title: Exposure to acid-suppressing drugs during pregnancy and the risk of asthma in childhood: an observational cohort study.
abstract: BACKGROUND
  Some research has suggested a potential link between prenatal exposure to proton pump inhibitors (PPIs) or H2 -receptor antagonists (H2 RAs) and the development of childhood asthma.
  
  
  OBJECTIVE
  To quantify the relative risk of asthma in children who experienced pre-natal exposure to PPIs and/or H2 RAs, adjusting for potential confounders.
  
  
  METHODS
  In this observational cohort study (NCT01787435), women aged 18-45 years with completed pregnancies between January 1996 and December 2010 were identified from The Health Improvement Network in the United Kingdom, and were linked to infants. Hazard ratios (HRs) were estimated using Cox proportional hazard models.
  
  
  RESULTS
  Our analysis identified 2371 prenatally exposed and 7745 unexposed infants. The incidence of asthma (per 1000 person-years) was 19.52 in the unexposed cohort, 23.88 in the PPI cohort and 32.16 in the H2 RA cohort. After adjusting for maternal healthcare utilisation during the year before pregnancy, the HR for asthma in infants whose mothers received prescriptions at any time during pregnancy was 1.12 (95% confidence interval: 0.88-1.44) for PPIs and 1.43 (1.20-1.70) for H2 RAs, when compared with unexposed infants. With further adjustment for maternal comorbidities and other medications, the HR for asthma was 1.03 (0.76-1.40) for PPIs and 1.32 (1.05-1.64) for H2 RAs.
  
  
  CONCLUSIONS
  Our analysis showed no association between prenatal exposure to PPIs and asthma in childhood after adjusting for confounders. The association found for H2 RAs may be explained largely by underlying environmental or genetic factors, as suggested by reductions in hazard ratio estimates following adjustment for maternal comorbidities.
authors.affiliation: Centro Español de Investigación Farmacoepidemiológica (CEIFE), Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Cea Soriano
authors.affiliation: Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Hernández-Díaz
authors.affiliation: AstraZeneca Gothenburg, Global Medicines Development, Mölndal, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Johansson
authors.affiliation: AstraZeneca Gothenburg, Global Medicines Development, Mölndal, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Nagy
authors.affiliation: Centro Español de Investigación Farmacoepidemiológica (CEIFE), Madrid, Spain.
authors.forename: L A
authors.initials: LA
authors.lastname: García-Rodríguez
mesh_terms: D001249:Asthma / Q000453:epidemiology*; D002648:Child; D015331:Cohort Studies; D005260:Female; D006635:Histamine H2 Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D016016:Proportional Hazards Models; D054328:Proton Pump Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D012306:Risk; D006113:United Kingdom; D055815:Young Adult
chemical_list: D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors