Abstract
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.