Tanja Gram Petersen1, Zeyan Liew2, Anne-Marie Nybo Andersen1, Guro L Andersen3, Per Kragh Andersen4, Torben Martinussen4, Jørn Olsen5, Cristina Rebordosa6, Mette Christophersen Tollånes7, Peter Uldall8, Allen J Wilcox9, Katrine Strandberg-Larsen1. 1. Section of Social Medicine, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. 2. Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA, USA. 3. Cerebral Palsy Register of Norway, Vestfold Hospital Trust, Tønsberg, Norway. 4. Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. 5. Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark. 6. Pharmacoepidemiology and Risk Management, Research Triangle Institute Health Solutions, Barcelona, Spain. 7. Domain for Mental and Physical Health, Norwegian Institute of Public Health, Bergen, Norway. 8. Pediatric Department, University Hospital Rigshospitalet, Copenhagen, Denmark. 9. Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA.
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.
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.
Authors: Laurence de Fays; Karen Van Malderen; Karen De Smet; Javier Sawchik; Veerle Verlinden; Jamila Hamdani; Jean-Michel Dogné; Bernard Dan Journal: Dev Med Child Neurol Date: 2015-04-07 Impact factor: 5.449
Authors: Liona C Poon; Andrew Shennan; Jonathan A Hyett; Anil Kapur; Eran Hadar; Hema Divakar; Fionnuala McAuliffe; Fabricio da Silva Costa; Peter von Dadelszen; Harold David McIntyre; Anne B Kihara; Gian Carlo Di Renzo; Roberto Romero; Mary D'Alton; Vincenzo Berghella; Kypros H Nicolaides; Moshe Hod Journal: Int J Gynaecol Obstet Date: 2019-05 Impact factor: 3.561
Authors: Ram Patel; Katelyn Sushko; John van den Anker; Samira Samiee-Zafarghandy Journal: Int J Environ Res Public Health Date: 2022-02-14 Impact factor: 3.390
Authors: Anadeijda J E M C Landman; Emilie V J van Limburg Stirum; Janneke van 't Hooft; Aleid G Leemhuis; Martijn J J Finken; Anneloes L van Baar; Tessa J Roseboom; Anita C J Ravelli; Madelon van Wely; Jaap Oosterlaan; Rebecca C Painter; Eva Pajkrt; Martijn A Oudijk; Marjon A de Boer Journal: BMJ Open Date: 2022-08-08 Impact factor: 3.006
Authors: Mollie E Wood; Angela Lupattelli; Kristin Palmsten; Gretchen Bandoli; Caroline Hurault-Delarue; Christine Damase-Michel; Christina D Chambers; Hedvig M E Nordeng; Marleen M H J van Gelder Journal: Epidemiol Rev Date: 2022-01-14 Impact factor: 6.222