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

Abstract

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 microg/d ICS (beclomethasone dipropionate-chlorofluorocarbone equivalent) with women taking >1000 microg/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 microg/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 microg/d (adjusted risk ratio, 1.63; 95% CI, 1.02-2.60). On the other hand, women who used >0 to 1000 microg/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.