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Avella-Garcia, C. B., Julvez, J., Fortuny, J., Rebordosa, C., Garcia-Esteban, R., Galan, I. R., Tardon, A., Rodriguez-Bernal, C. L., Iniguez, C., Andiarena, A., Santa-Marina, L., Sunyer, J

Acetaminophen use in pregnancy and neurodevelopment: attention function and autism spectrum symptoms

Int.J Epidemiol, 2016, PMID: 27353198

BACKGROUND: Acetaminophen 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. METHODS: This 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. RESULTS: Over 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 beta = -0.75, -0.13--0.02). CAST scores were increased in ever-exposed males (beta = 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 (beta = -0.18, -0.36-0.00) in females, and CAST scores in males (beta = 1.91, 0.44-3.38). CONCLUSIONS: Prenatal 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

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