Clinical Review

The short cervix and preterm birth: 8 key questions and evidence-based answers

OBG Manag. 2014 July;26(7):29,30,32-34,36-38.

References

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2. Adams MM, Elam-Evans LD, Wilson HG, Gilbertz DA. Rates of and factors associated with recurrence of preterm delivery. JAMA. 2000;283(12):1591–1596.

3. Ananth CV, Getahun D, Peltier MR, Salihu HM, Vintzileos AM. Recurrence of spontaneous versus medically indicated preterm birth. Am J Obstet Gynecol 2006;195(3):643–650.

4. To MS, Skentou CA, Royston P, Yu CK, Nicolaides KH. Prediction of patient-specific risk of early preterm delivery using maternal history and sonographic measurement of cervical length: A population-based prospective study. Ultrasound Obstet Gynecol. 2006;27(4):362–367.

5. Guzman ER, Ananth CV. Cervical length and spontaneous prematurity: Laying the foundation for future interventional randomized trials for the short cervix. Ultrasound Obstet Gynecol. 2001;18(3):195–199.

6. Heath VC, Southall TR, Souka AP, Elisseou A, Nicolaides KH. Cervical length at 23 weeks of gestation: Prediction of spontaneous preterm delivery. Ultrasound Obstet Gynecol. 1998;12(5):312–317.

7. Berghella V, Roman A, Daskalakis C, Ness A, Baxter JK. Gestational age at cervical length measurement and incidence of preterm birth. Obstet Gynecol. 2007;110(2 Pt 1):311–317.

8. Berghella V, Keeler SM, To MS, Althuisius SM, Rust OA. Effectiveness of cerclage according to severity of cervical length shortening: A meta-analysis. Ultrasound Obstet Gynecol. 2010;35(4):468–473.

9. Iams JD, Goldenberg RL, Meis PJ, 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(9):567–572.

10. Werner EF, Han CS, Pettker CM, et al. Universal cervical-length screening to prevent preterm birth: A cost-effectiveness analysis. Ultrasound Obstet Gynecol. 2011;38 (1):32–37.

11. Cahill AG, Odibo AO, Caughey AB, et al. Universal cervical length screening and treatment with vaginal progesterone to prevent preterm birth: A decision and economic analysis. Am J Obstet Gynecol. 2010;202(6):548.e1–e8.

12. Friedman AM, Srinivas SK, Parry S, Elovitz MA, Wang E, Schwartz N. Can transabdominal ultrasound be used as a screening test for short cervical length? Am J Obstet Gynecol. 2013;208(3):190.e1–e7.

13. American College of Radiology, American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Society of Radiologists in Ultrasound. ACR–ACOG–AIUM–SRU Practice Guideline for the Performance of Obstetrical Ultrasound. http://www.acr.org/Quality-Safety/Standards-Guidelines/Practice-Guidelines-by-Modality/~/media/ACR/Documents/PGTS/guidelines/US_Obstetrical.pdf. Accessed June 16, 2014.

14. Owen J, Yost N, Berghella V, et al. Mid-trimester endovaginal sonography in women at high risk for spontaneous preterm birth. JAMA. 2001;286(11):1340–1348.

15. Iams JD, Goldenberg RL, Mercer BM, et al. The Preterm Prediction Study: Recurrence risk of spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol. 1998;178(5):1035–1040.

16. Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH; Fetal Medicine Foundation Second Trimester Screening Group. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med. 2007;357(5):462–469.

17. Hassan SS, Romero R, Vidyadhari D, et al; PREGNANT Trial. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: A multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2011;38(1):18–31.

18. Owen J, Hankins G, Iams JD, 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(4):375.e1–e8.

19. Namouz S, Porat S, Okun N, Windrim R, Farine D. Emergency cerclage: literature review. Obstet Gynecol Surv. 2013;68(5):379–388.

20. Cockwell HA, Smith GN. Cervical incompetence and the role of emergency cerclage. J Obstet Gynaecol Can. 2005;27(2):123–129.

21. Goya M, Pratcorona L, Merced C, et al. Cervical pessary in pregnant women with a short cervix (PECEP): An open-label randomised controlled trial. Lancet. 2012;379(9828):1800–1806.

22. Mendelson CR. Minireview: fetal-maternal hormonal signaling in pregnancy and labor. Mol Endocrinol. 2009;23(7):947–954.

23. Meis PJ, Klebanoff M, Thom E, et al; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003;348(24):2379–2385. Erratum: N England J Med. 2003;349(13):1299.

24. O’Brien JM, Adair CD, Lewis DF, et al. Progesterone vaginal gel for the reduction of recurrent preterm birth: Primary results from a randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol 2007;30(5):687–696.

25. Grobman WA, Thom EA, Spong CY, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network. 17 alpha-hydroxyprogesterone caproate to prevent prematurity in nulliparas with cervical length less than 30 mm. Am J Obstet Gynecol. 2012;207(5):390.e1–e8.

26. Rouse DJ, Caritis SN, Peaceman AM, et al; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. A trial of 17 alpha-hydroxyprogesterone caproate to prevent prematurity in twins. N Engl J Med. 2007;357(5):454–461.

27. Caritis SN, Rouse DJ, Peaceman AM, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Maternal-Fetal Medicine Units (MFMU) Network. Prevention of preterm birth in triplets using 17 alpha-hydroxyprogesterone caproate: A randomized controlled trial. Obstet Gynecol. 2009;113(2 Pt 1):285–292.

28. Rode L, Klein K, Nicolaides KH, Krampl-Bettelheim E, Tabor A; PREDICT Group. Prevention of preterm delivery in twin gestations (PREDICT): A multicenter, randomized, placebo-controlled trial on the effect of vaginal micronized progesterone. Ultrasound Obstet Gynecol. 2011;38(3):272–280.

29. Norman JE, Mackenzie F, Owen P, et al. Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): A randomised, double-blind, placebo-controlled study and meta-analysis. Lancet. 2009;373(9680):2034–2040.

30. Romero R, Nicolaides K, Conde-Agudelo A, et al. Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: A systematic review and metaanalysis of individual patient data. Am J Obstet Gynecol. 2012;206(2):124.e1–e19.

31. Liem S, Schuit E, Hegeman M, et al. Cervical pessaries for prevention of preterm birth in women with a multiple pregnancy (ProTWIN): A multicentre, open-label randomised controlled trial. Lancet. 2013;382(9901):1341–1349.

32. Berghella V, Odibo AO, To MS, Rust OA, Althuisius SM. Cerclage for short cervix on ultrasonography: Meta-analysis of trials using individual patient-level data. Obstet Gynecol. 2005;106(1):181–189.

The degree of cervical shortening that has “qualified” women for study enrollment has varied between studies, with upper limits ranging from 15 to 25 mm. Berghella and colleagues performed a patient-level meta-analysis to determine whether efficacy of the cerclage varied by cervical length at the time of placement.⁸ They examined 552 women with singleton gestations from four randomized controlled trials that included 208 women with a short cervix and a history of spontaneous PTB. They found a significant reduction in the rate of preterm delivery before 35 weeks’ gestation among women with singleton pregnancies, a short cervix, and a history of spontaneous PTB; the reduction did not vary by the degree of cervical shortening. However, there was no significant reduction in the rate of PTB among the subset of women without a history of spontaneous PTB.

Berghella and colleagues estimated that, if a cervical cerclage were offered to the 8% of women with a prior spontaneous PTB and a cervical length of less than 25 mm, more than 6,500 newborns would be saved each year from perinatal death associated with prematurity.⁸

The placement of a “rescue” cerclage in the setting of cervical dilation with or without prolapsing membranes is associated with high rates of maternal and neonatal morbidity, regardless of the patient’s obstetric history. However, cerclage placement in this setting may be associated with better outcomes than expectant management with bed rest alone.¹⁹ Patients should be carefully counseled about this procedure, including the risk of infection and the possibility that pregnancy may be prolonged only from a previable to a periviable gestational age. Decisions as to whether a patient is a candidate for rescue cerclage should be made in consultation with a maternal-fetal medicine specialist.²⁰

6. Is a cervical pessary beneficial?
The pessary is another “mechanical” treatment similar to cerclage, and it may be helpful in reducing the incidence of PTB among women with a short cervix. In the largest study of this approach, 16,000 primarily low-risk women with singleton gestations were screened for a short cervix. Of these, 385 women with a cervical length of less than 25 mm were randomly assigned to undergo Arabin pessary placement or expectant management.²¹

Among those who received the pessary, the odds ratio (OR) for PTB before 34 weeks was significantly reduced (OR, 0.18; 95% confidence interval [CI], 0.08–0.37), and the OR for adverse composite neonatal outcome also was significantly reduced (OR, 0.14; 95% CI, 0.04–0.39).²¹

The Arabin pessary is not currently approved by the US Food and Drug Administration for this indication in the United States, nor is it available for insertion outside of research studies. Other ring-shaped pessaries are available in the United States, but their use in the setting of a short cervix is considered experimental and off-label. Additional studies of this promising intervention are currently under way.

7. Who is a candidate for supplemental progesterone?
Progesterone is a naturally occurring hormone essential to the maintenance of pregnancy. It has an overall quiescent effect on the myometrium, is known to have anti-inflammatory properties, and inhibits cervical ripening.²² It has been studied in a number of different formulations and doses.

Vaginal progesterone supplementation has been shown to reduce the risk of PTB among women with a shortened cervix regardless of their pregnancy history.^16,17,23,24 In the largest trials of unselected general obstetrics populations (including women with and without a history of PTB), use of vaginal progesterone among women with a short cervix reduced the rates of very early spontaneous PTB (<28 and <32 weeks’ gestation) by 40% to 50%.^16,17 As expected, progesterone also was associated with a significant reduction in the rates of respiratory distress syndrome and composite neonatal morbidity.

Intramuscular (IM) progesterone supplementation has been shown to reduce the rate of recurrent PTB among women with a history of spontaneous PTB. When caring for a woman with a history of PTB who is found to have a short cervix, IM progesterone should be offered if the woman is not already taking it. IM progesterone has not been proven effective among nulliparous women who are incidentally found to have a short cervix; it should not be offered in this situation.²⁵

8. Should the care of women carrying twins or triplets be managed differently?
Yes. Although women with multiple gestations are at higher risk for PTB than women carrying a singleton fetus, no interventions have proven to be effective in this population. Many studies have been limited to twin gestations as a group, with an inability to perform subgroup analyses or enroll women who also have a short cervix, due to sample size and power issues.