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Professor Thornton described the evidence relating to both. The following is a summary of the key messages.


The aim of tocolysis should be to delay delivery in order to improve perinatal mortality and morbidity. However, although tocolytics have been shown to reduce the odds of delivery by 24 hours (Odds Ratio 0.47; 95%CI 0.29-0.77), 48hours (OR 0.57; 95% CI 0.38-0.83) and seven days (OR 0.60; 95%CI 0.38-0.95) this has not been accompanied by a subsequent improvement in neonatal outcome (Reference1). The reasons for this may be several fold. Many of the original studies were undertaken prior to the use of antenatal steroids- therefore the delay was not utilised optimally. Some studies considered wide gestation ranges including those babies at later (34-36 week) gestation where a short term delivery delay is much less likely to impact on survival. Tocolytics may have adverse effects either directly or as a result of inappropriate prolongation of pregnancy in an adverse intrauterine environment e.g. abruption.

Thus despite the current lack of evidence for a clear improvement in perinatal outcome, tocolytics may be used where there is no contraindication to pregnancy prolongation and the extra time in utero can be used to good effect e.g. administration of antenatal steroids and transfer to a unit with neonatal facilities if required.

Which Tocolytic?

The beta agonists, especially ritodrine, have been extensively used but have adverse maternal side effects. These include tremor, palpitations, tachycardia, headache, nausea, dyspnoea, hyperglycaemia and hypokalaemia. There have also been some maternal deaths reported. There usage requires strict monitoring with particular attention toward fluid balance. The recent RCOG review of tocolysis- posted for comment- concludes that ridodrine no longer appears to be the drug of choice and recommends either atosiban or nifedipine as alternatives (Reference2).

The oxytocin antagonist, atosiban, has a comparable effect on delivery delay to the beta agonists but fewer maternal side effects (Reference3,Reference4,Reference5).

Nifedipine is associated with a greater chance of delivery delay, less maternal side effects and less neonatal respiratory distress syndrome than the beta agonists (Reference6). There is a theoretical risk to the fetus, from animal studies (Reference7), although human clinical studies have so far failed to show a similar result (Reference8).

To date there is insufficient evidence regarding glyceryl trinitrate and indomethacin and delivery delay. Indomethacin is associated with a possible increased risk of fetal renal impairment and premature closure of the ductus arteriosus.

The MAGnet (magnesium and neurological endpoints trial) revealed an increased neonatal mortality with magnesium sulphate (Reference9).


1.Gyetvai K, Hannah ME, Hodnett ED, Ohlsson A. Tocolysis for premature labour a systematic review. Obstet Gynecol 1999; 94: 869-77, Abstract

2. Tocolytic drugs for women in preterm labour. RCOG guideline- under review

3. The French/Australian Atosiban Investigators Group. Treatment of preterm labor with the oxytocin antagonist atosiban: a double-blind, randomized, controlled comparison with salbutamol. Eur J Obstet Gynecol Reprod Biol. 2001; 98(2):177-85, Abstract

4. The Worldwide Atosiban versus Beta-agonists Study Group.Effectiveness and safety of the oxytocin antagonist atosiban versus beta-adrenergic agonists in the treatment of preterm labour. BJOG. 2001; 108(2): 133-42, Abstract

5. Moutquin JM, Sherman D, Cohen H, Mohide PT, Hochner-Celnikier D et al. Double-blind, randomized, controlled trial of atosiban and ritodrine in the treatment of  preterm labor: a multicenter effectiveness and safety study.Am J Obstet Gynecol. 2000;182(5):1191-9, Abstract

6. Tsatsaris V, Papatsonis D, Goffinet F, Dekker G, Carbonne B. Tocolysis with nifedipine or beta-adrenergic agonists: a meta analysis. Obstet Gynecol 2001; 97: 840-847, Abstract

7. Blea CW, Barnard JM, Magness RR, Phenertton TM, Hendricks SK. Effect of nifedipine on fetal and maternal hemodynamics and blood gases in the pregnant ewe. Am J Obstet Gynecol 1997; 176: 922-30, Abstract

8. Mari G. Kirshon B. Moise KJ Jr. Lee W. Cotton DB. Doppler assessment of the fetal and uteroplacental circulation during nifedipine therapy for preterm labor. American Journal of Obstetrics & Gynecology. 1989; 161: 1514-8, Abstract

9. Mittendorf R. Is tocolytic magnesium sulphate associated with increased total paediatric mortality? Lancet 1997; 350, Abstract

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