Meta-analysis of Nifedipine versus Beta-sympathomimetic Agents for Tocolysis during Preterm Labour

Abstract

Objective: successful tocolysis during preterm labour enables the clinician to gain time in order to administer corticosteroids to the labouring woman in an effort to promote fetal lung maturation and reduce neonatal morbidity and mortality. Our current meta-analysis compared the effectiveness of nifedipine and beta-sympathomimetic agents in achieving tocolysis at 48 hours. In addition a comparison of maternal side effects was made.Data Sources: studies were identified through Ovid MEDLINE (1966 to December 1996). The following MEDLINE search terms were included, using both major MeSH headings and textwords: “tocolysic agents,” “nifedipine,” “calcium channel blocker(s)” and “dihydropyridines.” All Abstracts, review articles and letters were read, and their bibliographies searched for relevant additional articles.Methods of Study Selection: prospective studies were selected if they included more than 20 subjects, provided a formal definition of preterm labour, compared nifedipine with another sympathomimetic agent, randomly allocated subjects to treatment and examined rates for successful tocolysis at 48 hours. Nine randomized clinical trials were identified, of which seven were eligible for our meta-analysis.Tabulation, Integration and Results: data were extracted by a single, non-blinded reviewer for study design, interventions, rates of successful tocolysis at 48 hours, number of extra days achieved with each agent and any significant drug side effects. Both a fixed-effects and random-effects model were used for the meta-analysis. The mean gestational age among the 217 women randomized to receive nifedipine was 31.2 weeks (range 22 to 35 weeks), compared to the 207 women receiving beta-agonists (30.9 weeks; range 22 to 35 weeks). Six trials used intravenous ritodrine in the beta-mimetic arm, while another initiated therapy with magnesium sulphate, thereafter switching to oral terbutaline. Based on an intention-to-treat analysis, short-term tocolysis was favoured slightly with the use of nifedipine (pooled odds ratio [OR] 1.34, 95% CI 0.83 to 2.15). An on-treatment analysis also favoured nifedipine (pooled OR 1.27, 95% CI 0.83 to 1.95). Due to the presence of a significant degree of heterogeneity across these studies, the data were also analysed using a random-effects model, with similar findings to those above. Nifedipine appeared to prolong pregnancy by a mean of 8.6 days (95% CI 5.8 to 11.5 days) over beta-agonists (p=0.03). There were significantly fewer serious side effects observed with nifedipine than with beta-agonists (pooled OR 0.22, 95% CI 0.06 to 0.80). There were eight instances in which beta-agonists were stopped due to serious adverse side effects, compared to only one instance with nifedipine (pooled OR 0.29, 95% CI 0.08 to 1.06).Conclusions: the available data suggest that there is no apparent difference, and possibly a greater tocolytic effect at both 48 hours and up to the time of delivery, with nifedipine, compared to beta-sympathomimetic agents. The number of serious maternal side effects with nifedipine are also fewer. In certain situations where sympathomimetics are poorly tolerated, oral or sublingual nifedipine can be tried for the medical management of preterm labour. A large randomized clinical trial is needed to compare the neonatal outcomes of the therapies, in addition to their relative cost, ease of administration and major maternal side effects.