Working Paper Review Version 2 This version is not peer-reviewed

Paracetamol (Acetaminophen) use in infants and children was never shown to be safe for neurodevelopment: A systematic review with citation tracking.

Version 1 : Received: 2 November 2020 / Approved: 4 November 2020 / Online: 4 November 2020 (08:24:52 CET)
Version 2 : Received: 13 October 2021 / Approved: 19 October 2021 / Online: 19 October 2021 (10:13:55 CEST)

A peer-reviewed article of this Preprint also exists.

Cendejas-Hernandez, J., Sarafian, JT., Lawton, V., Palkar, A., Anderson, L.G., Larivière, V. & Parker, W. (2022) Paracetamol (Acetaminophen) Use in Infants and Children was Never Shown to be Safe for Neurodevelopment: A Systematic Review with Citation Tracking. European J. Pediatrics: https://doi.org/10.1007/s00431-022-04407-w. Cendejas-Hernandez, J., Sarafian, JT., Lawton, V., Palkar, A., Anderson, L.G., Larivière, V. & Parker, W. (2022) Paracetamol (Acetaminophen) Use in Infants and Children was Never Shown to be Safe for Neurodevelopment: A Systematic Review with Citation Tracking. European J. Pediatrics: https://doi.org/10.1007/s00431-022-04407-w.

Abstract

Background: Although widely believed to be safe for use in infants and children when used as directed, increasing evidence indicates that early life exposure to paracetamol (acetaminophen) may cause long-term neurodevelopmental problems. Further, recent studies in animal models demonstrate that cognitive development is exquisitely sensitive to paracetamol exposure during early development. In this study, evidence for the claim that paracetamol is safe was evaluated using a systematic literature search. Methods: Publications on PubMed between 1974 and 2017 that contained the keywords “infant” and either “paracetamol” or “acetaminophen” were considered. Of those initial 3096 papers, 218 were identified that made claims that paracetamol was safe for use with infants or children. From these 218, a total of 103 papers were identified as sources of authority for the safety claim. Results and Conclusions: A total of 52 papers contained actual experiments designed to test safety, and had a median follow-up time of 48 hours. None monitored neurodevelopment. Further, no trial considered total exposure to drug since birth, eliminating the possibility that the effects of drug exposure on long-term neurodevelopment could be accurately assessed. On the other hand, abundant and sufficient evidence was found to conclude that paracetamol does not induce acute liver damage in babies or children when used as directed.

Keywords

behavior; neurodevelopment; infant; child; autism

Subject

Medicine and Pharmacology, Immunology and Allergy

Comments (1)

Comment 1
Received: 19 October 2021
Commenter: William Parker
Commenter's Conflict of Interests: Author
Comment: The original manuscript was revised when an anonymous reviewer pointed out that, in the original version, we may have overlooked a study that (a) showed that paracetamol (acetaminophen) was safe for neurodevelopment, but which (b) had never been cited by another author. 

To test this reviewer's idea, we revised the original study, including papers which (a) contained experiments and (b) claims that use of paracetamol in babies or children is safe. 

This revision includes over a dozen more studies than the original manuscript, but these additional studies did not change the conclusion of the original study: Paracetamol was never shown to be safe for neurodevelopment when used as directed for babies and children.
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