Claudia B Avella-Garcia1,2,3,4,5, Jordi Julvez1,3,6, Joan Fortuny7, Cristina Rebordosa7, Raquel García-Esteban1,3,6, Isolina Riaño Galán8, Adonina Tardón6,9, Clara L Rodríguez-Bernal10, Carmen Iñiguez10, Ainara Andiarena11,12, Loreto Santa-Marina6,12,13, Jordi Sunyer1,3,4,5. 1. Center for Research in Environmental Epidemiology (CREAL). 2. Unitat Docent de Medicina Preventiva i Salut Publica H. Mar-UPF-ASPB. 3. IMIM (Hospital del Mar Medical Research Institute). 4. Universitat Pompeu Fabra (UPF). 5. Universitat Autònoma de Barcelona, Barcelona, Spain. 6. CIBER Epidemiología y Salud Pública (CIBERESP), Spain. 7. RTI Health Solutions, Barcelona, Spain. 8. Servicio de Pediatria, Hospital San Agustin, Aviles Asturias, Spain. 9. Public Health Department, University of Oviedo, Oviedo, Spain. 10. Environment and Health Area, CSISP-FISABIO-REDISSEC, Valencia, Spain. 11. Basic Psychological Processes and Development Department, Faculty of Psychology, University of the Basque Country, Gipuzkoa. 12. Health Research Institute, Biodonostia, San Sebastián, Spain. 13. Public Health Division of Gipuzkoa, Gipuzkoa, Basque Government, Spain.
Abstract
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 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). 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.
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 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). 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.
Authors: Zeyan Liew; Marianthi-Anna Kioumourtzoglou; Andrea L Roberts; Éilis J O'Reilly; Alberto Ascherio; Marc G Weisskopf Journal: Am J Epidemiol Date: 2019-04-01 Impact factor: 4.897
Authors: Andréa D Bertoldi; Sheryl L Rifas-Shiman; Alexandra Crispim Boing; Tatiane da Silva Dal Pizzol; Vanessa Iribarrem Avena Miranda; Marysabel Pinto Telis Silveira; Mariângela Freitas Silveira; Marlos R Domingues; Ina S Santos; Diego G Bassani; Luciana Tovo-Rodrigues; Emily Oken Journal: Paediatr Perinat Epidemiol Date: 2020-01-22 Impact factor: 3.980
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