Tocolysis in the management of multiple pregnancy
Correspondence: Professor J. W. Dudenhausen, Charité/Campus Virchow Klinikum, Humboldt Universität zu Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany.
Over the years, tocolysis for multiple pregnancy has been discussed for prophylaxis and therapy of preterm labour. Several papers with controlled trials about the prophylactic effect of tocolytic agents could not measure any benefit. However, established preterm labour with progressive cervical change should be promptly treated with tocolytic agents1,2.
The most rigorous scientific evaluation was performed using treatment with the beta-agonists. Some papers have supported the value of treatment for 24–48 hours, but the effect of prolonged tocolysis with beta-agonists is not sufficiently documented. Evaluating the most effective beta-agonist is also confounded by the heterogeneity that exists between randomised controlled trials, for example different dosages and gestational ages. Intravenous beta-agonists are equally efficacious in singleton versus twin pregnancy. In women with twins and triplets intravenous tocolysis prolonged gestation for 48–72 hours3, however, in comparison with placebo the prolonged use of beta-agonists has not been effective in preventing preterm delivery4. The side effects of beta-agonists, such as pulmonary oedema, cardiac arrhythmias, hyperglycaemia and hypokalaemia, are described in several papers. In pregnancies with multiple gestation, there is a higher risk of the development of pulmonary oedema, cardiomyopathy, myocardial ischaemia and maternal tachyarrhythmias with beta-agonists4.
Alternative tocolytic agents, such as magnesium sulphate or calcium channel blockers, have been proposed because of the high frequency of maternal side effects associated with the beta-agonists5. However, data on the effects of these agents in preterm labour in multiple pregnancies are poor.
Indomethacin, used for the treatment of preterm labour in multiple pregnancy, has been shown to be an effective agent. However, this treatment is not without risk because of premature closure of the ductus arteriosus. Nevertheless indomethacin is effective for the treatment of polyhydramnios and is therefore sometimes used in monochorionic twins with twin–twin transfusion syndrome.
In the future, atosiban, a competitive antagonist of oxytocin receptors, may have an important role as a tocolytic agent in multiple pregnancies. This agent has demonstrated advantages in both the maternal and fetal safety profile while the outcome for newborns is comparable with other tocolytic agents, particularly in multiple pregnancies. Atosiban will also be indicated for the treatment of mothers with preterm labour and other risk factors, such as heart disease or severe diabetes mellitus.