Asthma and lower airway disease
High doses of inhaled corticosteroids during the first trimester of pregnancy and congenital malformations

https://doi.org/10.1016/j.jaci.2009.09.025Get rights and content

Background

Although reassuring data exist on the use of low-to-moderate doses of inhaled corticosteroids (ICSs) during pregnancy, there are inadequate data for women receiving high doses.

Objective

To investigate the association between doses of ICS during the first trimester of pregnancy and the risk of congenital malformations among women with asthma.

Methods

We conducted a cohort study of 13,280 pregnancies of women with asthma (1990-2002) by linking 3 administrative databases from Quebec (Canada). By using generalized estimation equation models, we compared women taking >0 to 1000 μg/d ICS (beclomethasone dipropionate–chlorofluorocarbone equivalent) with women taking >1000 μg/d and those not taking ICSs. The main outcome measures were all and major congenital malformations.

Results

We identified 1257 infants with a congenital malformation (9.5%) and 782 infants with a major malformation (5.9%). We found that women who used >1000 μg/d ICS (n = 154) were significantly more likely (63%) to have a baby with a malformation than the 4392 women who used >0 to 1000 μg/d (adjusted risk ratio, 1.63; 95% CI, 1.02-2.60). On the other hand, women who used >0 to 1000 μg/d were not found to be more at risk than women who did not use ICSs during the first trimester (n = 8734). Nonsignificant trends of similar magnitude were found for major malformations.

Conclusions

Our study adds evidence on the safety of low-to-moderate doses of ICS taken during the first trimester but raises concerns about high doses. However, we cannot rule out the possibility of residual confounding by severity in this association.

Section snippets

Source of data

Data for this study were retrieved from 3 administrative databases from the Canadian province of Quebec. The database of the Régie de l'assurance-maladie du Québec (RAMQ) provides information on medical services dispensed to all residents of Quebec and prescribed medications filled in community pharmacies for residents insured by the RAMQ Drug Insurance Plan, about 42% of the residents of the province.19 These include the elderly, and the recipients of social welfare since 1980, and since

Results

The cohort was formed of 13,280 pregnancies from 10,099 women with asthma: 2570 women (25.5%) contributed 2 pregnancies or more to the analysis. Only 154 women used more than 1000 μg/d ICS (1.1%), whereas 4392 (33.1%) used a daily dose varying between >0 and 1000 μg/d, and 8734 (65.8%) did not use any ICSs during the first trimester. Among patients using more than 1000 μg/d, 33% filled prescriptions of beclomethasone dipropionate only, 38% filled prescriptions of fluticasone propionate only,

Discussion

In this study, we observed that women who took high doses of ICSs during the first trimester of pregnancy were 63% more likely to have a baby with a congenital malformation than women taking low to moderate doses of ICSs. This study also showed no increased risk of congenital malformation with low to moderate doses of ICSs compared with nonusers of ICSs. Nonsignificant associations of similar magnitude were observed for major malformations.

This study is the first to observe a statistically

References (43)

  • M. Silverman et al.

    Outcome of pregnancy in a randomized controlled study of patients with asthma exposed to budesonide

    Ann Allergy Asthma Immunol

    (2005)
  • C. Marceau et al.

    Persistence, adherence, and effectiveness of combination therapy among adult patients with asthma

    J Allergy Clin Immunol

    (2006)
  • M.J. Martel et al.

    Use of short-acting beta2-agonists during pregnancy and the risk of pregnancy-induced hypertension

    J Allergy Clin Immunol

    (2007)
  • R. Tamblyn et al.

    The use of prescription claims databases in pharmacoepidemiological research: the accuracy and comprehensiveness of the prescription claims database in Quebec

    J Clin Epidemiol

    (1995)
  • K.F. Rabe et al.

    Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study

    Lancet

    (2006)
  • G. Braems

    Fetal hypoxemia on a molecular level: adaptive changes in the hypothalamic-pituitary-adrenal (HPA) axis and the lungs

    Eur J Obstet Gynecol Reprod Biol

    (2003)
  • L. Cousins

    Fetal oxygenation, assessment of fetal well-being, and obstetric management of the pregnant patient with asthma

    J Allergy Clin Immunol

    (1999)
  • E.S. Guy et al.

    Acute asthma in pregnancy

    Crit Care Clin

    (2004)
  • B.R. Danielsson et al.

    Teratogenicity by the hERG potassium channel blocking drug almokalant: use of hypoxia marker gives evidence for a hypoxia-related mechanism mediated via embryonic arrhythmia

    Toxicol Appl Pharmacol

    (2003)
  • Managing asthma during pregnancy: recommendations for pharmacologic treatment—2004 update

    J Allergy Clin Immunol

    (2005)
  • C. Olesen et al.

    Drug use in first pregnancy and lactation: a population-based survey among Danish women. The EUROMAP group

    Eur J Clin Pharmacol

    (1999)
  • Cited by (82)

    • Managing Asthma During Pregnancy and the Postpartum Period

      2023, Journal of Allergy and Clinical Immunology: In Practice
    • The obstetric aspects of maternal asthma

      2022, Best Practice and Research: Clinical Obstetrics and Gynaecology
    • Personalized Treatment of Asthma: The Importance of Sex and Gender Differences

      2022, Journal of Allergy and Clinical Immunology: In Practice
    • Asthma in Pregnancy

      2021, Encyclopedia of Respiratory Medicine, Second Edition
    • The management of asthma during pregnancy

      2021, Clinical Pharmacology During Pregnancy
    View all citing articles on Scopus

    L.B. and C.L. are the recipients of a Salary Award from the Fonds de la recherche en santé du Québec (FRSQ).This study was funded through grants received from the FRSQ, the Canadian Institutes of Health Research, and the Canadian Foundation for Innovation. The research was completely independent from the funders.

    Disclosure of potential conflict of interest: L. Blais receives research support from AstraZeneca and Amgen. M.-F. Beauchesne receives honoraria for CE programs from AstraZeneca, GSK Canada, and BI/Pfizer Canada. C. Lemière receives research support from NIOSH and GlaxoSmithKline. The other author declares that she has no conflict of interest.

    View full text