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


METHODS
Prospective cohort study.


METHODS
28 hospitals in the Netherlands and Belgium.


METHODS
1920 consecutive women treated with tocolytics for threatened preterm labour.


METHODS
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.
de Heus
Roel
R
Department of Perinatology and Gynaecology, University Medical Centre Utrecht, KJ.02.507.0/PO Box 85090, Utrecht, Netherlands. R.deHeus-2@umcutrecht.nl
Mol
Ben Willem
BW
Erwich
Jan-Jaap H M
JJ
van Geijn
Herman P
HP
Gyselaers
Wilfried J
WJ
Hanssens
Myriam
M
Härmark
Linda
L
van Holsbeke
Caroline D
CD
Duvekot
Johannes J
JJ
Schobben
Fred F A M
FF
Wolf
Hans
H
Visser
Gerard H A
GH
D000318:Adrenergic beta-Agonists / Q000009:adverse effects; D000328:Adult; D001530:Belgium; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008423:Maternal Age; D009426:Netherlands; D007752:Obstetric Labor, Premature / Q000517:prevention & control*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced*; D011446:Prospective Studies; D015149:Tocolytic Agents / Q000009:adverse effects*
D000318:Adrenergic beta-Agonists; D015149:Tocolytic Agents