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Association of Prenatal Acetaminophen Exposure With Risk of ADHD and ASD in Offspring: A systematic review and meta-analysis

Published online by Cambridge University Press:  26 August 2025

D. Carrazzoni Godoi ,
K. Guedes Amorim ,
R. Góes de Oliveira Galvão ,
A. C. Putini Vieira ,
L. Bussiki Corrêa da Costa Kotecki ,
D. Abraham Batista da Hora  and
S. A. de Souza Júnior
D. Carrazzoni Godoi*
Affiliation:
School of Psychology, Cardiff University, Cardiff, United Kingdom
K. Guedes Amorim
Affiliation:
Medical Sciences Center, Federal University of Paraíba, João Pessoa
R. Góes de Oliveira Galvão
Affiliation:
Escola Superior de Ciências da Saúde, Brasilia
A. C. Putini Vieira
Affiliation:
Universidade Santo Amaro, Santo Amaro
L. Bussiki Corrêa da Costa Kotecki
Affiliation:
Centro Universitário de Várzea Grande, Várzea Grande
D. Abraham Batista da Hora
Affiliation:
Universidade Federal do Amazonas, Manaus
S. A. de Souza Júnior
Affiliation:
Centro de Ciências da Saúde, Curso de Medicina, Universidade de Fortaleza Departament of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, Brazil
*
*Corresponding author.

Abstract

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Introduction

The association between prenatal acetaminophen exposure and the development of Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) remains a subject of considerable debate. Despite extensive research, the evidence regarding this relationship is conflicting.

Objectives

To perform a systematic review and meta-analysis of studies comparing the incidence of ADHD and ASD in patients that were either exposed or not exposed to acetaminophen prenatally.

Methods

We systematically searched Pubmed, Embase and Cochrane Central for eligible studies up until August 2024. Only studies which included participants with a medical diagnosis of ADHD/ASD and reported acetaminophen exposure as a binary measure were included. Available summary data was extracted from published reports and pooled with a random-effects model using odds ratios (OR) with 95% confidence intervals (CI). Hazard ratios (HR) adjusted for potential confounding factors were used for sensitivity analyses. All statistical analyses were conducted utilizing Review Manager 5.4.1. PROSPERO iD:CRD42024587662.

Results

We included five studies with a total of 2,647,536 patients with ADHD (150,741) / ASD (63,726), of whom 271,126 were exposed to acetaminophen prenatally and 2,376,410 were not exposed. Prenatal acetaminophen exposure was associated with an increased risk of developing ADHD (OR 1.30; 95% CI 1.17 to 1.45; p<0.01; I2 = 73%; Figure 1) and ASD (OR 1.17; 95% CI 1.14 - 1.20; p<0.01; I2 = 0%; Figure 2). Sensitivity analyses revealed that acetaminophen exposure during the third trimester of pregnancy was associated with an increased risk of ADHD (HR 1.26; 95% CI 1.07 to 1.47; p<0.01; I2 = 0%; Figure 3), but not during first (HR 1.10; 95% CI 0.97 to 1.26; p=0.13; I2 = 0%; Figure 3) and second (HR 1.07; 95% CI 0.95 to 1.19; p=0.26; I2 = 0%; Figure 3) trimesters.

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Conclusions

In this systematic review and meta-analysis, prenatal acetaminophen exposure was significantly associated with risk of developing ADHD and ASD, especially if exposure occurs in the third trimester of pregnancy.

Disclosure of Interest

None Declared

Information

Type
Abstract
Information
European Psychiatry , Volume 68 , Special Issue S1: Abstracts of the 33rd European Congress of Psychiatry , April 2025 , pp. S140 - S141
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of European Psychiatric Association
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