Frequently Asked Questions

TYLENOL® and Autism

This is not intended to represent a comprehensive analysis of the data or to support the use of our products beyond the current labeling. Due to reasons related to copyrights, we are not able to provide reprints for published literature.

There have been nine studies looking at the relationship between in utero exposure and autism diagnosis. The most methodologically robust studies (Okubo 2025, Ahlqvist 2024, Janecka 2018) show no evidence of an association; three studies (Mkhitaryan 2024, Saunders 2019, and Ji 2018) show no statistically significant association; and two studies (Ji 2020 and Liew 2016) show a statistically significant association but lack sufficient data to properly adjust for known confounders, including genetics/familial factors and indication for use. A recent study (Lee 2026) did not find an association between prenatal acetaminophen use and ASD after performing a sibling-matched analysis. While the study also performed a bidirectional analysis suggesting the presence of a potential unaddressed source of bias within the study, these findings do not materially alter the overall interpretation of the sibling control results (Lee 2026). There are also some studies that use screening tools to assess a relationship between in utero exposure and symptoms of autism. However, these studies have limited value in assessing a causal association for diagnosed autism as they are not a reliable tool for diagnosing autism.

*Kenvue continuously reviews the latest science and safety data on all our products. For the topic of use of acetaminophen during pregnancy and adverse fetal outcomes, Kenvue has performed rigorous review of related studies. The nine studies referenced in this section are those studies which measured the outcome of physician-diagnosed autism.

References

Ahlqvist, V. H., Sjöqvist, H., Dalman, C., Karlsson, H., Stephansson, O., Johansson, S., Magnusson, C., Gardner, R. M., & Lee, B. K. (2024). Acetaminophen Use During Pregnancy and Children's Risk of Autism, ADHD, and Intellectual Disability. JAMA, 331(14), 1205–1214. https://doi.org/10.1001/jama.2024.3172

Janecka, M., Kodesh, A., Levine, S. Z., Lusskin, S. I., Viktorin, A., Rahman, R., Buxbaum, J. D., Schlessinger, A., Sandin, S., & Reichenberg, A. (2018). Association of Autism Spectrum Disorder With Prenatal Exposure to Medication Affecting Neurotransmitter Systems. JAMA psychiatry, 75(12), 1217–1224. https://doi.org/10.1001/jamapsychiatry.2018.2728

Ji, Y., Riley, A. W., Lee, L. C., Hong, X., Wang, G., Tsai, H. J., Mueller, N. T., Pearson, C., Thermitus, J., Panjwani, A., Ji, H., Bartell, T. R., Burd, I., Fallin, M. D., & Wang, X. (2018). Maternal Biomarkers of Acetaminophen Use and Offspring Attention Deficit Hyperactivity Disorder. Brain sciences, 8(7), 127. https://doi.org/10.3390/brainsci8070127

Ji, Y., Azuine, R. E., Zhang, Y., Hou, W., Hong, X., Wang, G., Riley, A., Pearson, C., Zuckerman, B., & Wang, X. (2020). 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, 77(2), 180–189. https://doi.org/10.1001/jamapsychiatry.2019.3259

Lee, P. C., Chuang, Y. H., Hu, Y. H., Lin, C. N., Li, C. Y., Chen, Y. Y., Heck, J. E., Bellia, G., Zhuo, H., Arah, O. A., & Liew, Z. (2026). Maternal Acetaminophen Use and Child Neurodevelopment. JAMA pediatrics, 180(5), 527–534. https://doi.org/10.1001/jamapediatrics.2026.0071

Liew, Z., Ritz, B., Virk, J., & Olsen, J. (2016). Maternal use of acetaminophen during pregnancy and risk of autism spectrum disorders in childhood: A Danish national birth cohort study. Autism research : official journal of the International Society for Autism Research, 9(9), 951–958. https://doi.org/10.1002/aur.1591

Mkhitaryan, M., Avetisyan, T., Mkhoyan, A., Avetisyan, L., & Yenkoyan, K. (2024). A case-control study on pre-, peri-, and neonatal risk factors associated with autism spectrum disorder among Armenian children. Scientific reports, 14(1), 12308. https://doi.org/10.1038/s41598-024-63240-3

Okubo, Y., Hayakawa, I., Sugitate, R., & Nariai, H. (2026). Maternal Acetaminophen Use and Offspring's Neurodevelopmental Outcome: A Nationwide Birth Cohort Study. Paediatric and perinatal epidemiology, 40(1), 70–79. https://doi.org/10.1111/ppe.70071

Saunders, A., Woodland, J., & Gander, S. (2019). A Comparison of Prenatal Exposures in Children with and without a Diagnosis of Autism Spectrum Disorder. Cureus, 11(7), e5223. https://doi.org/10.7759/cureus.5223

My patients are asking about use of acetaminophen by infants and children and neurodevelopmental disorders including autism; what does the science say?

Studies looking at acetaminophen use in infants and children and autism have not established a causal association between the two. Several of the studies evaluating acetaminophen use in infants and children and autism were conducted in special or high-risk populations, such as preterm infants or neonates treated in NICU settings. Retrospective cohort studies in these populations (e.g., infants treated for patent ductus arteriosus or neonatal pain) generally did not find an association between acetaminophen exposure in infants and children and later diagnosis of ASD (Mashally et al., 2021; Juujärvi et al., 2021).

Clinically, acetaminophen is often used by physicians to treat patent ductus arteriosus (PDA) in preterm infants especially those with low gestational age due to fewer gastrointestinal and renal side effects (Mayo Clinic, 2025). Several studies have been conducted to evaluate if the use of acetaminophen to treat PDA is associated with adverse outcomes. No association between acetaminophen use during neonatal admission and adverse neurodevelopmental outcomes has been observed across these studies (Hock et al., 2023; Juujärvi et al., 2022; Oncel et al., 2017; Pearce et al., 2024; Zhong et al., 2023).

Whereas some studies have reported associations between acetaminophen use and neurodevelopmental outcomes, it is noteworthy that these findings come mainly from retrospective surveys or small studies that rely on parents remembering medication use years later, making them susceptible to recall bias and selection bias (Bittker et al., 2018; Bittker et al., 2020; Schultz et al., 2008). Moreover, these studies have insufficient data on key confounders such as genetics, familial factors, and indication of use, further limiting their reliability. As a result, these studies are of limited value in drawing any meaningful conclusions regarding an association between acetaminophen use in infants and children and the development of autism or ADHD.

To date we have identified one meta-analysis of six large European population-based birth cohorts (~73,900 mother–child pairs) which evaluated acetaminophen use in infants and children and ADHD or ASD symptoms (not specific to clinical diagnosis) (Alemany et al., 2021). This 2021 meta-analysis found no statistically significant association between acetaminophen use in infants and children and ASD symptoms (Alemany et al., 2021). It is important to acknowledge that many studies cannot fully account for illness and genetic and family related influences, which are well-known to play a large role in the risk of developing autism. Overall, when all epidemiological studies are considered together, the evidence does not support a causal relationship between acetaminophen use in infants and children and autism.

Do infants or children have impaired metabolism of acetaminophen that may possibly contribute to development of autism in children?

It has been hypothesized that impaired acetaminophen metabolism may contribute to the development of autism. Acetaminophen is metabolized primarily through the glucuronidation and sulfation metabolic pathways. Metabolism in infants or children have been measured or modelled and demonstrated functional glucuronidation and sulfation enzymes are present and determined that acetaminophen can be effectively metabolized in these age groups (Miller et al. 1976; Dela et al., 2026). Another study assessed I.V. acetaminophen metabolism. The study was a single center retrospective study, and clinical data and hepatic enzyme profiles (ALT, AST, γGT) were examined in 189 cases of neonates treated with I.V. paracetamol (Allegaert et al. 2008). The study found no significant increase in markers of hepatotoxicity, ALT, AST, or γGT. The authors concluded that this retrospective study on hepatic tolerance provides evidence on safety of acetaminophen in neonates.

Does acetaminophen use result in a reactive metabolite NAPQI in the human brain which results in autism?

It has also been hypothesized that formation of reactive metabolites of acetaminophen may be neurotoxic. NAPQI, or N-acetyl-p-benzoquinone imine, is a reactive and toxic byproduct formed in very minor amounts during the metabolism of acetaminophen in the liver; however, studies have concluded there is no potential for the generation of NAPQI from acetaminophen at any neurotoxic relevant levels in the brain (Ali et al., 2025). Acetaminophen is metabolized primarily through the glucuronidation and sulfation metabolic pathways; however, in the liver some acetaminophen metabolism may occur through CYP2E1 metabolism of acetaminophen into NAPQI—generally a minor metabolic pathway compared to the glucuronidation and sulfation metabolic pathways. In the body, NAPQI is detoxified and neutralized by glutathione, which is relatively abundant with sufficient capacity in the infant brain to conjugate and rapidly eliminate any nominal NAPQI that could theoretically be produced regardless of any factors that impact individual infant susceptibility because:

Human and animal studies and human physiology databases establish that there would be insufficient levels of the enzyme CYP2E1 present in the infant brain—indeed orders of magnitude below the levels present in the liver—to generate toxicologically relevant NAPQI, if any were generated at all.
The enzymes responsible for the production of glutathione (a primary mechanism that the body uses to detoxify and neutralize NAPQI and other toxins), glutathione-S-transferases (GSTs), and glutathione (GSH) mediated by GSTs, are relatively abundant with sufficient capacity in the infant brain to conjugate and rapidly eliminate any nominal NAPQI that could theoretically be present (Aoyama, 2021; Iskusnykh et al., 2022; Knapen et al., 1999).
Other compelling pharmacokinetic data for infants and acetaminophen shows that acetaminophen would be sufficiently metabolized through other metabolic routes, including glucuronidation (Miller et al. 1976; Dela et al., 2026).

Taken together, the formation of toxicologically relevant concentrations of NAPQI in the infant brain is not supported by the predominant metabolic pathways for acetaminophen in infants and sufficient levels of glutathione to neutralize NAPQI. Available evidence does not support the formation of toxic levels of NAPQI in the infant brain from acetaminophen use.

Does acetaminophen use by infants and children induce oxidative stress and increase neuronal injury which may lead to autism?

Although oxidative stress is frequently invoked as potential biological mechanism leading to autism, there is no reliable evidence establishing a causal or exposure-specific link between acetaminophen use and oxidative stress causing neuronal injury. A retrospective assessment of the literature indicates that at approved, therapeutic doses, acetaminophen use does not cause oxidative stress in humans. There are, however, studies reporting that at therapeutic doses, acetaminophen may instead decrease oxidative damage to cells and organs (Alisi et al., 2012, Morita et al., 2022, Zhao et al., 2017, Janz et al. 2015). Taking the literature as a whole, the results from in vitro, in vivo, and clinical literature on acetaminophen and oxidative stress demonstrate that acetaminophen intake at concentrations similar to approved human doses can scavenge specific free radicals, decrease oxidative stress (Alisi et al., 2012, Morita et al., 2022) and prevent cognitive deficits associated with oxidative stress in animal models (Zhao et al., 2017). Finally, a randomized clinical trial reported by Janz et al. (2015) that oral administration of acetaminophen in adults may reduce biomarkers of lipid peroxidation, a biomarker of oxidative damage.

Studies suggesting that acetaminophen intake may result in oxidative stress may be a result of artifact 4-aminophenol (4-AP) and similar compounds causing false-positive results in horseradish peroxidase assays, a common enzyme used in analytical studies to measure oxidative stress because they are oxidized by the enzyme to form reactive intermediates (Tarnowski et al., 2018). Additionally, a recent publication, Meyer et al. (2024), called into question the validity of many in vitro models that assess oxidative stress, noting that some methods are measuring normal cellular processes, or are not used appropriately.

Is acetaminophen use during or after circumcisions associated with autism?

It has been speculated that administration of acetaminophen after circumcisions may be associated with the development of autism. There is no evidence that giving infants acetaminophen, during or after circumcision, has any effect on the development of autism. Three studies cited in the Citizen Petition discussed below attempt to link the use of acetaminophen during or after circumcision and the development of autism, Miani et al. (2020), Frisch et al. (2015), and Howard et al. (1994). One study referenced did not include autism and does not include any information on acetaminophen use Miani et al. (2020). Another of the studies reported that circumcised boys had a higher risk of autism, did not collect information on analgesic use and states that the study was “unable to address the paracetamol (acetaminophen) hypothesis directly.” Frisch et al. (2015). In addition, this study compared two disparate populations that contain uncontrolled confounding, further limiting the study’s findings (Frisch et al. 2015). The third study evaluated analgesic activity at the time of circumcision; however, the study did not assess use related to autism or ADHD (Howard et al. 1994).

Recently, the U.S. Food and Drug Administration received a Citizen Petition requesting changes or administrative actions to the labeling of over-the-counter products containing acetaminophen related to Early-Life Exposure Risks (Docket FDA-2025-P-6262). Kenvue has performed a rigorous review of the science, and the full Kenvue assessment of the science in the response to the Citizen Petition is here.

References:

Alemany S, Avella-García C, Liew Z, et al. 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;36(10):993-1004. doi:10.1007/s10654-021-00754-4

Ali, N. A., Kennon-McGill, S., Parker, L. D., James, L. P., Fantegrossi, W. E., & McGill, M. R. (2025). NAPQI is absent in the mouse brain after sub-hepatotoxic and hepatotoxic doses of acetaminophen. Toxicological sciences: an official journal of the Society of Toxicology, 205(2), 274–278. https://doi.org/10.1093/toxsci/kfaf034

Alisi, M. A., Brufani, M., Cazzolla, N., Ceccacci, F., Dragone, P., Felici, M., ... & Russo, V. (2012). DPPH radical scavenging activity of paracetamol analogues. Tetrahedron, 68(49), 10180-10187.

Allegaert K, Rayyan M, De Rijdt T, Van Beek F, Naulaers G. Hepatic tolerance of repeated intravenous paracetamol administration in neonates. Paediatr Anaesth. 2008 May;18(5):388-92. doi: 10.1111/j.1460-9592.2008.02535.x. PMID: 18384338.

Aoyama, K. (2021). Glutathione in the Brain. Int J Mol Sci, 22(9). https://doi.org/10.3390/ijms22095010

Bittker SS, Bell KR. Acetaminophen, antibiotics, ear infection, breastfeeding, vitamin D drops, and autism: an epidemiological study. Neuropsychiatr Dis Treat. 2018;14:1399-1414. Published 2018 May 31. doi:10.2147/NDT.S158811

Bittker SS, Bell KR. Postnatal Acetaminophen and Potential Risk of Autism Spectrum Disorder among Males. Behav Sci (Basel). 2020;10(1):26. Published 2020 Jan 1. doi:10.3390/bs10010026

Dela, An, et al. "Development of a Quantitative Systems Toxicology Model to Predict Drug-Induced Liver Injury in Pediatrics." American Conference of Pharmacometrics. International Society of Pharmacometrics, 2026.

Frisch M, Simonsen J. Ritual circumcision and risk of autism spectrum disorder in 0- to 9-year-old boys: national cohort study in Denmark. J R Soc Med. 2015 Jul;108(7):266-79. doi: 10.1177/0141076814565942. PMID: 25573114; PMCID: PMC4530408.

Höck M, Sappler M, Hammerl M, et al. Prophylactic low-dose paracetamol for ductal closure and neurodevelopmental outcome in very preterm infants. Acta Paediatr. 2023;112(8):1706-1714. doi:10.1111/apa.16806

Howard CR, Howard FM, Weitzman ML. Acetaminophen analgesia in neonatal circumcision: the effect on pain. Pediatrics. 1994 Apr;93(4):641-6. PMID: 8134222.

Iskusnykh, I.Y., Zakharova, A.A., Pathak, D. (2022). Glutathione in Brain Disorders and Aging. Molecules, 27(1). https://doi.org/10.3390/molecules27010324

Janz DR, Bastarache JA, Rice TW, Bernard GR, Warren MA, Wickersham N, Sills G, Oates JA, Roberts LJ 2nd, Ware LB; Acetaminophen for the Reduction of Oxidative Injury in Severe Sepsis Study Group. Randomized, placebo-controlled trial of acetaminophen for the reduction of oxidative injury in severe sepsis: the Acetaminophen for the Reduction of Oxidative Injury in Severe Sepsis trial. Crit Care Med. 2015 Mar;43(3):534-41. doi: 10.1097/CCM.0000000000000718. PMID: 25474535; PMCID: PMC4336619.

Juujärvi S, Saarela T, Hallman M, Aikio O. Trial of paracetamol for premature newborns: five-year follow-up. J Matern Fetal Neonatal Med. 2022;35(25):5210-5212. doi:10.1080/14767058.2021.1875444

Juujärvi S, Saarela T, Pokka T, Hallman M, Aikio O. Intravenous paracetamol for neonates: long-term diseases not escalated during 5 years of follow-up. Arch Dis Child Fetal Neonatal Ed. 2021;106(2):178-183. doi:10.1136/archdischild-2020-319069

Knapen, M.F., Zusterzeel, P.L., Peters, W.H., Steegers, E.A. (1999). Glutathione and glutathione related enzymes in reproduction. A review. Eur J Obstet Gynecol Reprod Biol, 82(2): 171-184. https://doi.org/10.1016/s0301-2115(98)00242-5

Mashally S, Banihani R, Jasani B, et al. Is late treatment with acetaminophen safe and effective in avoiding surgical ligation among extremely preterm neonates with persistent patent ductus arteriosus?. J Perinatol. 2021;41(10):2519-2525. doi:10.1038/s41372-021-01194-4

Mayo Clinic. Patent ductus arteriosus (PDA) - symptoms and causes. Mayo Clinic. Published 2025. https://www.mayoclinic.org/diseases-conditions/patent-ductus-arteriosus/symptoms-causes/syc-20376145

Meyer, F., Bitsch, A., Forman, H. J., Fragoulis, A., Ghezzi, P., Henschenmacher, B., Kellner, R., Kuhne, J., Ludwig, T., Sachno, D., Schmid, G., Tsaioun, K., Verbeek, J., & Wright, R. (2024). The effects of radiofrequency electromagnetic field exposure on biomarkers of oxidative stress in vivo and in vitro: A systematic review of experimental studies. Environment international, 194, 108940. https://doi.org/10.1016/j.envint.2024.108940

Miani, A., Di Bernardo, G. A., Højgaard, A. D., Earp, B. D., Zak, P. J., Landau, A. M., Hoppe, J., & Winterdahl, M. (2020). Neonatal male circumcision is associated with altered adult socio-affective processing. Heliyon, 6(11), e05566. https://doi.org/10.1016/j.heliyon.2020.e05566

Miller, R. P., Roberts, R. J., & Fischer, L. J. (1976). Acetaminophen elimination kinetics in neonates, children, and adults. Clinical pharmacology and therapeutics, 19(3), 284–294. https://doi.org/10.1002/cpt1976193284

Morita, C., Tokunaga, Y., Ueda, Y., Ono, M., Kinoshita, H., Kurogi, K., Sakakibara, Y., Suiko, M., Liu, M. C., & Yasuda, S. (2022). Investigation of radical scavenging effects of acetaminophen, p-aminophenol and their O-sulfated conjugates. The Journal of toxicological sciences, 47(10), 421–428. https://doi.org/10.2131/jts.47.421

Oncel MY, Eras Z, Uras N, Canpolat FE, Erdeve O, Oguz SS. Neurodevelopmental Outcomes of Preterm Infants Treated with Oral Paracetamol Versus Ibuprofen for Patent Ductus Arteriosus. Am J Perinatol. 2017;34(12):1185-1189. doi:10.1055/s-0037-1601564

Pearce A, Saunders L, Dunlop A, Abbas A. Neurodevelopmental outcomes following paracetamol use for treatment of patent ductus arteriosus: A review. Acta Paediatr. 2024;113(11):2378-2383. doi:10.1111/apa.17415

Schultz ST, Klonoff-Cohen HS, Wingard DL, Akshoomoff NA, Macera CA, Ji M. Acetaminophen (paracetamol) use, measles-mumps-rubella vaccination, and autistic disorder: the results of a parent survey. Autism. 2008;12(3):293-307. doi:10.1177/1362361307089518

Tarnowski, M., Barozet, A., Johansson, C., Eriksson, P.-O., Engkvist, O., Walsh, J., Nissink, J.W.M. (2018). Utility of Resazurin, Horseradish Peroxidase, and NMR Assays to Identify Redox-Related False-Positive Behavior in High-Throughput Screens. ASSAY and Drug Development Technologies, 16(3): 171–191. https://doi.org/10.1089/adt.2017.838.

Zhao, W. X., Zhang, J. H., Cao, J. B., Wang, W., Wang, D. X., Zhang, X. Y., Yu, J., Zhang, Y. Y., Zhang, Y. Z., & Mi, W. D. (2017). Acetaminophen attenuates lipopolysaccharide-induced cognitive impairment through antioxidant activity. Journal of neuroinflammation, 14(1), 17. https://doi.org/10.1186/s12974-016-0781-6

Zhong B, Tan K, Razak A, et al. Early neurodevelopmental outcomes of extreme preterm infants exposed to paracetamol: a retrospective cohort study. Pediatr Res. 2023;94(5):1714-1719. doi:10.1038/s41390-023-02649-4