The safety of tocolytics used for the inhibition of preterm labour

ABSTRACT

Introduction: Preterm birth is the major cause of neonatal mortality and morbidity worldwide and a huge cost burden on healthcare. Between 22 and 26 completed weeks of gestation, for every day that delivery is delayed, survival increases by 3%.

Areas covered: Following a systematic review of the literature, we have provided an overview of the use of tocolytics for the prevention of preterm birth and have examined the fetal and maternal adverse effects of the various tocolytic agents currently in use.

Expert opinion: No tocolytic currently in use was developed specifically to treat preterm labour so most have multi-organ side effects. β₂-agonists are relatively safe for the fetus but have rare and potentially serious maternal adverse effects. In contrast, prostaglandin synthetase inhibitors have potentially serious side effects for the fetus and neonate but have mild maternal gastrointestinal side effects. In Europe, the choice of first line therapy is either atosiban or nifedipine. The evidence base for atosiban is much more robust than for nifedipine. While their efficacy is similar, atosiban has placebo level side effects and is safer than nifedipine but is much more expensive.

KEYWORDS:

• Atosiban
• adverse events
• beta-agonists
• calcium channel blockers
• nifedipine
• oxytocin receptor antagonists
• preterm birth
• preterm labour
• prostaglandin synthetase inhibitors
• ritodrine
• safety
• tocolytics

Article highlights

• No tocolytic currently in use was developed specifically to treat preterm labour

• Most tocolytics apart from atosiban have multi-organ side effects.

• β₂-agonists are relatively safe for the fetus but have rare and potentially serious maternal adverse effects.

• Prostaglandin synthetase inhibitors have potentially serious side effects for the fetus and neonate but have mild maternal gastrointestinal side effects.

• The evidence base for atosiban is much more robust than that for nifedipine.

• While their efficacy is similar, atosiban has placebo level side effects and is safer than nifedipine but is much more expensive.

This box summarizes key points contained in the article.

Acknowledgments

R.F.L accepted the commission, and with J.S.J., proposed a framework for the manuscript and provided guidance for the search strategy. C.D.L carried out the search, extracted the data, synthesized the evidence and provided the first draft of the manuscript. R.F.L wrote the Expert Opinion Section and all three co-authors contributed to the subsequent drafts and the final version.

Declaration of interest

In the past, RF.Lamont has advised or given lectures on conferences organised or supported by Glaxo-Smith-Klein, Sanofi-Synthelabo and Ferring Pharmaceuticals pertaining to PTB in general and tocolytics in particular. Currently R.F.Lamont is a member of an Independent Drug Monitoring Committee for a randomised controlled trial of a tocolytic agent. Currently, J.S.Jørgensen is an advisor to and has lectured on conferences organised or supported by Ferring Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed