The widespread prescribing of corticosteroids in medicine includes many clinical situations during pregnancy, which naturally raises concerns about the safety of these drugs in pregnant women. Over the past several years, information on this topic has begun to accumulate, providing stronger evidence about the safety of inhaled corticosteroids in this population.
Most recently, in October, the largest study to date, conducted by the Organization of Teratology Information Services (OTIS), on the use of medications for asthma during pregnancy and their effects on fetal growth was published. The main finding was that treatment of pregnant women with β2-agonists and inhaled steroids did not have adverse effects on fetal growth and that systemic corticosteroids had a minimal effect on birth weight and length.
The prospective study compared birth size and the incidence of babies born small for gestational age (SGA) in 654 infants whose mothers had taken inhaled or systemic corticosteroids and β2-agonists for asthma during pregnancy with birth size and incidence of SGA in 303 infants whose mothers did not have asthma. Women from North America were enrolled between 1998 and 2003. There were no significant differences in the incidence of SGA for weight between the groups. There was a small reduction in birth weight among those exposed to systemic steroids: In this group, the mean birth weight, adjusted for other risk factors, was 3,373 g, compared with a mean of 3,540 g among controls, 3,552 g among those exposed to β2-agonists only, and 3,524 g among those exposed to inhaled steroids.
Mean birth weight and mean birth length, adjusted for risk factors, among infants whose mothers had been treated with inhaled steroids were not significantly different from those of controls or of infants whose mothers had used β2-agonists only. The adjusted mean birth lengths were 51.3 cm in the inhaled steroid group and 51.5 cm in the β2-agonist group.
The authors, from the University of California, San Diego and the OTIS Research Group, concluded that these results were “reassuring and support the recommendations of adequate control of severe asthma during pregnancy,” and that “the modest effect of systemic steroids on fetal growth should be weighed against the necessity to achieve adequate control of severe persistent asthma and to prevent hypoxia during pregnancy” (J. Allergy Clin. Immunol. 2005;116:503–9).
While these conclusions are not novel, this study is a major breakthrough because it combines information from teratology information centers in North America to provide much larger numbers than were available previously.
Women and physicians should be informed there are some risks: In 2000, my colleagues and I published a metaanalysis of all available studies of women who were given high-dose steroids during pregnancy for various reasons. The results clearly indicated that the use of systemic steroids during the first trimester was associated with a two- to threefold greater risk of oral clefts. This finding was consistent with extensive animal data that have shown the same association.
However, inhaled corticosteroids, commonly used as first-line therapy for asthma, result in an extremely low systemic dose, and none of the available reviews on the use of inhaled steroids during pregnancy have found any association with a greater risk of oral clefts. The β2-agonist albuterol is not teratogenic.
There is emerging evidence that repeated weekly corticosteroid injections for fetal lung maturation in cases of premature rupture of the membranes may result in brain damage in some babies. But this is not relevant to the use of inhaled corticosteroids in pregnant women with asthma.
Therefore, based on this recent study and previous data, pregnant women should be encouraged not to neglect their asthma therapy because of concerns about potential effects on the fetus. The risks include higher rates of perinatal complications, mostly prematurity, when asthma is poorly controlled. We are aware of fatal cases of women who stopped much-needed asthma treatment during pregnancy.
The authors of an editorial accompanying the OTIS study state that inhaled steroids “do not seem to significantly impair fetal growth,” but add that “before ruling out with confidence any potential adverse effect” of inhaled steroids on fetal growth, “there is a need for larger studies adequately powered to answer this question” (J. Allergy Clin. Immunol. 2005;116:501–2). While I agree that we always need more studies, the risk-benefit ratios should dictate optimal treatment of maternal asthma.