High doses of inhaled corticosteroids during the first trimester of pregnancy and congenital malformations

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 mu g/d ICS (beclomethasone dipropionate-chlorofluorocarbone equivalent) with women taking >1000 mu g/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 mu g/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 mu g/d (adjusted risk ratio, 1.63; 95% CI, 1.02-2.60). On the other hand, women who used >0 to 1000 mu g/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. (J Allergy Clin Immunol 2009;124:1229-34.)