Cervical Length and Spontaneous Preterm Birth

Introduction

Preterm birth (PTB) touches communities everywhere. Around the world, one in 10 babies is born too early. The toll is more than 15,000,000 babies per year. The deep impact of this problem has fostered widespread efforts to use the best available medical practices to address it. Accordingly, the U.S. PTB rate fell from 10.44% to 9.57% from 2007–2014, although, unfortunately, preliminary 2015 birth data shows an increase (to 9.62%). Risk of PTB is inversely associated with cervical length (CL), and midtrimester CL is currently the strongest clinical risk factor for PTB. This chapter addresses the (1) clinical significance of a short cervix, (2) pathophysiology of cervical shortening, (3) ultrasound (US) technique for cervical measurement, and (4) management options for the short cervix.

Disease

Definition

The cervix is a cylindric anatomic structure with a central canal that forms the lower part of the uterus. It has a dual role: first, it must remain closed throughout pregnancy to allow fetal growth and development during pregnancy, and then open completely at term to allow fetal passage. The responsible molecular and biomechanic mechanisms are incompletely elucidated.

The inverse relationship between CL and PTB risk was identified 20 years ago; specifically, the shorter the cervix, the greater the risk. The definition of a short cervix depends on gestational age and fetal number, but the cutoff is usually 20–30 mm. The most common definition is less than 25 mm, but significance varies with gestational age; 25 mm corresponds to the first percentile at 18 weeks, the third percentile at 22 weeks, the fifth percentile at 24 weeks, and the 10th percentile at 28 weeks of gestation. The definition of 25 mm is also widely applied to twin gestation, and short cervix is more common in multiples; in the National Institute of Child Health and Human Development Maternal Fetal Medicine Unit (NICHD MFMU) network's Preterm Prediction Study, 18% of women with twins had a short cervix in the midtrimester, compared to 9% in singletons. Another definition of a short cervix is 10–20 mm; this definition was used in a randomized, double-blinded, placebo-controlled trial of vaginal progesterone for PTB prevention. Another common definition is less than 15 mm because the risk of PTB increases exponentially below that value.

Prevalence and Epidemiology

The predictive accuracy of a short cervix for spontaneous PTB depends on the length of the cervix, gestational age at testing, fetal number, and risk factors for PTB ( Table 124.1 ).

TABLE 124.1

RISK OF SPONTANEOUS PRETERM BIRTH BEFORE 35 WEEKS' GESTATION

Incidence Spb <35 Weeks' Gestation	Risk	Characteristics
>50%	Highest risk	Singleton, candidate for a physical examination–indicated cerclage; or cervix <15 mm, history of SPB, no cerclage; twin, cervix <15 mm
20%–50%	High risk	Singleton, cervix <15 mm, no history of SPB, no therapy; or cervix 15–25 mm, history of SPB, no therapy; or cervix <25 mm + progesterone ± cerclage; Twin, cervix 15–25 mm
10%–20%	Medium risk	Singleton, cervix >25 mm, history of SPB or other risk factor; or cervix 15–25 mm, no history of SPB; Twin, cervix >25 mm
<10%	Low risk	Singleton; no history of SPB or other risk factor

SPB , Spontaneous preterm birth.

Length of Cervix

As noted earlier, the risk of PTB increases as the cervix shortens. In an NICHD MFMU network trial, transvaginal CL was measured in asymptomatic women at 24 weeks of gestation to predict PTB before 35 weeks. The relative risk (RR) increased steadily as CL shortened, and reached its highest (RR = 14) when the cervix was less than or equal to 13 mm. A systematic review of 17 studies of asymptomatic singletons reported a significantly increased risk of PTB with CL <25 mm before 34 weeks of gestation; the likelihood ratio was 6.29 (95% confidence interval [CI], 3.29–12.02).

Gestational Age at Testing

A short cervix before 20 weeks of gestation has a worse prognosis than a short cervix later in pregnancy. In a systematic review of 17 pooled studies of asymptomatic singletons, the likelihood ratio for PTB was increased if the gestational age at testing was less than 20 weeks compared with 20 to 24 weeks. This finding is not surprising; 25 mm corresponds to the first percentile at 18 weeks but the 10th percentile at 28 weeks, so a 25-mm cervix at 18 weeks is more concerning.

Risk Factors for Preterm Birth

The sensitivity of CL for predicting PTB depends on the patient population. For instance, multiple gestation increases the PTB risk, but a short cervix increases it further. In the Preterm Prediction study, the risk of PTB in twins with CL 25 mm or less was similar to that for singletons with CL 15 mm or less. A systematic review of 11 pooled studies of asymptomatic twins found an 18.5% baseline risk of PTB before 34 weeks' gestation compared with 29%–48% when the cervix was less than 25 mm. In singleton pregnancy, women with a history of spontaneous PTB and a short cervix are at highest risk; in an unselected, low-risk patient population, the sensitivity of a CL less than 25 mm for predicting PTB before 35 weeks of gestation was 37.3%, but in a population of women at high risk based on a prior history of PTB, the sensitivity increased to 69%.

Etiology and Pathophysiology

Although a short cervix is clearly associated with PTB, the question of whether a short cervix is a “cause” of PTB (i.e., cervical insufficiency or “weakness”) or a “consequence” of a pathophysiology unrelated to cervical “weakness” is unclear.

Infection/Inflammation

In a study of 52 women with cervical dilation at least 1.5 cm, without active labor (contractions or bleeding), 80% had evidence of infection/inflammation. Positive amniotic fluid culture was present in half of cases and, even when this was negative, evidence of inflammation (higher intraamniotic interleukin-6 levels) was often present.

Similarly, infection/inflammation is common in the setting of a short cervix (less than 25 mm), particularly with a very short cervix. In a study of 401 patients admitted for preterm labor at 22 to 35 weeks of gestation, microbial invasion was more prevalent when the cervix was less than 15 mm (26.3%) compared with 15 to 25 mm (3.8%). In another study in which a panel of inflammatory cytokines was studied as a function of CL, most inflammatory cytokines became elevated at a CL less than or equal to 5 mm.

These studies confirm that intraamniotic infection and inflammation are common when the cervix is short.

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