Subgroup analyses by cervical length cut-offs revealed that in women with cervical length 15.9 mm or less, cerclage was associated with significant prevention of preterm birth cut-offs of less than 37, less than 35, less than 32, and less than 28 weeks of gestation (Table 3). For cervical length 16–24.9 mm, cerclage was associated with significant prevention of preterm birth at less than 37 and less than 24 weeks of gestation (Table 3).
In women with previous preterm birth and cervical length less than 25 mm detected before 20 weeks of gestation, cerclage was associated with significant prevention of preterm birth at less than 35weeks and a significant reduction in perinatal mortality (RR 0.49, 95% CI 0.27–0.87; Table 3). In women with previous preterm birth at less than 24 weeks of gestation and cervical length less than 25 mm, cerclage was associated with significant prevention of preterm birth at less than 35 weeks of gestation and a significant reduction in perinatal mortality (Table 3).
After more than 50 years since its introduction in clinical medicine, our data show that cervical cerclage is beneficial in prevention of preterm birth and in improving perinatal mortality and morbidity in a specific population. The first investigators in the 1950s26,27 had proposed that a stitch of the cervix would benefit women with both previous early births and also cervical changes in the second trimester in the subsequent pregnancy. This meta-analysis of the five trials evaluating cerclage for women with previous spontaneous preterm birth, singleton gestations, and short cervical length less than 25 mm before 24 weeks of gestation shows a significant 30% reduction in recurrent preterm birth at less than 35weeks of gestation and a significant and clinically important 36% decrease in perinatal mortality and morbidity. It would take approximately 20 cerclage procedures to prevent one perinatal death.
The benefit of cerclage in this selected population is clear. All cut-offs for preterm births were decreased, as were neonatal mortality and morbidities, except for chronic lung disease (only reported by one trial). As can be seen, RRs were between 0.38 and 0.80 in Table 3 and between 0.28 and 0.65 for variables reported by most trials in Table 4. Results in the trials were remarkably consistent, with heterogeneity not significant, except in the analysis of birth weight less than 2,500 grams and neonatal intensive care unit admission. The beneficial effect of cerclage was significant with all cervical lengths less than 25 mm, with seemingly even greater effects with shorter cervical lengths. Also, the earlier the short cervical length was detected, the greater the benefit from cerclage may be (Table 3). More than half of the population included was derived from one trial,9 which then should be used most for clinical correlation.
Assuming approximately 8% of women have previous spontaneous preterm birth (approximately 344,000 women in the United States), of which half occurs before 34 weeks of gestation, approximately 32% would have a cervical length less than 25 mm develop before 24 weeks of gestation (approximately 110,000).9 The incidence of preterm birth at less than 37 weeks of gestation in this population would decrease from 61% to 40% (Table 3), so that 23,100 preterm births would be prevented. More than 6,500 newborns would be saved from perinatal death. The effect of this intervention is important but clearly is not the solution to the whole problem of preterm birth. Further progress in prevention based on short cervical length also will depend on further understanding of the pathophysiology of spontaneous preterm birth.
To optimally select patients for this intervention, cerclage effectiveness should be assessed separately in different populations. All cerclage trials should not be combined into one meta-analysis, because these procedures are performed for different indications and among varying populations. Results of such meta-analyses are not clinically interpretable.28 Cerclage has not been shown to be beneficial in other populations, including women with only previous preterm births,13,14 only short cervical length,4–7 multiple gestations,8,12 or other risk factors for preterm births.4–7,13,14 Given this information, the incidence of cerclage in the United States has significantly decreased.29 Cerclage should be offered only to women who have been shown to benefit from this procedure.
The diagnosis of cervical insufficiency is usually based on recurrent painless second-trimester cervical changes leading to early preterm births.30 Our control data show that singleton gestations with previous preterm birth found to have a painless cervical length less than 25 mm before 24 weeks of gestation have a 61% incidence of birth before 37 weeks of gestation and 30% before 32 weeks of gestation compared to general U.S. population incidences of 12% and 2%, respectively.31 It is plausible that women with previous preterm birth with painless cervical length shortening to less than 25 mm in the subsequent pregnancy before 24 weeks of gestation do have a clinically significant component of cervical insufficiency, and that is why cerclage is beneficial.
Strengths of our study are the inclusion of only randomized trials and the consistency of the results with minimal heterogeneity. It is remarkable that the results of the latest, largest trial9 confirmed and were consistent with the meta-analysis of the first trials.8 This meta-analysis differs from the previous meta-analysis8 we reported on cerclage in that we have now restricted the analysis to only women with previous preterm birth, singleton gestations, and short cervical length. The largest randomized trial performed with this population was recently published9 and is now added to the analysis. Moreover, perinatal mortality and morbidities are now available and presented in detail. In addition, by using individual patient-level data, we were able to provide information on outcomes not available by using summary statistics from the original trials and to perform specific subgroup analyses. This method of analyzing individual patient level data has been shown to be most reliable in addressing questions unresolved by individual clinical trials.32
Limitations of our study are those inherent to any meta-analysis. Although we are not aware of unpublished trials on this topic, publication bias cannot be excluded. Other interventions such as tocolytics, activity restriction, antibiotics, and hormonal therapy were not consistent among patients in different trials. None of these interventions has been definitively proven to benefit this selected group of women. Weekly 17-alpha hydroxyprogesterone caproate, beginning at 16–20 weeks of gestation and continuing until 36 weeks of gestation or delivery is currently recommended for women with previous spontaneous preterm birth, because it has been shown to significantly reduce the risk of preterm birth.33 Whether this formulation of progesterone has a cumulative effect on prolonging gestation in women who receive ultrasound-indicated cerclage has recently come into question, with a secondary analysis demonstrating no significant additive benefit of progesterone to cerclage.34 Given these results, it is unlikely that this intervention would alter the results of our analysis, but more research is needed on the interaction of cerclage and progesterone as preventive interventions for preterm birth.
Change in practice is complex and poorly understood and should be based on consistent data from many studies. These results, consistent in five different trials, offer level 1 evidence for benefit from cerclage in a selected population of women at high risk. There is already evidence that history-indicated cerclage, performed for obstetrical risk factors such as previous preterm birth, can be safely replaced by selecting women (ie, those with previous preterm birth) for cerclage based on cervical length screening.18–20 Women with previous spontaneous preterm birth (between 16 and 34 weeks) and singleton gestation can be offered safe and effective screening with transvaginal ultrasonography. Based on data from the largest trial, this screening should start at approximately 16 weeks and continue every 2 weeks until 23 6/7 weeks, unless the cervical length is 25–29 mm, in which case weekly screening is performed.9 If cervical length less than 25 mm develops, then the risks and benefits of cerclage should be discussed and cerclage may be recommended for prevention of recurrent preterm birth.
1. Harris-Requejo J, Merialdi M. The global impact of preterm birth. In: Berghella V, editor. Preterm birth: prevention and management. Oxford (UK): Wiley-Blackwell; 2010. p. 1–7.
2. Iams JD, Goldenberg RL, Meis PJ, Mercer BM, Moawad A, Das A, et al. The length of the cervix and the risk of spontaneous premature delivery. National Institute of Child Health and Human Development Maternal Fetal Medicine Unit Network. N Engl J Med 1996;334:567–72.
3. Owen J, Yost N, Berghella V, Thom E, Swain M, Dildy GA III, et al. Mid-trimester endovaginal sonography in women at high risk for spontaneous preterm birth. JAMA 2001;286:1340–88.
4. Rust OA, Atlas RO, Reed J, van Gaalen J, Balducci J. Revisiting the short cervix detected by transvaginal ultrasound in the second trimester: why cerclage therapy may not help. Am J Obstet Gynecol 2001;185:1098–105.
5. Althuisius SM, Dekker GA, Hummel P, Bekedam DJ, van Geijn HP. Final results of the Cervical Incompetence Prevention Randomized Cerclage Trial (CIPRACT): therapeutic cerclage with bed rest versus bed rest alone. Am J Obstet Gynecol 2001;185:1106–12.
6. To MS, Alfirevic Z, Heath VC, Cicero S, Cacho AM, Williamson PR, et al. Cervical cerclage for prevention of preterm delivery in women with short cervix: randomised controlled trial. Lancet 2004;363:1849–53.
7. Berghella V, Odibo AO, Tolosa JE. Cerclage for prevention of preterm birth in women with a short cervix found on transvaginal ultrasound examination: a randomized trial. Am J Obstet Gynecol 2004;191:1311–7.
8. Berghella V, Odibo AO, To MS, Rust OA, Althuisius SM. Cerclage for short cervix on ultrasound: Meta-analysis of trials using individual patient-level data. Obstet Gynecol 2005;106:181–9.
9. Owen J, Harnkins G, Iams JD, Berghella V, Sheffield JS, Perez-Delboy A, et al. Multicenter randomized trial of cerclage for preterm birth prevention in high-risk women with shortened midtrimester cervical length. Am J Obstet Gynecol 2009;201:375.e1–8.
10. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of randomized clinical trials: is blinding necessary? Control Clin Trails 1996;17:1–12.
11. Moher D, Liberati A, Tetzlaff J, Altman DG, for the PRISMA group. Preferred reporting itmes for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009;339:332–6.
12. Dor J, Shalev J, Mashiach S, Blankstein J, Serr DM. Elective cervical suture of twin pregnancies diagnosed ultrasonically in the first trimester following induced ovulation. Gynecol Obstet Invest 1982;13:55–60.
13. Lazar P, Gueguen S. Multicentred controlled trial of cervical cerclage in women at moderate risk of preterm delivery. Br J Obstet Gynecol 1984;91:731–5.
14. Rush RW, McPherson K, Jones L, Chalmers I, Grant A. A randomized controlled trial of cervical cerclage in women at high risk of spontaneous preterm delivery. Br J Obstet Gynecol 1984;91:724–30.
15. MRC/RCOG Working Party on Cervical Cerclage. Final report of the Medical Research Council/Royal College of Obstetricians and Gynaecologists multicentre randomized trial of cervical cerclage. Br J Obstet Gynecol 1993;100:516–23.
16. Ezechi OC, Kalu BKE, Nwokoro CA. Prophylactic cerclage for the prevention of preterm delivery. Internat J Gynecol Obstet 2004;85:283–4.
17. Szeverényi M, Chalmels J, Grant A, Nagy T, Nagy J, Balogh I, et al. Surgical cerclage in the treatment of cervical incompetence during pregnancy (determining the legitimacy of the procedure) [Hungarian]. Orv Hetil 1992;133:1823–6.
18. Kassanos D, Salamalekis E, Vitoratos N, Panayotopoulos N, Loghis C, Creatsas C. The value of transvaginal ultrasonography in diagnosis and management of cervical incompetence. Clin Exp Obstet Gynecol 2001;28:266–8.
19. Althuisius SM, Dekker GA, van Geijn HP, Bekedam DJ, Hummel P. Cervical incompetence prevention randomized cerclage trial (CIPRACT): study design and preliminary results. Am J Obstet Gynecol 2000;183:823–9.
20. Beigi A, Zarrinkoub F. Elective versus ultrasound-indicated cervical cerclage in women at risk for cervical incompetence. MJIRI 2005;19:103–7.
21. Simcox R, Seed PT, Bennett P, Teoh TG, Poston L, Shennan AH. A randomized controlled trial of cervical scanning vs history to determine cerclage in women at high risk of preterm birth (CIRCLE trial). Am J Obstet Gynecol 2009;200:623.e1–6.
22. Förster F, During R, Schwarzlos G. Treatment of cervical incompetence-cerclage or supportive therapy. [Therapy of cervix insufficiency–cerclage or support pessary?]. Zentralbl Gynakol 1986;108:230–7.
23. Caspi E, Schneider DF, Mor Z, Langer R, Weinraub Z, Bukovsky I. Cervical internal os cerclage: description of a new technique and comparison with shirodkar operation. Am J Perinatol 1990;7:347–9.
24. Keeler SM, Kiefer D, Rochon M, Quinones JN, Novetsky AP, Rust O. A randomized trial of cerclage vs. 17 alpha-hydroxyprogesterone caproate for treatment of short cervix. J Perinat Med 2009;37:473–9.
25. Owen J, Szychowski J, for the Vaginal Ultrasound Cerclage Trial. Neonatal morbidities in a multicenter randomized trial of ultrasound-indicated cerclage for shortened cervical length. Am J Obstet Gynecol 2011;204:s17–8.
26. McDonald IA. Suture of the cervix for inevitable miscarriage. J Obstet Gynaecol Br Emp 1957;64:346–50.
27. Shirodkar VN. A new method of operative treatment for habitual abortion in the second trimester of pregnancy. Antiseptic 1955;52:299–300.
28. Drakeley AJ, Roberts D, Alfirevic Z. Cervical stitch (cerclage) for preventing pregnancy loss in women. The Cochrane Database of Systematic Reviews 2003, Issue 1.
29. Osterman MJK, Martin JA, Menacker F. Expanded health data from the new birth certificate, 2006. National vital statistics reports; Vol. 58, no. 5. Hyattsville (MD): National Center for Health Statistics; 2009.
30. Cervical insufficiency. ACOG Practice Bulletin No. 48. American College of Obstetricians and Gynecologists. Obstet Gynecol 2003;102:1091–9.
31. Hamilton BE, Martin JA, Ventura SJ. Births: Preliminary data for 2008. National vital statistics reports; Vol. 58, no. 16. Hyattsville (MD): National Center for Health Statistics; 2010.
32. Oxman AD, Clarke MJ, Stewart LA. From science to practice. Meta-analyses using individual patient data are needed. JAMA 1995;274:845–6.
33. Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med 2003;348:2379–85.
34. Berghella V, Figueroa D, Szychowski JM, Owen J, Hankins GD, Iams JD, et al. Vaginal Ultrasound Trial Consortium. 17-alpha-hydroxyprogesterone caproate for the prevention of preterm birth in women with prior preterm birth and a short cervical length. Am J Obstet Gynecol 2010;202:351.e1–6.