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

Ester Garne, Anne Vinkel Hansen, Joan Morris, Louise Zaupper, Marie-Claude Addor, Ingeborg Barisic, Miriam Gatt, Nathalie Lelong, Kari Klungsoyr, Mary O'Mahony, Vera Nelen, Amanda Neville, Anna Pierini, David Tucker, Hermien de Walle, Awi Wiesel, Maria Loane, Helen Dolk

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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 b2-agonists compared with nonchromosomal control registrations. Odds of exposure to salbutamol were similar. Nonsignificant ORs of exposure to inhaled b2-agonists were found for spina bifida, cleft lip, anal atresia, severe congenital heartdefects 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). Exploratoryanalyses found an association between renal dysplasia and exposure to the combination of long-acting b2-agonists and inhaled corticosteroids (OR, 3.95; 95% CI, 1.99-7.85).

Conclusions: The study confirmed increased odds of firsttrimester exposure to inhaled b2-agonists for cleft palate andgastroschisis and found a potential new signal for renal dysplasia associated with combined long-acting b2-agonists and inhaled corticosteroids. Use of inhaled corticosteroids duringthe first trimester of pregnancy seems to be safe in relation to the risk for a range of specific major congenital anomalies.
LanguageEnglish
Pages1496-1502.e7
JournalJournal of Allergy and Clinical Immunology
Volume136
Issue number6
Early online date26 Jul 2015
DOIs
Publication statusPublished - Dec 2015

Fingerprint

Case-Control Studies
Imperforate Anus
Asthma
Odds Ratio
Cleft Lip
First Pregnancy Trimester
Pregnancy
Hypospadias
Adrenal Cortex Hormones
Gastroschisis
Kidney
Spinal Dysraphism
Tetralogy of Fallot
Albuterol
Cleft Palate
Registries
Pregnant Women
Steroids
Population

Keywords

  • Asthma medication
  • congenital anomalies
  • pregnancy
  • first trimester exposure
  • inhaled b2-agonists
  • inhaled corticosteroids

Cite this

Garne, Ester ; Vinkel Hansen, Anne ; Morris, Joan ; Zaupper, Louise ; Addor, Marie-Claude ; Barisic, Ingeborg ; Gatt, Miriam ; Lelong, Nathalie ; Klungsoyr, Kari ; O'Mahony, Mary ; Nelen, Vera ; Neville, Amanda ; Pierini, Anna ; Tucker, David ; de Walle, Hermien ; Wiesel, Awi ; Loane, Maria ; Dolk, Helen. / Use of asthma medication during pregnancy and risk of specific congenital anomalies: A European case-malformed control study. 2015 ; Vol. 136, No. 6. pp. 1496-1502.e7.
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abstract = "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 b2-agonists compared with nonchromosomal control registrations. Odds of exposure to salbutamol were similar. Nonsignificant ORs of exposure to inhaled b2-agonists were found for spina bifida, cleft lip, anal atresia, severe congenital heartdefects 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). Exploratoryanalyses found an association between renal dysplasia and exposure to the combination of long-acting b2-agonists and inhaled corticosteroids (OR, 3.95; 95{\%} CI, 1.99-7.85).Conclusions: The study confirmed increased odds of firsttrimester exposure to inhaled b2-agonists for cleft palate andgastroschisis and found a potential new signal for renal dysplasia associated with combined long-acting b2-agonists and inhaled corticosteroids. Use of inhaled corticosteroids duringthe first trimester of pregnancy seems to be safe in relation to the risk for a range of specific major congenital anomalies.",
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Garne, E, Vinkel Hansen, A, Morris, J, Zaupper, L, Addor, M-C, Barisic, I, Gatt, M, Lelong, N, Klungsoyr, K, O'Mahony, M, Nelen, V, Neville, A, Pierini, A, Tucker, D, de Walle, H, Wiesel, A, Loane, M & Dolk, H 2015, 'Use of asthma medication during pregnancy and risk of specific congenital anomalies: A European case-malformed control study', vol. 136, no. 6, pp. 1496-1502.e7. https://doi.org/10.1016/j.jaci.2015.05.043

Use of asthma medication during pregnancy and risk of specific congenital anomalies: A European case-malformed control study. / Garne, Ester; Vinkel Hansen, Anne; Morris, Joan; Zaupper, Louise; Addor, Marie-Claude; Barisic, Ingeborg; Gatt, Miriam; Lelong, Nathalie; Klungsoyr, Kari; O'Mahony, Mary; Nelen, Vera; Neville, Amanda; Pierini, Anna; Tucker, David; de Walle, Hermien; Wiesel, Awi; Loane, Maria; Dolk, Helen.

Vol. 136, No. 6, 12.2015, p. 1496-1502.e7.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Use of asthma medication during pregnancy and risk of specific congenital anomalies: A European case-malformed control study

AU - Garne, Ester

AU - Vinkel Hansen, Anne

AU - Morris, Joan

AU - Zaupper, Louise

AU - Addor, Marie-Claude

AU - Barisic, Ingeborg

AU - Gatt, Miriam

AU - Lelong, Nathalie

AU - Klungsoyr, Kari

AU - O'Mahony, Mary

AU - Nelen, Vera

AU - Neville, Amanda

AU - Pierini, Anna

AU - Tucker, David

AU - de Walle, Hermien

AU - Wiesel, Awi

AU - Loane, Maria

AU - Dolk, Helen

PY - 2015/12

Y1 - 2015/12

N2 - 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 b2-agonists compared with nonchromosomal control registrations. Odds of exposure to salbutamol were similar. Nonsignificant ORs of exposure to inhaled b2-agonists were found for spina bifida, cleft lip, anal atresia, severe congenital heartdefects 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). Exploratoryanalyses found an association between renal dysplasia and exposure to the combination of long-acting b2-agonists and inhaled corticosteroids (OR, 3.95; 95% CI, 1.99-7.85).Conclusions: The study confirmed increased odds of firsttrimester exposure to inhaled b2-agonists for cleft palate andgastroschisis and found a potential new signal for renal dysplasia associated with combined long-acting b2-agonists and inhaled corticosteroids. Use of inhaled corticosteroids duringthe first trimester of pregnancy seems to be safe in relation to the risk for a range of specific major congenital anomalies.

AB - 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 b2-agonists compared with nonchromosomal control registrations. Odds of exposure to salbutamol were similar. Nonsignificant ORs of exposure to inhaled b2-agonists were found for spina bifida, cleft lip, anal atresia, severe congenital heartdefects 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). Exploratoryanalyses found an association between renal dysplasia and exposure to the combination of long-acting b2-agonists and inhaled corticosteroids (OR, 3.95; 95% CI, 1.99-7.85).Conclusions: The study confirmed increased odds of firsttrimester exposure to inhaled b2-agonists for cleft palate andgastroschisis and found a potential new signal for renal dysplasia associated with combined long-acting b2-agonists and inhaled corticosteroids. Use of inhaled corticosteroids duringthe first trimester of pregnancy seems to be safe in relation to the risk for a range of specific major congenital anomalies.

KW - Asthma medication

KW - congenital anomalies

KW - pregnancy

KW - first trimester exposure

KW - inhaled b2-agonists

KW - inhaled corticosteroids

U2 - 10.1016/j.jaci.2015.05.043

DO - 10.1016/j.jaci.2015.05.043

M3 - Article

VL - 136

SP - 1496-1502.e7

IS - 6

ER -