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Use of paracetamol, ibuprofen or aspirin in pregnancy and risk of cerebral palsy in the child

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  • Tanja Gram Petersen, University of Copenhagen
  • ,
  • Zeyan Liew
  • Anne-Marie Nybo Andersen, University of Copenhagen
  • ,
  • Guro L Andersen, Cerebral Palsy Register of Norway
  • ,
  • Per Kragh Andersen, University of Copenhagen
  • ,
  • Torben Martinussen, University of Copenhagen
  • ,
  • Jørn Olsen
  • Cristina Rebordosa, Research Triangle Institute Health Solutions, Barcelona
  • ,
  • Mette Christophersen Tollånes, Norwegian Institute of Public Health
  • ,
  • Peter Uldall, Rigshospitalet
  • ,
  • Allen J Wilcox, National Institute of Environmental Health Sciences
  • ,
  • Katrine Strandberg-Larsen, University of Copenhagen

Background: It has been debated whether mild analgesics, mainly paracetamol, adversely affect aspects of neurodevelopment. We examined whether mother's use of paracetamol, aspirin or ibuprofen in pregnancy is associated with increased risk of cerebral palsy (CP) in the child.

Method: We included 185 617 mother-child pairs from the Danish National Birth Cohort and the Norwegian Mother and Child Cohort Study. We created harmonized definitions of analgesic use in pregnancy, as well as indications for analgesic use and other potential confounders. Children with CP were identified in nationwide registers. We estimated the average causal effect of analgesics on risk of CP using marginal structural models with stabilized inverse probability weights.

Results: Paracetamol use was reported in 49% of all pregnancies, aspirin in 3% and ibuprofen in 4%. Prenatal exposure to paracetamol ever in pregnancy was associated with increased risk of overall CP [adjusted odds ratio (aOR) 1.3, 95% confidence interval (CI): 1.0-1.7] and unilateral spastic CP (aOR 1.5, 95% CI: 1.0-2.2). The association appeared to be driven by an increased risk of unilateral spastic CP in children exposed in second trimester (aOR 1.6, 95% CI: 1.0-2.5). Children ever prenatally exposed to aspirin in pregnancy had an elevated risk of bilateral spastic CP (aOR 2.4, 95% CI: 1.1-5.3) compared with unexposed.

Conclusion: We observed an increased risk of spastic CP in children prenatally exposed to paracetamol and aspirin. Although we controlled for several important indications for analgesic use, we cannot exclude the possibility of confounding by underlying diseases.

Original languageEnglish
JournalInternational Journal of Epidemiology
Pages (from-to)121-130
Number of pages10
Publication statusPublished - 1 Feb 2018

    Research areas

  • Acetaminophen/adverse effects, Adult, Analgesics, Non-Narcotic/adverse effects, Aspirin/adverse effects, Cerebral Palsy/chemically induced, Cohort Studies, Female, Humans, Ibuprofen/adverse effects, Infant, Infant, Newborn, Logistic Models, Male, Norway/epidemiology, Pregnancy, Pregnancy Outcome, Prenatal Exposure Delayed Effects/chemically induced, Risk Factors, Young Adult

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