A Risk-Benefit Assessment of Therapies for Premature Labour

Abstract

Prematurity is the leading cause of neonatal morbidity and mortality, yet the incidence of preterm birth has not declined despite the use of multiple pharmacological agents to treat preterm labour. After reviewing the literature we conclude the following. beta-Agonists have been shown to prolong gestation for 24 to 48 hours; however, these agents have not been shown to decrease neonatal morbidity or mortality. Adverse effects are inevitable and can be life-threatening. There are no proven benefits to mother or fetus with long term therapy. More data are needed regarding the tolerability and efficacy of calcium antagonists before routine clinical use can be recommended. Oxytocin antagonists should be considered investigational drugs and further studies are needed to evaluate their effectiveness in the treatment of preterm labour. Furthermore, the tolerability of oxytocin antagonists in both mother and fetus has not been adequately established. Indomethacin, a prostaglandin inhibitor, has been shown to delay delivery in a limited number of randomised placebo-controlled clinical trials. Sulindac appears promising but has never been evaluated in a well controlled trial. Neonatal adverse effects appear to be minimal with prostaglandin inhibitors as long as the duration of treatment is short (<48 to 72 hours) and the gestational age is <32 weeks. Magnesium sulfate appears to inhibit myometrial contractility but is ineffective at prolonging gestation or preventing preterm birth. Furthermore, magnesium has not been shown to decrease neonatal morbidity or mortality; in fact, some investigators have shown an increase in infant mortality with this agent. There are no data to support adjunctive antimicrobial therapy for the treatment of preterm labour. Oral maintenance therapy with any of these tocolytic agents has not been shown to decrease the rate of preterm birth or recurrent preterm labour.

The interval to spontaneous delivery following discontinuation of maintenance tocolysis

“…The decision to discontinue maintenance tocolysis in the near-term period may be influenced by several recent reviews and meta-analyses that have questioned the efficacy of tocolytic therapy in the treatment of preterm labor and maintenance tocolysis after uterine quiescence [1,11,12]. Indeed, the subject of when to use tocolytics, which route and agent, and for how long is often hotly debated.…”

Preterm Birth: A Review

“…Tocoytics have been used for over 40 years with the aim of preventing PTB by arresting PTL but there is no good evidence that this is successful [7,[766][767][768][769][770][771][772][773]. No sufficiently powered study exists to show an improvement in neonatal outcome and most tocolytics have significant maternal and fetal side effects [7,[766][767][768][769][770][771][772][773].…”

“…No sufficiently powered study exists to show an improvement in neonatal outcome and most tocolytics have significant maternal and fetal side effects [7,[766][767][768][769][770][771][772][773].…”

A review of the role for magnesium sulphate in preterm labour

“…The only RCTs comparing tocolytic MgSO 4 to a physiological saline control failed to show any demonstrable measure of efficacy, and certainly no improvement in perinatal outcomes. 11,12 In addition to the Cochrane study discussed above, other reviews and metaanalyses by investigators in the United States, 13,14 Canada 15 and Britain 16 have all failed to report any evidence of tocolytic efficacy for MgSO 4 , whereas each report has articulated concerns over maternal and fetal safety. For an in-depth analysis of existing tocolytic MgSO 4 RCTs, as well as a relevant meta-analysis of compatible trials, please refer to one of our previous reviews.…”