Prenatal Paracetamol Exposure and Offspring ADHD Risk: A Narrative Review of Evidence, Plausibility, and Implications
DOI:
https://doi.org/10.12775/QS.2026.68.74297Keywords
Paracetamol, ADHD, pregnancy, neurodevelopment, prenatalAbstract
Background: Paracetamol is the most commonly used analgesic and antipyretic during pregnancy. Concurrently, attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition. Recent evidence has raised concerns regarding the potential impact of prenatal paracetamol exposure on offspring ADHD risk.
Objective: To examine the current evidence linking prenatal paracetamol exposure to ADHD, evaluate biological plausibility, and assess clinical and public health implications.
Methods: This narrative review synthesized findings from prospective cohort studies, case–control studies, and meta-analyses published mostly within the past decade and indexed in PubMed, PMC, Lancet.
Results: Several observational cohort studies and meta-analyses report modest associations between prenatal paracetamol exposure and increased risk of ADHD. Meta-analyses and umbrella reviews highlight moderate heterogeneity and substantial vulnerability to residual confounding, particularly confounding by indication and shared familial factors. Importantly, large nationwide cohort studies incorporating sibling-controlled analyses suggest that previously observed relationships may largely reflect genetic, environmental, or maternal health-related confounding rather than causal effects.
Conclusion: Recent reviews emphasize that while observed associations warrant a precautionary approach, the available evidence from observational studies cannot establish a causal link between typical prenatal acetaminophen (paracetamol) use and ADHD diagnosis in children. As such it is still present as first-line treatment, when clinically indicated, used at the lowest effective dose and shortest duration according to regulatory agencies such as EMA.
References
1.Prasad S, Kumminimana R. Attention-deficit/hyperactivity disorder: insights, advances and challenges in research and practice. Postep Psychiatr Neurol. 2025 Sep;34(3):196-206. doi: 10.5114/ppn.2025.153717. Epub 2025 Aug 25. PMID: 40959688; PMCID: PMC12435561.
2. Palladino VS, McNeill R, Reif A, Kittel-Schneider S. Genetic risk factors and gene-environment interactions in adult and childhood attention-deficit/hyperactivity disorder. Psychiatr Genet. 2019 Jun;29(3):63-78. doi: 10.1097/YPG.0000000000000220. PMID: 30741787.
3. Kian N, Samieefar N, Rezaei N. Prenatal risk factors and genetic causes of ADHD in children. World J Pediatr. 2022 May;18(5):308-319. doi: 10.1007/s12519-022-00524-6. Epub 2022 Mar 2. PMID: 35235183.
4. Al-Kuraishy HM, Al-Gareeb AI, Albuhadily AK, Abd El-Maksoud EM, Shokr MM, Alexiou A, Papadakis M, Batiha GE. Paracetamol: the potential therapeutic pathways defining its clinical use. Inflammopharmacology. 2025 Jun;33(6):2907-2918. doi: 10.1007/s10787-025-01779-x. Epub 2025 May 22. PMID: 40402381
5. Ayoub SS. Paracetamol (acetaminophen): A familiar drug with an unexplained mechanism of action. Temperature (Austin). 2021 Mar 16;8(4):351-371. doi: 10.1080/23328940.2021.1886392. PMID: 34901318; PMCID: PMC8654482.
6. Hamurtekin Y, Nouilati A, Demirbatir C, Hamurtekin E. The Contribution of Serotonergic Receptors and Nitric Oxide Systems in the Analgesic Effect of Acetaminophen: An Overview of the Last Decade. Turk J Pharm Sci. 2020 Feb;17(1):119-126. doi: 10.4274/tjps.galenos.2018.35403. Epub 2020 Feb 19. PMID: 32454770; PMCID: PMC7227872.
7. Conings S, Tseke F, Van den Broeck A, Qi B, Paulus J, Amant F, Annaert P, Van Calsteren K. Transplacental transport of paracetamol and its phase II metabolites using the ex vivo placenta perfusion model. Toxicol Appl Pharmacol. 2019 May 1;370:14-23. doi: 10.1016/j.taap.2019.03.004. Epub 2019 Mar 5. PMID: 30849458.
8. Coughtrie MW. Ontogeny of Human Conjugating Enzymes. Drug Metab Lett. 2015;9(2):99-108. doi: 10.2174/1872312809666150602151213. PMID: 26031463.
9. Ahlqvist VH, Sjöqvist H, Dalman C, Karlsson H, Stephansson O, Johansson S, Magnusson C, Gardner RM, Lee BK. Acetaminophen Use During Pregnancy and Children's Risk of Autism, ADHD, and Intellectual Disability. JAMA. 2024 Apr 9;331(14):1205-1214. doi: 10.1001/jama.2024.3172. PMID: 38592388; PMCID: PMC11004836.
10. Sznajder KK, Teti DM, Kjerulff KH. Maternal use of acetaminophen during pregnancy and neurobehavioral problems in offspring at 3 years: A prospective cohort study. PLoS One. 2022;17(9):e0272593. doi:10.1371/journal.pone.0272593
11. Sheikh J, Allotey J, Sobhy S, Plana MN, Martinez-Barros H, Naidu H, Junaid F, Sofat R, Mol BW, Kenny LC, Gladstone M, Teede H, Zamora J, Thangaratinam S. Maternal paracetamol (acetaminophen) use during pregnancy and risk of autism spectrum disorder and attention deficit/hyperactivity disorder in offspring: umbrella review of systematic reviews. BMJ. 2025 Nov 9;391:e088141. doi: 10.1136/bmj-2025-088141. PMID: 41207796.
12. Brandlistuen RE, Ystrom E, Nulman I, Koren G, Nordeng H. Prenatal paracetamol exposure and child neurodevelopment: a sibling-controlled cohort study. Int J Epidemiol. 2013 Dec;42(6):1702-13. doi: 10.1093/ije/dyt183. Epub 2013 Oct 24. PMID: 24163279; PMCID: PMC3887567.
13. Gustavson K, Ystrom E, Ask H, Ask Torvik F, Hornig M, Susser E, Lipkin WI, Lupattelli A, Stoltenberg C, Magnus P, Mjaaland S, Askeland RB, Walle KM, Bresnahan M, Nordeng H, Reichborn-Kjennerud T. Acetaminophen use during pregnancy and offspring attention deficit hyperactivity disorder - a longitudinal sibling control study. JCPP Adv. 2021 Jun 22;1(2):e12020. doi: 10.1002/jcv2.12020. PMID: 37431475; PMCID: PMC10242945.
14. Magnus P, Birke C, Vejrup K, Haugan A, Alsaker E, Daltveit AK, Handal M, Haugen M, Høiseth G, Knudsen GP, Paltiel L, Schreuder P, Tambs K, Vold L, Stoltenberg C. Cohort Profile Update: The Norwegian Mother and Child Cohort Study (MoBa). Int J Epidemiol. 2016 Apr;45(2):382-8. doi: 10.1093/ije/dyw029. Epub 2016 Apr 10. PMID: 27063603.
15. Damkier P, Gram EB, Ceulemans M, Panchaud A, Cleary B, Chambers C, Weber-Schoendorfer C, Kennedy D, Hodson K, Grant KS, Diav-Citrin O, Običan SG, Shechtman S, Alwan S. Acetaminophen in Pregnancy and Attention-Deficit and Hyperactivity Disorder and Autism Spectrum Disorder. Obstet Gynecol. 2025 Feb 1;145(2):168-176. doi: 10.1097/AOG.0000000000005802. Epub 2024 Dec 5. PMID: 39637384.
16. Bérard A, Cottin J, Leal LF, Picot C, Pleau J, Friedman JM, Damkier P, Cucherat M, Alwan S, Jurek L, Winn LM, Carleton BC, Bertoldi AD, Grandi SM, Masarwa R, Dodin P, Ceulemans M, Platt RW, Nourredine M, Gram EB, Veroniki AA, Massardier J, Tricco AC. Systematic Review and Meta-Analysis: Acetaminophen Use During Pregnancy and the Risk of Neurodevelopmental Disorders in Childhood. J Am Acad Child Adolesc Psychiatry. 2025 Oct 6:S0890-8567(25)02106-9. doi: 10.1016/j.jaac.2025.09.031. Epub ahead of print. PMID: 41062061.
17. Bauer AZ, Kriebel D, Herbert MR, Bornehag CG, Swan SH. Prenatal paracetamol exposure and child neurodevelopment: A review. Horm Behav. 2018 May;101:125-147. doi: 10.1016/j.yhbeh.2018.01.003. Epub 2018 Feb 3. PMID: 29341895.
18. Prada D, Ritz B, Bauer AZ, Baccarelli AA. Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology. Environ Health. 2025 Aug 14;24(1):56. doi: 10.1186/s12940-025-01208-0. PMID: 40804730; PMCID: PMC12351903.
19. Liew Z, Ritz B, Rebordosa C, Lee PC, Olsen J. Acetaminophen use during pregnancy, behavioral problems, and hyperkinetic disorders. JAMA Pediatr. 2014 Apr;168(4):313-20. doi: 10.1001/jamapediatrics.2013.4914. PMID: 24566677.
20. Alemany S, Avella-García C, Liew Z, García-Esteban R, Inoue K, Cadman T, López-Vicente M, González L, Riaño Galán I, Andiarena A, Casas M, Margetaki K, Strandberg-Larsen K, Lawlor DA, El Marroun H, Tiemeier H, Iñiguez C, Tardón A, Santa-Marina L, Júlvez J, Porta D, Chatzi L, Sunyer J. 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. Eur J Epidemiol. 2021 Oct;36(10):993-1004. doi: 10.1007/s10654-021-00754-4. Epub 2021 May 28. PMID: 34046850; PMCID: PMC8542535.
21. Tai S, Patel S, Downes K, Rogers J, Chu-Han Huang H. Maternal and offspring outcomes associated with prescribed ADHD medication in pregnancy: a systematic review. Arch Womens Ment Health. 2025 Dec;28(6):1425-1446. doi: 10.1007/s00737-025-01621-x. Epub 2025 Oct 14. PMID: 41083615; PMCID: PMC12702805.
22. Baker BH, Burris HH, Bloomquist TR, Boivin A, Gillet V, Larouche A, Takser L, Bellenger JP, Pasquier JC, Baccarelli AA. Association of Prenatal Acetaminophen Exposure Measured in Meconium With Adverse Birth Outcomes in a Canadian Birth Cohort. Front Pediatr. 2022 Apr 5;10:828089. doi: 10.3389/fped.2022.828089. PMID: 35450103; PMCID: PMC9017809.
23. Ji Y, Azuine RE, Zhang Y, Hou W, Hong X, Wang G, Riley A, Pearson C, Zuckerman B, Wang X. Association of Cord Plasma Biomarkers of In Utero Acetaminophen Exposure With Risk of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in Childhood. JAMA Psychiatry. 2020 Feb 1;77(2):180-189. doi: 10.1001/jamapsychiatry.2019.3259. PMID: 31664451; PMCID: PMC6822099.
24. Bauer AZ, Swan SH, Kriebel D, Liew Z, Taylor HS, Bornehag CG, Andrade AM, Olsen J, Jensen RH, Mitchell RT, Skakkebaek NE, Jégou B, Kristensen DM. Paracetamol use during pregnancy - a call for precautionary action. Nat Rev Endocrinol. 2021 Dec;17(12):757-766. doi: 10.1038/s41574-021-00553-7. Epub 2021 Sep 23. PMID: 34556849; PMCID: PMC8580820.
25. Antoun S, Ellul P, Peyre H, Rosenzwajg M, Gressens P, Klatzmann D, Delorme R. Fever during pregnancy as a risk factor for neurodevelopmental disorders: results from a systematic review and meta-analysis. Mol Autism. 2021 Sep 18;12(1):60. doi: 10.1186/s13229-021-00464-4. PMID: 34537069; PMCID: PMC8449704.
26. Cree RA, Bitsko RH, Danielson ML, Wanga V, Holbrook J, Flory K, Kubicek LF, Evans SW, Owens JS, Cuffe SP. Surveillance of ADHD Among Children in the United States: Validity and Reliability of Parent Report of Provider Diagnosis. J Atten Disord. 2023 Jan;27(2):111-123. doi: 10.1177/10870547221131979. Epub 2022 Nov 3. PMID: 36326292; PMCID: PMC9843610
27. Setyawan J, Fridman M, Grebla R, Harpin V, Korst LM, Quintero J. Variation in Presentation, Diagnosis, and Management of Children and Adolescents With ADHD Across European Countries. J Atten Disord. 2018 Aug;22(10):911-923. doi: 10.1177/1087054715597410. Epub 2015 Aug 5. PMID: 26246588.
28. Ystrom E, Gustavson K, Brandlistuen RE, Knudsen GP, Magnus P, Susser E, Davey Smith G, Stoltenberg C, Surén P, Håberg SE, Hornig M, Lipkin WI, Nordeng H, Reichborn-Kjennerud T. Prenatal Exposure to Acetaminophen and Risk of ADHD. Pediatrics. 2017 Nov;140(5):e20163840. doi: 10.1542/peds.2016-3840. PMID: 29084830; PMCID: PMC5654387.
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Copyright (c) 2026 Anna Olborska, Bartłomiej Maciej Wrochna, Agnieszka Brzozowska, Gabriela Stondzik, Anna Izabela Garbacz, Paweł Kosiorek, Agnieszka Radziwonka, Tomasz Julian Majszyk, Jacek Głuski, Patrycja Anna Borowiecka, Aleksandra Węglarz, Ada Niezgoda

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