Randomized trial of inhaled beclomethasone dipropionate versus theophylline for moderate asthma during pregnancy

https://doi.org/10.1016/j.ajog.2003.09.071Get rights and content

Abstract

Objective

This study was undertaken to compare the efficacy of inhaled beclomethasone dipropionate to oral theophylline for the prevention of asthma exacerbation(s) requiring medical intervention.

Study design

A prospective, double-blind, double placebo-controlled randomized clinical trial of pregnant women with moderate asthma was performed.

Results

There was no significant difference (P = .554) in the proportion of asthma exacerbations among the 194 women in the beclomethasone cohort (18.0%) versus the 191 in the theophylline cohort (20.4%; risk ratio [RR] = 0.9, 95% CI = 0.6-1.3). The beclomethasone cohort had significantly lower incidences of discontinuing study medications caused by side effects (RR = 0.3, 95% CI = 0.1-0.9; P = .016), and proportion of study visits with forced expiratory volume expired in 1 second (FEV1) less than 80% predicted (0.284±0.331 vs 0.284±0.221, P = .039). There were no significant differences in treatment failure, compliance, or proportion of peak expiratory flow rate less than 80% predicted. There were no significant differences in maternal or perinatal outcomes.

Conclusion

The treatment of moderate asthma with inhaled beclomethasone versus oral theophylline resulted in similar rates of asthma exacerbations and similar obstetric and perinatal outcomes. These results favor the use of inhaled corticosteroids for moderate asthma during pregnancy because of the improved FEV1 and because theophylline had more side effects and requires serum monitoring.

Section snippets

Methods

This study was designed and sponsored by the National Institute of Child Health and Human Development (NICHD) and the NHLBI. It was conducted at 13 centers of the Maternal-Fetal Medicine Units Network (MFMU) of the NICHD. This was a prospective, double-blind, double placebo-controlled randomized trial. Case finding was by questioning all women presenting for prenatal care about having physician-diagnosed asthma. Informed written consent was obtained for all participants, and the study was

Results

A total of 4975 women were screened for eligibility; 147 were excluded because they had been enrolled in an asthma study3., 7. either in the present or an earlier pregnancy (Figure 1), 199 were randomly assigned to receive oral theophylline, and 199 received inhaled beclomethasone. A total of 13 (3.3%) were lost to follow-up before primary outcome determination. Only 34 (8.5%) participants did not take any asthma medications during pregnancy before enrollment. Although self-reported smoking was

Comment

We found no significant differences in the proportion of women experiencing at least 1 asthma exacerbation. In the beclomethasone cohort, 18.0% had a primary outcome compared with 20.4% in the theophylline cohort; to detect this magnitude of difference with 80% power, a study would require approximately 8000 participants. The theophylline cohort had a significantly increased proportion of FEV1 less than 80% predicted, and a greater proportion discontinued study medications because of side

Participating institutions and staff members

National Heart Lung and Blood Institute: J. Kiley

National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units: University of Pittsburgh Magee Women's Hospital—P. Heine, M. Cotroneo, E. Daugherty; University of Tennessee—B. Sibai, R. Ramsey; University of Alabama at Birmingham—W. Andrews, R. Copper, S. Tate, A. Northen; Wayne State University—Y. Sorokin, G. S. Norman, A. Millinder; University of Cincinnati—T. A. Siddiqi, N. Elder, V. Pemberton; Wake Forest

References (24)

  • National Asthma Education and Prevention Program Expert Panel Report 2: guidelines for the Diagnosis and Management of...
  • W.C Mabie et al.

    Clinical observations an asthma in pregnancy

    J Matern Fetal Med

    (1992)
  • Cited by (84)

    • Use of Asthma Medication During Gestation and Risk of Specific Congenital Anomalies

      2023, Immunology and Allergy Clinics of North America
      Citation Excerpt :

      Concerns raised about a potential association of congenital anomalies and moderate- to high-dose ICSs have been examined. A previous literature review32 summarizing the risk of congenital malformations with the use of ICSs in pregnancy found that in 15 separate studies29,33–46 comparing women with asthma using any ICS versus women with asthma not using ICS the adjusted relative risk ranged from 0.4 to 1.1. Bakhireva and colleagues35 were the only investigators to report a significantly increased risk of congenital anomalies associated with ICS use when they compared 438 pregnant women using ICSs during pregnancy with nonasthmatic control pregnant women (4.1% vs 0.3% presence of major anomalies, respectively, P = <0.05).

    • Management of asthma during pregnancy

      2021, Revue des Maladies Respiratoires
    • Respiratory Disease in Pregnancy

      2016, Obstetrics: Normal and Problem Pregnancies
    • Antiasthmatic and cough medication

      2015, Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment: Third Edition
    View all citing articles on Scopus

    Supported by grants from the National Institute of Child Health and Human Development (HD21410, HD21414, HD21434, HD27869, HD27917, HD27905, HD27889, HD27860, HD27861, HD27915, HD27883, HD34122, HD34116, HD34208, HD34136, and HD36801) and the National Heart Lung and Blood Institute.

    Presented at the Society of Maternal Fetal Medicine 2001 annual meeting, Reno, Nev.

    View full text