title: Prenatal Paracetamol Exposure and Wheezing in Childhood: Causation or Confounding?
abstract: BACKGROUND
  Several studies have reported an increased risk of wheezing in the children of mothers who used paracetamol during pregnancy. We evaluated to what extent this association is explained by confounding.
  
  
  METHODS
  We investigated the association between maternal paracetamol use in the first and third trimester of pregnancy and ever wheezing or recurrent wheezing/asthma in infants in the NINFEA cohort study. Risks ratios (RR) and 95% confidence intervals (CI) were estimated after adjustment for confounders, including maternal infections and antibiotic use during pregnancy.
  
  
  RESULTS
  The prevalence of maternal paracetamol use was 30.6% during the first and 36.7% during the third trimester of pregnancy. The prevalence of ever wheezing and recurrent wheezing/asthma was 16.9% and 5.6%, respectively. After full adjustment, the RR for ever wheezing decreased from 1.25 [1.07-1.47] to 1.10 [0.94-1.30] in the first, and from 1.26 [1.08-1.47] to 1.10 [0.93-1.29] in the third trimester. A similar pattern was observed for recurrent wheezing/asthma. Duration of maternal paracetamol use was not associated with either outcome. Further analyses on paracetamol use for three non-infectious disorders (sciatica, migraine, and headache) revealed no increased risk of wheezing in children.
  
  
  CONCLUSIONS
  The association between maternal paracetamol use during pregnancy and infant wheezing is mainly, if not completely explained by confounding.
authors: Cancer Epidemiology Unit, Department of Medical Sciences, AOU Città della Salute e della Scienza di Torino, CPO Piemonte, CERMS, and University of Turin, Turin, Italy.
authors: Enrica
authors: E
authors: Migliore
authors: Cancer Epidemiology Unit, Department of Medical Sciences, AOU Città della Salute e della Scienza di Torino, CPO Piemonte, CERMS, and University of Turin, Turin, Italy.
authors: Daniela
authors: D
authors: Zugna
authors: Cancer Epidemiology Unit, Department of Medical Sciences, AOU Città della Salute e della Scienza di Torino, CPO Piemonte, CERMS, and University of Turin, Turin, Italy.
authors: Claudia
authors: C
authors: Galassi
authors: Cancer Epidemiology Unit, Department of Medical Sciences, AOU Città della Salute e della Scienza di Torino, CPO Piemonte, CERMS, and University of Turin, Turin, Italy.
authors: Franco
authors: F
authors: Merletti
authors: Woman and Child Health Department, Pediatrics and Neonatology Division, Ospedale Versilia, Viareggio, Italy.
authors: Luigi
authors: L
authors: Gagliardi
authors: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors: Laura
authors: L
authors: Rasero
authors: Cancer Epidemiology Unit, Department of Medical Sciences, AOU Città della Salute e della Scienza di Torino, CPO Piemonte, CERMS, and University of Turin, Turin, Italy.
authors: Morena
authors: M
authors: Trevisan
authors: Unit of Epidemiology, 'Anna Meyer' Children's University Hospital, Florence, Italy.
authors: Franca
authors: F
authors: Rusconi
authors: Cancer Epidemiology Unit, Department of Medical Sciences, AOU Città della Salute e della Scienza di Torino, CPO Piemonte, CERMS, and University of Turin, Turin, Italy.
authors: Lorenzo
authors: L
authors: Richiardi
mesh_terms: D000328:Adult; D002675:Child, Preschool; D015331:Cohort Studies; D016001:Confidence Intervals; D015986:Confounding Factors, Epidemiologic; D003710:Demography; D005260:Female; D006801:Humans; D016017:Odds Ratio; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011263:Pregnancy Trimester, Third; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology* / Q000473:pathology*; D012008:Recurrence; D012135:Respiratory Sounds / Q000209:etiology*