Professor Thornton described
the evidence relating to both. The following is a summary
of the key messages.
Tocolysis
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 ( 1).
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 (2).
The oxytocin antagonist, atosiban, has a comparable
effect on delivery delay to the beta agonists but fewer
maternal side effects (3,4,5).
Nifedipine is associated with a greater chance of
delivery delay, less maternal side effects and less
neonatal respiratory distress syndrome than the beta
agonists (6).
There is a theoretical risk to the fetus, from animal
studies (7),
although human clinical studies have so far failed
to show a similar result (8).
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 (9).
References
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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