Preterm birth is the leading cause of perinatal morbidity and mortality, accounting for 85% of neonatal deaths. One in eight babies was born preterm in 2005, and preterm birth accounts for over 500,000 newborns per year in the United States alone.53 Moreover, the complications of preterm birth can be devastating, as prematurity is the leading identifiable cause of neurologic handicap. The annual cost to the United States as a result of preterm birth is in excess of $26 billion.53
Currently, there are no accurate means of early diagnosis, prevention, or effective treatment of preterm birth. Many interventions have been proposed to reduce the rate of prematurity, without success. Uterine activity monitoring has been used to identify activation of the myometrium, fetal fibronectin to detect decidual-membrane activation, and cervical sonography to identify preterm cervical ripening. However, there is no evidence that the identification of maternal risk factors,54,55, and 56 the use of home uterine monitoring,57,58 or antibiotic administration to patients with a positive cervico/vaginal fetal fibronectin test can reduce the rate of prematurity.59 Similarly, pharmacologic inhibition of uterine contractility (tocolysis) has not reduced the rate of preterm birth or neonatal complications.
It is well established that a sonographic short cervix is a powerful predictor of spontaneous preterm birth.35,49,50,56,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75, and 76 Cervical sonography has been used most widely to assess the risk for spontaneous preterm birth in 3 groups: (1) asymptomatic patients, (2) patients at high risk for preterm delivery and/or mid-trimester loss, and (3) patients presenting with preterm labor.
Cervical Examination in Asymptomatic Patients
Cervical Length in the Prediction of Preterm Delivery in Asymptomatic Patients
Several studies have measured the cervical length of pregnant women using transabdominal, endovaginal, and transperineal ultrasound. In most cases, the cervical length is stable in the first 30 weeks of pregnancy both in nulliparous and in multiparous women who deliver at term, and a progressive, although not substantial, shortening of the cervix occurs in the third trimester of pregnancy.60,61,76,77 Median or mean cervical lengths in low-risk populations in the mid-trimester are shown in Table 28-1.
Table 28-1CERVICAL LENGTH (MEDIAN OR MEAN) IN LOW-RISK POPULATIONS IN THE MID-TRIMESTER ||Download (.pdf) Table 28-1 CERVICAL LENGTH (MEDIAN OR MEAN) IN LOW-RISK POPULATIONS IN THE MID-TRIMESTER
|Author ||Year ||N ||Cervical Length (mm) |
|Ayers et al.267 ||1988 ||150 ||52 |
|Podobnik et al.268 ||1988 ||80 ||48 |
|Andersen et al.76 ||1990 ||125 ||41 |
|Kushnir et al.60 ||1990 ||24 ||48 |
|Andersen35 ||1991 ||77 ||42 |
|Murakawa et al.125 ||1993 ||177 ||37 |
|Zorzoli et al.85 ||1994 ||154 ||42 |
|Iams et al.63 ||1995 ||106 ||37 |
|Iams et al.49 ||1996 ||2915 ||35 |
|Cook and Ellwood90 ||1996 ||41 ||41 |
|Tongsong et al.269 ||1997 ||175 ||42 |
|Heath et al.66 ||1998 ||1252 ||38 |
|Hassan et al.70 ||2000 ||6877 ||37.5 |
One of the earliest studies to evaluate the relationship between a sonographic short cervix and the risk of spontaneous preterm birth was conducted by Andersen et al76 in a cohort of 113 women in which patients were evaluated by transabdominal and transvaginal sonography, along with manual assessment of the cervix on one occasion before 30 weeks' gestation. The patient population, with an overall prematurity rate of 15%, was not separated into low-risk and high-risk categories. The authors reported that a cervical length of less than 39 mm is associated with a 25% risk of preterm delivery, while a long cervix (defined as a cervical length ≥39 mm) decreases the risk of preterm birth (6.7%).76 Furthermore, the risk of spontaneous preterm birth was inversely related to the cervical length. These findings have been confirmed by other investigators, both in low-risk49,50,56,60,61,63,64,66,67, and 68,70,71,73,75,76,77,78,79,80, and 81 and high-risk asymptomatic patients.45,65,69,72,74,82,83, and 84 Table 28-2 describes the details of some of the studies with adequate information to allow calculation of diagnostic indices and predictive values. Our review focuses on the highlights of some of the studies that have significantly contributed to the understanding of the value of cervical sonography in screening for patients at risk for spontaneous preterm birth.
Table 28-2DIAGNOSTIC INDICES OF SONOGRAPHIC CERVICAL LENGTH IN LOW-RISK, ASYMPTOMATIC PREGNANT WOMEN ACCORDING TO DIFFERENT CERVICAL LENGTH CUTOFFS ||Download (.pdf) Table 28-2 DIAGNOSTIC INDICES OF SONOGRAPHIC CERVICAL LENGTH IN LOW-RISK, ASYMPTOMATIC PREGNANT WOMEN ACCORDING TO DIFFERENT CERVICAL LENGTH CUTOFFS
|Author ||Year ||N ||Definition of PTD (wk) ||Prevalence of PTD (mm) ||Gestation (wk) ||Cutoff (%) ||Sensitivity (%) ||Specificity (%) ||PPV (%) ||NPV (%) |
|Andersen et al.76 ||1990 ||113 ||<30 ||<39 ||<37 ||15 ||76 ||59 ||25 ||93 |
|Tongsong et al.81 ||1995 ||730 ||28-30 ||≤35 ||<37 ||12 ||66 ||62 ||20 ||93 |
|Iams et al.49 ||1996 ||2915 ||24 ||<20 ||<35 ||4 ||23 ||97 ||26 ||97 |
|Taipale and Hiilesmaa67 ||1998 ||3694 ||18-22 ||≤25 ||<37 ||2 ||6 ||100 ||39 ||99 |
|Heath et al.151 ||1998 ||2702 ||23 ||≤15 ||≤32 ||1.5 ||58 ||99 ||52 ||99 |
|Hassan et al.70 ||2000 ||6877 ||14-24 ||≤15 ||≤32 ||3.6 ||8 ||99 ||47 ||97 |
The Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development (NICHD) conducted a prospective cohort study entitled the "Preterm Prediction Study." The value of clinical, demographic, microbiologic, biochemical, and sonographic parameters in the prediction of preterm birth were examined. Iams et al49 reported the cardinal observations of cervical sonography. A total of 2915 low-risk asymptomatic patients were examined at 24 weeks' gestation and at 28 weeks by transvaginal sonography to evaluate the cervix and calculate the risk of delivery prior to 35 weeks. The shorter the cervix, the greater the risk of spontaneous preterm birth (Figure 28-8). An exponential increase in the relative risk of delivering before 35 weeks was described (Figure 28-9). The diagnostic indices for different cutoff values of cervical length, funneling, and Bishop score are displayed in Table 28-3. This large study confirmed the results of Andersen et al76 indicating that a short cervix increases the risk for preterm delivery while a long cervix decreases such risk, and extended the observations by allowing discernment of the comparative value of cervical length with other predictors of preterm delivery (demographic, biochemical, microbiologic, and clinical).56
Table 28-3SENSITIVITY, SPECIFICITY, AND PREDICTIVE VALUE OF CERVICAL LENGTH, FUNNELING, AND BISHOP SCORE FOR PRETERM DELIVERY BEFORE 35 WEEKS OF GESTATION ||Download (.pdf) Table 28-3 SENSITIVITY, SPECIFICITY, AND PREDICTIVE VALUE OF CERVICAL LENGTH, FUNNELING, AND BISHOP SCORE FOR PRETERM DELIVERY BEFORE 35 WEEKS OF GESTATION
| ||Cervix at 24 wk ||Cervix at 28 wk |
|Variable ||≤ 20 mm ||≤25 mm ||≤30 mm ||Presence of Funnel ||Bishop Score ≥6 ||Bishop Score ≥4 ||≤20 mm ||≤25 mm ||≤30 mm ||Presence of Funnel ||Bishop Score ≥6 ||Bishop Score ≥4 |
|% Sensitivity ||23.0 ||37.3 ||54.0 ||25.4 ||7.9 ||27.6 ||31.3 ||49.4 ||69.9 ||32.5 ||15.8 ||42.5 |
|% Specificity ||97.0 ||92.2 ||76.3 ||94.5 ||99.4 ||90.9 ||94.7 ||86.8 ||68.5 ||91.6 ||97.9 ||82.5 |
|% Positive predictive value ||25.7 ||17.8 ||9.3 ||17.3 ||38.5 ||12.1 ||16.7 ||11.3 ||7.0 ||11.6 ||25.6 ||9.9 |
|% Negative predictive value ||96.5 ||97.0 ||97.4 ||96.6 ||96.0 ||96.5 ||97.6 ||98.0 ||98.5 ||97.6 ||96.3 ||96.9 |
Distribution of subjects among percentiles for cervical length measured by transvaginal ultrasonography at 24 weeks of gestation (solid line) and relative risk of spontaneous preterm delivery before 35 weeks of gestation according to percentiles for cervical length (bars). (From Iams JD, Goldenberg RL, Meis PJ, et al. N Engl J Med 1996;334(9): 567-72, with permission from the authors.)
Estimated probability of spontaneous preterm delivery before 35 weeks of gestation from the logistic-regression analysis (blue line) and observed frequency of spontaneous preterm delivery (red line) according to cervical length measured by transvaginal ultrasonography at 24 weeks. (From Iams JD, Goldenberg RL, Meis PJ, et al. N Engl J Med 1996;334(9):567-72, with permission from the authors.)
An important series of studies reported by Heath et al66 and conducted at King's College Hospital in London examined the value of cervical sonography in the screening of preterm birth. Cervical length was measured by transvaginal sonography in a low-risk population of 2567 patients with known outcome. (For the distribution of cervical length at 23 weeks of gestation, see Figure 28-10). Patients with a history of preterm birth, of Afro-Caribbean origin, of low maternal age (<20 years) and low body mass index had a shorter cervix than those without such risk factors. However, when logistic regression analysis was used to examine the contribution of all these parameters to the prediction of preterm birth (≤32 weeks), a short cervix was the only predictor of outcome.66 These findings suggest that clinical and demographic risk factors associated with preterm birth operate by inducing cervical ripening. In this study,66 a cervix of 15 mm or less at 23 weeks of gestation (1.7% of the population) identified 60% of patients who subsequently had a spontaneous preterm birth at less than 32 weeks and 80% of those who had a spontaneous preterm birth at ≤30 weeks.
Distribution of cervical length at 23 weeks of gestation in 1252 low-risk patients managed expectantly. (From Heath VC, Southall TR, Souka AP, Elisseou A, Nicolaides KH. Ultrasound Obstet Gynecol 1998;12(5):312-7, with permission from the authors.)
We conducted a retrospective cohort study70 of 6877 women with cervical sonography performed between 14 and 24 weeks. Examinations were conducted transabdominally and, in cases of cervical length less than 30 mm or suboptimal visualization, transvaginally. A cervical length of 15 mm or less had a positive predictive value of 48%, a negative predictive value of 97%, a sensitivity of 8%, and a specificity of 99.7% for spontaneous preterm delivery at 32 weeks or less. A history of preterm delivery and African American ethnic group were also associated with the occurrence of spontaneous preterm birth, although the odds ratios were considerably lower than that of a short cervix. The low sensitivity of a short cervix in this study is similar to that reported by Taipale and Hiilesmaa67 in a large study in Finland. The apparent discrepancy among studies could be explained by the different gestational age at which ultrasound examination was conducted. We have evidence that a cervical length obtained later in gestation is more predictive of preterm delivery than those performed earlier.70 The study of Heath et al66 includes exams conducted at 23 weeks, whereas the exams by Hassan et al70 and Taipale and Hiilesmaa67 were performed at earlier gestational ages (Figure 28-1149,66,70,76).
Risk for spontaneous delivery according to sonographic cervical length from 4 large populations. (From Iams JD, Goldenberg RL, Meis PJ, et al. N Engl J Med 1996;334(9):567-72; Heath VC, Southall TR, Souka AP, Elisseou A, Nicolaides KH. Ultrasound Obstet Gynecol 1998;12(5):312-7; Hassan SS, Romero R, Berry SM, et al. Am J Obstet Gynecol 2000;182(6):1458-67; and Andersen HF, Nugent CE, Wanty SD, Hayashi RH. Am J Obstet Gynecol 1990;163(3):859-67, with permission from the authors.)
In conclusion, several studies have confirmed and extended the observations of Andersen et al76 in asymptomatic patients at low risk for preterm delivery.49,50,56,60,61,64,66,67,68,69,70, and 71,73,75,76,79,80, and 81,85,86,87,88, and 89
A short cervix of 15 mm or less in asymptomatic patients at 23 weeks identifies a population at high risk for spontaneous preterm delivery. However, at least one-third of patients who deliver preterm (<32 weeks) will not have a short cervix in the mid-trimester, and therefore cervical length with ultrasound is not a screening tool but rather a method for risk assessment. The high positive predictive value of a short cervix (nearly 50% for spontaneous preterm birth <32 weeks) has justified trials of intervention (see below under cervical cerclage and progesterone to prevent preterm birth).
Longitudinal Study of Cervical Ultrasound in Asymptomatic Patients
Zorzoli et al85 evaluated changes in the cervical dimension of 154 pregnant women at a mean gestational age of 12, 16, 20, 25, and 31 weeks in a population with a prevalence of prematurity of 1.9% (defined as <35 weeks). They reported that cervical length did not change significantly (P = .06) with gestational age, whereas the anteroposterior diameter at mid-portion (cervical width) of the cervix shortened with advancing gestational age. Multiparous women had longer and thicker cervices than primigravidae or women with previous cesarean sections or first trimester abortions. Similarly, Cook and Ellwood90 studied 41 patients longitudinally from 18 to 30 weeks' gestation. The cervical length and cervical diameter were followed every 2 weeks. Cervical length and diameter were constant in both nulliparous (n = 21) and primiparous (n = 20) women throughout the studied period. The mean cervical length in primiparous women was longer than that in nulliparous women (44.4 ± 5.1 mm vs 40.6 ± 4.7 mm; P <.001).90
In contrast to the earlier studies, two more recent longitudinal studies in nulliparous and parous women reported a decrease in cervical length with advancing gestation.Bergelin et al91 studied 19 healthy nulliparous women every 2 weeks from 22 weeks until delivery at term. In all but 1 patient, cervical length decreased and cervical width increased with advancing gestation. Three patterns of change in cervical length were observed: (1) a continuous decrease in 53% (10 of 19), (2) an accelerated shortening rate after approximately 30 weeks in 26% (5 of 19), and (3) a sudden shortening after 36 weeks in 16% (3 of 19) of patients. A similar study was conducted in 21 parous women. Patients were examined every 2 weeks from 24 weeks until delivery. Cervical length was unchanged in 3 women, but decreased in 18. As in the study with nulliparous patients, 3 patterns of cervical change were noted: (1) steady, continuous rate of decrease (n = 12; median 1.1 mm/wk, range 0.6 to 2.4); (2) accelerated rate of decrease towards the end of pregnancy (n = 4; median 3.0 mm/wk, range 1.5 to 4.8); (3) sudden drop in cervical length at term (n = 2).
Conflicting results have also been reported regarding whether multiparous women have a longer cervix than nulliparous women. Nulliparous women had a significantly longer cervix when compared to multiparous women in two studies,49,77 and in another, cervical length was comparable between multiparous and nulliparous women at 17 to 32 weeks,92 but at 33 weeks the cervix was longer in parous women.
Cervical Length in Predicting Preterm Delivery in High-Risk Singleton Gestations
Cook and Ellwood93 conducted a prospective cohort study in 120 women considered to be at risk for preterm delivery. The patients at risk included patients with a history of recurrent first trimester abortions, second trimester loss, previous preterm delivery (<34 weeks), previous cervical surgery, and uterine anomaly. Initial cervical assessment was performed between 9 and 29 weeks' gestation. Further assessment varied from weekly to monthly according to cervical findings and obstetric history. The cervical parameters measured were cervical length and diameter, and internal os dilation. Twenty-four patients (20%) delivered before 34 weeks of gestation. Cervical length was the only factor found to be of value in the prediction of preterm delivery. A cervical length of 20 mm or less before 20 weeks was associated with delivery before 34 weeks in 95% of women.
Guzman et al65 enrolled 469 high-risk patients between 15 and 24 weeks of gestation. High risk was defined as the presence of a history of spontaneous preterm birth before 37 weeks' gestation, prior mid-trimester loss, more than 2 terminations of pregnancy, cone biopsy, uterine malformation, previous cerclage, and diethylstilbestrol exposure. Transvaginal cervical sonography and transfundal pressure were performed and the shortest cervical length, funnel width, funnel length, and cervical index were recorded serially. A cervical length of 25 mm or less had a sensitivity, specificity, positive predictive value, and negative predictive value of 76%, 68%, 20%, and 96%, respectively, to identify preterm birth at less than 34 weeks of gestation. Cervical length was the best parameter in the prediction of preterm birth in women with prior mid-trimester losses. The authors suggested that using a cervical length of 15 mm or less had a sensitivity, specificity, positive predictive value, and negative predictive value of 81%, 72%, 29%, and 96%, respectively, in predicting spontaneous preterm delivery at less than 34 weeks. Cervical length was better at predicting earlier forms of prematurity (at <28 and <30 weeks) than later forms (<32 and <34 weeks).
Owen et al72 performed an observational study including 183 patients who had a history of spontaneous preterm birth before 32 weeks of gestation. The patients were enrolled between 16 and 19 weeks of gestation and followed every 2 weeks until 24 weeks of gestation. Forty-eight (26%) women delivered before 35 weeks of gestation. A short cervix (<25 mm) at the first scan was associated with a relative risk of 3.3 (95% CI = 2.1 to 5.0) for spontaneous preterm birth (<35 weeks). The sensitivity, specificity, and positive predictive values were 19%, 98%, and 75%, respectively. After controlling for cervical length, neither funneling nor dynamic shortening were independent predictors of spontaneous preterm birth. However, using the shortest cervical length on serial evaluations, after any dynamic shortening, the relative risk of a cervical length of less than 25 mm increased to 4.5 (95% CI = 2.7 to 7.6) with a sensitivity, specificity, and positive predictive value of 69%, 80%, and 55%, respectively. Thus, a serial measurement at up to 24 weeks significantly improved the sensitivity but lowered the positive predictive value of the test.
Subsequently, 2 secondary analyses82,94 were performed of the study by Owen et al.72 The first investigation evaluated the effect of gestational age at delivery of a prior preterm birth upon the predictive value of a sonographic short cervix. Patients were divided into 2 groups according to gestational age at delivery of a prior preterm birth: (1) before 23 weeks and (2) 23 to 31 weeks. There was no difference in the cervical length between groups (initial or shortest over study period, median 38 mm vs 37 mm, P = .54, and 30 mm vs 30 mm, P = .97), and a short cervix (<25 mm) had a similar positive predictive value in both groups (80% vs 71%, P > .99) for delivery before 35 weeks.94 Owen et al further noted that patients diagnosed with a short cervix prior to 22 weeks were more likely to deliver prior to 26 weeks than later (26 to 34 weeks).82
Durnwald et al74 performed a retrospective analysis of 188 women with at least 1 prior spontaneous preterm birth who underwent transvaginal ultrasound at 22 to 24 6/7 weeks. The authors reported that in patients with a short cervix (<25 mm) there was no difference in the rates of preterm birth at less than 32 or less than 35 weeks, irrespective of the number of prior preterm births (rate of delivery <32 weeks: patients with 1 prior preterm birth = 12.5% vs 2 or more prior preterm births = 21.5%, P = .47).
Crane and Hutchens95 performed a systematic review of 14 studies that evaluated the use of sonographic cervical length to predict preterm birth in patients at high risk for preterm birth. Patients with singleton pregnancies with a prior history of spontaneous preterm birth, uterine anomalies, or prior cervical excision procedures were included from this review. The primary outcome was delivery at less than 35 weeks' gestation. Patients with a history of spontaneous preterm delivery and a cervical length of less than 25 mm at less than 20 weeks had a positive likelihood ratio (LR) of 11.30 (95% CI = 3.59 to 35.57) and at 20 to 24 weeks an LR of 2.86 (95% CI = 2.12 to 3.87), respectively for delivery at less than 35 weeks.
Recently, Szychowski et al96 conducted an analysis of pre-randomization data from a multicenter trial evaluating the efficacy of cervical cerclage in women with a short cervix. Transvaginal sonographic cervical length was measured in 1014 high-risk women at 16 to 22 6/7 weeks gestation. The risk of cervical shortening in women who had a history of the earliest prior preterm birth at less than 24 weeks was significantly higher when compared to those who had a prior preterm birth at 24 to 33 weeks (relative risk [RR] 1.8, P < .0001). In addition, the time to cervical length shortening was significantly shorter in the early prior preterm birth group (hazard ratio = 2.2, P < .0001).
A sonographic short cervix is also predictive of preterm birth in other high-risk populations such as patients with uterine anomalies83 or those with multiple prior induced abortions.84
However, the increased risk for preterm birth in patients with a short cervix is not confined to patients with an a priori high risk. In a study97 of 109 asymptomatic patients with a short cervix (≤15 mm) diagnosed using transvaginal ultrasound between 14 and 24 weeks' gestation, it was found that the risk of very early preterm delivery (<24 weeks and <28 weeks) is not significantly different between high-risk (n = 42) and low-risk patients (n = 67) and the impact of an a priori risk (history of preterm delivery, late spontaneous abortion, or a cervical surgery) for preterm delivery begins to be significant only for later preterm deliveries (at 32 weeks).
Short Cervix and the Risk of Preterm Premature Rupture of Membranes and Subsequent Preterm Delivery
The Maternal-Fetal Medicine Units Network examined the relationship between a short cervix and preterm birth caused by preterm prelabor rupture of membranes (PROM).98 A total of 2929 patients were evaluated in 10 centers between 23 and 24 weeks of gestation. The frequency of preterm birth at less than 37 weeks of gestation was 14.4%. Preterm PROM at less than 35 weeks' gestation and at less than 37 weeks' gestation occurred in 2% and 4.5% of the patients, respectively, and this accounted for 32.6% of all preterm deliveries (<37 weeks). A short cervix, previous preterm birth caused by preterm PROM, and positive fetal fibronectin test were strong predictors for preterm birth caused by preterm PROM at both less than 35 and 37 weeks' gestation. Multivariate analysis indicated that a short cervical length at 23 to 24 weeks' gestation was consistently associated with preterm PROM among both nulliparous and multiparous women [at <35 weeks—nulliparous, odds ratio (OR) 9.9 (95% CI = 3.3 to 25.9) vs multiparous, OR 4.2 (2.0 to 8.9); and at <37 weeks—nulliparous, OR 3.7 (1.8 to 7.7) vs multiparous, OR 2.5 (1.4 to 4.5)].
Odibo et al99 demonstrated the relationship between a short cervix and preterm PROM leading to preterm birth in a high-risk population. The authors studied 69 women at high risk for preterm birth (by obstetric history and transvaginal cervical length <25 mm) between 14 and 24 weeks of gestation. The incidence of preterm PROM was 39% (27 of 69). Cervical length of less than 10 mm had a sensitivity, specificity, and positive and negative predictive values of 33%, 90%, 69%, and 68%, respectively, in predicting preterm PROM at less than 35 weeks of gestation.99
Later, Kishida et al100 evaluated 72 singleton pregnancies between 20 and 33 weeks. The authors reported that the presence of an IL-6 concentration of 240 pg/mL or more in cervical secretions and a cervical length of 28 mm or less conferred a probability of 58.1% for the development of preterm PROM.100
Cervical Length in Twin Pregnancies
Twin gestations occur in 1% of all pregnancies, and they are at increased risk of preterm birth. Several studies have examined the value of endovaginal sonography for the prediction of preterm delivery in twin pregnancies, and reported an increased risk for preterm birth in twin pregnancies with a sonographic short cervix.101,102,103,104,105,106,107,108,109,110,111,112,113,114,115, and 116
The Preterm Prediction Study of the NICHD Network of Maternal-Fetal Medicine Units examined risk factors for preterm delivery in twin gestations. Goldenberg et al103 reported that a short cervix, defined as a length of 25 mm or less, was more common in twin than in singleton gestations at 24 and 28 weeks. Moreover, at 24 weeks a short cervix was the only factor predictive of preterm birth. At 28 weeks, a positive fetal fibronectin test was significantly associated with spontaneous preterm birth at less than 32 weeks.
Souka et al106 studied the sonographic cervical length at 23 weeks' gestation in 215 twin pregnancies. The sensitivity of a short cervix defined as a length of 25 mm or less in the prediction of spontaneous preterm delivery at 28, 30, 32, and 34 weeks was 100%, 80%, 47%, and 35%, respectively (Table 28-4). The rate of spontaneous delivery at or before 32 weeks increased exponentially with decreasing cervical length measured at 23 weeks. An interesting observation was that the risk of preterm delivery for patients with a cervical length of 25 mm or less in twin pregnancies was similar to the risk in singleton pregnancies with a cervical length of 15 mm or less (52%). This has been interpreted as indicating that the cervical length required in twin gestations to confer protection against preterm delivery is greater than that of singleton gestations.
Table 28-4RATE OF IATROGENIC AND SPONTANEOUS DELIVERY AT DIFFERENT GESTATIONS AND SENSITIVITY FOR SPONTANEOUS DELIVERY ACCORDING TO CERVICAL LENGTH IN TWIN PREGNANCIES ||Download (.pdf) Table 28-4 RATE OF IATROGENIC AND SPONTANEOUS DELIVERY AT DIFFERENT GESTATIONS AND SENSITIVITY FOR SPONTANEOUS DELIVERY ACCORDING TO CERVICAL LENGTH IN TWIN PREGNANCIES
| || || || ||Cervical Length |
|Gestation (wk) ||n ||Iatrogenic Delivery ||Spontaneous Delivery ||≤15 mm ||≤25 mm ||≤35 mm ||≤45 mm |
|≤28 ||10 ||2 (0.9%) ||8 (3.8%) ||4 (50%) ||8 (100%) ||8 (100%) ||8 (100%) |
|≤30 ||13 ||3 (1.4%) ||10 (4.7%) ||4 (40%) ||8 (80%) ||9 (90%) ||10 (100%) |
|≤32 ||25 ||8 (3.8%) ||17 (8.0%) ||4 (24%) ||8 (47%) ||12 (71%) ||16 (94%) |
|≤34 ||59 ||22 (10.4%) ||37 (17.5%) ||4 (11%) ||13 (35%) ||21 (57%) ||34 (92%) |
Guzman et al107 reported a prospective longitudinal study of 131 twin pregnancies between 15 and 28 weeks of gestation. A short cervix (≤20 mm), regardless of gestational age, predicted preterm delivery as well as funnel width, funnel length, percentage of funneling, and cervical index.
Yang et al108 studied 65 twin pregnancies between 18 and 26 weeks' gestation. Transvaginal or translabial cervical sonography was used to evaluate cervical length and the presence of a funnel. The prevalence of preterm delivery (<35 weeks' gestation) was 23% (15 of 65). A cervical length of 25 mm or less and 30 mm or less was associated with a sensitivity of 27% and 53%, respectively, in predicting preterm delivery. The positive predictive value was 67% and 62%, respectively, for each cutoff (RR = 4.6 [95% CI = 2.0 to 10.3] and RR = 3.6 [1.6 to 7.8], respectively).
A long cervix in twin gestations is reassuring. Imseis et al105 reported that 97% of twin gestations with a cervical length of 35 mm or more delivered after 34 weeks of gestation.
Skentou et al109 evaluated 464 twin pregnancies at 23 weeks' gestation. The median cervical length was similar to singletons (36 mm). However, a greater proportion of twin pregnancies had a cervical length of 25 mm or less (12.9%109) when compared to singletons (8.4%117). The same held true for patients with a cervical length of 15 mm or less (4.5% in twins109 vs 1.5% in singletons117). Forty percent of patients with a twin gestation who delivered prior to 33 weeks had a cervical length of 20 mm or less.109
A prospective multicenter study included 251 twin pregnancies at 22 weeks of gestation and 215 at 27 weeks of gestation; of the population that was included at 22 weeks of gestation, for spontaneous delivery before 32 and 35 weeks of gestation, the sensitivity of cervical length ≤30 mm was 40% and 27%, respectively; the specificity was 89% and 90%, respectively. For the population that was included at 27 weeks, a cervical length of 25 mm or less had a sensitivity of 100% and 54%, and a specificity of 84% and 87% for the prediction of spontaneous preterm delivery prior to 32 and 35 weeks, respectively.111
A reference range for cervical length in 144 twin pregnancies that delivered after 34 weeks was reported by Fujita et al.118 An arbitrary cervical length measurement obtained at 13 to 32 weeks was used in the analysis. The mean cervical length decreased 0.8 mm per week (95% CI = −1.02 to −0.49) from 47 mm at 13 weeks to 32 mm at 32 weeks.118 Furthermore, the cervical shortening of those twin pregnancies that deliver preterm is more rapid than those who delivered at 36 weeks or later.112
Sonographic cervical length is also predictive of preterm birth in twin gestations in acute preterm labor and can distinguish those who will deliver within 7 days from those who will not.113 In a study of 87 twin pregnancies presenting in preterm labor, 80% (4 of 5) of patients with a cervical length of 1 to 5 mm delivered within 7 days, in contrast to 0% (0 of 21) of patients with a cervical length of greater than 25 mm.113 A cutoff of 25 mm (≤25) has been proposed for the risk assessment of preterm birth in twin pregnancies.113,115
Robyr et al,114 in an observational study, examined the utility of preoperative sonographic cervical length in predicting preterm birth in 137 cases of twin-to-twin transfusion syndrome (TTTS) undergoing laser coagulation of placental anastomoses before 26 weeks' gestation. The risk of delivery prior to 34 weeks was 74% in patients with a cervical length less than 30 mm. In addition, logistic regression analysis identified cervical length less than 30 mm (OR 3.53 [1.55 to 8.03]) and multiparous (OR 2.27 [1.09 to 4.74]) as independent risk factors for preterm birth at less than 34 weeks.114
Sonographic Evaluation of Cervical Length in Triplet Pregnancies
One study examined the value of cervical ultrasound in 32 triplet gestations. Progressive shortening of the cervix occurred with advancing gestational age. Cervical length in patients who delivered before 33 weeks was significantly shorter at 20, 29, and 31 weeks than that of patients who delivered at or after 33 weeks.119
Guzman et al120 conducted a prospective cohort study including 51 triplet gestations evaluated longitudinally between 15 and 28 weeks of gestation. Cervical assessment included cervical length, funnel width and length, percentage of funneling, and cervical index at rest and with transfundal pressure. A cervical length of 25 mm or less between 15 and 20 weeks' gestation had both a specificity and positive predictive value of 100% and a sensitivity of 50% in predicting delivery at less than 28 weeks of gestation. The sensitivity, specificity, positive predictive value, and negative predictive value of a short cervical length measured between 21 and 24 weeks and between 25 and 28 weeks were 86%, 79%, 40%, 97%, and 100%, 57%, 18%, 100%, respectively. The authors suggested that a cervical length of 25 mm or less between 15 and 24 weeks' gestation and 20 mm or less between 25 and 28 weeks' gestation were at least as good as other ultrasonographic cervical parameters for the prediction of spontaneous preterm birth in triplet gestation.
To et al121 measured the cervical length at 23 weeks of gestation in 38 triplet pregnancies. The rate of spontaneous preterm birth at less than 33 weeks was 16% (6 of 38). The shorter the cervix (at 23 weeks), the higher the rate of preterm delivery. Cervical length of 25 mm or less was present in 16% (6 of 38) of the patients. The sensitivity and positive predictive value for this cutoff were both 50% (3 of 6). The corresponding figures for cervical length of 15 mm or less were 8%, 33%, and 67%, respectively.
Maymon et al122 evaluated 45 triplet pregnant women longitudinally from 26 weeks of gestation. The prevalence of preterm delivery was 50% (spontaneous and indicated). Cervical length at 26 weeks' gestation was found to be a risk factor for preterm delivery (<33 weeks). A cervical length of 25 mm or less had a sensitivity, specificity, and positive and negative predictive values of 94%, 45%, 91%, and 70%, respectively. This study also indicated that the later the examination, the higher the sensitivity and positive predictive value. Maslovitz et al123 reported a sensitivity of 75%, specificity of 90%, positive predictive value of 83%, and negative predictive value of 81% for a sonographic cervical length of less than 25 mm at 14 to 20 weeks for the prediction of preterm birth prior to 32 weeks among 36 triplet pregnancies.
Cervical Examination in Patients Presenting with Preterm Labor
A meta-analysis of controlled trials in which patients with preterm labor were treated with either a placebo or β-adrenergic agents indicated that 47% of women treated with placebo deliver at term.124 This has been interpreted as indicating that many patients are falsely diagnosed to have preterm labor. Assessment of the likelihood of preterm delivery is of interest because it may influence important clinical decisions such as administration of tocolysis and steroids, as well as transfer to a tertiary care center and/or discharge from the hospital.
Importantly, Iams et al62 conducted a study of 60 singleton and twin pregnant women presenting with preterm labor. All patients with a cervix longer than 30 mm delivered at term. There is now compelling evidence that sonographic examination of the cervix in patients presenting with preterm labor can assist in the risk assessment for preterm delivery. The high negative predictive value for preterm birth associated with a long cervix has important clinical implications in symptomatic patients.62,113,125,126,127,128,129,130,131,132,133,134,135,136,137,138, and 139 Therefore, a sonographic short cervix is a powerful predictor of preterm birth in women in preterm labor. Gomez et al140 reported the use of sonographic of cervical length and fetal fibronectin test to predict spontaneous preterm delivery within 48 hours, 7 days, and 14 days of admission as well as delivery at 32 weeks or less and 35 weeks or less. A cervical length of less than 15 mm was the most powerful predictor of preterm birth within 48 hours (OR 9.7, P < .05). Both cervical length and fetal fibronectin were predictive of preterm birth within 7 and 14 days. When fetal fibronectin test results were added to those of a cervical length cutoff of less than 30 mm, there was significant improvement in the prediction of preterm delivery.140 Tsoi et al135 reported no significant contribution to preterm birth prediction by the use of fetal fibronectin, ethnicity, gestational age, body mass index, prior preterm birth, maternal age, parity smoking, or use of tocolytics. Similarly, in a study of 62 pregnant women presenting in preterm labor, only plasma proMMP-9 and cervical length (cutoff 15 mm) were significant predictors of preterm delivery within 7 days.134
Table 28-5 summarizes the results of some of the studies published to date that evaluated the use of sonographic cervical length in patients presenting in preterm labor. Although the studies have utilized different cervical length cutoffs, chosen based upon gestational age and prior pregnancy history, there is agreement that the shorter the cervix, the higher the risk for preterm delivery. In addition, in general, the sensitivity and positive predictive value for the prediction of preterm birth are relatively high.
Table 28-5MEASUREMENT OF CERVICAL LENGTH BY TRANSVAGINAL ULTRASOUND IN WOMEN WITH SYMPTOMS OF PRETERM LABOR ||Download (.pdf) Table 28-5 MEASUREMENT OF CERVICAL LENGTH BY TRANSVAGINAL ULTRASOUND IN WOMEN WITH SYMPTOMS OF PRETERM LABOR
|Reference ||Year ||N ||Gestation (wk) ||Cervical Length Cutoffa (mm) ||Outcomea ||Prevalence of Out-comea (%) ||Sensitivity (%) ||Specificity (%) ||PPV (%) ||NPV(%) |
|Murakawa et al.125 ||1993 ||32 ||18-37 || |
|34 ||<37 wk || |
|Iams et al.62 ||1994 ||60 ||24-35 ||<30 ||40 ||<36 wk ||100 ||44 ||55 ||100 |
|Gomez et al.126 ||1994 ||59 ||20-35 ||≤18 ||37 ||<36 wk ||73 ||78 ||67 ||83 |
|Rizzo et al.127 ||1996 ||108 ||24-36 ||≤20 ||43 ||<37 wk ||68 ||79 ||71 ||76 |
|Rozenberg et al.270 ||1997 ||76 ||24-34 ||≤26 ||26 ||<37 wk ||75 ||73 ||50 ||89 |
|Tsoi et al.128a ||2003 ||216 ||24-36 ||<15 ||37 ||Delivery within 7 d ||94 ||86 ||37.2 ||99.4 |
|Tsoi et al.133a ||2005 ||510 || |
|≤15 ||14.9 ||<35 wk ||71.1 ||90.6 ||56.8 ||94.7 |
|Daskalakis et al.132 ||2005 ||172 ||24-34 ||<20 || |
|<34 wk |
|Palacio et al.138 ||2007 ||116 || |
within 7 d <34 wk
|Eroglu et al.137 ||2007 ||51 ||24-35 || |
|19.6 ||<35 wk || |
|Schmitz et al.139 ||2008 ||395 || |
|≤30 || |
Delivery within 48 h
Delivery within 7 d
A systematic review of 7 studies evaluating the use of transvaginal ultrasound and cervical dilation in patients in preterm labor was conducted by Leitich et al.141 The authors subdivided patients into 3 groups: (1) patients with preterm labor, and (2) low-risk asymptomatic patients with early (20 to 24 weeks) or (3) late (27 to 32 weeks) sonographic cervical length. The optimal cutoff values for cervical length in patients in preterm labor ranged between 18 and 30 mm, with sensitivity between 68% and 100%, and specificity were between 44% and 79%.141
Several studies have demonstrated that the use of sonographic cervical length in labor and delivery can improve the management of patients in preterm labor by decreasing the number of unnecessary interventions. In addition, by applying specific management schemes that utilize a cervical length cutoff, both hospital stay and health care costs have been reduced.130,133,134,137,138,140,142,143,144, and 145 However, the utility of hospitalization in patients with a short cervix146 or repeat sonographic evaluation of the cervix after tocolysis has been completed has been questioned.147
A randomized controlled trial136 was conducted in 41 women with threatened preterm labor. Patients underwent a sonographic evaluation of the cervix or received the planned treatment (tocolytics and steroids). In the ultrasound group, patients with a cervical length greater than 15 mm had treatment withheld. A higher proportion of patients in the control group received steroid treatment despite remaining undelivered for more than a week when compared to those in the ultrasound group (14% [3 of 21] vs 90% [18 of 20], RR 0.16; 95% CI = 0.05 to 0.39). In addition, there was a significant difference in the duration of hospital stay between the 2 groups (median [range]; 0 hours [0 to 24] in the ultrasound group vs 24 hours [0 to 67], P < .0001).136 Larger studies are needed to assess the impact of the use of this management scheme on neonatal outcome.
Patients with preterm labor and a short cervix are at an increased risk for intrauterine infection/inflammation. Gomez et al148 conducted a study in 401 patients presenting with preterm labor and cervical dilation of less than 3 cm (as assessed by digital examination). All patients underwent amniocentesis. The prevalence of microbial invasion of the amniotic cavity (MIAC) was 7% (28 of 401). Patients with a short cervix (<15 mm) had a higher rate of microbial invasion of the amniotic cavity and preterm delivery at less than 35 weeks compared with those with a long cervix. (MIAC: short cervix, 26.3% [15 of 57] vs long cervix 3.8% [13 of 344], P < .05; and for preterm delivery <35 weeks: short cervix, 66.7% [38 of 57] vs long cervix, 13.5% [44 of 327], P < .01). Moreover, the rate of infection was higher in patients presenting at 30 weeks or less with a cervical length less than 15 mm when compared to those 15 mm or greater (43% [9 of 21] vs 3.9% [3 of 76], P < .05). The authors provided an estimated risk of MIAC in patients in preterm labor according to gestational age and cervical length (Table 28-6).
Table 28-6DIAGNOSTIC INDICES AND PREDICTIVE VALUES OF DIFFERENT ULTRASONOGRAPHIC CERVICAL BIOMETRIC FINDINGS IN THE IDENTIFICATION OF PRETERM DELIVERY IN PATIENTS WITH ACUTE PRETERM LABOR ||Download (.pdf) Table 28-6 DIAGNOSTIC INDICES AND PREDICTIVE VALUES OF DIFFERENT ULTRASONOGRAPHIC CERVICAL BIOMETRIC FINDINGS IN THE IDENTIFICATION OF PRETERM DELIVERY IN PATIENTS WITH ACUTE PRETERM LABOR
| ||Sensitivity ||Specificity ||PPV ||NPV ||Relative Risk (95% CI) |
|Cervical index ≥ 0.52 ||76% (16/21) ||94% (31/33) ||89% (16/18) ||86% (31/36) ||6.4 (2.8-14.7) |
|Cervical length ≤ 18 mm ||73% (16/22) ||78% (29/37) ||67% (16/24) ||83% (29/35) ||3.9 (1.8-8.5) |
|Funnel width ≥ 6 mm ||67% (14/21) ||76% (25/33) ||64% (14/22) ||78% (25/32) ||2.0 (1.4-6.0) |
|Funnel length ≥ 9 mm ||71% (15/21) ||91% (30/33) ||83% (15/18) ||83% (30/36) ||5.0 (2.3-10.7) |
|Funneling present ||77% (17/22) ||54% (20/37) ||50% (17/34) ||80% (20/25) ||2.5 (1.1-5.9) |
An abnormal cervical index and the presence of funneling in patients in preterm labor also increases the risk of preterm delivery, as demonstrated by Gomez et al.126 Timor-Tritsch et al149 have studied the clinical significance of funneling for the prediction of preterm delivery in a population with symptoms of preterm labor. In 70 patients admitted to the hospital for threatened preterm labor, wedging of the internal os was associated with preterm delivery with a sensitivity of 100%, a specificity of 74%, a positive predictive value of 59%, and a negative predictive value of 100%.
In summary, cervical sonography is a powerful method to assess the risk of preterm delivery in patients presenting with preterm labor. In patients found to have a long cervix, it may be beneficial to avoid aggressive intervention. Patients in preterm labor who are diagnosed with a short cervix have an increased risk of intrauterine infection/ inflammation as well as a higher rate of preterm delivery, and thus may benefit from targeted interventions (ie, antibiotic and/or steroid administration and transfer to a center with a newborn special care unit). Further investigation into the most efficacious intervention for these patients is needed.