Risk of congenital anomalies after exposure to asthma medication in the first trimester of pregnancy - a cohort linkage study

Ester Garne, A Vinkel Hansen, Joan Morris, Sue Jordan, Kari Klungsoyr, Anders Engeland, David Tucker, Dan Thayer, Gareth Davies, Anne-Marie Nybo Andersen, Helen Dolk

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Objective To examine the effect of maternal exposure to asthma medications on the risk of congenital anomalies.Design Meta-analysis of aggregated data from three cohortstudies.Setting Linkage between healthcare databases and EUROCAT congenital anomaly registries.Population 519 242 pregnancies in Norway (2004–2010), Wales (2000–2010) and Funen, Denmark (2000–2010).Methods Exposure defined as having at least one prescription for asthma medications issued (Wales) or dispensed (Norway, Denmark) from 91 days before to 91 days after the pregnancy start date. Odds ratios (ORs) were estimated separately for each register and combined in meta-analyses.Main outcome measures ORs for all congenital anomalies and specific congenital anomalies.Results Overall exposure prevalence was 3.76%. For exposure to asthma medication in general, the adjusted OR (adjOR) for a major congenital anomaly was 1.21 (99% CI 1.09–1.34) after adjustment for maternal age and socioeconomic position. The OR of anal atresia was significantly increased in pregnancies exposedto inhaled corticosteroids (3.40; 99% CI 1.15–10.04). For severe congenital heart defects, an increased OR (1.97; 1.12–3.49) was associated with exposure to combination treatment with inhaled corticosteroids and long-acting beta-2-agonists. Associations with renal dysplasia were driven by exposure to short-acting beta-2-agonists (2.37; 1.20–4.67).Conclusion The increased risk of congenital anomalies for women taking asthma medication is small with little confounding by maternal age or socioeconomic status. The study confirmed the association of inhaled corticosteroids with anal atresia found in earlier research and found potential new associations withcombination treatment. The potential new associations should be interpreted with caution due to the large number of comparisons undertaken.
LanguageEnglish
Pages1609-1618
Number of pages10
JournalBJOG: An International Journal of Obstetrics and Gynaecology
Volume123
Issue number10
Early online date12 May 2016
DOIs
Publication statusPublished - Sep 2016

Fingerprint

First Pregnancy Trimester
Cohort Studies
Asthma
Odds Ratio
Imperforate Anus
Adrenal Cortex Hormones
Wales
Maternal Age
Denmark
Norway
Pregnancy
Meta-Analysis
Maternal Exposure
Congenital Heart Defects
Social Class
Prescriptions
Registries
Outcome Assessment (Health Care)
Databases
Delivery of Health Care

Keywords

  • Asthma medications
  • Congenital anomalies
  • First trimester exposure
  • Inhaled beta-2 agonists
  • Inhaled corticosteroids

Cite this

Garne, Ester ; Hansen, A Vinkel ; Morris, Joan ; Jordan, Sue ; Klungsoyr, Kari ; Engeland, Anders ; Tucker, David ; Thayer, Dan ; Davies, Gareth ; Nybo Andersen, Anne-Marie ; Dolk, Helen. / Risk of congenital anomalies after exposure to asthma medication in the first trimester of pregnancy - a cohort linkage study. In: BJOG: An International Journal of Obstetrics and Gynaecology. 2016 ; Vol. 123, No. 10. pp. 1609-1618.
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title = "Risk of congenital anomalies after exposure to asthma medication in the first trimester of pregnancy - a cohort linkage study",
abstract = "Objective To examine the effect of maternal exposure to asthma medications on the risk of congenital anomalies.Design Meta-analysis of aggregated data from three cohortstudies.Setting Linkage between healthcare databases and EUROCAT congenital anomaly registries.Population 519 242 pregnancies in Norway (2004–2010), Wales (2000–2010) and Funen, Denmark (2000–2010).Methods Exposure defined as having at least one prescription for asthma medications issued (Wales) or dispensed (Norway, Denmark) from 91 days before to 91 days after the pregnancy start date. Odds ratios (ORs) were estimated separately for each register and combined in meta-analyses.Main outcome measures ORs for all congenital anomalies and specific congenital anomalies.Results Overall exposure prevalence was 3.76{\%}. For exposure to asthma medication in general, the adjusted OR (adjOR) for a major congenital anomaly was 1.21 (99{\%} CI 1.09–1.34) after adjustment for maternal age and socioeconomic position. The OR of anal atresia was significantly increased in pregnancies exposedto inhaled corticosteroids (3.40; 99{\%} CI 1.15–10.04). For severe congenital heart defects, an increased OR (1.97; 1.12–3.49) was associated with exposure to combination treatment with inhaled corticosteroids and long-acting beta-2-agonists. Associations with renal dysplasia were driven by exposure to short-acting beta-2-agonists (2.37; 1.20–4.67).Conclusion The increased risk of congenital anomalies for women taking asthma medication is small with little confounding by maternal age or socioeconomic status. The study confirmed the association of inhaled corticosteroids with anal atresia found in earlier research and found potential new associations withcombination treatment. The potential new associations should be interpreted with caution due to the large number of comparisons undertaken.",
keywords = "Asthma medications, Congenital anomalies, First trimester exposure, Inhaled beta-2 agonists, Inhaled corticosteroids",
author = "Ester Garne and Hansen, {A Vinkel} and Joan Morris and Sue Jordan and Kari Klungsoyr and Anders Engeland and David Tucker and Dan Thayer and Gareth Davies and {Nybo Andersen}, Anne-Marie and Helen Dolk",
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Garne, E, Hansen, AV, Morris, J, Jordan, S, Klungsoyr, K, Engeland, A, Tucker, D, Thayer, D, Davies, G, Nybo Andersen, A-M & Dolk, H 2016, 'Risk of congenital anomalies after exposure to asthma medication in the first trimester of pregnancy - a cohort linkage study', BJOG: An International Journal of Obstetrics and Gynaecology, vol. 123, no. 10, pp. 1609-1618. https://doi.org/10.1111/1471-0528.14026

Risk of congenital anomalies after exposure to asthma medication in the first trimester of pregnancy - a cohort linkage study. / Garne, Ester; Hansen, A Vinkel; Morris, Joan; Jordan, Sue; Klungsoyr, Kari; Engeland, Anders; Tucker, David; Thayer, Dan; Davies, Gareth; Nybo Andersen, Anne-Marie; Dolk, Helen.

In: BJOG: An International Journal of Obstetrics and Gynaecology, Vol. 123, No. 10, 09.2016, p. 1609-1618.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Risk of congenital anomalies after exposure to asthma medication in the first trimester of pregnancy - a cohort linkage study

AU - Garne, Ester

AU - Hansen, A Vinkel

AU - Morris, Joan

AU - Jordan, Sue

AU - Klungsoyr, Kari

AU - Engeland, Anders

AU - Tucker, David

AU - Thayer, Dan

AU - Davies, Gareth

AU - Nybo Andersen, Anne-Marie

AU - Dolk, Helen

PY - 2016/9

Y1 - 2016/9

N2 - Objective To examine the effect of maternal exposure to asthma medications on the risk of congenital anomalies.Design Meta-analysis of aggregated data from three cohortstudies.Setting Linkage between healthcare databases and EUROCAT congenital anomaly registries.Population 519 242 pregnancies in Norway (2004–2010), Wales (2000–2010) and Funen, Denmark (2000–2010).Methods Exposure defined as having at least one prescription for asthma medications issued (Wales) or dispensed (Norway, Denmark) from 91 days before to 91 days after the pregnancy start date. Odds ratios (ORs) were estimated separately for each register and combined in meta-analyses.Main outcome measures ORs for all congenital anomalies and specific congenital anomalies.Results Overall exposure prevalence was 3.76%. For exposure to asthma medication in general, the adjusted OR (adjOR) for a major congenital anomaly was 1.21 (99% CI 1.09–1.34) after adjustment for maternal age and socioeconomic position. The OR of anal atresia was significantly increased in pregnancies exposedto inhaled corticosteroids (3.40; 99% CI 1.15–10.04). For severe congenital heart defects, an increased OR (1.97; 1.12–3.49) was associated with exposure to combination treatment with inhaled corticosteroids and long-acting beta-2-agonists. Associations with renal dysplasia were driven by exposure to short-acting beta-2-agonists (2.37; 1.20–4.67).Conclusion The increased risk of congenital anomalies for women taking asthma medication is small with little confounding by maternal age or socioeconomic status. The study confirmed the association of inhaled corticosteroids with anal atresia found in earlier research and found potential new associations withcombination treatment. The potential new associations should be interpreted with caution due to the large number of comparisons undertaken.

AB - Objective To examine the effect of maternal exposure to asthma medications on the risk of congenital anomalies.Design Meta-analysis of aggregated data from three cohortstudies.Setting Linkage between healthcare databases and EUROCAT congenital anomaly registries.Population 519 242 pregnancies in Norway (2004–2010), Wales (2000–2010) and Funen, Denmark (2000–2010).Methods Exposure defined as having at least one prescription for asthma medications issued (Wales) or dispensed (Norway, Denmark) from 91 days before to 91 days after the pregnancy start date. Odds ratios (ORs) were estimated separately for each register and combined in meta-analyses.Main outcome measures ORs for all congenital anomalies and specific congenital anomalies.Results Overall exposure prevalence was 3.76%. For exposure to asthma medication in general, the adjusted OR (adjOR) for a major congenital anomaly was 1.21 (99% CI 1.09–1.34) after adjustment for maternal age and socioeconomic position. The OR of anal atresia was significantly increased in pregnancies exposedto inhaled corticosteroids (3.40; 99% CI 1.15–10.04). For severe congenital heart defects, an increased OR (1.97; 1.12–3.49) was associated with exposure to combination treatment with inhaled corticosteroids and long-acting beta-2-agonists. Associations with renal dysplasia were driven by exposure to short-acting beta-2-agonists (2.37; 1.20–4.67).Conclusion The increased risk of congenital anomalies for women taking asthma medication is small with little confounding by maternal age or socioeconomic status. The study confirmed the association of inhaled corticosteroids with anal atresia found in earlier research and found potential new associations withcombination treatment. The potential new associations should be interpreted with caution due to the large number of comparisons undertaken.

KW - Asthma medications

KW - Congenital anomalies

KW - First trimester exposure

KW - Inhaled beta-2 agonists

KW - Inhaled corticosteroids

U2 - 10.1111/1471-0528.14026

DO - 10.1111/1471-0528.14026

M3 - Article

VL - 123

SP - 1609

EP - 1618

JO - BJOG: An International Journal of Obstetrics and Gynaecology

T2 - BJOG: An International Journal of Obstetrics and Gynaecology

JF - BJOG: An International Journal of Obstetrics and Gynaecology

SN - 1470-0328

IS - 10

ER -