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Int J Epidemiol. 2016 Dec 1;45(6):1998-2008. doi: 10.1093/ije/dyw192.

Neurodevelopmental problems at 18 months among children exposed to paracetamol in utero: a propensity score matched cohort study.

Author information

Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
PharmacoEpidemiology & Drug Safety Research Group, School of Pharmacy, University of Oslo, Oslo, Norway.
Department of Pediatrics, Radboudumc Amalia Children's Hospital.
Radboud REshape Innovation Center, Radboud University Medical Center, Nijmegen, The Netherlands.
Domain for Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway.



Previous studies showed that children exposed to paracetamol during fetal life might have an increased risk of neurodevelopmental problems. Since paracetamol is one of the most commonly used medications during pregnancy, even small increases in the risk of neurodevelopmental problems may have considerable implications for public health.


Using data from the Norwegian Mother and Child Cohort Study, we applied propensity score (PS) matching to examine associations between prenatal paracetamol exposure and neurodevelopmental problems among children at 18 months of age. Paracetamol use was classified into short-term (< 28 days) and long-term (≥ 28 days) of exposure.


Of the 51 200 pregnancies included in our study, 40.5% of mothers ( n  = 20 749) used paracetamol at least once during pregnancy. In the PS-matched analyses, long-term paracetamol exposure during pregnancy was associated with communication problems [odds ratio (OR): 1.38, 95% confidence interval (CI) 0.98-1.95) and delayed motor milestone attainment (OR: 1.35, 95% CI 1.07-1.70). We did not observe increased risks after short-term exposure. Sensitivity analyses for several indications showed similar effects as the PS-matched analyses, suggesting no confounding by indication.


Long-term exposure to paracetamol in utero was associated with modestly increased risks of motor milestone delay and impaired communication skills among children at 18 months. Caution is warranted when considering long-term use of paracetamol during pregnancy; however, women with severe pain conditions should not be deprived of appropriate pharmacotherapy.


MoBa; Norwegian Mother and Child Cohort Study; Paracetamol; acetaminophen; milestones; neurodevelopment; pregnancy; propensity scores

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