Use of inhaled steroids by pregnant asthmatic women does not reduce intrauterine growth

doi:10.1016/j.jaci.2003.11.046

Journal of Allergy and Clinical Immunology

Volume 113, Issue 3, March 2004, Pages 427-432

https://doi.org/10.1016/j.jaci.2003.11.046 Get rights and content

Abstract

Background

Inhaled steroids are recommended for the treatment of persistent asthma during pregnancy, but their potential effects on intrauterine growth have been inadequately evaluated.

Objective

The purpose of this study was to evaluate the association between maternal use of specific inhaled steroids and inhaled steroid dose during pregnancy and the incidence of infants who are small for gestational age (SGA) and mean birth weight.

Methods

Pregnant asthmatic women being treated with inhaled steroids were enrolled in the study before delivery by their managing allergists. Information regarding the specific inhaled steroid and daily dose used, requirement for oral steroids, occurrence of acute asthmatic episodes, maternal race, birth weight, gestational age, and congenital malformations was obtained for each patient. SGA was defined through use of a published normative sample of American births.

Results

A total of 474 women were enrolled in the study; of the 451 enrolled participants whose pregnancy ended in a singleton live birth, 396 (88%) completed the study. The incidence of infants with low birth weight, preterm births, and congenital malformations in this cohort was not greater than expected in the general population. The incidence of SGA was 7.1% (95% CI, 5.0% to 10.1%). No significant relationships between specific inhaled steroid or dose of inhaled steroid used and either SGA or mean birth weight were observed.

Conclusion

These data suggest that the use of inhaled steroids by pregnant asthmatic women does not reduce intrauterine growth and supports the recommendation that inhaled steroids should be used in the management of persistent asthma during pregnancy.

Section snippets

Subjects

Subjects were patients of allergists recruited through the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology between July 1996 and January 2002. Eligible subjects had asthma, were pregnant, and were being treated with inhaled steroids. Participating allergists invited all eligible patients to enter the study. Subjects were entered into the study before delivery. Informed consent was obtained for each subject by the subject's allergist

Results

A total of 474 women were enrolled in the study by 99 allergists from 35 states representing all regions of the country. Pregnancies that ended in spontaneous abortions (n = 15) or multiple births (n = 8) were not eligible for analysis of SGA. Of the remaining 451 enrolled participants, 396 (88%) had information available for this analysis. Of these 396 women, 85.6% were white and 14.4% were nonwhite, and 3.5% were smokers. Their ages ranged from 16 to 44 years (mean ± SEM, 30.0 ± 0.27 years);

Discussion

This study demonstrates with 95% certainty that the true incidence of SGA in infants of mothers treated by allergists with inhaled steroids does not exceed 10.1%. This study provides reassuring data that specific inhaled steroids do not lead to a restriction in fetal growth, regardless of the dose used.

This is the largest sample to date examining the potential effects that inhaled steroids may have on intrauterine growth as assessed by birth weight for gestational age. It is also the first

Acknowledgements

The following allergists enrolled patients into this study: Bernard Adelsberg, MD, Stephen Apalliski, MD, Donald W. Asbury, MD, Abdul H. Bahrainwala, MD, Solomon E. Barr, MD, Ulrich Bauer, MD, PC, Susan S. Berdy, MD, Rajesh G. Bhagat, MD, S. Allan Bock, MD, Mark E. Bubak, MD, Lawrence A. Cali-guirri, MD, Latha Chamarthy, MD, Jean A. Chapman, MD, Jim Chevalier, MD, Leonard Cohen, MD, Robert Coifman, MD, John D. Cosachov, DO, Linda Cox, MD, Andrew Davidson, MD, Kathleen C. Davis, MD, Robert J.

References (23)

S Alexander et al.
Perinatal outcomes in women with asthma during pregnancy
Obstet Gynecol
(1998)
M Schatz et al.
Outcomes of pregnancy in asthmatic women
Immunol Allergy Clin North Am
(2000)
M Schatz et al.
Intrauterine growth is related to gestational pulmonary function in pregnant asthmatic women
Chest
(1990)
B Kallen et al.
Congenital malformations after the use of inhaled budesonide in early pregnancy
Obstet Gynecol
(1999)
E Norjavaara et al.
Normal pregnancy outcomes in a population-based study including 2968 pregnant women exposed to budesonide
J Allergy Clin Immunol
(2003)
M Schatz et al.
The safety of asthma and allergy medications during pregnancy
J Allergy Clin Immunol
(1997)
GR Alexander et al.
A United States national reference for fetal growth
Obstet Gynecol
(1996)
M Schatz et al.
Outcomes of pregnancy in asthmatic women
Immunol Allergy Clin North Am
(2000)
RS Zeiger et al.
Effect of allergist intervention on patient-centered and societal outcomes: allergists as leaders, innovators, and educators
J Allergy Clin Immunol
(2000)
PJ Wendel et al.
Asthma treatment in pregnancy: a randomized controlled study
Am J Obstet Gynecol
(1996)

B Kallen et al.

Asthma during pregnancy—a population based study

Eur J Epidemiol

(2000)

Cited by (67)

Chronic Management of Asthma During Pregnancy
2023, Immunology and Allergy Clinics of North America
Use of Asthma Medication During Gestation and Risk of Specific Congenital Anomalies
2023, Immunology and Allergy Clinics of North America
Management of the Upper Airway Distress During Pregnancy
2023, Immunology and Allergy Clinics of North America
The safety of asthma medications during pregnancy and lactation: Clinical management and research priorities
2021, Journal of Allergy and Clinical Immunology
Asthma is one of the most common underlying diseases in women of reproductive age that can lead to potentially serious medical problems during pregnancy and lactation. A group of key stakeholders across multiple relevant disciplines was invited to take part in an effort to prioritize, strategize, and mobilize action steps to fill important gaps in knowledge regarding asthma medication safety in pregnancy and lactation. The stakeholders identified substantial gaps in the literature on the safety of asthma medications used during pregnancy and lactation and prioritized strategies to fill those gaps. Short-term action steps included linking data from existing complementary study designs (US and international claims data, single drug pregnancy registries, case-control studies, and coordinated systematic data systems). Long-term action steps included creating an asthma disease registry, incorporating the disease registry into electronic health record systems, and coordinating care across disciplines. The stakeholders also prioritized establishing new infrastructures/collaborations to perform research in pregnant and lactating women and to include patient perspectives throughout the process. To address the evidence gaps, and aid in populating product labels with data that inform clinical decision making, the consortium developed a plan to systematically obtain necessary data in the most efficient and timely manner.
Relative perinatal safety of salmeterol vs formoterol and fluticasone vs budesonide use during pregnancy
2014, Annals of Allergy, Asthma and Immunology
Citation Excerpt :
They found no statistically significant differences between ICS molecules for SGA and between users and nonusers of each drug for mean birth weight. For the comparison of fluticasone and budesonide, given the sample size of the cohorts, an α of 0.05, and the prevalence of SGA, the studies by Bakhireva et al19 and Namazy et al20 would have 80% power to detect an OR of 2.35 and 3.40, respectively. Clifton et al21 found a significant reduction in birthweight centile (BWC) and length centile (LC) in women using fluticasone-salmeterol (BWC, 34.8; LC, 51.0) compared with budesonide (BWC, 74.0; LC, 88.9), but no significant difference was observed in comparing budesonide and fluticasone (BWC, 53.6; LC, 74.1).21
Recent asthma guidelines endorse the safety of long-acting β₂-agonists (LABAs) and of mild and moderate doses of inhaled corticosteroids (ICSs) when required to control asthma during pregnancy, yet do not state a preferred medication within each class.
To estimate the relative perinatal safety with the use of salmeterol and formoterol (LABAs) and that of fluticasone and budesonide (ICSs) during pregnancy.
A subcohort of pregnancies from asthmatic women was selected from health care administrative databases of Quebec, Canada. Low birth weight (LBW) was defined as weight less than 2,500 g, preterm birth (PB) as delivery before 37 weeks of gestation, and small for gestational age (SGA) as a birth weight below the 10th percentile. The effect of treatment with salmeterol vs formoterol and fluticasone vs budesonide on the outcomes was determined with generalized estimating equation models.
The LABA and ICS subcohorts were composed of 547 (385 salmeterol and 162 formoterol users) and 3,798 (3,190 fluticasone and 608 budesonide users) pregnancies, respectively. No statistically significant differences were observed for LBW (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.44-1.88), PB (OR, 1.11; 95% CI, 0.56-2.23), and SGA (OR, 1.16; 95% CI, 0.67-2.02) newborns between women exposed to salmeterol vs formoterol or between women exposed to fluticasone vs budesonide (LBW: OR, 1.08; 95% CI, 0.76-1.52; PB: OR, 1.07; 95% CI, 0.78-1.49; and SGA, OR: 1.10; 95% CI, 0.85-1.44).
This study does not provide evidence of greater perinatal safety for one LABA or one ICS over the other.
Inhaled beclomethasone in pregnant asthmatic women - A systematic review
2014, Allergologia et Immunopathologia
Citation Excerpt :
Four articles10–13 published after 2003 were found in this review. Among these, two prospective studies had their data collection started before 2003 and discussed about the use of beclomethasone or inhaled corticosteroids, which more than a half of the sample used beclomethasone.12,13 The only two articles actually designed after the publication of 2003 and selected for this review are cohort studies taken from Canadian and Danish databases, with pregnant asthmatic women evaluated between 1990–200211 and 1996–2002.10
The aim of this study was to systematically review the safety and efficacy of inhaled beclomethasone for asthma treatment in pregnant women. We performed a systematic review in Medline, LILACS and SciELO electronic databases in December 2012. A total of 3433 articles were found by using the keywords asthma, pregnancy and beclomethasone. Among these, 1666 were from Medline, via PubMed, and 1767 were from LILACS and SciELO. Nine of these articles were selected. Only one paper suggested an increased foetal risk for congenital malformations, and one other for offspring endocrine and metabolic disturbances. Data are mostly reassuring, supporting the use of glucocorticoid inhalants during pregnancy, and we found no evidence of inferiority in relation to efficacy and safety of beclomethasone compared to other drugs used in pregnant asthmatic women.

View all citing articles on Scopus

^☆

Supported by an unrestricted grant to the American College of Allergy, Asthma and Immunology from Aventis Pharmaceuticals.

Presented at the Annual Meeting of the American Academy of Allergy, Asthma and Immunology, Denver, Colo, March 2003.

¹: Deceased.

View full text

Asthma, Rhinitis, other Respiratory DiseasesUse of inhaled steroids by pregnant asthmatic women does not reduce intrauterine growth☆

Abstract

Background

Objective

Methods

Results

Conclusion

Section snippets

Subjects

Results

Discussion

Acknowledgements

Obstet Gynecol

Immunol Allergy Clin North Am

Chest

Obstet Gynecol

J Allergy Clin Immunol

J Allergy Clin Immunol

Obstet Gynecol

Immunol Allergy Clin North Am

J Allergy Clin Immunol

Am J Obstet Gynecol

Asthma during pregnancy—a population based study

Eur J Epidemiol

Asthma, Rhinitis, other Respiratory Diseases
Use of inhaled steroids by pregnant asthmatic women does not reduce intrauterine growth☆