A review of pregnancy outcomes after exposure to orally inhaled or intranasal budesonide.

Background: Inadequately controlled rhinitis is associated with worsening asthma, one of the most common potentially serious causes of pregnancy complications. Recent evidence-based guidelines now stress the importance of inhaled corticosteroids as first-line therapy in controlling asthma during pregnancy, with preference given to budesonide. Both inhaled and intranasal budesonide formulations are rated Pregnancy Category B; all other inhaled and intranasal corticosteroids are rated Pregnancy Category C.

Objective: To review data from clinical and epidemiological studies investigating the effects of orally inhaled or intranasal budesonide on pregnancy outcomes.

Methods: Clinical and epidemiological studies on the effects of maternal exposure to orally inhaled or intranasal budesonide were identified through searches of the literature indexed on Medline or the Developmental and Reproductive Toxicology (DART) database through January 2005. The search terms used were: 'budesonide' and 'pregnancy'; 'pregnancy complications'; 'teratogens'; 'fetus'; 'embryo'; or 'toxicology'. The search was limited to English-language articles and those evaluating humans. Pertinent abstracts were identified from recent US asthma and allergy meetings.

Results: A total of five articles and three abstracts meeting the search criteria were identified. Retrospective epidemiological studies and a randomized, placebo-controlled, multicenter trial found no clinically or statistically significant effects on fetal outcomes among more than 6600 infants whose mothers were exposed to orally inhaled budesonide during pregnancy. Women who reported use of orally inhaled budesonide either during early pregnancy only or throughout pregnancy gave birth to infants of normal gestational age, birth weight, and length, with no increased rate of stillbirths, multiple births, or congenital malformations. In a retrospective case-control analysis, no association was found between inhaled budesonide or intranasal budesonide and the overall rate of infant cardiovascular defects. However, a marginally increased risk of less severe cardiovascular defects (odds ratio = 1.58, 95% confidence interval 1.02 to 2.46) was observed with intranasal budesonide in one analysis, possibly the result of a random association due to multiple testing or an unidentified confounder.

Conclusion: Maternal exposure to orally inhaled budesonide during pregnancy is not associated with an increased risk of congenital malformations or other adverse fetal outcomes in studies of more than 6600 infants. Data on pregnancy outcomes after maternal exposure to intranasal budesonide are limited, but the totality of evidence, including pharmacological studies showing a much lower systemic exposure after intranasal administration, indicates its safety profile is at least comparable with that of orally inhaled budesonide.