Asthma and lower airway disease
Use of asthma medication during pregnancy and risk of specific congenital anomalies: A European case-malformed control study

https://doi.org/10.1016/j.jaci.2015.05.043Get rights and content
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Background

Pregnant women with asthma need to take medication during pregnancy.

Objective

We sought to identify whether there is an increased risk of specific congenital anomalies after exposure to antiasthma medication in the first trimester of pregnancy.

Methods

We performed a population-based case-malformed control study testing signals identified in a literature review. Odds ratios (ORs) of exposure to the main groups of asthma medication were calculated for each of the 10 signal anomalies compared with registrations with nonchromosomal, nonsignal anomalies as control registrations. In addition, exploratory analyses were done for each nonsignal anomaly. The data set included 76,249 registrations of congenital anomalies from 13 EUROmediCAT registries.

Results

Cleft palate (OR, 1.63; 95% CI, 1.05-2.52) and gastroschisis (OR, 1.89; 95% CI, 1.12-3.20) had significantly increased odds of exposure to first-trimester use of inhaled β2-agonists compared with nonchromosomal control registrations. Odds of exposure to salbutamol were similar. Nonsignificant ORs of exposure to inhaled β2-agonists were found for spina bifida, cleft lip, anal atresia, severe congenital heart defects in general, or tetralogy of Fallot. None of the 4 literature signals of exposure to inhaled steroids were confirmed (cleft palate, cleft lip, anal atresia, and hypospadias). Exploratory analyses found an association between renal dysplasia and exposure to the combination of long-acting β2-agonists and inhaled corticosteroids (OR, 3.95; 95% CI, 1.99-7.85).

Conclusions

The study confirmed increased odds of first-trimester exposure to inhaled β2-agonists for cleft palate and gastroschisis and found a potential new signal for renal dysplasia associated with combined long-acting β2-agonists and inhaled corticosteroids. Use of inhaled corticosteroids during the first trimester of pregnancy seems to be safe in relation to the risk for a range of specific major congenital anomalies.

Key words

Asthma medication
congenital anomalies
pregnancy
first trimester exposure
inhaled β2-agonists
inhaled corticosteroids

Abbreviations used

ATC
Anatomical Therapeutic Chemical
OR
Odds ratio
TOPFA
Termination of pregnancy for fetal anomaly

Cited by (0)

Supported by the European Union under the Seventh Framework Programme (grant agreement HEALTH-F5-2011-260598). The funding source had no involvement in the study.

Disclosure of potential conflict of interest: E. Garne, A. V. Hansen, L. Zaupper, I. Barisic, K. Klungsøyr, M. O'Mahony, V. Nelen, A. Pierini, and H. de Walle have received research support from the European Union Framework 7 Programme. M. Gatt has received research support from the Ministry for Health, Directorate for Health Information and Research. A. J. Neville has received travel support from EUROCAT, is a member of the DIFK Cooper expert panel on isotrentinoin, and has received research support from Euromedicat (a partner is the FP7 project) and EUROMEDISAFE. D. Tucker has received travel support from EuroMedicat. A. Wiesel has received consultancy fees from Geburtenregister Mainzer Modell and has received travel support from EuroMedicat. M. Loane has received research and travel support from the European Union Framwork 7 Programme. H. Dolk has received research support from the European Commission Framework 7 and GlaxoSmithKline. The rest of the other authors declare they have no relevant conflicts of interest.