A risk-benefit assessment of therapies for premature labour

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. β-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.