Adverse drug reactions to tocolytic treatment for preterm labour: prospective cohort study
de Heus, Roel × Mol, Ben Willem Erwich, Jan-Jaap H M van Geijn, Herman P Gyselaers, Wilfried J Hanssens, Myriam Härmark, Linda van Holsbeke, Caroline D Duvekot, Johannes J Schobben, Fred F A M Wolf, Hans Visser, Gerard H A #
BMJ Pub. Group
BMJ - British Medical Journal vol:338 pages:1-6
OBJECTIVE: To evaluate the incidence of serious maternal complications after the use of various tocolytic drugs for the treatment of preterm labour in routine clinical situations. DESIGN: Prospective cohort study. SETTING: 28 hospitals in the Netherlands and Belgium. PARTICIPANTS: 1920 consecutive women treated with tocolytics for threatened preterm labour. MAIN OUTCOME MEASURES: Maternal adverse events (those suspected of being causally related to treatment were considered adverse drug reactions) leading to cessation of treatment. RESULTS: An independent panel evaluated the recorded adverse events, without knowledge of the type of tocolytic used. Of the 1920 women treated with tocolytics, 1327 received a single course of treatment (69.1%), 282 sequential courses (14.7%), and 311 combined courses (16.2%). Adverse drug reactions were categorised as serious or mild in 14 cases each. The overall incidence of serious adverse drug reaction was 0.7%. Compared with atosiban, the relative risk of an adverse drug reaction for single treatment with a beta adrenoceptor agonist was 22.0 (95% confidence interval 3.6 to 138.0) and for single treatment with a calcium antagonist was 12 (1.9 to 69). Multiple drug tocolysis led to five serious adverse drug reactions (1.6%). Multiple gestation, preterm rupture of membranes, and comorbidity were not independent risk factors for adverse drug reactions. CONCLUSIONS: The use of beta adrenoceptor agonists or multiple tocolytics for preventing preterm birth is associated with a high incidence of serious adverse drug reactions. Indometacin and atosiban were the only drugs not associated with serious adverse drug reactions. A direct comparison of the effectiveness of nifedipine and atosiban in postponing preterm delivery is needed.