CRD summary

The review assessed the effectiveness and safety of ritodrine hydrochloride in delaying delivery and decreasing the incidence of pre-term birth. Ritodrine may be useful for the short-term prolongation of pregnancy, but the high incidence of adverse reactions means that administration should be limited. The authors' conclusions reflect the evidence presented but the studies may be of poor quality.

Authors' objectives

To assess the effectiveness and safety of ritodrine hydrochloride in delaying delivery and decreasing the incidence of pre-term birth.

Searching

MEDLINE (1966 to October 2004), the Cochrane CENTRAL Register (Issue 3, 2004) and Igaku-Chuo-Zasshi (1983 to 2004) were searched for English language studies; the search terms were reported. The reference lists of all retrieved articles were also screened.

Study selection

Assessment of study quality

Two reviewers independently assessed the methodological quality of the included studies using five criteria based on the Cochrane Reviewers' Handbook: method of allocation concealment, blinding, sample size calculation, completeness of follow-up and explicit definition of threatened pre-term delivery.

Data extraction

A predefined set of data was extracted from the selected trials to create structured abstract tables. Relative risks (RRs) and 95% confidence intervals (CIs) were extracted. The data were extracted on an intention-to-treat (ITT) basis. The authors did not state how many reviewers performed the data extraction.

Methods of synthesis

Results of the review

Seventeen RCTs (n=1,928) were included.

Methodological quality.

The quality of the included studies was reported as being low, but no significant variation in quality was observed. No evidence of publication bias was identified using the funnel plot.

Intravenous ritodrine hydrochloride.

There was no statistically significant difference in perinatal mortality with intravenous ritodrine hydrochloride compared with control for the overall pooling (RR 1.19, 95% CI: 0.78, 1.81, p=0.46) or for any of the 5 subgroups. Similar results were found for neonatal RDS.

There was a statistically significant decrease in the proportion of births within 48 hours of initiation of treatment with intravenous ritodrine compared with control for the overall pooling and 2 subgroup analyses (studies reporting adequate ITT data, RR 0.68, 95% CI: 0.51, 0.91; excluding trials of only PROM, RR 0.72, 95% CI: 0.53, 0.98). However, statistical heterogeneity was found between the 7 studies in the subgroup analyses excluding trials of only PROM.

Subgroup analysis of studies reporting adequate ITT data suggested that ritodrine was effective for reducing the proportion of births within 7 days of treatment initiation among all pregnant women, including those with multiple pregnancy and those with PROM (RR 0.85, 95% CI: 0.74, 0.97). Subgroup analysis of studies excluding trials with only PROM showed similar effects.

No statistically significant decrease in the proportion of pre- term delivery (birth before 37 weeks' gestation) was observed in the overall pooling or subgroup analyses.

Analysis of studies reporting adequate ITT data showed a decrease in low birth weight infants (the proportion of live-born infants weighing less than 2,500 g) (RR 0.89, 95% CI 0.81, 0.99). There was no statistical heterogeneity across the trials. No statistically significant decrease was observed in any other pooling groups.

A statistically significant increase was found in the incidence of palpitation (RR 8.28, 95% CI: 5.70, 12.02; 5 studies) and chest pain (RR 10.55, 95% CI 3.55, 31.38; 2 studies). No statistical heterogeneity was found across studies.

Maintenance therapy with oral ritodrine hydrochloride.

There was no statistically significant difference between maintenance therapy with oral ritodrine hydrochloride and control for any outcomes.

Authors' conclusions

The effectiveness of intravenous ritodrine is limited. It may be useful for short-term prolongation of pregnancy, but the high incidence of adverse reactions means that administration should be limited. Current evidence fails to support the use of oral ritodrine and its use should be reconsidered.

CRD commentary

The review addressed a clear question that was defined in terms of the participants, interventions, outcomes and study design. Some relevant sources were searched and references of retrieved articles were screened, thereby limiting the possibility of publication bias. Furthermore, a formal assessment of publication bias suggests that this was not present in the review. However, the review was based on only a small number of studies. Only English language articles were included, which means that other relevant studies published in other languages might have been missed. The methods used to select the studies and extract the data were not described, and so it is not known whether any efforts were made to reduce reviewer error and bias. Study quality was assessed but the findings were not reported for individual studies, making it difficult to judge the quality of the evidence. However, the authors did comment that the quality was generally low.

Sensitivity analyses examined the effect of excluding studies which did not provide accurate data for ITT analysis. The characteristics of the included studies were presented in tables. Little information was presented about the intervention (in terms of dosage) and control, so comparability could not be adequately assessed. Sensitivity and subgroup analyses examining relevant differences did not significantly change the results. The review methods were poorly reported, and the potential for bias in the review should not be ignored. The authors' conclusions reflect the evidence presented but, given the limited information provided, the studies may be of poor quality.

Implications of the review for practice and research

Practice: The use of oral ritodrine should not be reconsidered as its use is not supported by current evidence. Although ritodrine may be useful for acute tocolysis or short-term prolongation of pregnancy, the high incidence of adverse reactions indicates that administration should be limited.

Research: Further research using well-controlled clinical trials should be conducted to assess the benefits of tocolytic agents in combination with antenatal steroids.

Funding

Partly supported by a Health and Labour Sciences Research Grant (Health Technology Assessment) from the Ministry of Health, Labour and Welfare, Japan.

Bibliographic details

Yaju Y, Nakayama T. Effectiveness and safety of ritodrine hydrochloride for the treatment of preterm labour: a systematic review. Pharmacoepidemiology and Drug Safety 2006; 15(11): 813-822. [PubMed: 16981213]

Indexing Status

Subject indexing assigned by NLM

MeSH

Administration, Oral; Chest Pain /chemically induced /epidemiology; Evidence-Based Medicine; Female; Humans; Incidence; Infusions, Intravenous; Obstetric Labor, Premature /drug therapy /epidemiology /prevention & control; Pregnancy; Pregnancy Outcome /epidemiology; Randomized Controlled Trials as Topic; Research Design; Risk Factors; Ritodrine /adverse effects /therapeutic use; Safety; Sensitivity and Specificity; Tocolysis /adverse effects /methods; Tocolytic Agents /adverse effects /therapeutic use; Treatment Outcome

AccessionNumber

12006009364

Database entry date

16/05/2008

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.