Preprint Review Version 2 Preserved in Portico This version is not peer-reviewed

Excessive Use of Paracetamol (Acetaminophen) during Early Development and Difficulties in Retrospective Analyses of Risks

Version 1 : Received: 2 November 2020 / Approved: 5 November 2020 / Online: 5 November 2020 (19:26:39 CET)
Version 2 : Received: 29 March 2022 / Approved: 30 March 2022 / Online: 30 March 2022 (05:47:18 CEST)

How to cite: Bono-Lunn, D.; Kuchibhatla, M.; Palkar, A.; Cendejas-Hernandez, J.; Sarafian, J.T.; Lawton, V.G.; Anderson, L.G.; Jones III, J.P.; Parker, W. Excessive Use of Paracetamol (Acetaminophen) during Early Development and Difficulties in Retrospective Analyses of Risks. Preprints 2020, 2020110224 (doi: 10.20944/preprints202011.0224.v2). Bono-Lunn, D.; Kuchibhatla, M.; Palkar, A.; Cendejas-Hernandez, J.; Sarafian, J.T.; Lawton, V.G.; Anderson, L.G.; Jones III, J.P.; Parker, W. Excessive Use of Paracetamol (Acetaminophen) during Early Development and Difficulties in Retrospective Analyses of Risks. Preprints 2020, 2020110224 (doi: 10.20944/preprints202011.0224.v2).

Abstract

A growing body of literature suggests a causative relationship between severe adverse neurological outcomes and early life exposure to paracetamol (acetaminophen) in the presence of oxidative stress. Review of the literature revealed that, although its use is not regularly monitored, paracetamol has achieved near universal acceptance, with exposure in some pediatric populations exceeding 90%. In addition, use of the drug as well as associated adverse outcomes may have risen as a result of pharmaceutical advertising rather than need, and inappropriate use of the drug, both in terms of dose and indication, is widespread. These findings indicate that many clinicians and patients do not, at the present time, evenly weigh the potential risks with the potential benefits of paracetamol exposure early in life. Although retrospective studies might be envisioned to further address the neurodevelopmental risks of paracetamol use during early development, in silico simulations demonstrated that such studies can be thwarted by very high rates of use of the drug combined with associations between paracetamol use and oxidative stressors that act as cofactors in the induction of neurodevelopmental injury. These findings suggest that, despite persistent uncertainty, clinicians and patients should be more aware of available information pointing toward the potential dangers for neurodevelopment of early life exposure to paracetamol. Most importantly, health care workers need to provide a more balanced view, weighing both risks and benefits, when providing advice for patients regarding paracetamol use during periods of brain development.

Keywords

acetaminophen; paracetamol; autism; pediatrics; safety

Subject

MEDICINE & PHARMACOLOGY, Pediatrics

Comments (1)

Comment 1
Received: 30 March 2022
Commenter: William Parker
Commenter's Conflict of Interests: Author
Comment: This revision of the manuscript contains two primary changes. First, the text has been modified to reflect recently gained appreciation for the fact that acetaminophen (paracetamol) can cause adverse neurological problems in laboratory animals even in the absence of excessive oxidative stress. Second, the computational work in the manuscript has been re-worked using a systematic approach. The systematic approach we used did not change the conclusions drawn in the original manuscript, but it provides a better overall view of how acetaminophen use affects the results of multivariate analysis.
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