Published 5 March 2009, doi:10.1136/bmj.b744
Cite this as: BMJ 2009;338:b744

Research

Adverse drug reactions to tocolytic treatment for preterm labour: prospective cohort study

Roel de Heus, registrar of obstetrics and gynaecology1, Ben Willem Mol, professor of perinatology and clinical epidemiology2,3, Jan-Jaap H M Erwich, gynaecologist and perinatologist4, Herman P van Geijn, professor of obstetrics5, Wilfried J Gyselaers, gynaecologist and perinatologist9, Myriam Hanssens, professor of obstetrics10, Linda Härmark, pharmacologist7, Caroline D van Holsbeke, gynaecologist and perinatologist9, Johannes J Duvekot, gynaecologist and perinatologist6, Fred F A M Schobben, professor of pharmacology8, Hans Wolf, gynaecologist and perinatologist3, Gerard H A Visser, professor of obstetrics1

1 Department of Perinatology and Gynaecology, University Medical Centre Utrecht, KJ.02.507.0/PO Box 85090, Utrecht, Netherlands, 2 Department of Perinatology and Gynaecology, Maxima Medical Centre, Veldhoven, Netherlands, 3 Department of Perinatology and Gynaecology, Academic Medical Centre, University of Amsterdam, Netherlands, 4 Department of Perinatology and Gynaecology, University Medical Centre Groningen, Netherlands, 5 Department of Obstetrics and Gynaecology, Free University Medical Centre, University of Amsterdam, 6 Department of Perinatology and Gynaecology, Erasmus University Medical Centre, Rotterdam, 7 Pharmacovigilance Centre Lareb, Hertogenbosch, Netherlands, 8 Department of Clinical Pharmacy, University Medical Centre, Utrecht, 9 Department of Perinatology and Gynaecology, Hospital Oost-Limburg, Genk, Belgium, 10 Department of Perinatology and Gynaecology, University Hospital of Leuven, Belgium

Correspondence to: R de Heus R.deHeus-2{at}umcutrecht.nl

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 β 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 β 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.

© Heus et al 2009
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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