High doses of inhaled corticosteroids during the first trimester of pregnancy and congenital malformations
Received 23 July 2009; received in revised form 16 September 2009; accepted 17 September 2009. published online 12 November 2009.
Background
Although reassuring data exist on the use of low-to-moderate doses of inhaled corticosteroids (ICSs) during pregnancy, there are inadequate data for women receiving high doses.
Objective
To investigate the association between doses of ICS during the first trimester of pregnancy and the risk of congenital malformations among women with asthma.
Methods
We conducted a cohort study of 13,280 pregnancies of women with asthma (1990-2002) by linking 3 administrative databases from Quebec (Canada). By using generalized estimation equation models, we compared women taking >0 to 1000 μg/d ICS (beclomethasone dipropionate–chlorofluorocarbone equivalent) with women taking >1000 μg/d and those not taking ICSs. The main outcome measures were all and major congenital malformations.
Results
We identified 1257 infants with a congenital malformation (9.5%) and 782 infants with a major malformation (5.9%). We found that women who used >1000 μg/d ICS (n = 154) were significantly more likely (63%) to have a baby with a malformation than the 4392 women who used >0 to 1000 μg/d (adjusted risk ratio, 1.63; 95% CI, 1.02-2.60). On the other hand, women who used >0 to 1000 μg/d were not found to be more at risk than women who did not use ICSs during the first trimester (n = 8734). Nonsignificant trends of similar magnitude were found for major malformations.
Conclusions
Our study adds evidence on the safety of low-to-moderate doses of ICS taken during the first trimester but raises concerns about high doses. However, we cannot rule out the possibility of residual confounding by severity in this association.
aFaculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada
bFaculty of Medicine, Université de Montréal, Montreal, Quebec, Canada
cHôpital du Sacré-Cœur de Montréal, Montreal, Quebec, Canada
dEndowment Pharmaceutical Chair AstraZeneca in Respiratory Health, Montreal, Quebec, Canada
Reprint requests: Lucie Blais, Université de Montréal, Faculté de pharmacie, CP 6128, succursale Centre-ville, Montréal (Québec), Canada H3C 3J7.
L.B. and C.L. are the recipients of a Salary Award from the Fonds de la recherche en santé du Québec (FRSQ).This study was funded through grants received from the FRSQ, the Canadian Institutes of Health Research, and the Canadian Foundation for Innovation. The research was completely independent from the funders.
Disclosure of potential conflict of interest: L. Blais receives research support from AstraZeneca and Amgen. M.-F. Beauchesne receives honoraria for CE programs from AstraZeneca, GSK Canada, and BI/Pfizer Canada. C. Lemière receives research support from NIOSH and GlaxoSmithKline. The other author declares that she has no conflict of interest.
ABSTRACT