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Keywords:

  • LEEP;
  • loop electrosurgical excision procedure;
  • meta-analysis;
  • preterm birth;
  • transvaginal ultrasonography;
  • uterine anomaly

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Objectives

To estimate the ability of cervical length measured by transvaginal ultrasonography in asymptomatic high-risk women to predict spontaneous preterm birth.

Methods

MEDLINE, PubMed, EMBASE and the Cochrane Library were searched for articles published in any language between January 1980 and July 2006, using the keywords ‘transvaginal ultrasonography’ or (‘cervix’ and (‘ultrasound’ or ‘ultrasonography’ or ‘sonography’)); and (‘preterm’ or ‘premature’) and (‘delivery’ or ‘labour/labor’ or ‘birth’), identifying cohort studies evaluating transvaginal ultrasonographic cervical length measurement in predicting preterm birth in asymptomatic women who were considered at increased risk (because of a history of spontaneous preterm birth, uterine anomalies or excisional cervical procedures), with intact membranes and singleton gestations. The primary analysis included all studies meeting the inclusion criteria. Secondary analyses were also performed specifically for (1) women with a history of spontaneous preterm birth; (2) those who had undergone an excisional cervical procedure; and (3) those with uterine anomalies.

Results

Fourteen of 322 articles identified (involving 2258 women) met the criteria for systematic review. Cervical length measured by transvaginal ultrasonography predicted spontaneous preterm birth. The shorter the cervical length cut-off the higher the positive likelihood ratio (LR). The most common cervical length cut-off was < 25 mm. Using this cut-off to predict spontaneous preterm birth at < 35 weeks, transvaginal ultrasonography at < 20 weeks' gestation revealed LR+ = 4.31 (95% CI, 3.08–6.01); at 20–24 weeks, LR+ = 2.78 (95% CI, 2.22–3.49); and at > 24 weeks, LR+ = 4.01 (95% CI, 2.53–6.34). In women with a history of spontaneous preterm birth (six studies involving 663 women) cervical length at < 20 weeks revealed LR+ = 11.30 (95% CI, 3.59–35.57) and at 20–24 weeks LR+ = 2.86 (95% CI, 2.12–3.87), but there were limited data on the use of cervical length of more than 24 weeks in this group (one study involving 42 women). In women who had had excisional cervical procedures, two studies presented data on cervical length (one at < 24 weeks and one at > 24 weeks), finding cervical length at < 24 weeks to be predictive of spontaneous preterm birth at < 35 weeks (LR+ = 2.91, 95% CI, 1.69–5.01). One study (of 64 women) evaluated cervical length in women with uterine anomalies, finding it predictive of spontaneous preterm birth at < 35 weeks (LR+ = 8.14, 95% CI, 3.12–21.25).

Conclusion

Cervical length measured by transvaginal ultrasonography in asymptomatic high-risk women predicts spontaneous preterm birth at < 35 weeks. Further research may be warranted to evaluate the use of transvaginal ultrasonography after 24 weeks' gestation in women with a history of spontaneous preterm birth, and in women with uterine anomalies. Copyright © 2008 ISUOG. Published by John Wiley & Sons, Ltd.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Preterm birth is a major cause of perinatal morbidity and mortality1–8, and despite improvements in perinatal management over the last two decades, the rate of preterm birth has not declined9–12. Preterm birth may be classified by its clinical presentation, including preterm premature rupture of membranes, spontaneous preterm labor or indicated delivery for maternal or fetal reasons13–16. A number of risk factors of preterm birth have been identified, one of the most important being a history of spontaneous preterm birth17–21.

Cervical length, as measured by transvaginal ultrasonography, has been shown to predict preterm birth in asymptomatic low-risk women as well as those presenting with threatened preterm labor22–30. Some studies have evaluated the use of transvaginal ultrasonography in asymptomatic high-risk women29, 31, but differences among them exist regarding the cervical length cut-off defined as abnormal, gestational age at which transvaginal ultrasonography was performed and the gestational age at preterm birth. Previous meta-analyses have addressed the use of transvaginal ultrasonography to predict preterm birth in asymptomatic women, including those with singleton and multiple gestations27, 29, and those presenting with threatened preterm labor27–29. None of these systematic reviews evaluated high-risk asymptomatic women (such as those with a history of spontaneous preterm birth) separately. The purpose of this meta-analysis was to estimate the ability of cervical length, as measured by transvaginal ultrasonography in asymptomatic high-risk women, in predicting spontaneous preterm birth.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

MEDLINE, PubMed, EMBASE and the Cochrane Library were searched for articles published in any language between January 1980 and July 2006, using the keywords ‘transvaginal ultrasonography’ or (‘cervix’ and (‘ultrasound’ or ‘ultrasonography’ or ‘sonography’)); and (‘preterm’ or ‘premature’) and (‘delivery’ or ‘labour/labor’ or ‘birth’) identifying cohort studies evaluating transvaginal ultrasonographic cervical-length measurement in predicting spontaneous preterm birth. References from these publications were searched manually and cross-referenced to identify additional relevant articles. Because of the lack of details regarding study methods and results, abstracts and unpublished works were not included.

Inclusion criteria were cohort studies that evaluated transvaginal ultrasonographic assessment of cervical length or funneling in predicting spontaneous preterm birth in asymptomatic women with intact membranes and singleton gestations who were considered at increased risk (such as those with a history of spontaneous preterm birth, uterine anomalies or excisional cervical procedures). Studies were ineligible if they were case-control studies, if they included low-risk women in their cohort, if they included multiple gestations, if there was double reporting of results, if only the abstract was available or if the data presented did not allow abstraction of data for the outcome of interest, i.e. preterm birth. Additional data analysis was provided for one published study to allow abstraction of data32.

The primary outcome of the systematic review was spontaneous preterm birth at < 35 weeks' gestation, with secondary outcomes of spontaneous preterm birth at < 37 weeks, < 32 weeks, < 30 weeks, < 28 weeks and < 26 weeks' gestation. Studies reporting on an outcome of spontaneous preterm birth at < 34 weeks were considered with those reporting spontaneous preterm birth at < 35 weeks, as both these gestational ages have similar outcomes. A variety of cervical-length cut-offs were used by the studies, so all the cut-offs described in the studies included in this systematic review were evaluated. If a study described the cervical-length cut-off as less than or equal to a certain length (e.g. ≤ 25 mm) the data were analyzed with studies with a cut-off of less than that length (e.g. < 25 mm). The timing of transvaginal ultrasonography was divided into three periods − 14 to 20 weeks, 20 + to 24 weeks, and after 24 weeks. We also report results for transvaginal ultrasonography for the time period < 24 weeks. If a study reported more than one time period within our chosen time period, we used the data from the latest time period (e.g. in evaluating data for < 24 weeks, if a study reported 15–20 weeks and 20 + up to 24 weeks we used data from the latter group). If there was significant overlap between time periods for the data in the study compared with our chosen time periods we did not use the data from the study in that particular analysis (e.g. data presented from 9 + to 32 weeks were not included in any of the three time periods). Meta-analyses were also performed specifically for (1) women with a history of preterm birth; (2) those who had undergone an excisional procedure for cervical dysplasia; and (3) those with uterine anomalies.

If the abstract described a study that did not meet the eligibility criteria, the study was not reviewed further. Published studies for all other abstracts were reviewed in detail. The review of studies was undertaken independently by the two co-authors, who agreed on which studies were eligible for inclusion in our systematic review. Any disagreements were resolved through discussion and consensus. The two co-authors abstracted data independently for the outcomes of interest.

Baseline data were analyzed descriptively. Statistical analyses were conducted using the program ‘Review Manager 4.27’ (Cochrane Collaboration, Oxford, UK). We calculated summary likelihood ratios (LR) and 95% confidence intervals (CI) for the outcomes of interest. Tests of heterogeneity among pooled results were conducted using a simple χ2 test. Fixed-effects models were used if there was no significant heterogeneity, and random-effects models if significant heterogeneity was present. Results were considered to be statistically significant if the 95% CI did not encompass 1.0 for the LR, or if the P-value was < 0.05. MOOSE guidelines for a meta-analysis of observational studies were followed33.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

The search yielded a total of 322 abstracts, of which 293 were excluded because they did not meet eligibility criteria. The remaining 29 studies were reviewed in detail31, 32, 34–60. Fifteen studies were not included for the following reasons: four studies included low-risk women in their cohorts37–40, three studies included multiple gestations41–43, two studies did not present data for the outcome of interest (preterm birth)44, 45, two studies did not present information in such a way as to allow abstraction of data into 2 × 2 tables36, 46, one study presented data that had been previously published47, one study did not present data on cervical length and was a secondary analysis of an earlier published study48, one study used translabial ultrasound for some women49 and one study was an editorial and so did not present new data35. The remaining 14 studies were included in the review. One of the included articles50 was a secondary analysis of an initial study31. Both publications were included in the present analysis as they presented data for different gestational ages of preterm birth. Five studies (six publications) evaluated only women with a history of preterm birth31, 50–54, two studies evaluated women with a history of excisional cervical procedures for dysplasia (e.g. loop electrosurgical excision procedure (LEEP) or cone biopsy)32, 55, one study examined women with uterine anomalies56 and the remaining five studies evaluated a combination of high-risk women34, 57–60.

The characteristics of the studies included in the review are presented in Table 1. Three studies (four publications) were blinded31, 50, 52, 54. Ten studies (eleven publications) were prospective31, 32, 34, 50, 54–60, and the remaining three were retrospective51–53. Table 2 summarizes the gestational age at the time of ultrasound, the cervical length cut-offs and the gestational age of the outcome, preterm birth. The most common cervical cut-off was < 25 mm (in 12 studies, 13 publications), with the most common outcome of preterm birth being a gestational age of < 35 (or < 34) weeks (reported in 14 studies). Five studies reported data for cervical length < 20 weeks31, 34, 54, 58, 59, four studies for 20 + to 24 weeks51, 52, 54, 58, 11 studies (12 publications) up to 24 weeks31, 34, 50–59 and three studies beyond 24 weeks32, 54, 60.

Table 1. Studies included in the review
ReferenceDescriptionnInclusion criteriaExclusion criteria
  1. D&C, dilatation and curettage; DES, diethylstilbestrol; LEEP, loop electrosurgical excision procedure; PPTB, previous preterm birth; PSPTB, previous spontaneous preterm birth; PTB, preterm birth.

Crane et al. (2006)32Prospective cohort  Test described  Not blinded75Prior LEEP  Singleton pregnancy 
Durnwald et al. (2005)51Retrospective cohort  Test described  Not blinded188PPTB 18 + 0 to 36 + 6 weeks  Singleton pregnancyMultiple gestation  Uterine anomalies  Prior cervical surgery
Airoldi et al. (2005)56Prospective cohort  Test described  Not blinded64Uterine anomaliesHistory indicated cerclage  Multiple gestation  Medically indicated PTB  Undelivered  Ultrasound information unavailable
de Carvalho et al. (2005)52Retrospective cohort  Test described  Blinded180PPTB < 37 weeksIndicated (elective) PTB
Berghella et al. (2004)55Prospective cohort  Test described  Not blinded109Prior excisional cervical biopsy (cold knife cone, LEEP, laser)Non excisional cervical procedures  Prophylactic cervical cerclage  Multiple gestation  Major fetal anomaly  Medically indicated PTB
Berghella et al. (2003)57Prospective cohort  Test described  Not blinded183PPTB 14–34 weeks  ≥ 2 D&C for termination of pregnancy  Müllerian anomaly  Cone biopsy  DES exposurePlacenta previa  Current drug abuse  Severe fetal anomalies  Induced PTB
To et al. (2002)53Retrospective cohort  Test described  Not blinded43PPTB 16–33 weeks  Singleton pregnancy 
Guzman et al. (2001)58Prospective cohort  Test described  Not blinded469Singleton pregnancy  Asymptomatic  PPTB 24–37 weeks  ≥ 2 D&C for termination of pregnancy  Cone biopsy  Uterine malformation  Previous cerclage  DES exposurePregnancy delivered for maternal or fetal indications
Owen et al. (2001)31 and (2004)50Prospective cohort  Test described  Blinded183PSPTB < 32 weeks  Singleton pregnancyChronic medical or obstetric problems   that may result in indicated PTB  History of substance abuse  Uterine anomalies  Cervical cerclage for clinical history of   cervical incompetence
Andrews et al. (2000)54Prospective cohort  Test described  Blinded69PSPTB 16–30 weeks  Singleton pregnancyMedical or obstetric complications  Signs or symptoms of preterm labor  History of cervical incompetence   requiring cerclage  Presentation > 28 weeks
Cook et al. (2000)59Prospective cohort  Test described  Not blinded120Singleton pregnancy  PPTB < 34 weeks  Previous spontaneous loss at 14–20   weeks  ≥ 3 D&C for termination of pregnancy  Cervical laser or cone biopsy  Uterine anomaly  Second-trimester bleedingElective delivery < 37 weeks
Berghella et al. (1999)34Prospective cohort  Test described  Not blinded168PSPTB 14–34 weeks  ≥ 2 D&C  Müllerian anomaly  Cone biopsy  DES exposureProphylactic cervical cerclage  Placenta previa  Current drug abuse  Severe fetal anomalies
Watson et al. (1999)60Prospective cohort  Test described  Not blinded407PPTB  Uterine anomaly  Extremes of maternal age  Maternal smokingIatrogenic PTB  Multiple gestation  Known fetal anomaly
Table 2. Cervical length cut-offs and gestational age of outcomes of the studies included
ReferenceGA at ultrasound (weeks) Cervical length cut-off (mm) GA at delivery (weeks)
  1. GA, gestational age.

Crane et al. (2006)3224–30< 10, < 15, < 20, < 25, < 30, < 35< 34, < 37
Durnwald et al. (2005)5122 + 0 to 24 + 6< 25< 32, < 35
Airoldi et al. (2005)5614 to 23 + 6< 25< 35
de Carvalho et al. (2005)5221–24≤ 10, ≤ 15, ≤ 20, ≤ 25, ≤ 30≤ 34
Berghella et al. (2004)5516 to 23 + 6< 25< 35
Berghella et al. (2003)5714 to 23 + 6< 20, < 25, < 30, < 35< 35
To et al. (2002)5312 to 23 + 6≤ 25< 34
Guzman et al. (2001)5815–20≤ 25< 28, < 30, < 32, < 34
 21–24  
 15–24  
Owen et al. (2001)31 and (2004)5016 to 18 + 6< 15, < 20, < 25, < 30< 26, < 35
 Up to 23 + 6  
Andrews et al. (2000)54< 20< 22, < 25, Funnel< 35
 20–24  
 25–29  
Cook et al. (2000)59Up to 20< 30< 34, < 37
 Up to 24  
 Up to 32  
Berghella et al. (1999)3414 to 17 + 6< 25, < 35< 35
 18 to 21 + 6  
Watson et al. (1999)6024–28≤ 15, ≤ 20, ≤ 25, ≤ 30, ≤ 35, ≤ 40, ≤ 45< 35

Tests of heterogeneity found no significant heterogeneity and so fixed-model effects were used for the meta-analyses. The likelihood ratios varied depending on the cervical length cut-off and the gestational age of the outcome of preterm birth, but overall cervical length appeared to predict spontaneous preterm birth as the confidence intervals did not include 1.0 (except < 35 mm at 14–20 weeks; < 10 mm or funneling at 20–24 weeks; and < 10 mm or funneling at or before 24 weeks) (Table 3). There appeared to be an inverse relationship between cervical length and the likelihood ratio for preterm birth, with the likelihood ratios for a positive test (LR + ) tending to be higher with lower cervical length cut-off. In addition, earlier gestational ages tended to have higher likelihood ratios for the same cervical length measurement. One study (involving 183 women) evaluated cervical length at < 24 weeks' gestation in predicting spontaneous preterm birth at < 26 weeks and found that a cervical length of < 25 mm had an LR + of 3.20 (95% CI, 2.29–4.49)50. Another study evaluated cervical length at < 20 weeks' gestation in predicting spontaneous preterm birth at < 28 and < 30 weeks and found that a cervical length of < 25 mm had an LR + of 3.62 (95% CI, 2.62–5.01) and 3.43 (95% CI, 2.46–4.78), respectively58. This study also evaluated cervical length at 20 + to 24 weeks' gestation in predicting spontaneous preterm birth at < 28 and < 30 weeks, finding an LR + of 3.84 (95% CI, 3.25–4.53) and 3.37 (95% CI, 2.47–4.60), respectively. The most common cervical length cut-off was < 25 mm. Using this cut-off to predict spontaneous preterm birth at < 35 weeks, cervical length at < 20 weeks revealed an LR + of 4.31 (95% CI, 3.08–6.01); at 20–24 weeks, an LR + of 2.78 (95% CI, 2.22–3.49); and at > 24 weeks, an LR + of 4.01 (95% CI, 2.53–6.34). The corresponding likelihood ratios for a negative test (LR−) for preterm birth at < 35 weeks were: at < 20 weeks, LR− = 0.68 (95% CI, 0.59–0.79); at 20–24 weeks, LR− = 0.55 (95% CI, 0.44–0.69); and at > 24 weeks, LR− = 0.72 (95% CI, 0.60–0.87). The use of a transvaginal ultrasonographic cervical length of < 25 mm at < 24 weeks to predict preterm birth at < 35 weeks revealed a sensitivity of 65.4%, specificity of 75.5%, positive predictive value of 33.0% and negative predictive value of 92.0%. Since—as mentioned above—only three studies (four publications) were blinded31, 50, 52, 54, a secondary analysis evaluating only blinded studies was performed, finding that a cervical length of < 25 mm predicted spontaneous preterm birth at < 35 weeks gestation (LR = 3.30, 95% CI, 2.54–4.30).

Table 3. Likelihood ratios (LR) of a positive test for cervical length measured by transvaginal ultrasonography in predicting spontaneous preterm birth (SPTB)
GA (weeks)Cervical length cut-off (mm)N; nSPTB < 32 weeks (LR (95% CI))N; nSPTB < 35 weeks (LR (95% CI))N; nSPTB < 37 weeks (LR (95% CI))
  1. GA, gestational age at time of ultrasound examination; n, sample size; N, number of studies.

< 20       
 < 15  1; 18330.53 (1.72–542.02)  
 < 20  1; 18314.06 (1.69–117.35)  
 < 22  1; 5321.94 (1.25–384.29)  
 < 251; 4153.18 (2.26–4.47)4; 7424.31 (3.08–6.01)  
 < 30  2; 2643.23 (2.03–5.15)  
 < 35  1; 911.32 (0.88–1.96)  
 Funnel  1; 5326.81 (1.57–457.07)  
20–24       
 < 10  1; 1806.20 (0.91–42.03)  
 < 15  1; 18011.37 (4.62–27.97)  
 < 20  1; 1806.56 (3.94–10.94)  
 < 22  1; 574.51 (1.15–17.64)  
 < 252; 5932.38 (1.67–3.39)4; 8302.78 (2.22–3.49)  
 < 30  1; 1801.75 (1.35–2.27)  
 Funnel  1; 572.71 (0.85–8.64)  
≤ 24       
 < 10  1; 1806.20 (0.91–42.03)  
 < 15  2; 36313.99 (5.63–34.80)  
 < 20  3; 5465.46 (3.66–8.14)  
 < 22  1; 574.51 (1.15–17.64)  
 < 252; 6572.31 (1.85–2.90)9; 14762.76 (2.41–3.17)  
 < 30  4; 6462.24 (1.87–2.69)  
 < 35  1; 1831.33 (1.17–1.52)  
 Funnel  1; 572.71 (0.85–8.64)  
> 24       
 < 15  2; 4825.64 (1.59–20.00)1; 7513.00 (1.30–130.48)
 < 20  2; 4825.16 (2.07–12.87)1; 756.50 (1.52–27.86)
 < 22  1; 424.51 (1.15–17.64)  
 < 25  3; 5244.01 (2.53–6.34)1; 758.38 (3.08–22.75)
 < 30  3; 6022.23 (1.64–3.02)2; 1952.27 (1.58–3.26)
 < 35  2; 4822.23 (1.65–3.01)1; 752.83 (2.03–3.93)
 Funnel  1; 423.21 (1.60–6.44)  

When evaluating studies specifically assessing women with a history of preterm birth, two studies (with 236 women) presented data for cervical length at < 20 weeks gestation31, 54, three studies (425 women) at 20 + to 24 weeks51, 52, 54 and only one study (42 women) beyond 24 weeks (Table 4)54. The likelihood ratios for a positive test in studies of women with a history of preterm birth were similar to the likelihood ratios of the primary analysis. The use of a transvaginal ultrasonographic cervical length of < 25 mm at < 24 weeks to predict preterm birth at < 35 weeks in this subgroup of women revealed a sensitivity of 60.3%, specificity of 78.5%, positive predictive value of 41.4% and negative predictive value of 88.7%.

Table 4. Likelihood ratios (LR) of a positive test for cervical length measured by transvaginal ultrasonography in predicting spontaneous preterm birth (SPTB) in women with a history of preterm birth
GA (weeks)Cervical length cut-off (mm)N; nSPTB < 32 weeks (LR (95% CI))N; nSPTB < 35 weeks (LR (95% CI))
  1. GA, gestational age at time of ultrasound examination; n, sample size; N, number of studies.

< 20     
 < 15  1; 18330.53 (1.72–542.02)
 < 20  1; 18314.06 (1.69–117.35)
 < 22  1; 5321.94 (1.25–384.29)
 < 25  2; 23611.30 (3.59–35.57)
 < 30  1; 1832.81 (1.60–4.94)
 Funnel  1; 5326.81 (1.57–457.07)
20–24     
 < 10  1; 1806.20 (0.91–42.03)
 < 15  1; 18011.37 (4.62–27.97)
 < 20  1; 1806.56 (3.94–10.94)
 < 22  1; 574.51 (1.15–17.64)
 < 251; 1881.77 (0.86–3.65)3; 4252.86 (2.12–3.87)
 < 30  1; 1801.75 (1.35–2.27)
 Funnel  1; 572.71 (0.85–8.64)
≤ 24     
 < 10  1; 1806.20 (0.91–42.03)
 < 15  2; 36313.99 (5.63–34.80)
 < 20  2; 3637.31 (4.32–12.37)
 < 22  1; 574.51 (1.15–17.64)
 < 251; 1881.77 (0.86–3.65)5; 6512.85 (2.30–3.52)
 < 30  2; 3632.09 (1.60–2.73)
 Funnel  1; 572.71 (0.85–8.64)
> 24     
 < 22  1; 423.67 (1.74–7.72)
 < 25  1; 423.26 (1.78–5.96)
 Funnel  1; 423.21 (1.60–6.44)

Two studies (184 women) presented data on women who had had an excisional procedure for cervical dysplasia (Table 5)32, 55. One study presented data separately for LEEP, cryotherapy and cone biopsy32. For the purposes of this review we used data from women who had had LEEP from this study. The other study presented data on women who had undergone a variety of excisional procedures (including LEEP, cold knife cone or laser cone), providing results for all excisional procedures, and for the individual procedures as well55. We included data from this study for all treatments in the main analysis, with information on women undergoing LEEP in a secondary analysis. This study revealed that cervical length of < 25 mm before 24 weeks' gestation is predictive of preterm birth. Cervical length measurement at 24 weeks or beyond was not predictive of preterm birth before 35 weeks, but was predictive of birth at < 37 weeks; however this was based on one study (75 women)32. One study (of 64 women) evaluated women with uterine anomalies, finding that a cervical length of < 25 mm is predictive of spontaneous preterm birth at < 35 weeks' gestation (LR + = 8.14; 95% CI, 3.12–21.25)56.

Table 5. Likelihood ratios (LR) of a positive test for cervical length measured by transvaginal ultrasonography in predicting spontaneous preterm birth (SPTB) in women who have had excisional procedures for cervical dysplasia
GA (weeks)Cervical length cut-off (mm)N; nSPTB < 35 weeks (LR (95% CI))N; nSPTB < 37 weeks (LR (95% CI))
  1. GA, gestational age at time of ultrasound examination; LEEP, loop electrosurgical excision procedure; n, sample size; N, number of studies.

≤ 24 (all cervical treatments)     
 < 251; 1092.91 (1.69–5.01)  
≤ 24 (LEEP)     
 < 251; 554.95 (1.72–14.24)  
> 24 (LEEP)     
 < 101; 753.65 (0.21–64.03)1; 7530.00 (1.54–583.89)
 < 151; 752.61 (0.16–42.32)1; 7513.00 (1.30–130.48)
 < 201; 754.80 (0.79–29.33)1; 756.50 (1.52–27.86)
 < 251; 753.43 (0.60–19.70)1; 758.38 (3.08–22.75)
 < 301; 752.00 (0.37–10.75)1; 757.58 (3.20–17.98)
 < 351, 752.40 (1.83–3.15)1; 752.83 (2.03–3.93)

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Our review confirms that a short cervical length measured by transvaginal ultrasonography identifies asymptomatic high-risk women at an increased risk for spontaneous preterm birth. There was an inverse relationship between cervical length and the likelihood ratio for preterm birth. There were a variety of gestational ages at which transvaginal ultrasonography was performed, cervical length cut-offs defining abnormal, and gestational ages of spontaneous preterm birth evaluated. The most common cervical length cut-off was < 25 mm, predicting spontaneous preterm birth at < 35 weeks' gestation. It would be useful if further studies of cervical length measured by transvaginal ultrasonography evaluated this cervical length and gestational age for spontaneous preterm birth, so that future results can be compared with those of currently available studies. We found short cervical length by transvaginal ultrasonography in women with a history of spontaneous preterm birth, as well as in women who have had excisional cervical procedures, to be predictive of recurrence of spontaneous preterm birth.

It is important that the shortcomings of the studies included in this meta-analysis be addressed. Only three studies (four publications) were blinded. Lack of blinding may have resulted in differences in the management of women with short cervices and possibly affected the outcome of spontaneous preterm birth. Therefore we performed a secondary analysis, finding that a cervical length of < 25 mm predicted spontaneous preterm birth at < 35 weeks' gestation. Some studies included women who had undergone cerclage placement34, 51, 53, 58 or used progesterone51 to try to prolong pregnancy. These treatments may affect cervical length measurement and/or the outcome of the gestational age at delivery. This may partly explain why the likelihood ratio for preterm birth at < 35 weeks with a cervical length of < 10 mm at < 24 weeks' gestation is less than the likelihood ratio for < 15 mm, and why the likelihood ratio for cervical length < 25 mm at 20–24 weeks is less than at < 20 weeks or > 24 weeks. Studies evaluating women with a history of spontaneous preterm birth included in this meta-analysis did not differentiate between those women having preterm premature rupture of membranes leading to preterm birth and those with spontaneous onset of labor with intact membranes. As the pathogenic processes may be different for these two broad etiological categories of preterm birth, it would be important to evaluate each subtype of preterm birth separately to determine whether, in both groups, cervical length measured by transvaginal ultrasonography has a similar predictive value. Some of the studies in this meta-analysis included a variety of risk factors that may have different risks for spontaneous preterm birth, including the risk factors of maternal age and smoking. These risk factors may not have the same risk for preterm birth as other risk factors such as a history of preterm birth and the presence of uterine anomalies1, 61. Therefore a secondary analysis was performed excluding the study by Watson et al., which included women who smoked or were of advanced maternal age as risk factors for preterm birth60, and the results were found to be similar to those of the primary meta-analysis.

Previous research has noted an association with excisional cervical procedures and adverse pregnancy outcomes, including spontaneous preterm birth62. Our review found only two studies specifically assessing cervical length in women who had undergone excisional cervical procedures (such as LEEP) (one study assessing cervical length at < 24 weeks and one study at > 24 weeks), finding a cervical length of < 25 mm at < 24 weeks to be predictive of spontaneous preterm birth at < 35 weeks. Further research would be useful for evaluating the use of cervical length after 24 weeks, as we found it to be predictive of spontaneous preterm birth before 37 weeks, but not before 34 weeks, probably owing to the small sample size of the study.

Research has shown that the presence of a uterine anomaly is a risk factor for preterm birth61. Only one study was identified in this meta-analysis that specifically evaluated only women with a uterine anomaly, finding an association with short cervical length by transvaginal ultrasonography and preterm birth56. Further studies would be useful to confirm these findings and also to determine whether transvaginal ultrasonography in women who have undergone surgical treatment for uterine anomaly (such as resection of a uterine septum) is also predictive of spontaneous preterm birth.

The most common gestational age of transvaginal ultrasonography was less than 24 weeks' gestation (specifically 20–24 weeks). This is consistent with the findings of previous systematic reviews27–29. Although several studies evaluated transvaginal ultrasonography in women beyond 24 weeks, only one study evaluated this timing of transvaginal ultrasonography specifically in women with a history of spontaneous preterm birth. Therefore further research of cervical length measured by transvaginal ultrasonography after 24 weeks' gestation in this subgroup of women may be warranted to determine if it is also predictive of spontaneous preterm birth. This information may be useful in the management of these women and may identify a group of high-risk women for future trials of interventions to reduce preterm birth.

In summary, cervical length measured by transvaginal ultrasonography in asymptomatic high-risk women is predictive of spontaneous preterm birth. The most common cervical length cut-off was less than 25 mm and the most common gestational age of preterm birth was less than 35 weeks' gestation. These findings were also consistent in the subgroup of women with a history of spontaneous preterm birth. Further research may be warranted to evaluate the use of transvaginal ultrasonography in the specific subtypes of spontaneous preterm birth (preterm premature rupture of membranes versus spontaneous onset of labor with intact membranes), in women with a history of preterm birth who have received progesterone treatment, after 24 weeks' gestation in women with a history of spontaneous preterm birth, and women who have been diagnosed with a uterine anomaly, including those who have undergone surgical resection of uterine anomaly.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Funding for this study was provided by the Health Care Foundation, Eastern Health.

References

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  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References
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