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Paediatr Perinat Epidemiol. 2019 Oct 21. doi: 10.1111/ppe.12596. [Epub ahead of print]

Associations of prenatal or infant exposure to acetaminophen or ibuprofen with mid-childhood executive function and behaviour.

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Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA.
Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Sophia Children's Hospital, Rotterdam, Netherlands.
Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.



Over-the-counter analgesics during pregnancy or infancy may be related to neurobehavioural problems in children, but little is known about effects of different analgesic types, dosage, and timing.


Examine associations of acetaminophen and ibuprofen use during pregnancy and infancy with executive function and behaviour problems in children.


We included 1225 mother-child pairs from Project Viva, a pre-birth cohort study. We assessed prenatal acetaminophen and ibuprofen use in early and mid-pregnancy and infant use in the first year of life using questionnaires. Parents and classroom teachers assessed child behaviours in mid-childhood (median 8 years), using the Behavior Rating Inventory of Executive Function (BRIEF) and the Strengths and Difficulties Questionnaire (SDQ), with higher scores indicating worse functioning for both. We examined associations of acetaminophen and ibuprofen use during pregnancy and infancy with mid-childhood neurobehavioural outcomes using linear regression models adjusted for potential confounders.


During pregnancy, 46.1% of mothers used acetaminophen ≥10 times and 18.4% used any ibuprofen. In the first year, 65.3% and 39.6% of infants received acetaminophen and ibuprofen ≥6 times, respectively. Higher (≥10 vs <10 times) prenatal acetaminophen (β 1.64 points; 95% confidence interval [CI] 0.59, 2.68) and any ibuprofen (β 1.56, 95% CI 0.19, 2.92) were associated with higher parent-rated BRIEF global scores. Patterns of association were linear across categories and were similar for other parent- and teacher-rated outcomes. Infancy exposure (≥6 vs <6 times) to acetaminophen (β 1.69, 95% CI 0.51, 2.87) and ibuprofen (β 1.40, 95% CI 0.25, 2.55) were associated with higher parent-rated BRIEF GEC scores but associations with teacher-rated scores were weaker.


Prenatal and early-life exposure to acetaminophen and ibuprofen were associated with poorer executive function and behaviour in childhood. These findings highlight the need for further research on the mechanisms through which analgesics may act on fetal and child brain development.


acetaminophen; child behaviour; child executive function; ibuprofen; infancy; pregnancy


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