Singapore Med J. 2006
May;47(5):361-6.
Tocolytic treatment for the management of preterm labour: a systematic
review.
Tan TC, Devendra K, Tan LK, Tan HK.
Department of General Obstetrics and Gynaecology, KK Women's and
Children's Hospital, Singapore. dr. Tctan@pacific.net.sg
Spontaneous preterm labour and delivery accounts for approximately
one-third of preterm births, which is the predominant cause of perinatal
mortality and morbidity. This review aims to evaluate the evidence on
the benefits and harms of five classes of tocolytic therapy, namely:
betamimetics, calcium channel blockers, magnesium, non-steroidal
anti-inflammatory agents, and atosiban. We performed a systematic review
of the effectiveness of tocolytics to stop uterine contractions
(first-line therapy). Reports of randomised controlled trials from
searches of MEDLINE, bibliographies of review articles, Cochrane
Collaboration and its Pregnancy and Childbirth Review Group between 1966
and 2003 were identified, using the search terms "randomised controlled
trial" (RCT), "preterm labor", "tocolysis", "betamimetics", "ritodrine",
"prostaglandin synthetase inhibitors", "indomethacin", "calcium channel
blockers", "nifedipine", "oxytocin receptor blockers", "atosiban", and
"magnesium sulphate". Studies on women with preterm labour comparing the
effects of a tocolytic with a placebo or no treatment that met our
inclusion criteria, were included. To our knowledge, the trials were
conducted mainly before 1999 and there were no placebo-controlled trials
after that. Of the 86 articles identified and evaluated, 14 first-line
studies met more stringent requirements for meta-analyses. Tocolytics
were associated with significant decreases in the odds of delivery
within 24 hours (odds-ratio [OR] 0.54, 95 percent confidence interval
[CI] 0.32-0.91) and 48 hours (OR 0.47, 95 percent CI 0.30-0.75). These
effects were significant for beta-agonists, atosiban and indomethacin,
but not magnesium sulphate. Maternal side effects significantly
associated with betamimetics were pulmonary oedema, cardiac arrhthymias
and hypokalaemia. Although calcium antagonists have not been evaluated
against placebo, comparative trials with beta-agonists have shown more
favourable neonatal outcomes and better prolongation of gestation. In
conclusion, the management of threatened preterm labour with first-line
tocolytic therapy can prolong gestation. However, the time gained in-utero
need to be optimised. There is no clear first-line tocolytic agent. The
use of tocolytic agents should be individualised and based on maternal
condition, potential side effects and gestational age.