Prenatal and postnatal exposure to acetaminophen in relation to autism spectrum and attention-deficit and hyperactivity symptoms in childhood: Meta-analysis in six European population-based cohorts

Author:

Alemany SilviaORCID,Avella-García Claudia,Liew Zeyan,García-Esteban Raquel,Inoue Kosuke,Cadman Tim,López-Vicente Mònica,González Llúcia,Riaño Galán Isolina,Andiarena Ainara,Casas Maribel,Margetaki Katerina,Strandberg-Larsen Katrine,Lawlor Deborah A.,El Marroun Hanan,Tiemeier Henning,Iñiguez Carmen,Tardón Adonina,Santa-Marina Loreto,Júlvez Jordi,Porta Daniela,Chatzi Leda,Sunyer Jordi

Abstract

AbstractThe potential etiological role of early acetaminophen exposure on Autism Spectrum Conditions (ASC) and Attention-Deficit/Hyperactivity Disorder (ADHD) is inconclusive. We aimed to study this association in a collaborative study of six European population-based birth/child cohorts. A total of 73,881 mother–child pairs were included in the study. Prenatal and postnatal (up to 18 months) acetaminophen exposure was assessed through maternal questionnaires or interviews. ASC and ADHD symptoms were assessed at 4–12 years of age using validated instruments. Children were classified as having borderline/clinical symptoms using recommended cutoffs for each instrument. Hospital diagnoses were also available in one cohort. Analyses were adjusted for child and maternal characteristics along with indications for acetaminophen use. Adjusted cohort-specific effect estimates were combined using random-effects meta-analysis. The proportion of children having borderline/clinical symptoms ranged between 0.9 and 12.9% for ASC and between 1.2 and 12.2% for ADHD. Results indicated that children prenatally exposed to acetaminophen were 19% and 21% more likely to subsequently have borderline or clinical ASC (OR = 1.19, 95% CI 1.07–1.33) and ADHD symptoms (OR = 1.21, 95% CI 1.07–1.36) compared to non-exposed children. Boys and girls showed higher odds for ASC and ADHD symptoms after prenatal exposure, though these associations were slightly stronger among boys. Postnatal exposure to acetaminophen was not associated with ASC or ADHD symptoms. These results replicate previous work and support providing clear information to pregnant women and their partners about potential long-term risks of acetaminophen use.

Funder

UK Medical Research Council and Wellcome

CERN

UK National Institute of Health Senior Investigator

European Union’s Horizon 2020

University of Bristol and UK Medical Research Council

Danish National Research Foundation

Danish Regional Committees

Pharmacy Foundation

Egmont Foundation

March of Dimes Birth Defects Foundation

Health Foundation

Novo Nordisk Foundation

Lundbeck Foundation

Danish Medical Research Council

Innovationsfonden

Nordea Foundation

Aarhus Ideas

University of Copenhagen Strategic Grant

Danish Council for Independent Research

Italian Ministry of Health

Italian Medicines Agency

Erasmus Medical Center

Erasmus University Rotterdam

Netherlands Organization for Health Research and Development

Netherlands Organization for Scientific Research

Ministry of Health, Welfare, and Sport

Ministry of Youth and Families

NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation

Vici project

European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant

Instituto de Salud Carlos III

Generalitat de Catalunya-CIRIT

Fundació la Marató de TV3

Spanish Ministry of Science and Innovation

CERCA Program

Juan de la Cierva – Incorporación Postdoctoral Contract awarded by Ministry of Economy, Industry and Competitiveness

Miguel Servet-II contract

Cátedra Telefónica, Universidad de Oviedo

CIBERESP

Obra Social Cajastur/Fundación Liberbank

Department of Health of the Basque Government

Provincial Government of Gipuzkoa

European Union

Generalitat Valenciana: FISABIO

Alicia Koplowitz Foundation 2017

the Greek Ministry of Health

National Institute of Environmental Health Sciences

Publisher

Springer Science and Business Media LLC

Subject

Epidemiology

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