title: Prenatal and infant exposure to acetaminophen and ibuprofen and the risk for wheeze and asthma in children.
abstract: BACKGROUND
  Several studies have reported an association between use of over-the-counter antipyretics during pregnancy or infancy and increased asthma risk. An important potential limitation of these observational studies is confounding by indication.
  
  
  OBJECTIVE
  We investigated the association of antipyretic intake during pregnancy and during the first year of life (infancy) with asthma-related outcomes before and after controlling for early-life respiratory tract infections.
  
  
  METHODS
  We included 1490 mother-child pairs in Project Viva, a longitudinal prebirth cohort study. We categorized prenatal acetaminophen exposure as the maximum intake (never, 1-9 times, or ≥10 times) in early pregnancy or midpregnancy and ibuprofen intake as presence or absence in early pregnancy. We expressed intake of antipyretics in infancy as never, 1 to 5 times, 6 to 10 times, or more than 10 times. We examined the associations of acetaminophen and ibuprofen (per unit increase in exposure category) during pregnancy and infancy with wheeze, asthma, and allergen sensitization in early childhood (3-5 years of age, n = 1419) and midchildhood (7-10 years of age, n = 1220).
  
  
  RESULTS
  Unadjusted models showed an increased asthma risk in early childhood for higher infant acetaminophen (odds ratio [OR], 1.21; 95% CI 1.04-1.41) and ibuprofen (OR, 1.35; 95% CI, 1.19-1.52) intake. Controlling for respiratory tract infections attenuated estimates for acetaminophen (OR, 1.03; 95% CI, 0.88-1.22) and ibuprofen (OR, 1.19; 95% CI, 1.05-1.36). Prenatal acetaminophen was associated with increased asthma (OR, 1.26; 95% CI, 1.02-1.58) in early childhood but not midchildhood.
  
  
  CONCLUSIONS
  Adjustment for respiratory tract infections in early life substantially diminished associations between infant antipyretic use and early childhood asthma. Respiratory tract infections should be accounted for in studies of antipyretics and asthma to mitigate bias caused by confounding by indication.
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Sordillo
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.
authors.forename: Christina V
authors.initials: CV
authors.lastname: Scirica
authors.affiliation: Obesity Prevention Program, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Mass.
authors.forename: Sheryl L
authors.initials: SL
authors.lastname: Rifas-Shiman
authors.affiliation: Obesity Prevention Program, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Mass.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Gillman
authors.affiliation: Child Health and Development Institute, Mount Sinai Hospital, New York, NY.
authors.forename: Supinda
authors.initials: S
authors.lastname: Bunyavanich
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Camargo
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Weiss
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.
authors.forename: Diane R
authors.initials: DR
authors.lastname: Gold
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass. Electronic address: augusto.litonjua@channing.harvard.edu.
authors.forename: Augusto A
authors.initials: AA
authors.lastname: Litonjua
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001249:Asthma / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D063868:Patient Outcome Assessment; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D012135:Respiratory Sounds / Q000209:etiology*; D012306:Risk
chemical_list: D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000082:Acetaminophen; D007052:Ibuprofen
keywords: Asthma; analgesic; antipyretic; respiratory infection