• Claudia B Avella-Garcia, Jordi Julvez, Joan Fortuny, Cristina Rebordosa, Raquel García-Esteban, Isolina Riaño Galán, Adonina Tardón, Clara L Rodríguez-Bernal, Carmen Iñiguez, Ainara Andiarena, Loreto Santa-Marina, and Jordi Sunyer.
• Center for Research in Environmental Epidemiology (CREAL).
• Int J Epidemiol. 2016 Dec 1; 45 (6): 198719961987-1996.

BackgroundAcetaminophen is extensively used during pregnancy. But there is a lack of population-representative cohort studies evaluating its effects on a range of neuropsychological and behavioural endpoints. We aimed to assess whether prenatal exposure to acetaminophen is adversely associated with neurodevelopmental outcomes at 1 and 5 years of age.MethodsThis Spanish birth cohort study included 2644 mother-child pairs recruited during pregnancy. The proportion of liveborn participants evaluated at 1 and 5 years was 88.8% and 79.9%, respectively. Use of acetaminophen was evaluated prospectively in two structured interviews. Ever/never use and frequency of use (never, sporadic, persistent) were measured. Main neurodevelopment outcomes were assessed using Childhood Autism Spectrum Test (CAST), Conner's Kiddie Continuous Performance Test (K-CPT) and ADHD-DSM-IV form list. Regression models were adjusted for social determinants and co-morbidities.ResultsOver 40% of mothers reported using acetaminophen. Ever-exposed offspring had higher risks of presenting more hyperactivity/impulsivity symptoms [incidence rate ratio (IRR) = 1.41, 95% confidence interval (CI) 1.01-1.98), K-CPT commission errors (IRR = 1.10, 1.03-1.17), and lower detectability scores (coefficient β = -0.75, -0.13--0.02). CAST scores were increased in ever-exposed males (β = 0.63, 0.09-1.18). Increased effect sizes of risks by frequency of use were observed for hyperactivity/impulsivity symptoms (IRR = 2.01, 0.95-4.24) in all children, K-CPT commission errors (IRR = 1.32, 1.05-1.66) and detectability (β = -0.18, -0.36-0.00) in females, and CAST scores in males (β = 1.91, 0.44-3.38).ConclusionsPrenatal acetaminophen exposure was associated with a greater number of autism spectrum symptoms in males and showed adverse effects on attention-related outcomes for both genders. These associations seem to be dependent on the frequency of exposure.© The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

This article appears in the collection: Is paracetamol/acetaminophen use in pregnancy associated with autism or attention-deficit-hyperactivity disorder?.

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