Systematic review finds no link between acetaminophen use in pregnancy and autism risk — Evidence Review
Published in The Lancet Obstetrics, Gynaecology & Women's Health, by researchers from City St George's, University of London
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Table of Contents
Taking acetaminophen (Tylenol) during pregnancy does not increase the risk of autism, ADHD, or intellectual disability in children, according to a comprehensive new analysis. While earlier studies suggested a possible association, most recent and higher-quality research—including this latest review published in The Lancet Obstetrics, Gynaecology & Women's Health—finds no evidence for a causal link.
- Multiple earlier observational studies found statistical associations between prenatal acetaminophen exposure and increased risks for neurodevelopmental outcomes, including autism and ADHD, but these studies had significant limitations, such as potential confounding and lack of sibling comparisons 1 2 4 5 8 9.
- The new review's findings are reinforced by recent large-scale sibling-control studies and meta-analyses that show associations disappear when adjusting for familial and genetic factors, suggesting previous links were likely due to confounding rather than a direct medication effect 6 9.
- Some systematic reviews still recommend caution or minimizing exposure, particularly regarding ADHD outcomes, due to lingering uncertainties about dosage, timing, and potential for residual confounding, though the consensus is shifting toward reassurance when acetaminophen is used as directed 4 5 8 9.
Study Overview and Key Findings
Concerns about the safety of acetaminophen use during pregnancy have grown in recent years, especially following reports linking the medication to higher risks of autism, ADHD, and intellectual disability in children. This prompted renewed investigation, as acetaminophen is widely recommended for pregnant women to manage pain or fever, and avoiding necessary treatment can pose risks to both mother and fetus. The current study addresses important methodological limitations of earlier research by leveraging sibling comparison designs and focusing on high-quality data to better isolate the effects of acetaminophen from confounding familial factors.
| Property | Value |
|---|---|
| Study Year | 2025 |
| Organization | City St George's, University of London |
| Journal Name | The Lancet Obstetrics, Gynaecology & Women's Health |
| Authors | Asma Khalil |
| Population | Children assessed for autism, ADHD, and intellectual disability |
| Sample Size | n=262,852, n=335,255, n=406,681 |
| Methods | Systematic Review |
| Outcome | Risk of autism, ADHD, and intellectual disability |
| Results | No increased risk of autism, ADHD, or intellectual disability from acetaminophen |
Literature Review: Related Studies
We searched the Consensus paper database, which contains over 200 million research papers, to identify relevant studies on acetaminophen use during pregnancy and neurodevelopmental outcomes. The following search queries were used:
- acetaminophen pregnancy autism risk
- Tylenol ADHD intellectual disability outcomes
- pregnancy pain relief safety studies
| Topic | Key Findings |
|---|---|
| Do prenatal acetaminophen exposures increase risk for autism, ADHD, or intellectual disability? | - Several observational studies report associations between acetaminophen use in pregnancy and increased risk of autism spectrum disorder (ASD), ADHD, or cognitive deficits, especially with higher or prolonged exposure 1 2 3 4 5 8 9. - Recent sibling-control and high-quality meta-analyses do not find evidence for a causal relationship, suggesting prior associations are likely due to confounding 6 9. |
| How do research methods and confounding factors affect observed associations? | - Earlier studies often lacked adequate adjustment for genetic and familial confounding, leading to possible overestimation of risk 1 2 3 4 5. - Sibling comparison studies and advanced statistical methods show that when confounding is controlled, associations between acetaminophen and neurodevelopmental disorders are greatly reduced or eliminated 6 9. |
| What are current recommendations for pain management during pregnancy? | - Paracetamol (acetaminophen) remains the first-line analgesic for mild to moderate pain in pregnancy; NSAIDs are generally avoided in the third trimester due to known fetal risks 12. - Multimodal approaches combining nonpharmacological and pharmacological therapies are recommended for optimal pain control with minimal risk 13. |
| Are there risks associated with untreated pain or alternative pain relief options in pregnancy? | - Untreated pain and fever during pregnancy can lead to adverse maternal and fetal outcomes, making safe pain management important 12. - Alternatives such as epidural or opioid analgesia have distinct risks and benefits; epidurals reduce pain effectively but may increase rates of assisted vaginal delivery, while opioids carry risk of neonatal abstinence syndrome 10 12 14. |
Do prenatal acetaminophen exposures increase risk for autism, ADHD, or intellectual disability?
Earlier observational studies reported statistical associations between prenatal acetaminophen exposure and increased risks for autism, ADHD, or intellectual disabilities, particularly with frequent or prolonged use. However, these associations have not held up in more recent analyses that control for confounding variables, especially familial and genetic factors. The latest systematic review and sibling comparison studies find no evidence for a causal relationship.
- Observational cohort and meta-analytic studies found elevated risks for ASD, ADHD, or cognitive impairment with prenatal acetaminophen exposure, especially with longer duration of use 1 2 3 4 5 8 9.
- Associations were strongest for hyperactivity and attention-related outcomes, with some studies reporting increased effect sizes with higher exposure frequency 1 4 5 8.
- The most recent and methodologically robust studies, including sibling-control analyses and large meta-analyses, do not support a causal link and suggest prior findings were likely due to confounding 6 9.
- The new study's results align with the latest evidence, indicating that acetaminophen, when used as directed, does not increase neurodevelopmental risks 6 9.
How do research methods and confounding factors affect observed associations?
Many earlier studies did not adequately control for confounding factors such as genetic susceptibility, family environment, or reasons for acetaminophen use (e.g., maternal fever). Sibling comparison studies and advanced statistical methods have helped clarify that these confounders explain much of the previously reported associations.
- Traditional observational designs may overestimate risk by failing to account for shared genetic and environmental factors 1 2 3 4 5.
- Sibling comparison studies, which control for familial confounding, consistently show null or reversed associations between prenatal acetaminophen exposure and neurodevelopmental outcomes 6 9.
- Sensitivity analyses indicate that unmeasured confounding and exposure misclassification further bias earlier findings toward spurious associations 9.
- The comprehensive approach of the new review, emphasizing high-quality and sibling comparison studies, strengthens the case for no causal relationship 6 9.
What are current recommendations for pain management during pregnancy?
Guidelines continue to recommend acetaminophen as the first-line analgesic for pregnant women, particularly for mild to moderate pain or fever. Nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided in the third trimester due to established fetal risks. Nonpharmacological interventions and multimodal strategies are also encouraged.
- Paracetamol (acetaminophen) is widely regarded as safe for short-term use during pregnancy, and remains the recommended first-line agent 12.
- NSAIDs are contraindicated in late pregnancy due to risk of premature closure of the ductus arteriosus and other fetal complications 12.
- Multimodal pain management, combining pharmacological and nonpharmacological approaches, is considered optimal for many pain conditions during pregnancy 13.
- The new study's findings support continued use of acetaminophen as directed, in line with current international guidelines 12 13.
Are there risks associated with untreated pain or alternative pain relief options in pregnancy?
Managing pain and fever during pregnancy is important, as untreated symptoms can harm both maternal and fetal health. Alternative analgesics, such as opioids or epidural anesthesia, have their own safety profiles and potential complications.
- Untreated maternal pain or fever has been linked to adverse outcomes including preterm birth, preeclampsia, and impaired fetal development, highlighting the need for effective pain management 12.
- Epidural analgesia is safe and effective for labor pain but may increase rates of assisted vaginal delivery; recent protocols reduce this risk 10.
- Opioid use should be limited due to risks of neonatal abstinence syndrome and other adverse effects, especially with prolonged or late pregnancy exposure 12 14.
- The reassurance provided by the new study supports the safe use of acetaminophen to manage pain and fever, avoiding unnecessary reliance on riskier alternatives 12 13.
Future Research Questions
Despite recent advances and reassuring findings, several important research questions remain. Further studies are needed to address uncertainties regarding timing, dosage, and long-term outcomes, as well as to explore potential differences across populations and individual susceptibility.
| Research Question | Relevance |
|---|---|
| Does trimester of acetaminophen exposure in pregnancy impact risk for neurodevelopmental disorders? | Timing of exposure could influence fetal brain development, but current data are insufficient to assess trimester-specific risks 4 9. Understanding this could refine safety guidelines for acetaminophen use across pregnancy stages. |
| Are there dose-dependent effects of prenatal acetaminophen exposure on child neurodevelopment? | Some observational studies suggest stronger associations with higher or prolonged acetaminophen use 1 3 4 5 8. Clarifying whether dose-response relationships exist is key for evidence-based recommendations. |
| Do maternal indications for acetaminophen use (e.g. fever, pain) confound the relationship with neurodevelopmental outcomes? | Maternal health conditions prompting acetaminophen use may themselves be linked to child outcomes, making it important to disentangle medication effects from indication-related risk 1 4 9. |
| Are there genetic or biological factors that modify susceptibility to acetaminophen effects in pregnancy? | Studies increasingly suggest genetic and familial factors account for observed associations; identifying subgroups with increased vulnerability could further optimize guidance 6 9. |
| What are the long-term neurodevelopmental outcomes of prenatal acetaminophen exposure beyond early childhood? | Most available studies focus on outcomes in early to middle childhood; investigating impacts into adolescence and adulthood will provide a more comprehensive safety profile 4 5 8 9. |