Preterm labour: Update on prediction and prevention strategies

Current Opinion in Obstetrics and Gynecology

Volumn 18, Issue 6, 2006, Pages 618-624

  Chandiramani, Manju ^a,b   Shennan, Andrew ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b ST THOMAS HOSPITAL   (United Kingdom)

Author keywords

Antibiotics; Cervical cerclage; Fetal fibronectin; Nonsteroidal anti inflammatory drugs (NSAIDs); Preterm birth; Transvaginal ultrasonography

Indexed keywords

ANTIBIOTIC AGENT; BIOCHEMICAL MARKER; FIBRONECTIN; METRONIDAZOLE; NONSTEROID ANTIINFLAMMATORY AGENT; PROGESTERONE; ROFECOXIB;

ANAMNESIS; CERCLAGE; CLINICAL TRIAL; DELIVERY; HIGH RISK POPULATION; HUMAN; NEWBORN MORBIDITY; NEWBORN MORTALITY; PATHOPHYSIOLOGY; PREDICTION; PREMATURE LABOR; PREVENTION STUDY; PRIORITY JOURNAL; REVIEW; SCREENING TEST; TOCOLYSIS; TRANSVAGINAL ECHOGRAPHY; VAGINITIS;

ANTI-BACTERIAL AGENTS; BIOLOGICAL MARKERS; CERCLAGE, CERVICAL; CYCLOOXYGENASE 2 INHIBITORS; FEMALE; FIBRONECTINS; HUMANS; OBSTETRIC LABOR, PREMATURE; PREGNANCY; PREGNANCY OUTCOME; PREMATURE BIRTH; PROGESTERONE; RISK FACTORS; TOCOLYSIS; UTERINE CERVICAL INCOMPETENCE;

EID: 33751016805     PISSN: 1040872X     EISSN: None     Source Type: Journal    
DOI: 10.1097/GCO.0b013e3280106228     Document Type: Review

References (62)

1. Slattery MM, Morrison JJ. Preterm delivery. Lancet 2002; 360:1489-1497.
2. th Annual Report: Confidential Enquiries into Stillbirths and Deaths in Infancy (CESDI). London: HMSO; 1999.
3. Steer P. The epidemiology of preterm labour. BJOG 2005; 112 (S1):1-3. This is an excellent review of the epidemiology of preterm labour, focusing on its definition, gestational length, ethnic differences and causes.
4. Crowley P. Prophylactic corticosteroids for preterm birth. Cochrane Database Syst Rev 1996; (1):CD000065.
5. Langhoff-Roos J, Kesmodel U, Jacobsson B, et al. Spontaneous preterm delivery in primiparous women at low risk in Denmark: population based study. BMJ 2006; 332:937-939. This study showed a 22% increase in the crude national preterm delivery rates (before 37 completed weeks' gestation) in Denmark from 1995 to 2004.
6. Shennan AH, Bewley S. Why should preterm births be rising? BMJ 2006; 332:924-925. This editorial discusses the increase in PTBs and the considerable implications that face society should this continue.
7. Romero R, Espinoza J, Mazor M, Chaiworapongsa T. The preterm parturition syndrome. In: Critchley H, Bennett P, Thornton S, editors. Preterm Birth. London: RCOG Press; 2004. pp. 28-60.
8. Goffinet F. Primary predictors of preterm labour. BJOG 2005; 112 (S1):38-47. This review focuses on primary predictors of preterm labour including demographic, socio-economic and psychosocial factors, history, prenatal surveillance, symptoms during pregnancy. It discusses the use and effectiveness of these predictors and the value of new markers in a low-risk population.
9. Burnett AF. Radical trachelectomy with laparoscopic lymphadenectomy: review of oncologic and obstetrical outcomes. Curr Opin Obstet Gynecol 2006; 18:8-13. This review discusses the effectiveness of trachelectomy in preserving fertility through case series of 50 and 56 pregnancies, highlighting pregnancy outcomes.
10. Berkowitz G, Papiernik E. Epidemiology of preterm birth. Epidemiol Rev 1993; 15:414-443.
11. Gardosi J, Kady SM, Francis A. Fetal growth, maturity and preterm birth. In: Critchley H, Bennett P, Thornton S, editors. Preterm Birth. London: RCOG Press; 2004. pp. 61-72.
12. McLean M, Walters WA, Smith R. Prediction and early diagnosis of preterm labor: a critical review. Obstet Gynecol Surv 1993; 43:209-225.
13. Tekesin I, Eberhart LHJ, Schaeffer V, et al. Evaluation and validation of a new risk score (CLEOPATRA score) to predict the probability of premature delivery for patients with threatened preterm labor. Ultrasound Obstet Gynecol 2005; 26:699-706. This is an evaluation and validation of a clinically useful tool to predict the probability of PTB in symptomatic patients.
14. Leitich H. Secondary predictors of preterm labour. BJOG 2005; 112(S1):48-50. This excellent reviewdiscusses fFn, cervical ultrasonography, bacterial vaginosis and other inflammatory markers and the use of multiple marker tests in predicting PTB.
15. Jackson GM, Edwin SS, Varner MW, et al. Regulation of fetal fibronectin production in human amnion cells. J Soc Gynecol Investig 1996; 3:85-88.
16. Shennan A, Jones G, Hawken J, et al. Fetal fibronectin test predicts delivery before 30 weeks of gestation in high risk women, but increases anxiety. BJOG 2005; 112:293-298. This observational study assessed the efficacy of cervico-vaginal fetal fibronectin as a predictor of spontaneous preterm birth in a high-risk antenatal population and to evaluate the psychological impact of fetal fibronectin testing.
17. Honest H, Khan KS. Preterm birth. In: Critchley H, Bennett P, Thornton S, editors. Preterm labour and the cervicovaginal fetal fibronectin test. London: RCOG Press; 2004. pp. 181-187.
18. Abenhaim HA, Morin L, Benjamin A. Does availability of fetal fibronectin testing in the management of threatened preterm labour affect the utilisation of hospital resources? J Obstet Gynaecol Can 2005; 27:689-694. This study compared the rates, duration and costs of hospitalization for a prospective cohort of women who presented with preterm labour after fFn testing became available with a historical baseline cohort who presented with preterm labour before fFN was available.
19. Gomez R, Romero R, Medina L, et al. Cervicovaginal fibronectin improves the prediction of preterm delivery based on sonographic cervical length in patients with preterm uterine contractions and intact membranes. Am J Obstet Gynecol 2005; 192:350-359. This study examined the diagnostic performance of ultrasonographic measurement of cervical length and vaginal fetal fibronectin determination in the prediction of pretermdelivery in patients with pretermuterine contractions and intact membranes.
20. Schmitz T, Maillard F, Bessard-Bacquaert S, et al. Selective use of fetal fibronectin detection after cervical length measurement to predict spontaneous preterm delivery in women with preterm labor. Am J Obstet Gynecol 2006; 194:138-143. This study showed that fFn detection was significantly (P < 0.001) more specific than cervical length measurement. For selective use of fFn detection after cervical length measurement, the test was considered positive if cervical length was £15mm or if cervical length was between 16 and 30mm with fFn >50 ng/mL.
21. Groom KM, Shennan AH, Bennett PR. Ultrasound-indicated cervical cerclage: outcome depends on preoperative length and presence of visible membranes at time of cerclage. Am J Obstet Gynecol 2002; 187:445-449.
22. Romero R, Espinoza J, Erez O, Hassan S. The role of cervical cerclage in obstetric practice: can the patient who could benefit from this procedure be identified? Am J Obstet Gynecol 2006; 194:1-9. This excellent editorial critically examines 'cervical insufficiency', the value and limitations of cervical sonography as a risk assessment tool, the role of cerclage and the role of inflammation in the outcome of cerclage placement.
23. Hassan SS, Romero R, Berry SM, et al. Patients with an ultrasonographic cervical length ≤15mm have nearly a 50% risk of early spontaneous preterm delivery. Am J Obstet Gynecol 2000; 182:1458-1467.
24. Rust OA, Atlas RO, Kimmel S, et al. Does the presence of a funnel increase the risk of adverse perinatal outcome in a patient with a short cervix. Am J Obstet Gynecol 2005; 192:1060-1066. This study of 279 patients determined that the disruption of the internal os is a significant factor for adverse perinatal outcome and that cervical funnelling is best measured as a categorical variable (present or absent).
25. Espinoza J, Goncalves LF, Romero R, et al. The prevalence and clinical significance of amniotic fluid 'sludge' in patients with preterm labor and intact membranes. Ultrasound Obstet Gynecol 2005; 25:346-352. This retrospective study of 84 patients with preterm labour and intact membranes and 298 patients with uncomplicated term pregnancies concluded that the prevalence of amniotic fluid 'sludge' in symptomatic patients is a risk factor for microbial invasion of the amniotic cavity, histological chorioamnionitis and impending preterm delivery.
26. Daskalasis G, Thomakos N, Hatziioannou L, et al. Cervical assessment in women with threatened preterm labor. J Matern Fetal Neonatal Med 2005; 17:309-312. This study prospectively examined the clinical value of cervical assessment by transvaginal ultrasonography in 172 women with singleton pregnancies and symptoms of preterm labour.
27. Goldenberg RL, Iams JD, Mercer BM, et al. The Preterm Prediction Study: the value of new vs standard risk factors in predicting early and all spontaneous preterm births. Am J Public Health 1998; 88:233-238.
28. Lettieri L, Vintzileos AM, Rodis JF, et al. Does 'idiopathic' preterm labor resulting in preterm birth exist? Am J Obstet Gynecol 1993; 168:1480-1485.
29. Zanardo V, Vedovato S, Trevisanuto DD, et al. Histological chorioamnionitis and neonatal leukemoid reaction in low-birth-weight infants. Human Pathology 2006; 37:87-91. This describes a prospective histological study of placentas of 223 preterm infants, which determined that histological chorioamnionitis (HCA) placental findings increase the risk for neonatal leukemoid reaction. The leukemoid reaction in low-birth-weight neonates with HCA is significantly associated with earlier delivery and bronchopulmonary dysplasia.
30. Romero R, Gonzalez R, Sepulveda W, et al. Infection and labor. VIII. Microbial invasion of the amniotic cavity in patients with suspected cervical incompetence: prevalence and clinical significance. Am J Obstet Gynecol 1992; 167:1086-1091.
31. Hassan S, Romero R, Hendler I, et al. A sonographic short cervix as the only clinical manifestation of intra-amnionitic infection. J Perinat Med 2006; 34:13-19. This was a retrospective cohort study of 152 patients with a short cervix, of which 57 had amniotic fluid analysis to determine the rate of microbial invasion of the amniotic cavity and intra-amniotic inflammation in patients with a cervical length <25mm in the mid-trimester.
32. Carey JC, Klebanoff MA. Is a change in the vaginal flora associated with an increased risk of preterm birth. Am J Obstet Gynecol 2005; 192:1341-1347. This study determined if a change in vaginal flora was associated with an increased risk of PTB and if metronidazole therapy before 32 weeks increased the risk of PTB.
33. Ruetschi U, Rosen A, Karlsson G, et al. Proteomic analysis using protein chips to detect biomarkers in cervical and amniotic fluid in women with intraamniotic inflammation. J Proteome Res 2005; 4:2236-2242. This study analysed amniotic and cervical fluid samples from 27 patients with signs of threatening PTB with or without intra-amniotic inflammation by surface-enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF-MS) to identify novel biomarkers.
34. Goldenberg RL, Goepfert AR, Ramsey PS. Biochemical markers for the prediction of preterm birth. Am J Obstet Gynecol 2005; 192:S36-S46. This review discusses the sources of biological fluid and the use and predictive values for PTB. It emphasizes that a test for any discussed substances should not be introduced into clinical practice until the use of the test, which is followed by an appropriate investigation, leads to a reduction in PTB.
35. Al-Omari WR, Al-Shammaa HB, Al-Tikriti EM, Ahmed KW. Atosiban and nifedipine in acute tocolysis: a comparative study. Eur J Obstet Gynecol Reprod Biol 2006; Jan 27. [Epub ahead of print] This was an interventional, randomized, controlled trial of 63 women with preterm labour varying from 24 to 35 completed weeks of gestation which determined that atosiban and nifedipine are equally effective and efficacious in acute tocolysis.
36. Kashanian M, Akbarian AR, Soltanzadeh M. Atosiban and nifedipin for the treatment of preterm labor. Int J Gynaecol Obstet 2005; 91:10-14. This randomized controlled study of 80 pregnant women with preterm labour between 26 and 34 weeks of pregnancy determined that atosiban is effective and safe for the acute treatment of preterm labour with minimal side effects, and it can be an option in the treatment of preterm labour, especially in patients with heart disease and multiple pregnancies.
37. Cockwell HA, Smith GN. Cervical competence and the role of emergency cerclage. J Obstet Gynaecol Can 2005; 27:123-129. This describes a small study of 12 patients with cerclage insertion and presents a literature review of 638 women to evaluate the role of emergency cerclage for women presenting with a dilated external cervical os and bulging or 'hour-glassing' membranes.
38. Weiner CP, Lee K, Buhimschi CS, et al. Proteomic biomarkers that predict the clinical success of rescue cerclage. Am J Obstet Gynecol 2005; 192:710-718. In this study, amniocentesis was performed to facilitate rescue cerclage in 37 consecutive women with painless dilatation (>2 cm) and no detectable uterine activity for 4 h before cerclage with 39 women with a sonographic normal pregnancy and cervix as controls. A proteomic fingerprint was generated and the mass-restricted score for inflammation calculated. Peaks corresponding to free haemoglobin chains were sought as evidence of decidual haemorrhage or intraamniotic bleeding.
39. Althisius SM, van Geijn HP. Strategies for prevention: cervical cerclage. BJOG 2005; 112 (S1):51-56. This review discusses the use of primary, secondary and tertiary cerclage to manage women at high risk of PTB due to cervical incompetence at different stages of pregnancy.
40. Simcox R, Shennan A. Cervical cerclage: a review. Int J Surg (in press).
41. Lazar P, Gueguen S, Dreyfus J, et al. Multicentred controlled trial of cervical cerclage in women at moderate risk of preterm delivery. BJOG 1984; 91:731-735.
42. Rush RW, Isaacs S, McPherson K, et al. A randomized controlled trial of cervical cerclage in women at high risk of spontaneous preterm delivery. BJOG 1984; 91:724-730.
43. MRC/RCOG Working Party on Cervical Cerclage. Final report of the Medical Research Council/Royal College of Obstetricians and Gynaecologists multicentre randomised trial of cervical cerclage. BJOG 1993; 100: 516-523.
44. Shennan A, Jones B. The cervix and prematurity: aetiology, prediction and prevention. Semin Fetal Neonatal Med 2004; 9:471-479.
45. Berghella A, Odibo AO, To M, et al. Cerclage for short cervix on ultrasonography: meta-analysis of trials using individual patient-level data. Obstet Gynecol 2005; 106:181-189. This excellent meta-analysis identified four well conducted trials. In a total population, PTB <35 weeks of gestation occurred in 29.2% of the cerclage group compared with 34.8% of the non-cerclage group (RR 0.84, 95% CI 0.67-1.06).
46. To MS, Alfirevic Z, Heath VC, et al. Cervical cerclage for prevention of preterm delivery in women with short cervix: randomised controlled trial. Lancet 2004; 363:1849-1853.
47. Sakai M, Shiozaki A, Tabata M, et al. Evaluation of effectiveness of prophylactic cerclage of a short cervix according to interleukin-8 in cervical mucus. Am J Obstet Gynecol 2006; 194:14-19. This study of 16 508 women with singleton pregnancies measured cervical length and IL-8 concentration in the cervical mucus at 20 and 24 weeks of gestation and identified 246 women who had a short cervix. Cervical cerclage was associated with a decrease in premature delivery in patients with cervical shortening and normal IL-8 concentrations. Conversely, elevated IL-8 concentrations in the presence of a short cervix increased the premature delivery rate.
48. Farquharson RG, Topping J, Quenby SM. Transabdominal cerclage: the significance of dual pathology and increased preterm delivery. BJOG 2005; 112:1424-1426. This is a description of 40 cases where strict adherence to an investigation protocol and consistent treatment plan is implemented to explore transabdominal cerclage, the significance of dual pathology and increased preterm delivery.
49. Dodd JM, Flenady V, Cincotta R, Crowther CA. Prenatal administration of progesterone for preventing preterm birth (review). Cochrane Database Syst Rev 2006; (1): CD004947. This excellent review assesses the benefits and harms of progesterone administration during pregnancy to prevent PTB by evaluating all published and unpublished randomized controlled trials, in which progesterone was given by any route to prevent PTB. The meta-analysis involved 988 women: for all women administered progesterone, there was a reduction in the risk of PTB <37 weeks (six studies, 988 women, RR 0.65, 95% CI 0.54-0.79) and <34 weeks (1 study, 142 women, RR0.15, 95% CI 0.04-0.64).
50. Meis PJ. 17 hydroxyprogesterone for the prevention of preterm delivery. Obstet Gynecol 2005; 105:1128-1135. This excellent review focuses much of its discussion on the publication of two large randomized trials of 17 α-hydroxyprogesterone caproate and progesterone suppositories for the prevention of PTB. It discusses the actions of progesterone, early and more recent trials, safety, choice of drug and indications for treatment.
51. Schindler AE. Role of progestogens for the prevention of premature birth. J Steroid Biochem Mol Biol 2005; 97:435-438. This review discusses the value of progesterone use, reviews published data and advocates the consideration of vaginal progesterone and intramuscular 17 α-hydroxyprogesterone caproate as possible treatment options for the prevention of PTB.
52. Di Renzo GC, Rosati A, Mattei A, et al. The changing role of progesterone in preterm labour. BJOG 2005; 112 (S1):57-60. This review discusses the use of progesterone in threatened miscarriage, recurrent miscarriage and preterm labour and concludes that it is more effective when administered intramuscularly in these three pathologies.
53. Lamont RF. Can antibiotics prevent preterm birth: the pro and con debate. BJOG 2005; 112 (S1):67-73. This is an excellent review, which discusses the case for and against using prophylactic antibiotics to prevent PTB. It concludes that the prophylactic use of antibiotics for the prevention of PTB is more likely to be successful if they are used in women with abnormal genital tract flora, early in pregnancy before inflammation and tissue damage can occur, in women with the greatest degree of abnormal genital tract flora and in women with a predisposition to mount a damaging inflammatory response to infection.
54. McDonald H, Brocklehurst P, Parsons J. Antibiotics for treating bacterial vaginosis in pregnancy. Cochrane Database Syst Rev 2005; (1):CD000262. This is a Cochrane review of the effects of antibiotic treatment on bacterial vaginosis in pregnancy including 13 trials involving 5300 women. Antibiotic therapy was effective at eradicating bacterial vaginosis during pregnancy but treatment was not significant in reducing the risk of PTB <37 weeks.
55. Okum N, Gronau KA, Hannah ME. Antibiotics for bacterial vaginosis or Trichomonas vaginalis in pregnancy: a systematic review. Obstet Gynecol 2005; 105:857-868. This systematic review is in contradiction to conclusions of others in suggesting that there is no evidence to support the use of antibiotic treatment for bacterial vaginosis or Trichomonas vaginalis in pregnancy to reduce the risk of PTB or its associated morbidities in low or high-risk women.
56. Larsson P-G, Bergstrom M, Forsum U, et al. Bacterial vaginosis. Transmission, role in genital tract infection and pregnancy outcome: an enigma. Review article III. APMIS 2005; 113:233-245. This meta-analysis suggests that treatment of bacterial vaginosis in early pregnancy could significantly reduce SPB, with an odds ratio of 0.83 (95% CI 0.71-0.96). The authors suggested that a prospective trial should include 9506 women with bacterial vaginosis, of which half should be treated.
57. Varma R, Gupta JK. Antibiotic treatment of bacterial vaginosis in pregnancy: multiple meta-analyses and dilemmas in interpretation. Eur J Obstet Gynecol Reprod Biol 2006; 124:10-14. This meta-analysis had a RR of 0.73 (95% CI 0.55-0.98) based on 6188 women with bacterial vaginosis.
58. Larsson P-G, Fahraeus L, Carlsson B, et al. Late miscarriage and preterm birth after treatment with clindamycin: a randomised consent design study according to Zelen. BJOG 2006; 113:629-637. This was a randomized consent design for clinical trials according to Zelen in Sweden, which screened a total of 9025 women in early pregnancy, of which 819 with a Nugent score of 6 and above were considered to have vaginosis and treated according to Zelen allocation.
59. Klebanoff MA, Hillier SL, Nugent RP. Is bacterial vaginosis a stronger risk factor for preterm birth when it is diagnosed earlier in gestation. Am J Obstet Gynecol 2005; 192:470-477. This is an analysis of 12 937 women who were screened for bacterial vaginosis as part of a previously conducted clinical trial. The OR of PTB in bacterial vaginosis-positive versus bacterial vaginosis-negative women ranged from 1.1 to 1.6 and did not vary significantly by gestational age at which bacterial vaginosis was screened for and diagnosed.
60. Andrew WW, Klebanoff MA, Thome EA, et al. Midpregnancy genitourinary tract infection with Chlamydia trachomatis: association with subsequent preterm delivery in women with bacterial vaginosis and Trichomonas vaginalis. Am J Obstet Gynecol 2006; 194:493-500. This was an ancillary investigation including a secondary analysis of the relationship between genitourinary Chlamydia infection and subsequent PTB in 2470 women who were enrolled in two randomized controlled trials.
61. Shennan Ah, Crawshaw S, Briley A, et al. A randomised controlled trial of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin: the PREMET study. BJOG 2006; 113:65-74. This describes a randomized placebo-controlled trial conducted in 14 UK hospitals of 900 pregnancies screened for fFN at 24 and 27 weeks of gestation. Metronidazole did not reduce early PTB in high-risk pregnant women selected by history and a positive vaginal fFN test. In fact, preterm delivery may be increased by metronidazole therapy.
62. Groom KM, Shennan AH, Jones BA, et al. TOCOX: a randomised, double-blind, placebo-controlled trial of rofecoxib (a COX-2-specific prostaglandin inhibitor) for the prevention of preterm delivery in women at high risk. BJOG 2005; 112:725-730. This was a randomized, double-blind, placebo-controlled trial of 98 singleton pregnancies at high risk of preterm labour to assess the safety and efficacy of the long-term prophylactic use of rofecoxib (cox-2-specific inhibitor). It did not reduce the incidence of early preterm delivery <30 weeks and was associated with an increased risk of delivery before 37 weeks in women at high risk.