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. 2009 Spring;2(2):107–115.

Management of Pregnancies With Cervical Shortening: A Very Short Cervix Is a Very Big Problem

Hee Joong Lee *, Tae Chul Park *, Errol R Norwitz †
PMCID: PMC2709324  PMID: 19609405

Abstract

Preterm birth (PTB), defined as birth before 37 weeks of gestation, is the leading cause of perinatal morbidity and mortality. PTB is a major cause of long-term health problems in neonates, including respiratory distress syndrome, chronic lung disease (bronchopulmonary dysplasia), infection, intraventricular hemorrhage, and severe neurologic deficit. In the absence of reliable clinical predictors of PTB, obstetric care providers should focus their attention on the 2 best and most widely accepted methods of identifying women at high risk of PTB in both nullipara and multipara: fetal fibronectin and cervical length measurements.

Key words: Preterm birth, Cervical length measurement, Cervicovaginal fetal fibronectin

Preterm birth (PTB), defined as birth before 37 weeks of gestation, complicates more than 12% of deliveries and is the leading cause of perinatal morbidity and mortality.1–5 Of all neonatal deaths, 75% to 95% occur as a result of preterm delivery.6 The prognosis for individual preterm infants depends primarily on gestational age at birth. Mortality rises from about 2% for infants born at or after 32 weeks to more than 90% for those born at 23 weeks.7 The risk of severe handicap in survivors is more than 60% for those born at 23 weeks and less than 5% by 32 weeks.8–10 PTB is also a major cause of long-term health problems in neonates, including respiratory distress syndrome, chronic lung disease (bronchopulmonary dysplasia), infection, intraventricular hemorrhage, and severe neurologic deficit.11,12 Unfortunately, despite intensive research efforts, we cannot effectively stop preterm labor and there has been no decrease in the overall incidence of PTB over the past 30 years.13–16

Can We Accurately Predict Preterm Delivery?

Clinical Features Are Not Reliable

A history of a prior spontaneous PTB is the best demographic predictor for a recurrent PTB, but it is not useful for nullipara. There are 4 major groups of tests that have been developed to identify women at high risk for PTB: home uterine activity monitoring (HUAM), risk factor scoring, cervical length measurements, and biochemical/endocrine markers. Unfortunately, measurement of the frequency of uterine contractions is not clinically useful for predicting PTB,17 and HUAM has been largely abandoned. A number of epidemiologic, demographic, and historic risk factors for PTB have been identified including, among others, multiple pregnancy, black race, reduced prepregnancy maternal body mass index (< 19.8 kg/m2), bacterial vaginosis, vaginal bleeding, smoking, and illicit drug use (cocaine).18,19 However, risk factor scoring has proven to be of limited benefit in identifying women at risk of PTB, and reliance on risk factor scoring alone will fail to identify more than 50% of women who deliver preterm.20 Most importantly, perhaps, premonitory symptoms and signs—including reported uterine contractions (regular or irregular), pelvic pressure, backache, increased vaginal discharge, or vaginal bleeding—that have traditionally been the cornerstone of clinical assessment for PTB—have been shown to be nonspecific and poorly predictive of a subsequent PTB.17,21

Direct digital examination of the cervix is subjective and may be misleading, especially in multipara. For this reason, serial digital examination of the cervix throughout pregnancy has not been shown to significantly improve pregnancy outcome.22 However, sonographic measurement of residual cervical length (CL) does appear to accurately identify women at risk for PTB.23 A number of biochemical/ endocrine markers have been studied as potential predictors of PTB.24 The most widely used and consistently supported of these markers is cervicovaginal fetal fibronectin (fFN).25,26 In the absence of reliable clinical predictors of PTB, obstetric care providers should be focusing their attention on the 2 best and most widely accepted methods of identifying women at high risk of PTB in both nullipara and multipara: fFN and CL measurements (Figure 1).

Figure 1.

Figure 1

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Risk of spontaneous preterm birth (SPTB) before 32 weeks of gestation according to various risk factors. BMI, body mass index; fFN, fetal fibronectin; RR, relative risk. Data from Goldenberg RL et al.19

fFN

Fetal fibronectin is a fetal glycoprotein found at the interface between the maternal decidua and fetal amniochorion. It serves as the glue that holds the fetal membranes down to the underlying uterine tissues. fFN is normally present in the cervicovaginal secretions of pregnant women before 20 weeks of gestation and again at term, but should be absent between 22 and 37 weeks.26,27 Elevated levels of fFN in the cervicovaginal discharge (defined as > 50 ng/mL) has been shown to be a reliable predictor of subsequent PTB in the setting of intact membranes, and likely represents premature separation of the fetal membranes from the underlying maternal decidua.27 It is approved by the US Food and Drug Administration (FDA) and recommended by The American College of Obstetricians and Gynecologists (ACOG) for this indication. Interestingly, markedly elevated levels of cervicovaginal fFN from 13 to 22 weeks of gestation have also been associated with an increased risk of spontaneous PTB,26,27 but the test is not FDA approved nor ACOG recommended at this gestational age. The detection of fFN in the cervicovaginal discharge at 22 to 24 weeks of gestation is associated with a delivery rate of only 13% by 28 weeks of gestation and 36% by 37 weeks.28 The major value of the fFN test lies in its high negative predictive value. At least 99% of symptomatic patients with a negative fFN will not deliver within 7 days.29

Cervical Length Measurements

The gold standard for the measurement of CL in pregnancy is transvaginal ultrasonography (TVS) using sterile technique, which has many advantages when compared with digital examination. TVS is objective, reproducible, and acceptable to patients.30 Cervical changes such as dilatation of the internal cervical os with funneling (beaking) of the membranes can be easily appreciated by TVS, but not by digital examination.31 Moreover, TVS appears to be safe and does not increase the risk of ascending infection even in patients with preterm premature rupture of membranes (PROM).32,33

A number of sonographic features of the cervix on TVS have been correlated with PTB, including funneling of the membranes and the presence of debris within the adjacent amniotic fluid,34 but the most consistent association is with the so-called residual CL, which refers to the measurement of closed cervix (canal length) between the internal os and external os. The CL measurement should be acquired in the sagittal view using TVS while the bladder is empty and without excessive pressure applied by the transvaginal probe. This measurement has an interobserver variation of 5% to 10%.35 It has been suggested that the process of cervical shortening begins with dilatation of the internal os leading to funneling and progressive shortening of the CL.36 Dr. Jay Iams has described the appearance of the cervix on TVS over time as a progression of the letters T, Y, V, and U (Trust Your Vaginal Ultrasound) representing the progressive increasing funneling and decreasing CL (Figure 2).37 Although some degree of cervical shortening may be explained by normal biologic variance, it is likely that most cases of cervical shortening result from pathologic processes such as inflammation, hemorrhage, premature uterine contraction, or uterine overdistension.19,38

Figure 2.

Figure 2

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Sonographic appearance of the cervix on transvaginal sonography with progressive effacement and shortening: Trust Your Vaginal Ultrasound. Reproduced with permission from Iams JD.37

In unselected or low-risk pregnancies, the CL does not change significantly between 20 and 30 weeks of gestation with a median CL of 35 mm (10th–90th percentile, 25 mm and 45 mm, respectively) at 22 weeks of gestation and 33.7 mm at 28 weeks.39 In women at high risk for spontaneous PTB, average CL measurements are 36.7 mm at 15 weeks, 35.7 mm at 20 weeks, and 33.8 mm at 25 weeks.40 After 28 weeks, however, even women who deliver at term begin to have cervical shortening.40 For these reasons, CL measurements prior to 16 weeks and after 32 weeks are of little use in predicting women at risk of PTB. Transvaginal CL measurements between 16 and 24 weeks of gestation, however, have been shown to be very useful for predicting PTB in high-risk pregnancies.41

Shortened CL is a risk factor for PTB in both low- and high-risk pregnancies. As discussed above, a strong inverse correlation exists between CL and PTB. The risk of spontaneous PTB increases as CL decreases. In low-risk pregnancies, women with a cervix that is shorter than 25 mm (10th percentile) at 24 weeks have a 6-fold increase in the risk of spontaneous PTB before 35 weeks of gestation compared with women with values above 40 mm (75th percentile).39 Only 2% of low-risk pregnancies at 22 to 24 weeks of gestation will have a CL shorter than 15 mm, but 60% of these women will deliver before 28 weeks of gestation and 90% will deliver before 32 weeks.42 In a prospective study of 705 high-risk women, the risk of spontaneous PTB before 35 weeks decreased by approximately 6% for each additional millimeter of CL (P = .001) and by approximately 5% for each additional week of pregnancy during which the CL was measured (P = .004).40 Although it is controversial, most authorities use a cutoff of shorter than 25 mm to define a short CL at 22 to 24 weeks of gestation in both low- and high-risk pregnancies.39,43 Routine measurement of CL to identify women at risk for spontaneous PTB is not currently recommended in otherwise low-risk pregnancies because of the low positive predictive value and absence of proven effective interventions.43–48 However, serial measurements of CL should be performed in high-risk women to better identify those pregnancies at risk for spontaneous PTB prior to 35 weeks of gestation (Table 1).39,43–48

Table 1.

Observational Studies Comparing Cervical Length Measured by Transvaginal Ultrasound With the Risk of Spontaneous Preterm Birth

Author (Year) Gestational Age at Evaluation (wk) No. Population Gestational Age End Point (wk) Preterm Birth Rate (%) Cervical Length Cutoff (mm) Sensitivity Specificity Positive Predictive Value
Tongsong et al (1995)44 28–30 730 Unselected <37 12.5 ≤30 0.31 0.87 0.26
Iams et al (1996)39 24 2915 Unselected <35 4.3 ≤25 0.37 0.92 0.18
Taipale and Hiilesmaa (1998)45 18–22 3695 Unselected <35 0.8 ≤31 0.19 0.91 0.018
Berghella et al (1997)46 14–22 96 High-risk <35 18 <25 0.59 0.85 0.45
Andrews et al (2000)47 15–20 53 High-risk <35 30 ≤22 0.86 1.0 1.0
Owen et al (2001)48 16–24 183 High-risk <35 26 <25 0.69 0.80 0.55
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Reprinted with permission from American Journal of Obstetrics and Gynecology, Vol. 188, Owen J et al, “Vaginal sonography and cervical incompetence,” pp. 586–596, Copyright 2003, with permission from Elsevier.43

CL Measurements Combined With fFN

Cervical length measurements and fFN measurements are independent risk factors for PTB. The risk of spontaneous PTB is higher if both tests are abnormal than if only 1 is abnormal. For example, in a prospective, observational study of 3076 asymptomatic high- and low-risk pregnancies, women with a positive fFN and a CL shorter than 25 mm had a 33.3% risk of spontaneous PTB prior to 30 weeks of gestation compared with a 6.2% risk if they had only 1 of these findings and a 1.3% risk if both markers were absent.38

Similarly, the risk of recurrent PTB in asymptomatic women with a prior spontaneous PTB is different depending on the fFN and CL measurements. In this setting, a positive fFN at 22 to 24 weeks of gestation is associated with a 2- to 4-fold increased risk of recurrent PTB prior to 35 weeks, and the recurrence risk increases exponentially with decreasing CL irrespective of the fFN.49 In this cohort, the tests were also additive. The recurrence risk in women with a positive fFN was 65% if the CL at 22 to 24 weeks of gestation was less than 25 mm, but only 25% if the CL was more than 35 mm. In women with a negative fFN, the recurrence risk was 25% if the CL was less than 25 mm and 7% if the CL was more than 35 mm (Figure 3).49

Figure 3.

Figure 3

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Risk of preterm birth (PTB) before 35 weeks of gestation in women with a history of a prior spontaneous PTB with or without cervicovaginal fetal fibronectin (fFN) and/or sonographic cervical length (CL) at 22 to 24 weeks of gestation. Data from Iams JD et al.49

Even in women with symptoms of preterm labor, PTB is highly unlikely if the CL is longer than 30 mm or if the fFN is negative.43 In such women, selective use of fFN after CL measurement is more specific than CL alone for predicting PTB (81% vs 63%, respectively).50 In light of these and other data showing conclusively that combined use of the CL measurement by TVS and cervicovaginal fFN is more effective for predicting PTB than any of these methods alone, 2-step testing should be performed in all women with symptoms of preterm labor to better identify those women at risk of PTB. To demonstrate the utility of such an approach, Hincz and colleagues51 performed sonographic measurement of CL in 82 women with symptoms of preterm labor. A CL of less than 20 mm was regarded as a positive (abnormal) result for the prediction of PTB and a CL of greater than 31 mm was interpreted as a negative (normal) test. Cervicovaginal fFN was performed only in patients with a CL of 21 to 31 mm. In this cohort, the 2-step approach had an overall sensitivity of 86%, specificity of 90%, positive predictive value of 63%, and negative predictive value of 97% for predicting delivery within 28 days.51

Treatments for Women With a Short Cervix

A number of interventions have been proposed in an attempt to prevent PTB in women at high risk.

Bed Rest, Tocolytics, and Cervical Cerclage

Bed rest and hydration are often recommended in an attempt to prevent PTB in women at high risk, but there is no consistent evidence that they are able to delay delivery.52 Similarly, tocolytic medications are often prescribed with a view to preventing PTB. Again, there are no reliable and consistent data to suggest that any tocolytic agent can delay delivery for longer than 24 to 48 hours.53 Although it is not unreasonable to use tocolytics in the acute setting to delay delivery for 24 to 48 hours to administer the first course of antenatal corticosteroids and to transfer the patient to a tertiary care center, if indicated, there is no place for routine administration of long-term maintenance tocolysis.54,55 If maintenance tocolysis is offered, it should be clear to the patient that it is being done to make her more comfortable, to minimize her anxiety, and to decrease phone calls and visits to hospital at 3:00 AM, but that it will not prevent PTB.

Cervical cerclage has been widely used as a surgical method to prevent recurrent midtrimester pregnancy loss in women at risk. Elective (prophylactic) cerclage placement at 13 to 15 weeks of gestation may benefit some women with proven cervical insufficiency. Although highly contentious, more recent data suggest that cervical cerclage may reduce the risk of PTB in that subgroup of asymptomatic singleton pregnancies with both cervical shortening on TVS and a history of a prior spontaneous PTB.56–61 Of note, the only randomized, controlled clinical trial on the use of cervical cerclage to prevent PTB in women with cervical shortening showed no benefit.61 Cervical cerclage placement does not appear to prevent PTB in women with multiple pregnancies.56,57

Progesterone

Progesterone supplementation (not treatment) is being increasingly accepted as an effective intervention to prevent PTB in select women, although it has not yet received FDA approval for this indication. Although not all studies have shown a benefit,62 there is increasing evidence to suggest that progesterone supplementation from 16 to 20 weeks of gestation through 34 to 36 weeks of gestation may prevent preterm birth in some women at high risk by virtue of a prior spontaneous PTB63,64 or cervical shortening.65

In a randomized clinical trial, weekly intramuscular injections of 17 alpha-hydroxyprogesterone caproate (17P) (250 mg) from 16 to 20 weeks of gestation through 36 weeks of gestation significantly reduced the risk of spontaneous PTB prior to 37 weeks by 33% in 459 women at high risk by virtue of a prior spontaneous PTB.63 This translated into a significant reduction in the rates of complications of prematurity, including necrotizing enterocolitis, intraventricular hemorrhage, and need for supplemental oxygen.63 In another randomized clinical trial, the daily use of progesterone (100 mg) by vaginal suppository between 24 and 34 weeks of gestation in a similar high-risk population of 142 women significantly reduced the frequency of preterm uterine contractions (by 56%) and the risk of spontaneous delivery before 37 weeks (by 51%).64 More recently, 413 low-risk women with asymptomatic cervical shortening (< 15 mm) at 20 to 24 weeks of gestation were randomized to vaginal progesterone (200 mg daily) or matching placebo from 24 weeks through 34 weeks of gestation. Those women randomized to progesterone had a significantly lower rate of spontaneous PTB prior to 34 weeks compared with those who received placebo (19.2% vs 34.4%, respectively; a reduction of 44.2%).65 The study was not adequately powered to demonstrate a significant reduction in perinatal mortality or neonatal morbidity.

Several recent studies have investigated the utility of progesterone supplementation to preterm PTB in twin pregnancies and found it to be ineffective.66–68 Whether this is due to inadequate dosing of progesterone in these studies as has been suggested by some investigators or whether it speaks to a different mechanism of PTB in twins as compared with singletons is not known.

To date, studies looking at the safety of 17P and vaginal progesterone have found no increase in the rate of congenital anomalies in infants exposed to these agents starting in the second trimester of pregnancy.63,64 However, the ideal progesterone formulation, the most appropriate route of administration, and the long-term safety of these medications still remain unclear. At this time, therefore, progesterone supplementation should be used only in women at high risk of a PTB by virtue of a prior spontaneous preterm delivery or cervical shortening.5 Until these outstanding issues have been resolved, progesterone supplementation should not be recommended to all pregnant women.

Indomethacin, Vaginal Pessary, Folic Acid, and Omega-3 Fatty Acids

A number of other management strategies have been recommended to prevent PTB, although the data in this regard are limited and additional clinical trials with larger numbers are needed. Indomethacin, for example, may confer some benefit in preventing PTB in some high-risk women. In a clinical trial, indomethacin treatment of asymptomatic women with cervical shortening in the second trimester who declined cervical cerclage significantly reduced the rate of spontaneous PTB before 24 weeks, although it did not change the overall rate of spontaneous PTB before 35 weeks.69 Insertion of a vaginal pessary may be effective in preventing spontaneous PTB in singleton pregnancies before 36 weeks and in twins before 32 weeks.70 Dietary manipulation has also been proposed as a way of preventing preterm birth in both low- and high-risk populations, including prepregnancy supplementation with folic acid71 and omega-3 fatty acid supplementation throughout pregnancy.72

A Management Algorithm for Women With Cervical Shortening

Existing data suggest that waiting for patients to present with symptoms of preterm labor (such as regular uterine contractions and pelvic pressure) is a highly inaccurate and unreliable method of identifying women at risk of PTB. Obstetric care providers should be focusing instead on objective tests to identify women at risk, including CL by TVS and cervicovaginal fFN. To assist in this initiative, we have included 2 clinical algorithms: one for symptomatic women (Figure 4) and the other for high-risk asymptomatic women such as women with a prior spontaneous PTB prior to 35 weeks or a multiple pregnancy (Figure 5).

Figure 4.

Figure 4

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Proposed clinical algorithm for the management of women with symptoms suggestive of preterm labor. CL, cervical length; fFN, fetal fibronectin.

Figure 5.

Figure 5

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Proposed clinical algorithm for the management of asymptomatic women at high risk for spontaneous preterm birth. *Progesterone administration by intramuscular injection of 17 alpha-hydroxyprogesterone caproate or vaginal suppository between 16 to 24 weeks of gestation and 34 to 36 weeks of gestation. †A positive fetal fibronectin (fFN) refers to fFN levels of ≥50 ng/mL in cervicovaginal secretions from 22.0 through 34.6 weeks of gestation. CL, cervical length.

Conclusions

Both CL measurements and cervicovaginal fFN are objective and reliable screening tests to identify women at risk of spontaneous PTB. Serial CL measurements on TVS from 16 weeks of gestation to 30 to 32 weeks of gestation with or without fFN testing from 22 through 35 weeks in women at high risk will help to individualize management, prevent unnecessary hospitalization and obstetric intervention, and improve perinatal outcome by optimizing the timing of antenatal steroid therapy and transfer to a tertiary care center. The combined use of CL and fFN is more effective than reliance on any single test alone. In addition to optimizing perinatal outcome in pregnancies destined to deliver preterm, recent data suggest that progesterone supplementation in women with cervical shortening may be able to significantly delay delivery and prevent PTB in some women.

Main Points.

  • Elevated levels of fetal fibronectin (fFN) in the cervicovaginal discharge have been shown to be a reliable predictor of subsequent preterm birth (PTB) in the setting of intact membranes.

  • The gold standard for the measurement of cervical length (CL) in pregnancy is transvaginal ultrasonography (TVS) using sterile technique; it is objective, reproducible, and acceptable to patients.

  • Cervical length measurements and fFN measurements are independent risk factors for PTB, and the risk of spontaneous PTB is higher if both fFN and CL tests are abnormal than if only 1 is abnormal.

  • Bed rest and hydration are often recommended in an attempt to prevent PTB in women at high risk, but there is no consistent evidence that they are able to delay delivery.

  • There is increasing evidence to suggest that progesterone supplementation from 16 to 20 weeks of gestation through 34 to 36 weeks of gestation may prevent preterm birth in some women at high risk due to prior spontaneous PTB or cervical shortening.

  • Obstetric care providers should focus on objective tests to identify women at risk of PTB, including CL by TVS and cervicovaginal fFN.

Footnotes

Dr. Norwitz is a member of the Speakers Bureau for Hologic, Inc.

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