Cervical Length at 28–32 Weeks of Gestation Predicts Preterm Birth : Maternal-Fetal Medicine

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Original Article

Cervical Length at 28–32 Weeks of Gestation Predicts Preterm Birth

Zhang, Mengying1; Zhang, Xiaoxiao1; Yang, Huixia1,2; Shi, Chunyan1,∗

Editor(s): Pan, Yang

Author Information
doi: 10.1097/FM9.0000000000000074
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Abstract

Introduction

Preterm delivery is defined as delivery before 37 weeks of gestation.1 Preterm delivery has an incidence of 5%–12%2 and is the main cause of perinatal mortality and morbidity. The accurate diagnosis and prediction of preterm delivery remains a major concern in obstetrics. Numerous investigations have demonstrated that cervical length (CL), as determined by transvaginal sonography at 20–24 weeks of gestation, can predict preterm delivery, with the relative risk (RR) for preterm delivery increasing with decreased CL.3–5 The administration of progesterone for women with a short cervix can significantly reduce the preterm delivery rate, and has become one of the main methods to prevent preterm delivery in recent years.6,7

Previously, we demonstrated that, in Beijing, the incidence of a short cervix at 20–24 weeks of gestation (CL ≤25 mm) was 0.2%–0.45%, in contrast to 3% in European countries.3,4,8,9 Although a shorter CL was found to be associated with a higher rate of preterm delivery, the ability to predict preterm delivery still remains low.8 Although few studies focus on using late trimester CL to predict preterm delivery, cervical shortening at 28–32 weeks of gestation may still predict preterm delivery.8 Therefore, the aim of the present study was to evaluate the ability of CL at 28–32 weeks of gestation to predict preterm delivery and preterm premature rupture of membranes (PPROM) in a large sample of women.

Materials and methods

Participants

It was a retrospective cohort study that a total of 14,953 singleton pregnant women who delivered after 28 weeks of gestation at the Peking University First Hospital from June 2008 to December 2012 were retrospectively reviewed. All women underwent transvaginal sonography between 28 and 32 weeks of gestation. It was a hospital protocol of universal screening. Exclusion criteria: (1) twins; (2) suspicious PPROM; (3) fetal congenital malformation or fetal death in utero. Clinical characteristics and pregnancy outcomes were collected. This study had approval by a decision of the Ethics Committee of Peking University First Hospital, Peking, China (decision number: YS2018YFC100223), which waived the need for informed consent.

Spontaneous preterm was defined as: four contractions every 20 minutes or eight contractions every 60 minutes, accompanied by cervical shortening ≥80% and dilation of the cervix.

PPROM was defined as: premature rupture of the membrane before 37 weeks gestation.2

CL measurement

CL was assessed using transvaginal sonography. Before the examination, each patient was asked to completely empty her bladder. The patients were placed in the dorsal lithotomy position. The vaginal probe was covered with a sterile condom with sterile gel applied on both the inside and outside. The transducer was withdrawn slightly until the image blurred and then was gently reinserted with minimal pressure to restore a clear image of the cervix. CL was measured in the sagittal plane, with the internal and external os and the endocervical canal as landmarks. When the cervical canal was curved, CL was measured in multiple linear segments. The shortest of three measurements was recorded. Each examination was performed for a minimum of three minutes to allow time for the development of a “funnel” (defined as a protrusion of the amniotic membranes at least 3 mm into the internal cervical os as measured along the lateral border of the funnel). The presence or absence of a funnel and its length were recorded. Measurement was not performed during uterine contractions.

Statistical analysis

Analyses were performed using SPSS 19.0 (IBM Corp., Armonk, NY, USA). CL is expressed as mean ± standard deviation, and categorical variables are expressed as frequencies and percentages. Differences between continuous variables with a normal distribution were evaluated using t-tests. The RR was calculated to assess group differences in the likelihood of an event occurring. P < 0.05 were considered statistically significant.

Results

Clinical characteristics and constituent ratios of preterm delivery

The mean age was (30.5 ± 4.1) years, and the mean gravidity was (1.8 ± 1.2). The overall incidence of preterm delivery was 5.7% (858/14,953). Specifically, the incidence of therapeutic preterm delivery was 2.1% (318/14,953), of spontaneous preterm delivery was 0.89% (133/14,953), and of PPROM was 2.7% (407/14,953). The constituent ratios of preterm delivery according to gestational week are shown in Figure 1. There were 92 deliveries with 28–31+6 weeks of gestation (92/858, 10.7%), 125 with 32–33+6 weeks of gestation (125/858, 14.6%), and 641 with 34–36+6 weeks of gestation (641/858, 74.7%).

F1
Figure 1:
Constituent ratios of preterm delivery.

CL at 28–32 weeks of gestation

The mean CL was (35.6 ± 5.5) mm, with a CL ≥30 mm accounting for 93.8% of cases (14,024/14,953), CL between 25 mm and <30 mm accounting for 3.7% of cases (547/14,953), CL between 15 mm and <25 mm accounting for 2.1% of cases (313/14,953), and CL <15 mm accounting for 0.5% of cases (69/14,953).

Relationship between CL and preterm delivery (spontaneous preterm delivery and PPROM)

CL and spontaneous preterm delivery rate

Excluding the 318 women with a therapeutic preterm delivery, the preterm delivery rate was 3.7% (540/14,635). There were 391 preterm deliveries (2.8%, 391/13,728) in women with a CL ≥30 mm, 53 preterm deliveries (9.9%, 53/538) in women with a CL between 25 mm and <30 mm, 65 preterm deliveries (21.5%, 65/303) in women with a CL between 15 mm and <25 mm, and 31 preterm deliveries (31/66) in women with a CL <15 mm. The RR for spontaneous preterm delivery for a woman with a CL between 25 mm and <30 mm was 3.7, for a woman with a CL between 15 mm and <25 mm the RR was 9.3, and for a woman with a CL <15 mm the RR was 30.2 (P < 0.05) (Fig. 2 and Table 1).

F2
Figure 2:
CL during 28–32 weeks gestation and preterm delivery rate. CL: Cervical length.
Table 1 - CL at 28–32 weeks of gestation and preterm delivery risk.
Cervical length (mm) Total (n) Preterm delivery rate, n (%) RR (95% CI)
≥30 13 728 391 (2.8)
25–<30 538 53 (9.9) 3.7 (2.8, 5.0)
15–<25 303 65 (21.5) 9.3 (7.0, 12.5)
<15 66 31 (47.0) 30.2 (18.4, 49.5)
CI: Confidence interval; CL: Cervical length; RR: Relative risk; –: Not applicable.

CL and preterm delivery before 35 weeks of gestation

Excluding the 318 women with a therapeutic preterm delivery, the rate of spontaneous preterm delivery occurring before 35 weeks of gestation was 1.1% (161/14,635). There were 92 preterm deliveries before 35 weeks of gestation (0.7%, 92/13,728) in women with a CL ≥30 mm, 19 preterm deliveries before 35 weeks of gestation (3.5%, 19/538) in women with a CL between 25 mm and <30 mm, 29 preterm deliveries before 35 weeks of gestation (9.6%, 29/303) in women with a CL between 15 mm and <25 mm, and 21 preterm deliveries before 35 weeks of gestation (31.8%, 21/66) in women with a CL <15 mm. The RR for spontaneous preterm delivery before 35 weeks of gestation for women with a CL between 25 mm and <30 mm was 5.4, for women with a CL between 15 mm and <25 mm the RR was 15.7, and for women with a CL <15 mm the RR was 69.1 (P < 0.05) (Fig. 3 and Table 2).

F3
Figure 3:
CL during 28–32 weeks gestation and preterm delivery rate before 35 weeks of gestation. CL: Cervical length.
Table 2 - CL at 28–32 weeks of gestation and risk for preterm delivery occurring before 35 weeks of gestation.
Cervical length (mm) Total (n) Preterm delivery before 35 weeks, n (%) RR (95% CI)
≥30 13,728 92 (0.7)
25–<30 538 19 (3.5) 5.4 (3.3, 9.0)
15–<25 303 29 (9.6) 15.7 (10.2, 24.2)
<15 66 21 (31.8) 69.1 (39.6, 120.7)
CI: Confidence interval; CL: Cervical length; RR: Relative risk; –: Not applicable.

The ability of CL during the late trimester to predict preterm delivery

The sensitivity, specificity, and positive and negative predictive values for a CL ≤25 mm at 28–32 weeks of gestation as the cut-off value for predicting preterm delivery were 19.8%, 97.5%, 23.4%, and 96.9%, respectively. For predicting preterm delivery occurring before 35 weeks of gestation, the sensitivity, specificity, and positive and negative predictive values for a CL ≤25 mm at 28–32 weeks of gestation as the cut-off value were 30.0%, 97.2%, 11.8%, and 99.1%, respectively (Table 3).

Table 3 - Prediction of preterm delivery using CL at 28–32 weeks of gestation (CL ≤25 mm).
Items Preterm delivery at <37 weeks Preterm delivery at <35 weeks
Sensitivity (%) 19.8 30.0
Specificity (%) 97.5 97.2
Positive predictive value (%) 23.4 11.8
Negative predictive value (%) 96.9 99.1
CL: Cervical length.

CL and PPROM

PPROM occurred in 407 pregnant women (2.7%, 407/14,953). The CL at 28–32 weeks of gestation in women with PPROM (31.9 ± 7.4) mm was significantly shorter than that in women without PPROM (34.0 ± 8.3) mm. The incidence of PPROM for women with a CL ≤25 mm at 28–32 weeks of gestation (19.4%, 79/407) was significantly lower than that for women with a CL >25 mm (80.6%, 328/407; P < 0.05). The incidence of PPROM for women with a CL ≥30 mm was 2.4% (328/13,728), for women with a CL between 25 mm and <30 mm the incidence was 5.9% (32/538), for women with a CL between 15 mm and <25 mm the incidence was 11.6% (35/303), for women with a CL <15 mm the incidence was 18.2% (12/66). The RR for PPROM in women with a CL between 25 mm and <30 mm was 2.6, for women with a CL between 15 mm and <25 mm the RR was 5.3, and for women with a CL <15 mm the RR was 8.2 (P < 0.05) (Table 4).

Table 4 - CL and PPROM risk.
Cervical length (mm) Total (n) PPROM, n (%) RR (95% CI)
≥30 13,728 328 (2.4)
25–<30 538 32 (5.9) 2.6 (2.8, 3.8)
15–<25 303 35 (11.6) 5.3 (3.7, 7.7)
<15 66 12 (18.2) 8.2 (4.2, 15.8)
CL: Cervical length; PPROM: Preterm premature rupture of membranes;–: Not applicable.

Discussion

The incidence of preterm delivery in China has been reported to be 5%–7%.10 In the present study, the incidence was 5.7%, which is higher than the reported rate of 4.5% during 1993–2002 at the Peking University First Hospital.8 One reason for the increased rate of preterm delivery is the growing number of therapeutic preterm deliveries. However, the extensive application of assisted reproductive technology has led to an increasing number of multiple pregnancies, which are also associated with preterm deliveries. Moreover, in the present study, PPROM accounted for nearly half of the total number of preterm deliveries, and occurred three times more frequently than spontaneous preterm delivery. This proportion is quite different from that reported in other countries, for which therapeutic, spontaneous, and PPROM accounted for a third of the preterm deliveries each.2,11 Thus, greater attention to PPROM in needed, including the development of effective prevention methods. The distribution of preterm delivery in terms of the weeks of gestation was similar with that reported worldwide, with late trimester preterm deliveries accounting for 75% of preterm deliveries.2

In the present study, we evaluated the relationship between the CL at 28–32 weeks of gestation and preterm delivery using a large, extensive sample. We discovered that in this stage of gestation, the CL could still predict preterm delivery. A previous study showed that the RR for preterm delivery for a CL between 25 and 30 mm at 22–24 weeks of gestation was 5.2, while that for a CL between 15 and 25 mm was 11.1, and that for a CL <15 mm was 13.8.8 However, in the present study, with CL measured at 28–32 weeks, the respective RRs for preterm delivery were 3.7, 9.3, and 30.2. Furthermore, CL measured at 28–32 weeks of gestation had a higher sensitivity for the prediction of preterm delivery than that reported for CL measured at 22–24 weeks (19.8% vs. 3%), with high specificity (97.5%) and negative predictive value (96.9%). The sensitivity and specificity were even higher for the prediction of preterm delivery occurring before 35 weeks of gestation. Although the sensitivity of a CL ≤25 mm at 28–32 weeks of gestation as the cut-off value for the prediction of preterm delivery was not high, the sensitivity increased 10.2% for the prediction of preterm delivery occurring before 35 weeks of gestation, with a negative predictive value of almost 100%. Given that the majority of perinatal mortality and morbidity occur before 35 weeks of gestation, predicting preterm delivery occurring before 35 weeks is clinically meaningful.2,3 The positive predictive value and sensitivity of CL may not be high due to the diverse factors involved in preterm delivery; thus, additional methods are needed to improve prediction of preterm delivery.

The present study also analyzed the relationship between the CL and PPROM. Women with PPROM had a significantly shorter CL at 28–32 weeks of gestation compared to that of women without PPROM. The risk of PPROM in women with a shorter CL at 28–32 weeks of gestation was 6.8 times that of women with a CL in the normal range, which suggests that CL shortening and subclinical infection may be related. In pregnant women with a short cervix, infection of the genital tract and inflammation should be monitored. Donders et al.12 reported that cervical shortening was related to vaginitis. Similarly, Holst et al.13 showed that cervical shortening could predict chorioamnionitis, and the sensitivity and specificity of a CL <15 mm for predicting a threatened preterm premature birth was 72% and 83%, respectively. In a previous study of preterm cases from 2009 to 2012 at our hospital, we found that placental chorioamnionitis was closely related to preterm delivery.14 Therefore, in the late trimester, physicians should focus on the detection and treatment of inflammation in women with a short cervix. In addition to providing patients with a consultation that informs them of the risk of PPROM, further research is needed regarding the mechanism of cervical shortening causing PPROM.

Progesterone has been widely used to prevent preterm delivery. A previous meta-analysis of 775 women found out that treatment with vaginal progesterone in asymptomatic women with a short cervix (≤25 mm) was associated with a significant reduction in the rate of preterm births (<35 weeks; RR: 0.69; 95% confidence interval 0.55–0.88).15 Therefore, the use of progesterone in late trimester women with a short cervix appears to be an effective method for reducing preterm delivery. This may be especially relevant for Chinese women as we previously reported that although the incidence of preterm birth increased with a shorter CL, only 0.2% of Chinese women had a short CL at 20–24 weeks of gestation, much lower than that for European and American countries.8 Our team discovered that although the incidence of preterm increasing with the shorter of CL, but only 0.2% women had short CL during 20–24 weeks of gestation, significantly less than what foreign literatures have reported.8 To et al.16 reported that the percentage of women with CL ≤15 mm at 20–24 weeks of gestation was 1.6%. The report by Salomon et al.17 suggested that the proportion of women with cervical shortening was significantly higher than our results. Differences in the proportion of cervical shortening might be related to differences in race and lifestyle. Most pregnant women in China pay attention to bedrest, especially during the early- and mid-trimesters. Therefore, preventing preterm birth by screening the CL at 20–24 weeks of gestation may be limited. Through this study, we found that cervical shortening during 28–32 weeks pregnancy had a better predictive value for preterm birth before 35 weeks, and further research needed to be carried out prospectively on vaginal application of progesterone in the prevention of preterm birth.

The study had several limitations. First, the study design was of a retrospective nature. Second, the present study was not a multicenter study; however, the extensive sample size renders the conclusions valuable.

In conclusion, cervical shortening at 28–32 weeks of gestation valuably predicted preterm delivery; however, due to the complexity and diversity of the causes of preterm delivery, the sensitivity was not satisfactory. In addition, an improved understanding of the pathophysiology underlying preterm delivery is needed to engender a more accurate method for predicting preterm delivery, reducing preterm birth, and improving the outcomes of preterm infants.

Funding

This study was supported by the Special Fund for Health Development research in The Capital (No. 2016-3-4075).

Author Contributions

Mengying Zhang had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Chunyan Shi. Acquisition of data: Xiaoxiao Zhang. Analyzing ultrasound video clips with the Pixel Flux method: Xiaoxiao Zhang. Analysis and interpretation of data: Mengying Zhang. Drafting of the manuscript: Mengying Zhang, Xiaoxiao Zhang, Chunyan Shi, Huixia Yang.

Conflicts of Interest

None.

Editor Note

Huixia Yang is an Editor-in-Chief of Maternal-Fetal Medicine. The article was subject to the journal's standard procedures, with peer review handled independently of this editor and their research groups.

References

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Keywords:

Cervical length measurement; Preterm delivery; Pregnancy trimester, third; Forecasting

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