Adverse drug reactions to tocolytic treatment for preterm labour: prospective cohort study
BMJ 2009; 338 doi: https://doi.org/10.1136/bmj.b744 (Published 06 March 2009) Cite this as: BMJ 2009;338:b744
- Roel de Heus, registrar of obstetrics and gynaecology1,
- Ben Willem Mol, professor of perinatology and clinical epidemiology23,
- 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
- 1Department of Perinatology and Gynaecology, University Medical Centre Utrecht, KJ.02.507.0/PO Box 85090, Utrecht, Netherlands
- 2Department of Perinatology and Gynaecology, Maxima Medical Centre, Veldhoven, Netherlands
- 3Department of Perinatology and Gynaecology, Academic Medical Centre, University of Amsterdam, Netherlands
- 4Department of Perinatology and Gynaecology, University Medical Centre Groningen, Netherlands
- 5Department of Obstetrics and Gynaecology, Free University Medical Centre, University of Amsterdam
- 6Department of Perinatology and Gynaecology, Erasmus University Medical Centre, Rotterdam
- 7Pharmacovigilance Centre Lareb, Hertogenbosch, Netherlands
- 8Department of Clinical Pharmacy, University Medical Centre, Utrecht
- 9Department of Perinatology and Gynaecology, Hospital Oost-Limburg, Genk, Belgium
- 10Department of Perinatology and Gynaecology, University Hospital of Leuven, Belgium
- Correspondence to: R de Heus R.deHeus-2{at}umcutrecht.nl
- Accepted 2 December 2008
Abstract
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.
Footnotes
The participating hospitals were: Academic Medical Centre Amsterdam, Hans Wolf; Lucas Andreas Hospital Amsterdam, Celine M Radder; Free University Medical Centre Amsterdam, Herman P van Geijn, Annemiek C Bolte; Sint Augustinus Hospital, Antwerpen, Tina BVBA Vanderheijden; University Hospital Antwerpen, Yves Jacquemyn; Gelre Hospital Apeldoorn, Anjoke JM Huisjes; General Hospital Klina Brasschaat, Patricia Crijns; Maas and Kempen Hospital, Dirk Lauwagie; Sint Jan Hospital, Brugge, Anne Loccufier; Bronovo Hospital, the Hague, Casper AG Holleboom; University Hospital Gent, Walter Parewijck, Marleen Temmerman; Hospital Oost-Limburg Genk, Wilfried J Gyselaers, Caroline van Holsbeke; University Medical Centre Groningen, Jan-Jaap HM Erwich; Atrium Medical Centre Heerlen, Frans JME Roumen; Sint Fransiscus Hospital, Jan Schreurs; University Hospital Leuven, Myriam Hanssens; Maria Hospital Noord-Limburg Neerpelt, Bart Bollen; Sint Antonius Hospital Nieuwegein, Erik van Beek; Canisius-Wilhelmina Hospital Nijmegen, Jan MJ Sporken; Erasmus Medical Centre, Rotterdam, Hans J Duvekot; Laurentius Hospital Roermond, Chantal BM Wingen; Saint Trudo Hospital, Sint Truiden, Christa Eerdekens; Twee Steden Hospital, Tilburg, Addy P Drogtrop; Sint Jozef Hospital Turnhout, Jan Aerts, Myrrith Hulsbergen; University Medical Centre Utrecht, Margo Graatsma, Gerard HA Visser; Maxima Medical Centre Veldhoven, Ben-Willem Mol; and Isala Hospital Zwolle, Jim van Eijck.
Contributors: All authors had full access to the data (including statistical reports and tables) in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Funding: This research was funded by an unconditional grant from Ferring Pharmaceuticals BV, Hoofddorp, The Netherlands.
Competing interests: WJG did a retrospective cohort study on tocolysis in 2006 (not published) which was supported by an unconditional grant from Ferring Pharmaceuticals.
Ethical approval: This study was approved by the medical review ethics committee of University Medical Centre Utrecht.
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