Study Offers Reassurance on Inhaled Corticosteroid Use for Asthma in Pregnancy

Women with asthma who continued taking inhaled corticosteroids during the first trimester of pregnancy did not suffer higher rates of adverse outcomes compared with those who discontinued use, a South Korean nationwide cohort study found.

After controlling for confounding, there were no statistically significant differences in maternal or neonatal outcomes. The risks per 1,000 pregnancies for the following outcomes among those who continued versus discontinued inhaled corticosteroids in the first trimester were:

• Gestational diabetes: 145.6 vs 131.9 (weighted risk ratio [RR] 1.05, 95% CI 0.90-1.22)
• Preeclampsia: 21.8 vs 13.3 (weighted RR 1.14, 95% CI 0.74-1.75)
• Preterm birth: 131.4 vs 128.6 (weighted RR 0.95, 95% CI 0.82-1.11)
• Low birth weight: 77.5 vs 58.3 (weighted RR 1.11, 95% CI 0.89-1.39)
• Congenital malformations: 57.6 vs 42.2 (weighted RR 1.22, 95% CI 0.94-1.56)

Continued inhaled corticosteroid use wasn’t associated with increased risks of other maternal and neonatal outcomes as well, and the findings persisted across subgroup and sensitivity analyses, reported Yunha Noh, PharmD, PhD, of Chonnam National University in Gwangju, South Korea, and colleagues in JAMA Network Open.

“Consistent with prior cohort studies, we observed no increased risk of major maternal or neonatal outcomes associated with first trimester ICS [inhaled corticosteroids] continuation,” the authors wrote, noting that the similarity in outcomes should be interpreted in the context of potential baseline severity differences and that patients’ asthma should still be managed on an individual basis.

About 3% to 12% of pregnant women have asthma worldwide, of whom 20% experience exacerbations. Asthma in pregnancy has been linked with adverse outcomes in mothers as well as their offspring, especially when inadequately controlled. Guidelines recommend that pregnant women continue therapies including inhaled corticosteroids, though it’s still very common for women to discontinue use early in pregnancy.

Some research suggests that inhaler discontinuation could exacerbate asthma symptoms and harm the pregnancy, but other research has found no differences in outcomes. Authors noted this disconnect may be from heterogenous and limited study designs.

To address this gap, authors aimed to evaluate the association between continuing inhaled corticosteroids in the first trimester of pregnancy and major maternal and neonatal outcomes in a population-based cohort study.

Researchers looked at mother-child data from January 2009 to December 2023 from two databases: South Korea’s National Health Information Service, which has longitudinal health records for 50 million people, and the National Health Screening Program for Infants and Children, which has information on birth weight.

Eligible pregnant individuals were ages 15 to 50 and had a live-birth delivery between April 2010 and December 2022. Participants also had at least one ICD coded diagnosis for asthma and at least two prescriptions for inhaled corticosteroids in the 6 months before their last menstrual period. Included inhaled corticosteroids were beclomethasone, budesonide, fluticasone, triamcinolone, and ciclesonide (Alvesco), either as single agents or as part of combination inhalers.

Maternal outcomes included preeclampsia, gestational diabetes, obstructed labor, antepartum hemorrhage, premature rupture of membranes, and preterm birth; neonatal outcomes included hypoxia or asphyxia, low birth weight, and congenital malformations.

Out of 3,909,084 pregnancies, there were 6,105 that met study criteria. Only 34.5% of these women continued using inhaled corticosteroids in the first trimester (2,108 women, mean age 33.2) while 65.5% discontinued use (3,997 women, mean age 32.9).

Compared with discontinuers, those who continued taking inhaled corticosteroids had a higher proportion of women giving birth for the first time (50.0% vs 37.6%) as well as lower use of antibiotics (86.2% vs 92.7%), nonsteroidal anti-inflammatory drugs (NSAIDs; 68.3% vs 78.1%), acetaminophen (67.0% vs 74.3%), and dihydrocodeine (59.5% vs 72.5%). Continuers also had higher use of high-dose (≥180 mg) oral corticosteroids (17.5% vs 8.4%) but lower use of low-dose (≥50 mg) oral corticosteroids (7.4% vs 13.0%) than discontinuers, which authors noted indicates higher underlying disease severity.

Those prescribed antibiotics, dihydrocodeine, NSAIDs, and a higher number of asthma medication classes were less likely to continue taking inhaled corticosteroids, while women using high-dose oral corticosteroids, long-acting β-agonist combinations, and who had frequent respiratory-related outpatient visits were more likely to continue use.

“Taken together, these observations suggest that inadequate asthma control may increase maternal and neonatal risks, highlighting the importance of maintaining optimal asthma control throughout pregnancy,” they concluded.

The authors noted some limitations, including that prescription records may not reflect medication use and adherence, the potential for misclassification, the influence of unmeasured confounders, and potential selection bias from only including live births. Also, the results do not imply causality due to the study’s design.