ENTIS Position Statement: Paracetamol in Pregnancy and Autism Spectrum Disorder

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ENTIS does not support the recent claims relating to autism risk following paracetamol use in pregnancy

Summary: Paracetamol (also known as acetaminophen and APAP) is commonly used by pregnant women and is generally the drug of choice for treating pain and fever during pregnancy. Numerous studies have investigated neurodevelopmental outcomes following in utero exposure to paracetamol, with highly inconsistent results. A 2025 review of the pivotal epidemiological evidence concluded that in utero paracetamol exposure is unlikely to confer a clinically important increased risk of autism spectrum disorder (ASD), and that the current evidence does not warrant changes to clinical guidelines on the treatment of fever and pain in pregnancy. It is important that maternal pain and fever are adequately managed during pregnancy and where required, paracetamol use should not be avoided.

Further details:

  • Effective management of pain and fever in pregnancy is crucial.
    • Pain and fever during pregnancy can affect the woman’s physical and mental health, as well as her ability to carry out normal activities of daily living. Uncontrolled pain and fever can also have adverse effects on the developing fetus, and may increase the risk of outcomes such as miscarriage, malformation, growth restriction and preterm delivery. Access to safe and effective treatment is important for all pregnant women to minimise these potential risks.
  • Paracetamol is the first line treatment for pain and fever during pregnancy:
    • Other treatment options carry risks to both the woman and fetus. Non-steroidal anti-inflammatory drugs (NSAIDs) should not be routinely used from 20 weeks’ gestational age due to adverse fetal effects. Opioid analgesics can cause neonatal withdrawal effects/respiratory depression and carry a significant misuse potential, while gabapentinoids (pregabalin, gabapentin) lack adequate safety data and are not suitable options for the treatment of mild pain.
  • Evidence on paracetamol use in pregnancy and autism spectrum disorder (ASD) risk is highly inconsistent:
    • A 2025 review of the pivotal epidemiological evidence concluded that in utero paracetamol exposure is unlikely to confer a clinically important increased risk of ASD, and that the evidence does not warrant changes to clinical guidelines on the treatment of fever and pain in pregnancy.
    • Most studies reporting associations between in utero paracetamol exposure and ASD are impacted by important biases. Methodological weaknesses include selection bias and inconsistencies in adjustment for confounding factors (co-variable risk factors for ASD), particularly genetic and familial factors which strongly influence the likelihood of ASD. The most robust studies, which employ exposure discordant siblings as comparators to control for shared genetic and environmental risk factors which influence ASD outcome, demonstrate substantially weaker or no associations, thereby indicating that study findings are heavily influenced by residual confounding (see Gustavson et al. 2021, Ahlqvist et al. 2024, and Okubo et al. 2025 for further information).
  • Study results from observational epidemiological studies require careful interpretation:
    • Epidemiological studies observe outcomes resulting from real world behaviours and exposures, without intervention or randomisation. Consequently, there can be factors that influence observed outcomes other than the exposures and co-variables that have been considered in the analysis.
    • Observational study designs carry a high risk of being influenced by hidden or unmeasured events (data confounding). It can be difficult to distinguish between a true cause-and-effect relationship, or other explanations, for any given association with this study design.

Conclusion: Current evidence does not support the relationship between paracetamol and ASD. Significant harm may arise from the avoidance of paracetamol for pain and fever. It is recommended that pregnant women seek advice from their healthcare professional if they have concerns relating to paracetamol use.

Key references:

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.

Alemany S, Avella-Garcia C, Liew Z, Garcia-Esteban R, Inoue K, Cadman T, 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. European journal of epidemiology. 2021;36(10):993-1004.
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 May;34(3):309-317. doi: 10.1111/ppe.12615. Epub 2020 Jan 9. PMID: 31916282.

Brandlistuen RE, Ystrom E, Nulman I, Koren G, Nordeng H. Prenatal paracetamol exposure and child neurodevelopment: a sibling-controlled cohort study. International journal of epidemiology. 2013.

Avella-Garcia CB, Julvez J, Fortuny J, Rebordosa C, Garcia-Esteban R, Galan IR, et al. Acetaminophen use in pregnancy and neurodevelopment: attention function and autism spectrum symptoms. International journal of epidemiology. 2016;45(6):1987-96.

Stergiakouli E, Thapar A, Davey Smith G. Association of Acetaminophen Use During Pregnancy With Behavioral Problems in Childhood: Evidence Against Confounding. JAMA Pediatr. 2016;170(10):964-70

Streissguth AP, Treder RP, Barr HM, Shepard TH, Bleyer WA, Sampson PD, et al. Aspirin and acetaminophen use by pregnant women and subsequent child IQ and attention decrements. Teratology. 1987;35(2):211-9.

Liew Z, Bach CC, Asarnow RF, Ritz B, Olsen J. Paracetamol use during pregnancy and attention and executive function in offspring at age 5 years. International journal of epidemiology. 2016;45(6):2009-17.

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.

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.

Okubo Y, Hayakawa I, Sugitate R, Nariai H. Maternal Acetaminophen Use and Offspring’s Neurodevelopmental Outcome: A Nationwide Birth Cohort Study. Paediatr Perinat Epidemiol. 2025 Sep 2. doi: 10.1111/ppe.70071. Epub ahead of print. PMID: 40898607.

UK Teratology Information Service (UKTIS). Therapeutic use of paracetamol in pregnancy. 2023 (version 2.0). Available here.

UK Teratology Information Service (UKTIS). Use of non-steroidal anti-inflammatory drugs (NSAIDs) in pregnancy. 2023 (version 4.0). Available here.

UK Teratology Information Service (UKTIS). Pain management in pregnancy. 2019 (version 3.1). Available here.

European Network of Teratology Information Services (ENTIS). Position statement on acetaminophen (paracetamol) in pregnancy. 2021. Available here.

Links to supporting statements:

Medicines and Healthcare products Regulatory Agency (MHRA) – MHRA confirms taking paracetamol during pregnancy remains safe and there is no evidence it causes autism in children

Royal College of Obstetricians and Gynaecologists (RCOG) – RCOG issues advice for pregnant women and people on the use of paracetamol to manage fever and pain

Royal Pharmaceutical Society (RPS) – Use of paracetamol during pregnancy

London School of Hygiene and Tropical Medicine – Paracetamol use during pregnancy does not increase risk of autism

The American College of Obstetricians and Gynaecologists (ACOG) – ACOG affirms safety and benefits of acetaminophen during pregnancy

Society for Maternal Fetal Medicine (SMFM) – SMFM statement on acetaminophen use during pregnancy and autism

European Medicines Agency (EMA) – Use of paracetamol during pregnancy unchanged in the EU