The uterine cervix plays a central role in the maintenance of normal pregnancy and in parturition. Thus, cervical disorders have been implicated in common obstetrical complications, such as “cervical insufficiency,”¹ preterm labor, and abnormal term parturition.² Yet, there is an incomplete understanding of the physiology and pathology of untimely cervical effacement and dilation during pregnancy. Midtrimester cervical dilation is a major diagnostic and therapeutic challenge and a subject of intense debate among clinicians and researchers.

During most of a normal pregnancy, the cervix remains firm and closed, despite a progressive increase in the size of the fetus and uterine distention. At the end of pregnancy and during labor, the cervix changes consistency (softens), shortens and thins (effaces), and dilates to allow the expulsion of the conceptus. Labor, delivery, and the postpartum period are accompanied by dramatic changes in the uterine cervix.^3-10 The term “cervical ripening” refers to the anatomic, biophysical, and biochemical processes that underlie the changes in cervical consistency, effacement, and dilation that generally precede the onset of spontaneous labor. Contrary to what was believed for many years, cervical ripening is an active metabolic process affecting the extracellular matrix components of the cervix. These changes increase cervical compliance. Untimely cervical ripening could result in complications of pregnancy. For example, failure of the cervix to ripen before myometrial activation at term (ie, onset of increased uterine contractility) may be the cause of a prolonged latent phase of labor; preterm premature cervical ripening may lead to midtrimester spontaneous abortion or spontaneous preterm labor and delivery.

The uterine cervix is essentially a connective tissue organ, with smooth muscle cells accounting for only 10% to 15% of the distal part of the cervix.¹¹ The ability of the cervix to retain the conceptus during pregnancy is unlikely to depend upon a traditional sphincteric mechanism. Indeed, perfusion of strips of human cervix with vasopressin, a hormone that stimulates smooth muscle contraction, results in a very modest contractile response in comparison to that induced by vasopressin in strips from the uterine isthmus and the fundus, which contain more muscle.¹²

It is now understood that the normal function of the uterine cervix during pregnancy depends largely upon the regulation of connective tissue metabolism. This tissue is formed by abundant extracellular matrix that surrounds individual cells. The major components of the extracellular matrix are collagen, proteoaminoglycans, elastin, and various glycoproteins such as fibronectins.¹¹ Collagen is considered the most important component of the extracellular matrix, determining the tensile strength of fibrous connective tissue. Changes in cervical characteristics during pregnancy have been attributed to changes in collagen content and metabolism.¹³ Proteoaminoglycans have also been implicated in cervical physiology. The proteoaminoglycan decorin has a high affinity for collagen and can cover the surface of the collagen fibrils, stabilizing them and promoting the formation of thicker collagen bundles or fibers. The predominant proteoglycan in the nonpregnant state is decorin, and in the pregnant state it is biglycan.¹⁴

Cervical Ripening

The biochemical events that have been implicated in cervical change during pregnancy and labor and delivery include (1) decreased collagen fiber alignment, (2) increased collagen solubility, (3) increased collagenolytic activity (both collagenase and leukocyte elastase), (4) increased interleukins (IL-1, IL-8, tumor necrosis factor α), and (5) increased matrix metalloproteinases (MMPs [matrix degrading enzymes])—MMP-1 and MMP-8 when compared to nonripe cervices.^6,7,11,15

Petersen and Uldbjerg¹⁶ compared the cervical collagen content in nonpregnant patients with a history of “cervical incompetence” to normal nonpregnant women. Cervical incompetence was defined as “patients where no other cause of cervical incompetence could be deduced from the history and where the first pregnancy sustained beyond the 12th week of pregnancy ended with a late spontaneous abortion or preterm delivery.” Patients with “cervical incompetence” by history had a markedly lower cervical hydroxyproline concentration and higher extractability (thought to represent collagen concentration solubility) when compared to normal parous patients. In addition, parous women had significantly lower hydroxyproline concentrations in the cervix when compared to nulligravidae and nulliparous women. The authors also identified a cutoff level of 13 mg of hydroxyproline per mg–wet weight of collagen, with a sensitivity of 0.9 and a specificity of 0.8, for the identification of women with “cervical incompetence.”¹⁶

Liggins first likened cervical ripening to an inflammatory process.¹⁷ This concept has influenced research in cervical biology. However, recent observations have challenged the importance of inflammation in cervical ripening.^9,10,18,19 Sakamoto et al⁹ demonstrated that there was no correlation between the degree of clinical cervical ripening and IL-8 concentrations in cervical tissue (although IL-8 concentrations in the cervical tissue did increase after labor and delivery).

Word et al¹⁰ reported an animal model in which parturition does not take place despite uterine contractions because of a rigid, inelastic cervix at term. Cervical ripening did not occur despite infiltration with neutrophils and macrophages of this tissue (mice had a transgene insertion on chromosome 6).¹⁰ Timmons and Mahendroo¹⁸ have challenged the traditional paradigm that the influx of inflammatory cells is a major regulatory event in the initiation of cervical ripening using steroid 5 α-reductase type 1 null mice (Srd5a1^–/–). The investigators found that cervical ripening does not require activation of a typical inflammatory response because macrophages, eosinophils, and myeloperoxidase activity did not increase during cervical ripening. Moreover, depletion of neutrophil numbers before birth has no effect on the timing or success of parturition. The authors proposed that normal cervical ripening does not require a typical inflammatory response and that inflammatory cells are recruited in preparation for the extensive cervical remodeling that occurs after birth when large amounts of hyaluronan and other extracellular matrix components (ie, collagen) must be removed.¹⁸ A recent microarray analysis of cervical tissue of women at term with a ripe and unripe cervix confirmed that inflammation-related genes did not emerge as differentially expressed with cervical ripening.¹⁹ Gene ontology analysis indicated that cervical ripening was associated with enrichment of specific biological processes (cell adhesion, regulation of locomotion) and metabolic functions (phosphate transfer). Furthermore, pathway analysis identified involvement of focal adhesion, extracellular matrix (ECM)-receptor interaction, cell communication, and cell adhesion molecule pathways.¹⁹

Several lines of evidence support the role of sex steroid hormones in cervical ripening, a concept that has important clinical implications. This evidence suggests (1) intravenous administration of 17 β-estradiol induces cervical ripening⁶; (2) estrogen stimulates collagen degradation in vitro⁶; (3) progesterone and 17 β-estradiol inhibit collagenolysis in uterine cervical fibroblasts by increasing production of tissue inhibitor of metalloproteinases (TIMP) and suppressing production of collagenase and stromelysin²⁰; and (4) administration of progesterone receptor antagonist induces cervical ripening in the first trimester pregnancy.²¹ However, recent experimental evidence indicates that the role of sex steroid hormones in cervical ripening is far more complex. For example, cervical ripening in the guinea pig begins long before a decrease in serum progesterone concentrations, suggesting that there must be a progesterone-independent mechanism capable of inducing cervical ripening in this species.²² With regard to the role of estrogens, the administration of estrogen to pregnant women does not consistently result in cervical ripening. Moreover, the administration of neither estradiol nor its precursor (androstenedione) induces cervical ripening in the presence of high concentrations of progesterone in guinea pigs.²² A puzzling observation is that the administration of estradiol to guinea pigs treated with onapristone (a progesterone receptor antagonist that induces cervical ripening) attenuates the cervical ripening normally induced by that compound. Therefore, further investigation is required to elucidate the precise role of sex steroids in cervical ripening.

Cervical Dilation

In contrast to cervical ripening, the processes of cervical dilation and postdelivery cervical remodeling are accompanied by invasion of inflammatory cells. Chemokines such as IL-8, CXCL1, CXCL2, CXCL3, CXCL5, and CCL20 have been implicated in the recruitment of neutrophils to the cervix.^5,7,17,23-33

Cervical modifications during pregnancy and parturition are not limited to physiological and biochemical changes (softening) but also involve anatomical changes (eg, effacement and dilation), which can be assessed with the use of ultrasound.

Sonographic imaging of the cervix is a less invasive, more reproducible, and more precise and objective method of assessing the cervical status when compared to digital examination. This is likely because a digital examination can only assess the external cervix rather than the internal cervical canal; nevertheless, digital palpation can render texture and softness. Effacement (or cervical shortening), changes in the anatomy of the internal os (funneling), endocervical canal dilation, and spontaneous modifications or induced (transfundal pressure) can be determined by ultrasound examination.

Technique and Pitfalls

The cervix can be examined using a transabdominal, endovaginal, and transperineal approach. We prefer the endovaginal technique for optimal assessment of the cervix because of the greater literature and reproducibility of this technique. The close proximity of the probe to the cervix and the use of a high-frequency transducer improve image quality. Transabdominal sonography requires a full bladder for adequate visualization of the cervix. Overdistension of the bladder compresses and artificially lengthens the cervix.^34,35 Andersen³⁵ demonstrated that cervical length measurements obtained in 186 pregnant women by transabdominal sonography were longer (5.2 mm on average) than those obtained using endovaginal sonography. In contrast to transabdominal ultrasound, endovaginal scanning does not require a distended bladder.

The transperineal technique can be used when an endovaginal transducer is not available, and it does not require a full bladder.^36-41 The cervical length can be properly visualized and measured adequately by transperineal sonography in about 80% of patients. However, the presence of air in the vagina may render the examination noninformative. In one study there was a high correlation between cervical length obtained by endovaginal and transperineal methods (interclass correlation coefficients = 0.83 [95% confidence interval 0.79-0.86]). Of interest, a recent study by Meijer-Hoogeveen et al⁴¹ reported that transvaginal sonographic imaging was preferable to patients when compared to transperineal ultrasound. Hertzberg et al³⁹ prospectively evaluated 64 pregnant women at 14 to 38.2 weeks by transvaginal and transperineal ultrasound. The reviewers of the images preferred transvaginal measurements of the cervix when compared to those obtained using the transperineal approach (P < .001), with the most common reasons reported as the presence of bowel gas, which obscured the cervical external os and other landmarks not clearly depicted in the transperineal images. The mean transvaginal cervical length obtained by endovaginal scan at 14 to 20 weeks’ gestation was significantly longer than that obtained by transperineal examination (34.1 mm vs 28.6 mm, P < .006).³⁹ Others have proposed that if the cervix is well visualized, the transperineal technique offers a sensitivity of 77%, false-positive rate of 17%, and relative risk of 4.5 with a cervical length of 32.5 mm, measured at 24 weeks, for the prediction of preterm birth prior to 36 weeks.⁴⁰

Technique

Before conducting an endovaginal ultrasound, patients are asked to empty their bladder; a full bladder can artificially “lengthen” the cervix. During the procedure, the patient lies in the supine position with flexed knees and hips. Some have proposed the use of the upright position to obtain the cervical length measurement,⁴² whereas others have reported a good correlation between measurements obtained in the supine and standing positions.⁴³ The probe is covered with either a glove or an appropriate sheath. There is no risk for microbial inoculation as a result of the use of the endovaginal probe.⁴⁴ Gel is placed between the transducer and the cover as well as on the surface sheath. The operator introduces the vaginal probe into the anterior fornix until a midline sagittal view of the cervix and lower uterine segment are seen. The internal os, external os, cervical canal, and endocervical mucosa should be clearly identified (Figure 29-1). The endocervical mucosa is used to define the upper edge of the cervix. Otherwise, cervical length may erroneously include part of the lower uterine segment.

Excessive pressure with the probe may elongate the cervix. To avoid this pitfall, the probe is slowly withdrawn until the image blurs and is subsequently reapplied with an amount of pressure sufficient to restore the image. This can be avoided by confirming equal cervical widths and density of the anterior and posterior lips of the endocervical canal (Figure 29-2).^45,46

The cervical length is measured by freezing the screen 3 separate times. The reliability of measurements is increased if the variation between the measurements is not more than 2 to 3 mm; the optimal length of examination averages 5 to 10 minutes. For clinical purposes, the shortest cervical length is reported, provided that the image is adequate. The examination is recorded on videotape, and the presence of a funnel or dynamic cervical change is noted. If dynamic change is noted, the shortest cervical length measured during this dynamic change is recorded. A funnel is defined as dilation of the upper portion of the cervical canal (Figure 29-3). This can only be recognized by confirming that the walls of the funnel are formed by endocervical mucosa. Otherwise, the covering wall of the lower uterine segment can be erroneously considered as a funnel.

When the cervical canal is curved, the cervical length can be determined by tracing along the canal or by adding the sum of 2 straight sections. To et al⁴⁷ concluded from a prospective study conducted in 301 women at 23 weeks’ gestation that the disparity of measurement, taken as a straight line or along the cervical canal, might not have any clinical significance because a short cervix (<16 mm) is always straight.

Technique is vital to accurate measurement. If the duration of the examination is too short and the patient has dynamic cervical changes during the examination, the cervical length may not represent the true baseline status of the cervix. This may account for some observations in which patients seem to gain cervical length over time. The contours of the anterior and posterior lip of the ectocervix are usually clearly defined. However, in some instances the boundaries of the ectocervix cannot be discerned. Rarely, in selected patients whose cervix cannot be adequately imaged, instillation of saline as a “contrast agent” into the vagina allows better recognition of the ectocervix.⁴⁸

Standardized measurements of a funnel are difficult because a funnel can be obliterated by pressure from the transducer, it is often transient, and a distended bladder can obscure it. Since the longer the funnel, the shorter the remaining cervical length,^49,50 it has been argued that the endocervical length contains most of the information required for the prediction of preterm delivery. Most favor cervical length measurement because it is far more reproducible than the assessment of funneling. The value of detecting funneling in the prediction of preterm delivery is reviewed later in this chapter. Rarely, the presence of a large endocervical polyp can obscure tissue planes and cause difficulties in imaging.⁵¹ Although cervical examination may appear simple to the experienced sonographer, certain patients may present significant challenges. For example, a cervix with an unusual orientation may be difficult to find. In a recent study, Yost et al⁵¹ reported that 27% of the scans performed in 60 women presented some anatomical or technical difficulty.

Therefore, several potential pitfalls should be avoided. These include: (1) excessive probe pressure (falsely long; Figure 29-4A), (2) failure to observe cervical shortening for enough time (falsely long), (3) failure to recognize a poorly developed lower uterine segment, (4) unequal size and density of the anterior and posterior lips (Figure 29-4B), (5) full bladder (Figure 29-5), (6) endocervical canal not visualized, and (7) lack of amniotic fluid “sludge” recognition (Figure 29-6) (the clinical significance of amniotic fluid “sludge” is reviewed later in this chapter).

Romero and colleagues have proposed that parturition has a common terminal pathway characterized by increased myometrial contractility, cervical ripening, and membrane/decidual activation.⁵² These processes are required for both term and preterm parturition. Normal labor at term is characterized by coordinated activation of these 3 mechanisms, and thus patients will present with increased uterine contractility, cervical effacement, and dilation and eventually rupture their membranes. However, premature activation of different components can occur in a coordinated or uncoordinated way. The premature coordinated activation of these mechanisms is observed in patients with classic preterm labor with progressive cervical dilation leading to preterm delivery. Preferential activation of the cervical ripening component in the midtrimester can lead to premature cervical dilation. Later in pregnancy some patients will complain of vaginal pressure and will be recognized to have cervical dilation and effacement out of proportion to the frequency and intensity of myometrial contractility. Although these patients are traditionally considered to have preterm labor, clearly cervical ripening is the main component of the terminal pathway activated in these particular cases.⁵² This model of preterm parturition is important because it suggests that premature cervical ripening may result in a spectrum of disease including from midtrimester abortion, some forms of preterm labor, and precipitous labor at term. Figure 29-7 describes the concepts outlined previously.

Preterm birth is the leading cause of perinatal morbidity and mortality, accounting for 85% of neonatal deaths. One in 10 babies was born preterm in 2015, 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,^54-56 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, though it is useful to provide sufficient time for antenatal corticosteroid administration.

It is well established that a sonographic short cervix is a powerful predictor of spontaneous preterm birth.^{35,49,50,56,60-76} 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 midtrimester 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 29-1.

Multiple authors have confirmed that a shortened cervix places the pregnant woman at risk for preterm delivery. 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-risk^{49,50,56,60,61,63,64,66-68,70,71,73,75-81} and high-risk asymptomatic patients.^{45,65,69,72,74,82-84} Table 29-2 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.

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 29-8). An exponential increase in the relative risk of delivering before 35 weeks was described (Figure 29-9). The diagnostic indices for different cutoff values of cervical length, funneling, and Bishop score are displayed in Table 29-3. This large study confirmed the previous results 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

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 29-10). 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 measuring 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 or less.

Romero and colleagues 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 ethnicity 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 29-11^49,66,70,76).

In conclusion, several studies have confirmed and extended the observations of short cervix in asymptomatic patients at low risk for preterm delivery.^{49,50,56,60,61,64,66-71,73,75,76,79-81,85-89}

A short cervix of 15 mm or less in asymptomatic patients at 23 weeks’ gestation 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 midtrimester, 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 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, 2 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 0.6-2.4); (2) accelerated rate of decrease towards the end of pregnancy (n = 4; median 3.0 mm/wk, range 1.5-4.8); (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 midtrimester 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 midtrimester 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 = 2.1-5.0) 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 = 2.7-7.6) 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 analyses^82,94 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 (26-34 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 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 = 3.59-35.57) and at 20 to 24 weeks an LR of 2.86 (95% CI = 2.12-3.87), respectively, for delivery at less than 35 weeks.

Recently, Szychowski et al⁹⁶ conducted an analysis of prerandomization 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 of 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). Furthermore, 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 less than both 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 = 3.3-25.9] vs multiparous, OR 4.2 [2.0-8.9]; and at <37 weeks—nulliparous, OR 3.7 [1.8-7.7] vs multiparous, OR 2.5 [1.4-4.5]).

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 they reported an increased risk for preterm birth in twin pregnancies with a sonographic short cervix.^101-116

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 29-4). 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.

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 = 2.0-10.3] and RR = 3.6 [1.6-7.8], 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 [1.55-8.03]) and multiparity (OR 2.27 [1.09-4.74]) 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.^{62,113,125-139} 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 29-5 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.