Cervix

A preterm birth (PTB) is defined as delivery that occurs between the 20th and 36th + 6 weeks of gestation regardless of the weight of the baby (WHO) (1). It accounts for 10% of all births and, in most cases, it starts spontaneously (75-80%). It is the leading cause of neonatal mortality and morbidity, including long term disabilities, and neurodevelopment delay (2).
During labour, modifications to the cervix such as effacement and dilation occur, which can be evaluated by digital examination. The inter-observer variation is well described especially during the first stages of labour. The ultrasonographic evaluation of the cervix has been developed to reduce that inter-observer variability and to help with the prediction of PTB (3).
Cervical ultrasound evaluation can be used to screen asymptomatic patients at risk of PTB and also to evaluate symptomatic pregnant women (4).

The major risk factor for PTB is having had a previous preterm delivery (OR 4.6-6). The risk varies according to the gestational age at delivery and the number of previous preterm deliveries (5). 
Multiple pregnancy, cervical dysplasia and cervical procedures (eg. Loop electrosurgical excision procedures), congenital uterine anomalies (eg. uterus didelphys), connective tissue diseases, myomas affecting the endometrial cavity, surgical abortion, genito-urinary infections and cesarean section due to prolonged second stage of labor are other major risk factors. Other minor risk factors are black race, inter-pregnancy interval of less than 12 months, obesity, young or advanced age pregnancy and smoking (6). Unfortunately, none of these risk factors, either singly, or in combination can reliably predict an individual patient’s risk for preterm delivery. 

The sonographic evaluation of the cervix using a transvaginal probe is the most accurate strategy to predict PTB either in asymptomatic or symptomatic pregnant women (5). The cervical length (CL) measurement is a highly reproducible, efficient and cost-effective measurement when predicting the risk of PTB. Many international societies (including ISUOG, FIGO, ACOG) support the CL measurement as a screening strategy to reduce the spontaneous PTB rate (5, 7,8).

Despite the relatively easy learning curve for measurement of the cervical length, the appropriate technique is crucial in order to correctly assess the risk of preterm birth. Certification of competence awarded by qualified entities after the completion of theoretical and practical courses is highly recommended to guarantee the efficiency of those measurements (9). 

a.    Cervical length measurement technique
The “ISUOG Practice Guideline on the role of ultrasound in the prediction of spontaneous preterm birth”, published in 2022, elucidates a step-by-step approach to measure the cervical length using a vaginal probe – Table 1 (5).

Table 1

A straight line between the internal and external os can be traced, ignoring the curvature of the cervix – Figure 1. Since the main goal is to identify a short cervix and short cervices always appear straight, tracing a curved line is not mandatory as it would not affect the subsequent management of that pregnancy (5).

b.    Using transabdominal probe
Using a transabdominal probe to evaluate the cervical length is not recommended since it is not as reproducible or as accurate as the transvaginal approach. However, some authors investigated its role as a screening strategy in low-risk pregnancies because it is less invasive and less time-consuming than using a transvaginal probe (10). 

Checking the cervix using a transabdominal approach might be challenging: defining the internal and external cervical os is difficult; the bony maternal pelvis and fetal parts might cause a shadow on the cervix; and finally, a partially filled bladder helps with the acoustic window but if over-distended also elongates the cervix – Figure 2

Although not recommended, some authors advocate a two-step approach to screening for short cervix: firstly, using a transabdominal probe and secondly using a transvaginal probe if a short cervix (using a higher cut-off, eg. less than 30 mm) is suspected (11,12). If transabdominal scanning is used to screen for a short cervical length, attention should be paid to the region of the internal cervical os to ensure that no funneling is present. If there is any concern, transvaginal scanning should be used to further investigate the cervical length.
Because the transabdominal probe is useful in excluding short cervix, this two-step approach could facilitate the implementation of a population-based screening strategy, at the time of the mid-trimester anomaly scan (which is routinely recommended worldwide).

c.    Defining short cervix
Some large population studies were designed to build reference values and define centiles for each gestational age. In the mid-trimester, a cut-off of ≤25 mm (5th centile at 24 weeks of gestation) identifies a rate of PTB <35 weeks of 18% (5,13).

ISUOG recommends that CL ≤25 mm should be used as a cut-off for the initiation of measures to prevent PTB in asymptomatic singleton pregnancies, irrespective of risk factor - Figure 3 (5).

d.    Other ultrasound markers
Other ultrasound markers can aid on the prediction of preterm birth, although in a less reproducible way and with a lower predictive value. They are especially useful when evaluating symptomatic women.

Funneling is defined as the protrusion of the membranes across the internal cervical os. It correlates with cervical effacement and can be seen with or without mechanical pressure on the cervix (eg. uterine contraction) – Figure 4 (14).

“Sludge” represents debris that concentrates near the cervical canal, such as microbes, blood clots, vernix or meconium. It is associated with infection and inflammation, increasing the risk of preterm birth - Figures 5 and 6 (15).

The “sliding sign” is observed if the anterior lip of the cervix slides on the posterior lip when gentle pressure is applied on the cervix using the transvaginal probe – video 1 (16). When this is seen, the cervix is often dilated on digital examination. 

Occasionally membranes are seen protruding through the cervix, or intermittently protruding through the cervix. Preterm contractions should be excluded in these cases. 

Cervical consistency index (CCI) represents the ratio between the anteroposterior diameter of the cervix before and after maximal compression with the vaginal probe – video 2. It correlates with the softness of the cervix, which is one of the modifications of the cervix during the first stages of labor (17). Similarly, cervical elastography, an ultrasound technique using specific mathematical algorithms, enables objective measurement of cervix stiffness – figure 7(18,19). Neither of these techniques are routinely used in clinical practice.
The anterior and posterior uterine-cervical angles correlate with the concept of “funneling”, meaning that the wider angle between the uterine wall and the cervical canal, the higher the risk of preterm birth (20, 21).

General health care before and during pregnancy is helpful in preventing preterm birth, namely smoking cessation, optimizing maternal weight, optimal treatment of other chronic diseases, planning of subsequent pregnancy by avoiding short inter-pregnancy interval and avoiding iatrogenic multiple pregnancy due to infertility interventions.
In addition, timely treatment of genitourinary infection (eg. asymptomatic bacteriuria) is an effective measure to prevent PTB (2,6).

Screening asymptomatic women for a short cervix, defined by a short cervical length, is the single most effective strategy to prevent preterm birth (2,5,6).

Universal mid-trimester measurement of the cervical length using transvaginal approach is advised by most of the international societies (ISUOG, FIGO, ACOG). It is cost-effective, although it requires high human and physical resources (2,5). 

a.    Treatment for asymptomatic women at higher risk of PTB
Identification of women at high risk for PTB helps to start preventive measures such as vaginal progesterone or cerclage.

Progesterone
Progesterone efficacy for  prevention of preterm birth has been tested in singleton and multiple pregnancies . Different dosing regimes have also been studied (eg 200mg, 400mg) as well as different routes of administration (eg. vaginal, intramuscular). The administration of vaginal progesterone 200mg daily is approved to prevent PTB in singleton pregnancies with a short cervix (detected on the mid-trimester scan) and as a primary strategy in pregnant women who have had a previous PTB (starting before the cervical length assessment in the mid-trimester scan) (22-24).

Other doses and routes were not consistently successful in preventing PTB, nor its application in different context (eg. multiple pregnancy), but further studies are ongoing (22-24).

Cerclage
Cervical cerclage is a surgical procedure that involves placing some stitches circumferentially around the cervix to allow for mechanical support and thus prevent dilatation. The procedure is most commonly performed through a vaginal approach, using   McDonald or Shirodkar techniques. Abdominal cerclage is commonly used when the vaginal approach is not possible or in a pregnancy with a prior failed vaginal stitch. These techniques are used to treat cervical insufficiency. 

Cervical insufficiency is defined as the inability of the cervix to sustain a pregnancy in the absence of clinical contractions. Usually, this condition leads to second trimester pregnancy-loss after painless cervical dilation (2).

 
Clinically, a history-indicated cerclage is performed after a prior pregnancy loss in the second or early third trimester and prior to 28 weeks), However, cervical insufficiency can also be diagnosed in a first pregnancy when a short cervix is detected on ultrasound before 24 weeks (ultrasound-guided diagnosis) or detected by physical-exam (dilation of the cervix or protrusion of membranes) – a physical-examination-guided diagnosis (26).

Cerclage can be used as a primary strategy for prevention of PTB, as in a case of history-guided cervical insufficiency, or as an added strategy after the diagnosis of progression of cervical shortening despite treatment with vaginal progesterone (2, 5, 26)

Other non-recommended strategies to secondary prevention of PTB
Bed rest, intramuscular progesterone and obstetric pessaries were found not to be effective in prevention of PTB in high-risk women with a singleton gestation (5).

b.    Multiple pregnancy
Multiple pregnancy is a major risk factor for PTB. Cervical length distribution in twins is skewed towards shorter lengths and a CL <25 mm at 20-24 weeks is associated with a 25% risk of having a PTB <28 weeks (5).

Considering the higher risk of PTB in twin pregnancies, the screening strategies should be equivalent to other high-risk pregnancies (eg. prior PTB in singleton pregnancy), meaning that serial CL measurement should take place during the second trimester.

In addition, as in singleton pregnancies, CL<25 mm is a pragmatic cut-off used to define short cervix before 24 weeks (5).

Regarding preventive methods, optimal management of a twin pregnancy with a short cervix remains controversial (27,28). Studies addressing efficacy of proven interventions in singletons, such as progesterone, has not been shown to be of similar efficacy in unselected twin pregnancies with specific indicators for use in the population (23). In addition, studies have failed to demonstrate efficacy of pessaries for short cervix in twin pregnancy (29). A recent systematic review by Francesco D´ Antonio and colleagues (2021) concluded that there is insufficient evidence to support the administration of progesterone, cerclage procedure or application of pessary in twin pregnancies in order to prevent PTB before 34 weeks. None of the treatments were effective in a non-selected population or in a high-risk population (CL <25 mm). However, cerclage was the most effective among all options (27).

Conversely, other studies have demonstrated an increased risk of adverse perinatal outcome and preterm birth in association with cerclage placement (30). The difficulty in endorsing a definitive management strategy has been due to the absence of adequately powered randomized controlled trials, heterogeneity in methodological design of studies included in systematic reviews, variations in CL measurement and dilation by which treatment is indicated (i.e. <25 mm, <15 mm, etc.) and whether decisions for individual therapies, such as placement of a cerclage should be predicted on ultrasound assessment of CL or physical exam-indicated placement.

The 2022 ISUOG clinical guideline recommends consideration of progesterone if a short cervix  is detected in women with multiple pregnancy, who are asymptomatic for preterm labor (34). Other authors individualize treatment and recommend the performance of cerclage if shortening and dilation of the cervix progresses, especially if progesterone therapy has been ongoing (27,28).

c.    Secondary prevention
 A combination of strategies is used to prevent PTB in singleton and twin pregnancies, as shown in the slides.

Threatened PTB is a condition where pregnant women present with uterine contractions and cervical modifications that ultimately will lead to PTB. It is a frequent obstetric syndrome accounting for one of the leading causes of presentation to obstetrical triage units.

Nearly 75% of women admitted for threatened PTB will deliver at term and identification of true preterm labor is mandatory in order to avoid unnecessary admission to hospital and treatment (2,5,6,32).

In a clinical setting where a woman presents with contractions and cervical modifications (real threatened preterm birth) four types of medical interventions will help reducing the burden of prematurity: in-utero transfer to a tertiary neonatal care center; corticosteroids for fetal maturation; antibiotics to prevent early sepsis caused by group-B streptococcus; and magnesium sulphate for fetal neuroprotection. Tocolysis might be indicated to complete the previous described procedures (33).

Concurrently with clinical and complementary exams, the cervical length measurement is the single most useful procedure in order to aid in the diagnosis of  preterm labor. Fixed values of <15 mm or 20 mm are routinely used to predict the higher risk of PTB within 7 days, which should prompt admission and further medical interventions to prevent PTB. On the other hand, a CL ≥ 30mm has a high negative predictive value, leading to exclusion of the diagnosis of active preterm labor (5).
 

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