CRD summary

This review evaluated the effects of progestational agents on the prevention of pre-term birth. The authors concluded that treatment initiated in the second trimester of pregnancy reduces the risks of pre-term delivery, but the effect on other clinical outcomes is uncertain. Although the conclusions are likely to be reliable, limited evidence means that their wider applicability is unclear.

Authors' objectives

To evaluate the effectiveness of progestational agents initiated in the second trimester to prevent pre-term birth.

Searching

MEDLINE (1996 to 2003), EMBASE (1980 to 2003), and the Cochrane Library were searched for published studies; the search terms were reported. The reference lists of retrieved studies and relevant systematic reviews were also checked for additional articles. There was no attempt to retrieve unpublished papers.

Study selection

Assessment of study quality

The authors reported on the method of randomisation, concealment of allocation, and whether the studies were blinded. The authors did not state how the validity assessment was performed.

Data extraction

Two reviewers independently extracted the data. Event rates were extracted for the outcomes in each comparison group.

Methods of synthesis

Results of the review

Three RCTs were included in the analysis (data from 648 women and 643 infants followed up). The women received progestational agents (n=399) or placebo (n=249).

All of the trials were double-blind. Two trials described the method of randomisation and the third reported concealment of allocation.

The use of progestational agents resulted in a statistically significantly lower risk of delivery less than 37 weeks' gestation than the placebo group (RR 0.57, 95% CI: 0.36, 0.90; 3 RCTs). There were no statistically significant effects on the risks of congenital anomalies (2 RCTs), spontaneous abortion (3 RCTs) or perinatal death (2 RCTs). There was no reported statistical heterogeneity in any of the pooled analyses.

Individual trials comparing progestational treatment with placebo showed statistically significant results for lower risk of delivery before 35 weeks' (RR 0.67, 95% CI: 0.48, 0.93), 34 weeks' (RR 0.15, 95 % CI: 0.04, 0.64) and 32 weeks' (RR 0.58, 95% CI: 0.37, 0.91) gestation. In addition, the risk of birth weight less than 2,500g was lower (RR 0.66, 95% CI: 0.51, 0.87) and mean birth weight was higher (WMD 475.0, 95% CI: 16.56, 933.44) in the treatment groups.

Authors' conclusions

Progestational agents initiated in the second trimester of pregnancy might reduce the risk of delivery less than 37 weeks' gestation for women at increased risk of spontaneous pre-term birth. The effect on neonatal outcome is uncertain.

CRD commentary

The review question was clear, with specific inclusion criteria for the interventions, participants, outcomes and study design. The search strategy was adequate, but the decision to exclude unpublished studies means that relevant articles might have been missed and could indicate publication bias. The review process appeared largely systematic and transparent, the validity assessment criteria applied were relevant, and the method of synthesis was appropriate. Although the authors' conclusions are likely to be reliable, the limited number of studies containing small sample sizes means that their generalisability to all women at risk is unclear. The authors appropriately acknowledged the importance of continued research in this area and made recommendations.

Implications of the review for practice and research

Practice: The authors stated that recommendations for the use of progestational agents should be offered cautiously and should consider uncertainties about their impact on other important clinical outcomes and possible adverse events.

Research: The authors stated that large, well-designed RCTs are needed to determine the effects of progestational treatment on perinatal mortality or serious neonatal morbidity. Future trials should also consider women with a wider range of risk factors for pre-term birth.

Bibliographic details

Mackenzie R, Walker M, Armson A, Hannah M E. Progesterone for the prevention of preterm birth among women at increased risk: a systematic review and meta-analysis of randomized controlled trials. American Journal of Obstetrics and Gynecology 2006; 194(5): 1234-1242. [PubMed: 16647905]

Indexing Status

Subject indexing assigned by NLM

MeSH

Drug Administration Schedule; Female; Humans; Obstetric Labor, Premature /etiology /prevention & control; Pregnancy; Pregnancy Trimester, Second; Progesterone /administration & dosage /therapeutic use; Progestins /administration & dosage /therapeutic use; Randomized Controlled Trials as Topic; Risk; Risk Factors

AccessionNumber

12006002254

Database entry date

30/09/2007

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.