Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology | Environmental Health

  • Rice D, Barone S, Jr. Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect 2000;108 Suppl 3(Suppl 3):511–33. https://doi.org/10.1289/ehp.00108s3511

  • Han VX, Patel S, Jones HF, et al. Maternal immune activation and neuroinflammation in human neurodevelopmental disorders. Nat Rev Neurol. 2021;17(9):564–79. https://doi.org/10.1038/s41582-021-00530-8.

    Article 

    Google Scholar
     

  • Rodrigues R, Lai MC, Beswick A, et al. Practitioner Review: Pharmacological treatment of attention-deficit/hyperactivity disorder symptoms in children and youth with autism spectrum disorder: a systematic review and meta-analysis. J Child Psychol Psychiatry. 2021;62(6):680–700. https://doi.org/10.1111/jcpp.13305.

    Article 

    Google Scholar
     

  • Mitchell KJ. The genetics of neurodevelopmental disease. Curr Opin Neurobiol. 2011;21(1):197–203. https://doi.org/10.1016/j.conb.2010.08.009.

    Article 
    CAS 

    Google Scholar
     

  • Piantadosi S, Byar DP, Green SB. The ecological fallacy. Am J Epidemiol. 1988;127(5):893–904. https://doi.org/10.1093/oxfordjournals.aje.a114892.

    Article 
    CAS 

    Google Scholar
     

  • de Castro CT, Pereira M, Dos Santos DB. Association between paracetamol use during pregnancy and perinatal outcomes: Prospective NISAMI cohort. PLoS ONE. 2022;17(4): e0267270. https://doi.org/10.1371/journal.pone.0267270.

    Article 
    CAS 

    Google Scholar
     

  • The American College of Obstetricians and Gynecologists. ACOG Response to Consensus Statement on Paracetamol Use During Pregnancy. Sept 29, 2021. https://www.acog.org/news/newsarticles/2021/09/response-to-consensus-statement-on-paracetamol-use-duringpregnancy#:~:text=Sep%2029%2C%202021-,ACOG%20Response%20to%20Consensus%20Statement%20on%20Paracetamol%20Use%20During%20Pregnancy,for%20a%20given%20clinical%20condition.

  • Bandoli G, Palmsten K, Chambers C. Acetaminophen use in pregnancy: Examining prevalence, timing, and indication of use in a prospective birth cohort. Paediatr Perinat Epidemiol. 2020;34(3):237–46. https://doi.org/10.1111/ppe.12595.

    Article 

    Google Scholar
     

  • Werler MM, Mitchell AA, Hernandez-Diaz S, et al. Use of over-the-counter medications during pregnancy. Am J Obstet Gynecol. 2005;193(3 Pt 1):771–7. https://doi.org/10.1016/j.ajog.2005.02.100.

    Article 

    Google Scholar
     

  • Banerjee TD, Middleton F, Faraone SV. Environmental risk factors for attention-deficit hyperactivity disorder. Acta Paediatr. 2007;96(9):1269–74. https://doi.org/10.1111/j.1651-2227.2007.00430.x.

    Article 

    Google Scholar
     

  • Khan FY, Kabiraj G, Ahmed MA, et al. A Systematic Review of the Link Between Autism Spectrum Disorder and Acetaminophen: A Mystery to Resolve. Cureus. 2022;14(7):e26995. https://doi.org/10.7759/cureus.26995.

    Article 

    Google Scholar
     

  • Kim JH, Kim JY, Lee J, et al. Environmental risk factors, protective factors, and peripheral biomarkers for ADHD: an umbrella review. Lancet Psychiatry. 2020;7(11):955–70. https://doi.org/10.1016/s2215-0366(20)30312-6.

    Article 

    Google Scholar
     

  • Masarwa R, Platt RW, Filion KB. Acetaminophen use during pregnancy and the risk of attention deficit hyperactivity disorder: A causal association or bias? Paediatr Perinat Epidemiol. 2020;34(3):309–17. https://doi.org/10.1111/ppe.12615.

    Article 

    Google Scholar
     

  • Patel R, Sushko K, van den Anker J, et al. Long-Term Safety of Prenatal and Neonatal Exposure to Paracetamol: A Systematic Review. Int J Environ Res Public Health. 2022;19(4):2128. https://doi.org/10.3390/ijerph19042128.

    Article 
    CAS 

    Google Scholar
     

  • Ricci C, Albanese CM, Pablo LA, et al. In utero acetaminophen exposure and child neurodevelopmental outcomes: Systematic review and meta-analysis. Paediatr Perinat Epidemiol. 2023;37(5):473–84. https://doi.org/10.1111/ppe.12963.

    Article 

    Google Scholar
     

  • Ystrom E, Gustavson K, Brandlistuen RE, et al. Prenatal Exposure to Acetaminophen and Risk of ADHD. Pediatrics. 2017;140(5):e20163840. https://doi.org/10.1542/peds.2016-3840.

    Article 

    Google Scholar
     

  • Baker BH, Bammler TK, Barrett ES, et al. Associations of maternal blood biomarkers of prenatal APAP exposure with placental gene expression and child attention deficit hyperactivity disorder. Nature Mental Health. 2025;3(3):318–31. https://doi.org/10.1038/s44220-025-00387-6.

    Article 

    Google Scholar
     

  • Pearce N, Vandenbroucke JP, Lawlor DA. Causal Inference in Environmental Epidemiology: Old and New Approaches. Epidemiology. 2019;30(3):311–6. https://doi.org/10.1097/ede.0000000000000987.

    Article 

    Google Scholar
     

  • Crump C, Sundquist J, Sundquist K. Preterm or Early Term Birth and Risk of Autism. Pediatrics. 2021;148(3):e2020032300. https://doi.org/10.1542/peds.2020-032300.

    Article 

    Google Scholar
     

  • 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. https://doi.org/10.1371/journal.pone.0272593.

    Article 
    CAS 

    Google Scholar
     

  • 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. https://doi.org/10.1007/s10654-021-00754-4.

    Article 
    CAS 

    Google Scholar
     

  • Ji Y, Azuine RE, Zhang Y, et al. Association of Cord Plasma Biomarkers of In Utero Acetaminophen Exposure With Risk of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in Childhood. JAMA Psychiat. 2020;77(2):180–9. https://doi.org/10.1001/jamapsychiatry.2019.3259.

    Article 

    Google Scholar
     

  • Chen MH, Pan TL, Wang PW, et al. Prenatal Exposure to Acetaminophen and the Risk of Attention-Deficit/Hyperactivity Disorder: A Nationwide Study in Taiwan. J Clin Psychiatry 2019;80(5):18m12612 https://doi.org/10.4088/JCP.18m12612

  • Liew Z, Kioumourtzoglou MA, Roberts AL, et al. Use of Negative Control Exposure Analysis to Evaluate Confounding: An Example of Acetaminophen Exposure and Attention-Deficit/Hyperactivity Disorder in Nurses’ Health Study II. Am J Epidemiol. 2019;188(4):768–75. https://doi.org/10.1093/aje/kwy288.

    Article 

    Google Scholar
     

  • Tovo-Rodrigues L, Schneider BC, Martins-Silva T, et al. Is intrauterine exposure to acetaminophen associated with emotional and hyperactivity problems during childhood? Findings from the 2004 Pelotas birth cohort. BMC Psychiatry. 2018;18(1):368. https://doi.org/10.1186/s12888-018-1942-1.

    Article 

    Google Scholar
     

  • Gustavson K, Ystrom E, Ask H, et al. Acetaminophen use during pregnancy and offspring attention deficit hyperactivity disorder – a longitudinal sibling control study. JCPP Adv. 2021;1(2):e12020. https://doi.org/10.1002/jcv2.12020.

    Article 

    Google Scholar
     

  • Liew Z, Ritz B, Virk J, et al. Maternal use of acetaminophen during pregnancy and risk of autism spectrum disorders in childhood: A Danish national birth cohort study. Autism Res. 2016;9(9):951–8. https://doi.org/10.1002/aur.1591.

    Article 

    Google Scholar
     

  • Avella-Garcia CB, Julvez J, Fortuny J, et al. Acetaminophen use in pregnancy and neurodevelopment: attention function and autism spectrum symptoms. Int J Epidemiol. 2016;45(6):1987–96. https://doi.org/10.1093/ije/dyw115.

    Article 

    Google Scholar
     

  • Stergiakouli E, Thapar A, Davey SG. Association of Acetaminophen Use During Pregnancy With Behavioral Problems in Childhood: Evidence Against Confounding. JAMA Pediatr. 2016;170(10):964–70. https://doi.org/10.1001/jamapediatrics.2016.1775.

    Article 

    Google Scholar
     

  • Thompson JM, Waldie KE, Wall CR, et al. Associations between acetaminophen use during pregnancy and ADHD symptoms measured at ages 7 and 11 years. PLoS ONE. 2014;9(9):e108210. https://doi.org/10.1371/journal.pone.0108210.

    Article 
    CAS 

    Google Scholar
     

  • Liew Z, Ritz B, Rebordosa C, et al. Acetaminophen use during pregnancy, behavioral problems, and hyperkinetic disorders. JAMA Pediatr. 2014;168(4):313–20. https://doi.org/10.1001/jamapediatrics.2013.4914.

    Article 

    Google Scholar
     

  • Streissguth AP, Treder RP, Barr HM, et al. Aspirin and acetaminophen use by pregnant women and subsequent child IQ and attention decrements. Teratology. 1987;35(2):211–9. https://doi.org/10.1002/tera.1420350207.

    Article 
    CAS 

    Google Scholar
     

  • Ahlqvist VH, Sjöqvist H, Dalman C, et al. Acetaminophen Use During Pregnancy and Children’s Risk of Autism, ADHD, and Intellectual Disability. JAMA. 2024;331(14):1205–14. https://doi.org/10.1001/jama.2024.3172.

    Article 
    CAS 

    Google Scholar
     

  • Woodbury ML, Cintora P, Ng S, et al. Examining the relationship of acetaminophen use during pregnancy with early language development in children. Pediatr Res. 2024;95(7):1883–96. https://doi.org/10.1038/s41390-023-02924-4.

    Article 
    CAS 

    Google Scholar
     

  • Baker BH, Lugo-Candelas C, Wu H, et al. Association of Prenatal Acetaminophen Exposure Measured in Meconium With Risk of Attention-Deficit/Hyperactivity Disorder Mediated by Frontoparietal Network Brain Connectivity. JAMA Pediatr. 2020;174(11):1073–81. https://doi.org/10.1001/jamapediatrics.2020.3080.

    Article 

    Google Scholar
     

  • Leppert B, Havdahl A, Riglin L, et al. Association of Maternal Neurodevelopmental Risk Alleles With Early-Life Exposures. JAMA Psychiat. 2019;76(8):834–42. https://doi.org/10.1001/jamapsychiatry.2019.0774.

    Article 

    Google Scholar
     

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

    Article 

    Google Scholar
     

  • Inoue K, Ritz B, Ernst A, et al. Behavioral Problems at Age 11 Years After Prenatal and Postnatal Exposure to Acetaminophen: Parent-Reported and Self-Reported Outcomes. Am J Epidemiol. 2021;190(6):1009–20. https://doi.org/10.1093/aje/kwaa257.

    Article 

    Google Scholar
     

  • Tronnes JN, Wood M, Lupattelli A, et al. Prenatal paracetamol exposure and neurodevelopmental outcomes in preschool-aged children. Paediatr Perinat Epidemiol. 2020;34(3):247–56. https://doi.org/10.1111/ppe.12568.

    Article 

    Google Scholar
     

  • Bertoldi AD, Rifas-Shiman SL, Boing AC, et al. Associations of acetaminophen use during pregnancy and the first year of life with neurodevelopment in early childhood. Paediatr Perinat Epidemiol. 2020;34(3):267–77. https://doi.org/10.1111/ppe.12632.

    Article 

    Google Scholar
     

  • Parker SE, Collett BR, Werler MM. Maternal acetaminophen use during pregnancy and childhood behavioural problems: Discrepancies between mother- and teacher-reported outcomes. Paediatr Perinat Epidemiol. 2020;34(3):299–308. https://doi.org/10.1111/ppe.12601.

    Article 

    Google Scholar
     

  • Rifas-Shiman SL, Cardenas A, Hivert MF, et al. Associations of prenatal or infant exposure to acetaminophen or ibuprofen with mid-childhood executive function and behaviour. Paediatr Perinat Epidemiol. 2020;34(3):287–98. https://doi.org/10.1111/ppe.12596.

    Article 

    Google Scholar
     

  • Tovo-Rodrigues L, Carpena MX, Martins-Silva T, et al. Low neurodevelopmental performance and behavioural/emotional problems at 24 and 48 months in Brazilian children exposed to acetaminophen during foetal development. Paediatr Perinat Epidemiol. 2020;34(3):278–86. https://doi.org/10.1111/ppe.12649.

    Article 

    Google Scholar
     

  • Golding J, Gregory S, Clark R, et al. Associations between paracetamol (acetaminophen) intake between 18 and 32 weeks gestation and neurocognitive outcomes in the child: A longitudinal cohort study. Paediatr Perinat Epidemiol. 2020;34(3):257–66. https://doi.org/10.1111/ppe.12582.

    Article 

    Google Scholar
     

  • Laue HE, Cassoulet R, Abdelouahab N, et al. Association Between Meconium Acetaminophen and Childhood Neurocognitive Development in GESTE, a Canadian Cohort Study. Toxicol Sci. 2019;167(1):138–44. https://doi.org/10.1093/toxsci/kfy222.

    Article 
    CAS 

    Google Scholar
     

  • Ruisch IH, Buitelaar JK, Glennon JC, et al. Pregnancy risk factors in relation to oppositional-defiant and conduct disorder symptoms in the Avon Longitudinal Study of Parents and Children. J Psychiatr Res. 2018;101:63–71. https://doi.org/10.1016/j.jpsychires.2018.02.020.

    Article 

    Google Scholar
     

  • Bornehag CG, Reichenberg A, Hallerback MU, et al. Prenatal exposure to acetaminophen and children’s language development at 30 months. Eur Psychiatry. 2018;51:98–103. https://doi.org/10.1016/j.eurpsy.2017.10.007.

    Article 

    Google Scholar
     

  • Skovlund E, Handal M, Selmer R, et al. Language competence and communication skills in 3-year-old children after prenatal exposure to analgesic opioids. Pharmacoepidemiol Drug Saf. 2017;26(6):625–34. https://doi.org/10.1002/pds.4170.

    Article 

    Google Scholar
     

  • Vlenterie R, Wood ME, Brandlistuen RE, et al. Neurodevelopmental problems at 18 months among children exposed to paracetamol in utero: a propensity score matched cohort study. Int J Epidemiol. 2016;45(6):1998–2008. https://doi.org/10.1093/ije/dyw192.

    Article 

    Google Scholar
     

  • Brandlistuen RE, Ystrom E, Nulman I, et al. Prenatal paracetamol exposure and child neurodevelopment: a sibling-controlled cohort study. Int J Epidemiol. 2013;42(6):1702–13. https://doi.org/10.1093/ije/dyt183.

    Article 

    Google Scholar
     

  • Zhou T, Shen Y, Lyu J, et al. Medication Usage Record-Based Predictive Modeling of Neurodevelopmental Abnormality in Infants under One Year: A Prospective Birth Cohort Study. Healthcare (Basel). 2024;12(7):713. https://doi.org/10.3390/healthcare12070713.

    Article 

    Google Scholar
     

  • Lakens D. Sample Size Justification. Collabra. Psychology. 2022;8(1):33267. https://doi.org/10.1525/collabra.33267.

    Article 

    Google Scholar
     

  • Frisell T, Öberg S, Kuja-Halkola R, et al. Sibling comparison designs: bias from non-shared confounders and measurement error. Epidemiology. 2012;23(5):713–20. https://doi.org/10.1097/EDE.0b013e31825fa230.

    Article 

    Google Scholar
     

  • Bauer AZ, Swan SH, Kriebel D, et al. Paracetamol use during pregnancy – a call for precautionary action. Nat Rev Endocrinol. 2021;17(12):757–66. https://doi.org/10.1038/s41574-021-00553-7.

    Article 
    CAS 

    Google Scholar
     

  • Antonucci R, Zaffanello M, Puxeddu E, et al. Use of non-steroidal anti-inflammatory drugs in pregnancy: impact on the fetus and newborn. Curr Drug Metab. 2012;13(4):474–90. https://doi.org/10.2174/138920012800166607.

    Article 
    CAS 

    Google Scholar
     

  • Black E, Khor KE, Kennedy D, et al. Medication Use and Pain Management in Pregnancy: A Critical Review. Pain Pract. 2019;19(8):875–99. https://doi.org/10.1111/papr.12814.

    Article 

    Google Scholar
     

  • National Institute for Health and Care Excellence. Intrapartum care for women with existing medical conditions or obstetric complications and their babies. April 25, 2019. https://www.nice.org.uk/guidance/ng121.

  • Levy G, Garrettson LK, Soda DM. Letter: Evidence of placental transfer of acetaminophen. Pediatrics. 1975;55(6):895.

    CAS 

    Google Scholar
     

  • Petersen JM, Ranker LR, Barnard-Mayers R, et al. A systematic review of quantitative bias analysis applied to epidemiological research. Int J Epidemiol. 2021;50(5):1708–30. https://doi.org/10.1093/ije/dyab061.

    Article 

    Google Scholar
     

  • Bond JC, Fox MP, Wise LA, et al. Quantitative Assessment of Systematic Bias: A Guide for Researchers. J Dent Res. 2023;102(12):1288–92. https://doi.org/10.1177/00220345231193314.

    Article 
    CAS 

    Google Scholar
     

  • Thacher JD, Högfeldt H, Vilhelmsson A, et al. Exposure to Paracetamol in Early Pregnancy and the Risk of Developing Cerebral Palsy: A Case-Control Study Using Serum Samples. J Pediatr. 2024;269: 113959. https://doi.org/10.1016/j.jpeds.2024.113959.

    Article 
    CAS 

    Google Scholar
     

  • Wolgast E, Lindh-Åstrand L, Lilliecreutz C. Women’s perceptions of medication use during pregnancy and breastfeeding-A Swedish cross-sectional questionnaire study. Acta Obstet Gynecol Scand. 2019;98(7):856–64. https://doi.org/10.1111/aogs.13570.

    Article 

    Google Scholar
     

  • Gustavson K, Torvik FA, Davey Smith G, et al. Familial confounding or measurement error? How to interpret findings from sibling and co-twin control studies. Eur J Epidemiol. 2024;39(6):587–603. https://doi.org/10.1007/s10654-024-01132-6.

    Article 

    Google Scholar
     

  • Sjölander A, Zetterqvist J. Confounders, Mediators, or Colliders: What Types of Shared Covariates Does a Sibling Comparison Design Control For? Epidemiology. 2017;28(4):540–7. https://doi.org/10.1097/ede.0000000000000649.

    Article 

    Google Scholar
     

  • Hay-Schmidt A, Finkielman OTE, Jensen BAH, et al. Prenatal exposure to paracetamol/acetaminophen and precursor aniline impairs masculinisation of male brain and behaviour. Reproduction. 2017;154(2):145–52. https://doi.org/10.1530/rep-17-0165.

    Article 
    CAS 

    Google Scholar
     

  • Anand NS, Raghavan R, Wang G, et al. Perinatal Acetaminophen Exposure and Childhood Attention-Deficit/Hyperactivity Disorder (ADHD): Exploring the Role of Umbilical Cord Plasma Metabolites in Oxidative Stress Pathways. Brain Sci. 2021;11(10):1302. https://doi.org/10.3390/brainsci11101302.

    Article 
    CAS 

    Google Scholar
     

  • Philippot G, Hosseini K, Yakub A, et al. Paracetamol (Acetaminophen) and its Effect on the Developing Mouse Brain. Front Toxicol. 2022;4:867748. https://doi.org/10.3389/ftox.2022.867748.

    Article 

    Google Scholar
     

  • Bührer C, Endesfelder S, Scheuer T, et al. Paracetamol (Acetaminophen) and the Developing Brain. Int J Mol Sci. 2021;22(20):11156. https://doi.org/10.3390/ijms222011156.

    Article 
    CAS 

    Google Scholar
     

  • Wong CT, Bestard-Lorigados I, Crawford DA. Autism-related behaviors in the cyclooxygenase-2-deficient mouse model. Genes Brain Behav. 2019;18(1):e12506. https://doi.org/10.1111/gbb.12506.

    Article 
    CAS 

    Google Scholar
     

  • Klein RM, Motomura VN, Debiasi JD, et al. Gestational paracetamol exposure induces core behaviors of neurodevelopmental disorders in infant rats and modifies response to a cannabinoid agonist in females. Neurotoxicol Teratol. 2023;99:107279. https://doi.org/10.1016/j.ntt.2023.107279.

    Article 
    CAS 

    Google Scholar
     

  • Spildrejorde M, Samara A, Sharma A, et al. Multi-omics approach reveals dysregulated genes during hESCs neuronal differentiation exposure to paracetamol. iScience 2023;26(10):107755. https://doi.org/10.1016/j.isci.2023.107755

  • Jones JP 3rd, Williamson L, Konsoula Z, et al. Evaluating the Role of Susceptibility Inducing Cofactors and of Acetaminophen in the Etiology of Autism Spectrum Disorder. Life (Basel). 2024;14(8):918. https://doi.org/10.3390/life14080918.

    Article 
    CAS 

    Google Scholar
     

  • Sjölander A, Frisell T, Kuja-Halkola R, et al. Carryover Effects in Sibling Comparison Designs. Epidemiology. 2016;27(6):852–8. https://doi.org/10.1097/ede.0000000000000541.

    Article 

    Google Scholar
     

  • Kriebel D, Tickner J, Epstein P, et al. The precautionary principle in environmental science. Environ Health Perspect. 2001;109(9):871–6. https://doi.org/10.1289/ehp.01109871.

    Article 
    CAS 

    Google Scholar
     

  • Weigand UW, Chou RC, Maulik D, et al. Assessment of biotransformation during transfer of propoxyphene and acetaminophen across the isolated perfused human placenta. Pediatr Pharmacol (New York). 1984;4(3):145–53.

    CAS 

    Google Scholar
     

  • Mian P, Allegaert K, Conings S, et al. Integration of Placental Transfer in a Fetal-Maternal Physiologically Based Pharmacokinetic Model to Characterize Acetaminophen Exposure and Metabolic Clearance in the Fetus. Clin Pharmacokinet. 2020;59(7):911–25. https://doi.org/10.1007/s40262-020-00861-7.

    Article 
    CAS 

    Google Scholar
     

  • Naga Rani MA, Joseph T, Narayanan R. Placental transfer of paracetamol. J Indian Med Assoc. 1989;87(8):182–3.

    CAS 

    Google Scholar
     

  • Brzezinski MR, Boutelet-Bochan H, Person RE, et al. Catalytic activity and quantitation of cytochrome P-450 2E1 in prenatal human brain. J Pharmacol Exp Ther. 1999;289(3):1648–53.

    CAS 

    Google Scholar
     

  • García-Suástegui WA, Ramos-Chávez LA, Rubio-Osornio M, et al. The Role of CYP2E1 in the Drug Metabolism or Bioactivation in the Brain. Oxid Med Cell Longev. 2017;2017:4680732. https://doi.org/10.1155/2017/4680732.

    Article 
    CAS 

    Google Scholar
     

  • O’Hara K, Wright IM, Schneider JJ, et al. Pharmacokinetics in neonatal prescribing: evidence base, paradigms and the future. Br J Clin Pharmacol. 2015;80(6):1281–8. https://doi.org/10.1111/bcp.12741.

    Article 

    Google Scholar
     

  • OFIRMEV. Acetaminophen injection 2018 [Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022450s011lbl.pdf. Accessed 10 Feb 2025.

  • Posadas I, Santos P, Blanco A, et al. Acetaminophen induces apoptosis in rat cortical neurons. PLoS ONE. 2010;5(12): e15360. https://doi.org/10.1371/journal.pone.0015360.

    Article 
    CAS 

    Google Scholar
     

  • da Silva MH, da Rosa EJ, de Carvalho NR, et al. Acute brain damage induced by acetaminophen in mice: effect of diphenyl diselenide on oxidative stress and mitochondrial dysfunction. Neurotox Res. 2012;21(3):334–44. https://doi.org/10.1007/s12640-011-9288-1.

    Article 
    CAS 

    Google Scholar
     

  • Mirrasekhian E, Nilsson JLA, Shionoya K, et al. The antipyretic effect of paracetamol occurs independent of transient receptor potential ankyrin 1-mediated hypothermia and is associated with prostaglandin inhibition in the brain. FASEB J. 2018;32(10):5751–9. https://doi.org/10.1096/fj.201800272R.

    Article 
    CAS 

    Google Scholar
     

  • Angelis D, Savani RC, Jagarapu J, et al. Part I. Mechanisms of actions and metabolism of acetaminophen related to the neonatal brain. Early Hum Dev 2021;159:105406. https://doi.org/10.1016/j.earlhumdev.2021.105406

  • Przybyła GW, Szychowski KA, Gmiński J. Paracetamol – An old drug with new mechanisms of action. Clin Exp Pharmacol Physiol. 2021;48(1):3–19. https://doi.org/10.1111/1440-1681.13392.

    Article 
    CAS 

    Google Scholar
     

  • Konkel L. Reproductive Headache? Investigating Acetaminophen as a Potential Endocrine Disruptor. Environ Health Perspect. 2018;126(3):032001. https://doi.org/10.1289/ehp2478.

    Article 
    CAS 

    Google Scholar
     

  • Kristensen DM, Mazaud-Guittot S, Gaudriault P, et al. Analgesic use – prevalence, biomonitoring and endocrine and reproductive effects. Nat Rev Endocrinol. 2016;12(7):381–93. https://doi.org/10.1038/nrendo.2016.55.

    Article 
    CAS 

    Google Scholar
     

  • Cohen IV, Cirulli ET, Mitchell MW, et al. Acetaminophen (Paracetamol) Use Modifies the Sulfation of Sex Hormones. EBioMedicine. 2018;28:316–23. https://doi.org/10.1016/j.ebiom.2018.01.033.

    Article 

    Google Scholar
     

  • McCarthy MM, Wright CL. Convergence of Sex Differences and the Neuroimmune System in Autism Spectrum Disorder. Biol Psychiatry. 2017;81(5):402–10. https://doi.org/10.1016/j.biopsych.2016.10.004.

    Article 
    CAS 

    Google Scholar
     

  • Jeong H, Mendizabal I, Berto S, et al. Evolution of DNA methylation in the human brain. Nat Commun. 2021;12(1):2021. https://doi.org/10.1038/s41467-021-21917-7.

    Article 
    CAS 

    Google Scholar
     

  • Spiers H, Hannon E, Schalkwyk LC, et al. Methylomic trajectories across human fetal brain development. Genome Res. 2015;25(3):338–52. https://doi.org/10.1101/gr.180273.114.

    Article 
    CAS 

    Google Scholar
     

  • Armstrong MJ, Jin Y, Allen EG, et al. Diverse and dynamic DNA modifications in brain and diseases. Hum Mol Genet. 2019;28(R2):R241–53. https://doi.org/10.1093/hmg/ddz179.

    Article 
    CAS 

    Google Scholar
     

  • Reichard J, Zimmer-Bensch G. The Epigenome in Neurodevelopmental Disorders. Front Neurosci. 2021;15: 776809. https://doi.org/10.3389/fnins.2021.776809.

    Article 

    Google Scholar
     

  • Addo KA, Bulka C, Dhingra R, et al. Acetaminophen use during pregnancy and DNA methylation in the placenta of the extremely low gestational age newborn (ELGAN) cohort. Environ Epigenet 2019;5(2):dvz010. https://doi.org/10.1093/eep/dvz010

  • Eslamimehr S, Jones AD, Anthony TM, et al. Association of prenatal acetaminophen use and acetaminophen metabolites with DNA methylation of newborns: analysis of two consecutive generations of the Isle of Wight birth cohort. Environ Epigenet 2022;8(1):dvac002. https://doi.org/10.1093/eep/dvac002

  • Gervin K, Nordeng H, Ystrom E, et al. Long-term prenatal exposure to paracetamol is associated with DNA methylation differences in children diagnosed with ADHD. Clin Epigenetics. 2017;9:77. https://doi.org/10.1186/s13148-017-0376-9.

    Article 
    CAS 

    Google Scholar
     

  • Olstad EW, Nordeng HME, Lyle R, et al. No impact of prenatal paracetamol and folic acid exposure on cord blood DNA methylation in children with attention-deficit/hyperactivity disorder. Front Genet. 2023;14:1204879. https://doi.org/10.3389/fgene.2023.1204879.

    Article 
    CAS 

    Google Scholar
     

  • Baker BH, Rafikian EE, Hamblin PB, et al. Sex-specific neurobehavioral and prefrontal cortex gene expression alterations following developmental acetaminophen exposure in mice. Neurobiol Dis. 2023;177: 105970. https://doi.org/10.1016/j.nbd.2022.105970.

    Article 
    CAS 

    Google Scholar
     

  • Huang Y, Qiu F, Dziegielewska KM, et al. Effects of paracetamol/acetaminophen on the expression of solute carriers (SLCs) in late-gestation fetal rat brain, choroid plexus and the placenta. Exp Physiol. 2024;109(3):427–44. https://doi.org/10.1113/ep091442.

    Article 
    CAS 

    Google Scholar
     

  • Ju XD, Zhang PH, Li Q, et al. Peripheral Blood Monocytes as Biomarkers of Neurodevelopmental Disorders: A Systematic Review and Meta-Analysis. Res Child Adolesc Psychopathol. 2025. https://doi.org/10.1007/s10802-025-01303-3.

    Article 

    Google Scholar
     

  • Hwang IW, Hong JH, Kwon BN, et al. Association of mitochondrial DNA 10398 A/G polymorphism with attention deficit and hyperactivity disorder in Korean children. Gene. 2017;630:8–12. https://doi.org/10.1016/j.gene.2017.08.004.

    Article 
    CAS 

    Google Scholar
     

  • Kovacheva E, Gevezova M, Mehterov N, et al. The Intersection of Mitophagy and Autism Spectrum Disorder: A Systematic Review. Int J Mol Sci. 2025;26(5):2217. https://doi.org/10.3390/ijms26052217.

    Article 
    CAS 

    Google Scholar
     

  • Visser SN, Danielson ML, Bitsko RH, et al. Trends in the parent-report of health care provider-diagnosed and medicated attention-deficit/hyperactivity disorder: United States, 2003–2011. J Am Acad Child Adolesc Psychiatry. 2014;53(1):34-46.e2. https://doi.org/10.1016/j.jaac.2013.09.001.

    Article 

    Google Scholar
     

  • Xu G, Strathearn L, Liu B, et al. Twenty-Year Trends in Diagnosed Attention-Deficit/Hyperactivity Disorder Among US Children and Adolescents, 1997–2016. JAMA Netw Open. 2018;1(4):e181471. https://doi.org/10.1001/jamanetworkopen.2018.1471.

    Article 

    Google Scholar
     

  • Zeidan J, Fombonne E, Scorah J, et al. Global prevalence of autism: A systematic review update. Autism Res. 2022;15(5):778–90. https://doi.org/10.1002/aur.2696.

    Article 

    Google Scholar
     

  • Prevention USCfDCa. Data and Statistics on ADHD 2024 [Available from: https://www.cdc.gov/adhd/data/index.html?utm_source=chatgpt.com. Accessed 10 Feb 2025.

  • Prevention USCfDCa. Data and Statistics on Autism Spectrum Disorder 2025 [Available from: https://www.cdc.gov/autism/data-research/?CDC_AAref_Val=https://www.cdc.gov/ncbddd/autism/data.html. Accessed 10 Feb 2025.


  • Source link

    Leave a Reply

    Your email address will not be published. Required fields are marked *