein-1 (pIGFBP-1) [31] 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.

In the largest study, which included 796 women with signs and symptoms of preterm labor, the sensitivities of PAMG-1 and fFN for spontaneous preterm birth within seven days were 50 percent (3/6) and 67 percent (4/6), respectively, and specificities were 98.4 percent (619/629) and 85.7 percent (539/629), respectively [30]. In a prospective study that compared PAMG-1 with pIGFBP-1 in women in preterm labor with intact membranes, dilation ≤3 cm, and cervical length 15 to 30 mm, both tests had similar sensitivity (75 to 85 percent) for delivery within seven days, but PAMG-1 was more specific (95 versus 77 percent) [32].

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 [33]. Because the clinical findings of early labor are poorly predictive of the diagnosis, over-diagnosis is common until labor is well established.

We use the following specific criteria: Uterine contractions (≥4 every 20 minutes or ≥8 in 60 minutes) plus

Cervical dilation ≥3 cm or

Cervical length <20 mm on transvaginal ultrasound or

Cervical length 20 to <30 mm on transvaginal ultrasound and positive fetal fibronectin

The contraction criteria are those used for selecting subjects in research settings. Before the use of ultrasound for measuring cervical length, research studies also required documented cervical change or cervical effacement ≥80 percent or cervical dilation >2 cm. These criteria were chosen because women who did not meet them were often ultimately diagnosed with false labor and went on to have a late preterm or term delivery [34].

APPROACH TO TRIAGE: SINGLETON GESTATIONS

≥34 weeks of gestation — Women in preterm labor at ≥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 obstetric complications associated with preterm labor, such as abruptio placentae, 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)".)

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, benefits, and controversies regarding steroid use after 34 weeks are discussed in detail separately. (See "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery", section on '34+0 or more weeks'.)

<34 weeks of gestation — In women <34 weeks with uterine contractions, cervical dilation ≥3 cm supports the diagnosis of preterm labor. We initiate treatment of preterm labor in these women to reduce the morbidity and mortality of preterm birth. Further diagnostic evaluation with sonographic measurement of cervical length or laboratory assessment of fetal fibronectin (fFN) is not performed because these tests do not enhance diagnostic accuracy in this setting. (See 'Initial treatment of women with preterm labor <34 weeks' below.)

The diagnosis of preterm labor is less clear in women with contractions, cervical dilation <3 cm, and intact membranes. Our approach to diagnosis and treatment in these cases is shown in the algorithm and discussed below (algorithm 1). The use of cervical length measurement, with fFN in selected cases, is based upon clinical experience and accumulating data on risk of preterm birth according to cervical length on transvaginal ultrasound, in the absence of abruption [2,33,35-39].

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 [40]. Since the test is expensive, reducing the number of women tested by one-third is advantageous [41-43].

If the fFN test is positive, we begin interventions to reduce morbidity associated with preterm birth (see 'Initial treatment of women with preterm labor <34 weeks' 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 [44]) [14].

Use of sonographic cervical length and fFN determinations to differentiate true labor from false labor in preterm symptomatic women is supported by the Society for Maternal-Fetal Medicine [45], 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 [40-42,46,47]. 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 'Initial treatment of women with preterm labor <34 weeks' below.)

Cervical length ≥30 mm — Approximately 50 percent of women with symptoms of preterm labor have a transvaginal ultrasound cervical length ≥30 mm [36]. 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 [40,41,46,47]. 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 obstetric 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)".)

APPROACH TO TRIAGE: TWIN GESTATIONS — 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 [48,49].

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

<34 weeks of gestation — For women with twin pregnancies <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 (fFN) does not enhance diagnostic accuracy. Treatment of preterm labor is initiated. (See 'Initial treatment of women with preterm labor <34 weeks' 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 cervical change on digital examination after a four- to six-hour period of observation are at low risk for preterm delivery, and can be discharged home, 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; therefore, we begin interventions to reduce morbidity associated with preterm birth. (See 'Initial treatment of women with preterm labor <34 weeks' below.)

Women with cervical length 25 to 35 mm on transvaginal ultrasound examination undergo fFN testing. If the test is positive, we begin interventions to reduce morbidity associated with preterm birth (see 'Initial treatment of women with preterm labor <34 weeks' below). If the test is negative, we discharge the patient after a 6- to 12-hour period of observation.

INITIAL TREATMENT OF WOMEN WITH PRETERM LABOR <34 WEEKS — 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 [50]:

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 14 days previously [50] and at ≤28 weeks of gestation [51]. (See "Antenatal corticosteroid therapy for reduction of neonatal respiratory 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 pregnancy after resolution of an episode of acute idiopathic preterm labor".)

Antibiotics for GBS chemoprophylaxis. (See "Early-onset neonatal group B streptococcal disease: Prevention", section on 'Special populations'.)

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 [52]. (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 labor and birth", section on 'Threatened or established 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, approximately 50 percent of women diagnosed with preterm labor deliver at term [53]. (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 [54-58].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Preterm labor and birth".)

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

General principles

Early signs and symptoms of both preterm and term labor are nonspecific 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.)

Singleton pregnancies

We use the following specific criteria for diagnosis of preterm labor: Uterine contractions (≥4 every 20 minutes or ≥8 in 60 minutes) and

-Cervical dilation ≥3 cm or

-Cervical length <20 mm on transvaginal ultrasound or

-Cervical length 20 to <30 mm on transvaginal ultrasound and positive fetal fibronectin (fFN)

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 '≥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 obstetric complications associated with preterm labor, such as placental abruption, chorioamnionitis, and preterm prelabor rupture of membranes, have been excluded. Women in preterm labor are admitted for delivery. (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 'Initial treatment of women with preterm labor <34 weeks' above.)

For pregnancies <34 weeks of gestation and cervical dilation <3 cm, transvaginal ultrasound measurement of cervical length and laboratory analysis of cervicovaginal fFN level help to support or exclude the diagnosis of preterm labor, as described in the algorithm (algorithm 1). For women diagnosed in preterm labor, 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 '<34 weeks of gestation' above.)

Twin pregnancies

The diagnosis of preterm labor in twin pregnancies is based on the same uterine contraction criteria as for singleton pregnancies, and management of preterm labor in twin gestations ≥34 weeks of gestation or <34 weeks with cervical dilation ≥3 cm is also similar to that for singletons, but cervical length criteria for triage of twin pregnancies <34 weeks with cervical dilation <3 cm is different. (See 'Approach to triage: Twin gestations' above.)

For twin pregnancies <34 weeks and cervical dilation <3 cm, transvaginal ultrasound measurement of cervical length and laboratory analysis of cervicovaginal fFN level help to support or exclude the diagnosis of preterm labor:

-Cervical length >35 mm and no cervical change on digital examination after a four- to six-hour period of observation – Low risk for preterm delivery: discharge.

-Cervical length <25 mm – High risk of preterm delivery: initiate interventions to reduce morbidity associated with preterm birth.

-Cervical length 25 to 35 mm – fFN testing. If positive, initiate interventions to reduce morbidity associated with preterm birth. If negative, discharge after a 6- to 12-hour period of observation.

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. Maccato ML, Pinell P, Martens MG, Faro S. Preterm labor and maternal hypoxia in patients with community-acquired pneumonia. Infect Dis Obstet Gynecol 1996; 4:221.
  5. Committee on Practice Bulletins—Obstetrics and the American Institute of Ultrasound in Medicine. Practice Bulletin No. 175: Ultrasound in Pregnancy. Obstet Gynecol 2016; 128:e241.
  6. 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.
  7. Roman AS, Koklanaris N, Paidas MJ, et al. "Blind" vaginal fetal fibronectin as a predictor of spontaneous preterm delivery. Obstet Gynecol 2005; 105:285.
  8. Berghella V, Palacio M, Ness A, et al. Cervical length screening for prevention of preterm birth in singleton pregnancy with threatened preterm labor: systematic review and meta-analysis of randomized controlled trials using individual patient-level data. Ultrasound Obstet Gynecol 2017; 49:322.
  9. Feinberg RF, Kliman HJ, Lockwood CJ. Is oncofetal fibronectin a trophoblast glue for human implantation? Am J Pathol 1991; 138:537.
  10. 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.
  11. Chuck AW, Thanh NX, Chari RS, et al. Post-Policy Implementation Review of Rapid Fetal Fibronectin (fFN) Testing for Preterm Labour in Alberta. J Obstet Gynaecol Can 2016; 38:659.
  12. Berghella V, Saccone G. Fetal fibronectin testing for reducing the risk of preterm birth. Cochrane Database Syst Rev 2019; 7:CD006843.
  13. Chiossi G, Saade GR, Sibai B, Berghella V. Using Cervical Length Measurement for Lower Spontaneous Preterm Birth Rates Among Women With Threatened Preterm Labor. Obstet Gynecol 2018; 132:102.
  14. 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.
  15. 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.
  16. McKenna DS, Chung K, Iams JD. Effect of digital cervical examination on the expression of fetal fibronectin. J Reprod Med 1999; 44:796.
  17. 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.
  18. 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.
  19. 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.
  20. http://www.ffntest.com/pdfs/rapid_ffn_product_insert_lettersize.pdf (Accessed on May 04, 2015).
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. 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.
  26. www.QUiPP.org.
  27. Watson HA, Carter J, Seed PT, et al. The QUiPP App: a safe alternative to a treat-all strategy for threatened preterm labor. Ultrasound Obstet Gynecol 2017; 50:342.
  28. Ehsanipoor RM, Swank ML, Jwa SC, et al. Placental α-Microglobulin-1 in Vaginal Secretions of Women with Evidence of Preterm Labor. Am J Perinatol 2016; 33:208.
  29. 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.
  30. Wing DA, Haeri S, Silber AC, et al. Placental Alpha Microglobulin-1 Compared With Fetal Fibronectin to Predict Preterm Delivery in Symptomatic Women. Obstet Gynecol 2017; 130:1183.
  31. 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.
  32. Nikolova T, Uotila J, Nikolova N, et al. Prediction of spontaneous preterm delivery in women presenting with premature labor: a comparison of placenta alpha microglobulin-1, phosphorylated insulin-like growth factor binding protein-1, and cervical length. Am J Obstet Gynecol 2018; 219:610.e1.
  33. Iams JD. Prediction and early detection of preterm labor. Obstet Gynecol 2003; 101:402.
  34. Chao TT, Bloom SL, Mitchell JS, et al. The diagnosis and natural history of false preterm labor. Obstet Gynecol 2011; 118:1301.
  35. 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.
  36. 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.
  37. 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.
  38. Tsoi E, Akmal S, Rane S, et al. Ultrasound assessment of cervical length in threatened preterm labor. Ultrasound Obstet Gynecol 2003; 21:552.
  39. Melamed N, Hiersch L, Domniz N, et al. Predictive value of cervical length in women with threatened preterm labor. Obstet Gynecol 2013; 122:1279.
  40. 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.
  41. 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.
  42. 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.
  43. van Baaren GJ, Vis JY, Wilms FF, et al. Cost-effectiveness of diagnostic testing strategies including cervical-length measurement and fibronectin testing in women with symptoms of preterm labor. Ultrasound Obstet Gynecol 2018; 51:596.
  44. 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.
  45. Society for Maternal-Fetal Medicine (SMFM). Electronic address: [email protected], 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.
  46. 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.
  47. 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.
  48. 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.
  49. 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.
  50. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics. Practice Bulletin No. 171: Management of Preterm Labor. Obstet Gynecol 2016; 128:e155.
  51. Zephyrin LC, Hong KN, Wapner RJ, et al. Gestational age-specific risks vs benefits of multicourse antenatal corticosteroids for preterm labor. Am J Obstet Gynecol 2013; 209:330.e1.
  52. Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 199: Use of Prophylactic Antibiotics in Labor and Delivery. Obstet Gynecol 2018; 132:e103.
  53. 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.
  54. Paules C, Pueyo V, Martí E, et al. Threatened preterm labor is a risk factor for impaired cognitive development in early childhood. Am J Obstet Gynecol 2017; 216:157.e1.
  55. 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; 216:89.
  56. Campbell MK, Cartier S, Xie B, et al. Determinants of small for gestational age birth at term. Paediatr Perinat Epidemiol 2012; 26:525.
  57. Espinoza J, Kusanovic JP, Kim CJ, et al. An episode of preterm labor is a risk factor for the birth of a small-for-gestational-age neonate. Am J Obstet Gynecol 2007; 196:574.e1.
  58. Zoabi L, Weintraub AY, Novak L, et al. Do patients who deliver at term after being hospitalized for preterm contractions have an increased risk for obstetrical complications? Arch Gynecol Obstet 2013; 288:537.
Topic 6798 Version 85.0

References

1 : Tocolytic therapy: a meta-analysis and decision analysis.

2 : Transvaginal cervical length measurement for prediction of preterm birth in women with threatened preterm labor: a meta-analysis.

3 : The rate of cervical change and the phenotype of spontaneous preterm birth.

4 : Preterm labor and maternal hypoxia in patients with community-acquired pneumonia.

5 : Practice Bulletin No. 175: Ultrasound in Pregnancy.

6 : A comparison of speculum and nonspeculum collection of cervicovaginal specimens for fetal fibronectin testing.

7 : "Blind" vaginal fetal fibronectin as a predictor of spontaneous preterm delivery.

8 : Cervical length screening for prevention of preterm birth in singleton pregnancy with threatened preterm labor: systematic review and meta-analysis of randomized controlled trials using individual patient-level data.

9 : Is oncofetal fibronectin a trophoblast glue for human implantation?

10 : Fetal fibronectin testing for prevention of preterm birth in singleton pregnancies with threatened preterm labor: a systematic review and metaanalysis of randomized controlled trials.

11 : Post-Policy Implementation Review of Rapid Fetal Fibronectin (fFN) Testing for Preterm Labour in Alberta.

12 : Fetal fibronectin testing for reducing the risk of preterm birth.

13 : Using Cervical Length Measurement for Lower Spontaneous Preterm Birth Rates Among Women With Threatened Preterm Labor.

14 : Rapid fetal fibronectin testing to predict preterm birth in women with symptoms of premature labour: a systematic review and cost analysis.

15 : Fetal fibronectin as a short-term predictor of preterm birth in symptomatic patients: a meta-analysis.

16 : Effect of digital cervical examination on the expression of fetal fibronectin.

17 : Prediction of spontaneous preterm birth using quantitative fetal fibronectin after recent sexual intercourse.

18 : Cervical fluid oncofetal fibronectin as a predictor of early ectopic pregnancy. Is it affected by blood contamination?

19 : Vaginal fetal fibronectin evaluation before and immediately after ultrasonographic vaginal cervical length measurements in symptomatic women at risk of preterm birth: a pilot study.

20 : Vaginal fetal fibronectin evaluation before and immediately after ultrasonographic vaginal cervical length measurements in symptomatic women at risk of preterm birth: a pilot study.

21 : Evaluation of a quantitative fetal fibronectin test for spontaneous preterm birth in symptomatic women.

22 : Endocervical and high vaginal quantitative fetal fibronectin in predicting preterm birth.

23 : Development and validation of a tool incorporating quantitative fetal fibronectin to predict spontaneous preterm birth in symptomatic women.

24 : The predictive value of quantitative fibronectin testing in combination with cervical length measurement in symptomatic women.

25 : Development and validation of a tool incorporating cervical length and quantitative fetal fibronectin to predict spontaneous preterm birth in asymptomatic high-risk women.

26 : Development and validation of a tool incorporating cervical length and quantitative fetal fibronectin to predict spontaneous preterm birth in asymptomatic high-risk women.

27 : The QUiPP App: a safe alternative to a treat-all strategy for threatened preterm labor.

28 : Placentalα-Microglobulin-1 in Vaginal Secretions of Women with Evidence of Preterm Labor.

29 : 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.

30 : Placental Alpha Microglobulin-1 Compared With Fetal Fibronectin to Predict Preterm Delivery in Symptomatic Women.

31 : 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.

32 : Prediction of spontaneous preterm delivery in women presenting with premature labor: a comparison of placenta alpha microglobulin-1, phosphorylated insulin-like growth factor binding protein-1, and cervical length.

33 : Prediction and early detection of preterm labor.

34 : The diagnosis and natural history of false preterm labor.

35 : Sonographic measurement of cervical length in threatened preterm labor in singleton pregnancies with intact membranes.

36 : Does knowledge of cervical length and fetal fibronectin affect management of women with threatened preterm labor? A randomized trial.

37 : Evaluation of threatened preterm delivery by transvaginal ultrasonographic measurement of cervical length.

38 : Ultrasound assessment of cervical length in threatened preterm labor.

39 : Predictive value of cervical length in women with threatened preterm labor.

40 : Predictive value of cervical length measurement and fibronectin testing in threatened preterm labor.

41 : Selective use of fetal fibronectin detection after cervical length measurement to predict spontaneous preterm delivery in women with preterm labor.

42 : Contingent use of fetal fibronectin testing and cervical length measurement in women with preterm labour.

43 : Cost-effectiveness of diagnostic testing strategies including cervical-length measurement and fibronectin testing in women with symptoms of preterm labor.

44 : Fetal fibronectin as a biomarker of preterm labor: a review of the literature and advances in its clinical use.

45 : The role of routine cervical length screening in selected high- and low-risk women for preterm birth prevention.

46 : Cervicovaginal fibronectin improves the prediction of preterm delivery based on sonographic cervical length in patients with preterm uterine contractions and intact membranes.

47 : Two-step test: the combined use of fetal fibronectin and sonographic examination of the uterine cervix for prediction of preterm delivery in symptomatic patients.

48 : Gestational age at cervical length and fetal fibronectin assessment and the incidence of spontaneous preterm birth in twins.

49 : Predictive value of cervical length in women with twin pregnancy presenting with threatened preterm labor.

50 : Practice Bulletin No. 171: Management of Preterm Labor.

51 : Gestational age-specific risks vs benefits of multicourse antenatal corticosteroids for preterm labor.

52 : ACOG Practice Bulletin No. 199: Use of Prophylactic Antibiotics in Labor and Delivery.

53 : What do we know about the natural outcomes of preterm labour? A systematic review and meta-analysis of women without tocolysis in preterm labour.

54 : Threatened preterm labor is a risk factor for impaired cognitive development in early childhood.

55 : Is an episode of suspected preterm labor that subsequently leads to a term delivery benign?

56 : Determinants of small for gestational age birth at term.

57 : An episode of preterm labor is a risk factor for the birth of a small-for-gestational-age neonate.

58 : Do patients who deliver at term after being hospitalized for preterm contractions have an increased risk for obstetrical complications?