5-Min Science: Does Tylenol Cause Autism?

This post builds on Allison Parshall's (2025) excellent Scientific American article, "Autism Has No Single Cause. Here’s How We Know." Disclaimer: Like Secretary Kennedy, I am not a physician. Readers should not use this post as medical advice. I encourage readers to discuss medical issues like Tylenol with their physician.

In the sterile corridors of obstetric practice, where every recommendation is weighed against decades of evidence, a quiet controversy has been simmering. At its center lies acetaminophen, the humble pain reliever known to millions as Tylenol, and a question that cuts to the heart of prenatal care: Could the medication pregnant women have trusted for generations be subtly reshaping the developing brain?

The stakes escalated dramatically in September 2025 when reports emerged that Health and Human Services Secretary Robert F. Kennedy Jr. planned to announce acetaminophen use during pregnancy as a cause of autism spectrum disorder (ASD). This comes amid promises from Kennedy to identify the "interventions" that are "almost certainly causing autism," despite the scientific community's consensus that autism arises from complex genetic and environmental interactions rather than single causes (Damkier et al., 2025; Masarwa et al., 2020).

The controversy illuminates a fundamental tension in modern medicine: how to balance emerging research signals against established safety profiles, especially when the lives of mothers and children hang in the balance.

The Evidence Landscape: Signal and Noise in the Data

ASD is best understood as a constellation of traits, social communication differences, repetitive behaviors, and sensory processing issues, that cluster together but vary widely. Many family members of autistic people show “milder” or subclinical traits, sometimes called the broader autism phenotype.

Acetaminophen, also known as paracetamol outside North America, represents one of the few pain relief options considered safe during pregnancy. More than 50% of pregnant women worldwide use acetaminophen, making it the most commonly used over-the-counter pain and fever medication during pregnancy (Damkier et al., 2025). This widespread use means that even small increases in risk could have significant public health implications.

The research picture is complex and sometimes contradictory. Meta-analyses, studies that combine results from multiple research projects, have frequently detected small but statistically significant associations between maternal acetaminophen use and neurodevelopmental disorders (NDDs) in children. These pooled analyses typically report relative risk increases in the range of 1.20-1.34 for attention-deficit/hyperactivity disorder (ADHD) and somewhat smaller estimates around 1.10-1.20 for autism spectrum disorder (Alemany et al., 2021; Gou et al., 2019; Kwok et al., 2022; Ricci et al., 2023).

To understand what these numbers mean in practical terms, consider this: if ADHD affects 5% of children in the general population, a relative risk of 1.25 would increase that to 6.25%, an absolute increase of just over one percentage point. For autism, with a baseline prevalence around 1.5%, a relative risk of 1.19 would translate to approximately 1.8%, an increase of about 0.3 percentage points.

But the most robust recent evidence tells a different story.

This sibling-comparison design is methodologically powerful because it controls for shared family factors, genetics, socioeconomic status, parenting styles, that might confound simpler population-level studies.

"Sibling comparisons allow us to control for familial characteristics that might explain an apparent relationship between acetaminophen use during pregnancy and risk of neurodevelopmental conditions," explains Brian Lee, an associate professor at Drexel University's Dornsife School of Public Health and co-author of the JAMA study.

The Mount Sinai Paradox: When Methodology Matters

Complicating the evidence landscape is a high-profile August 2024 study from Mount Sinai that applied the Navigation Guide Systematic Review methodology, a framework designed specifically for environmental health research, to 46 studies involving more than 100,000 participants. The researchers concluded there was "sufficient evidence" for an association between prenatal acetaminophen exposure and autism and ADHD, pointing to potential biological mechanisms including oxidative stress, hormonal disruption, and epigenetic modifications.

The Navigation Guide methodology differs from traditional meta-analysis in important ways. Rather than producing a single numerical estimate of risk, it provides a qualitative assessment of evidence strength across multiple study types, including human observational studies, animal research, and cellular studies. The approach allows researchers to assess and rate each study's risk of bias, such as selective reporting of outcomes or incomplete data, as well as the strength of evidence collectively.

However, the Mount Sinai findings stand in tension with the larger, more rigorous JAMA study. This apparent contradiction highlights a crucial issue in environmental health research: the challenge of separating true causal relationships from confounding by indication; the possibility that the underlying conditions prompting acetaminophen use, rather than the medication itself, account for observed associations.

The Medical Establishment Speaks: Consensus Amid Uncertainty

Despite emerging research signals, major medical organizations have maintained their positions supporting acetaminophen's safety profile during pregnancy.

Dr. Christopher Zahn, ACOG's chief of clinical practice, reinforced this position in September 2025, stating that "pregnant patients should not be frightened away from the many benefits of acetaminophen, which is safe and one of the few options pregnant people have for pain relief."

The Society for Maternal-Fetal Medicine has taken a similarly measured stance. In a 2025 statement, the organization emphasized that "untreated fever, particularly in the first trimester, increases the risk of miscarriage, birth defects, and premature birth, and untreated pain can lead to maternal depression, anxiety, and high blood pressure."

The FDA's position, last updated in 2015, acknowledges that studies on acetaminophen and neurodevelopmental outcomes "have potential limitations in their designs" and contain "conflicting results that prevented us from drawing reliable conclusions." As a result, the agency maintained its existing recommendations unchanged.

The Confounding Conundrum: Separating Cause from Coincidence

The challenge of establishing causation in acetaminophen research extends beyond methodological concerns to fundamental questions about why pregnant women take pain medication in the first place. Acetaminophen is typically used to treat fever, infection-related symptoms, and pain, each of which has independent associations with neurodevelopmental outcomes.

This creates what epidemiologists call "confounding by indication," a situation where the medical condition being treated, rather than the treatment itself, may account for observed outcomes. David Mandell, a professor of psychiatry studying autism at the University of Pennsylvania, explains: "For acetaminophen, researchers can't fully separate the effects of the medication from the effects of the underlying conditions that may lead people to take pain relievers during pregnancy."

The Swedish sibling study's strength lies in its ability to control for many of these confounding factors by comparing children within the same family. When such controls are applied, the associations between acetaminophen and neurodevelopmental disorders largely disappear, suggesting that family-level factors, rather than the medication itself, may explain apparent links observed in less rigorous studies.

The Autism Complexity: Why Simple Answers Fall Short

The search for acetaminophen's role in autism must be understood within the broader context of autism spectrum disorder itself. Autism doesn't have a single cause; it results from a complex mix of genetics and environment, with hundreds of genes linked to the condition and inherited or spontaneous genetic changes that can alter brain development.

The Autism Science Foundation emphasizes that "any association between acetaminophen and autism is based on limited, conflicting, and inconsistent science and is premature given the current science." The organization notes that autism research has identified hundreds of relevant genes, and while environmental factors during pregnancy matter, "it is disingenuous and misleading to boil autism's causes down to one simple thing."

This genetic complexity means that even well-established environmental risk factors typically show modest effect sizes. Advanced parental age, prematurity, and certain prenatal infections all demonstrate associations with autism risk, but none approach the deterministic power that simple cause-and-effect thinking might suggest.

As autism researcher Shafali Jeste from Children's Hospital Los Angeles explains, even for genetic mutations known to substantially increase autism risk, "if you have this mutation, it doesn't guarantee that you will have autism per se, but it increases the risk substantially." There are still other factors involved that researchers haven't fully characterized.

Risk, Benefit, and the Pregnant Patient's Dilemma

The acetaminophen debate ultimately centers on risk-benefit calculation for individual pregnant women facing real symptoms that require treatment. The FDA notes that "severe and persistent pain that is not effectively treated during pregnancy can result in depression, anxiety, and high blood pressure in the mother"; conditions that carry their own risks for both maternal and fetal health.

Even the Mount Sinai researchers, despite finding evidence for associations, acknowledge this clinical reality, recommending "judicious acetaminophen use—lowest effective dose, shortest duration—under medical guidance, tailored to individual risk-benefit assessments, rather than a broad limitation."

Biological Plausibility: Mechanisms in Search of Meaning

Researchers have proposed several biological pathways through which acetaminophen might influence fetal neurodevelopment. The medication readily crosses the placental barrier and could theoretically affect the developing brain through oxidative stress, disruption of endocannabinoid signaling, or interference with prostaglandin pathways crucial for brain development.

Animal studies have shown neurobehavioral changes following acetaminophen exposure, though often at doses or developmental timing that don't map cleanly onto human pregnancy (Damkier et al., 2025). Some researchers have also measured acetaminophen metabolites in umbilical cord blood, finding associations with later neurodevelopmental outcomes, though these studies remain limited by small sample sizes and potential confounding by acute illness at delivery.

However, the availability of proposed mechanisms doesn't establish causation at therapeutic doses in humans. As noted in recent systematic reviews, "mechanistic and translational data remain inconclusive at clinically relevant exposures" and "direct confirmation in humans at typical prenatal exposure levels is lacking" (Damkier et al., 2025).

Practical Guidance: Navigating Uncertainty

For healthcare providers and pregnant patients, the acetaminophen question requires balancing uncertain long-term risks against immediate, well-established benefits. The consensus among major medical organizations suggests that current evidence doesn't support changing clinical practice, while acknowledging the need for continued research and prudent use.

ACOG's guidance emphasizes that "any medication taken during pregnancy should be used only as needed, in moderation, and after the pregnant patient has consulted with their doctor;" advice that applies to acetaminophen as much as any other medication.

This approach aligns with broader principles of medication use in pregnancy: using the lowest effective dose for the shortest necessary duration while avoiding unnecessary or habitual use. For many conditions, fever, headache, acute pain, short-term acetaminophen use to maintain maternal comfort and health likely outweighs theoretical risks suggested by observational research.

The Kennedy Factor: Politics Meets Science

The current controversy has been amplified by the political dimensions surrounding RFK Jr.'s promised autism announcement. Kennedy has a history of promoting theories about autism causation that lack scientific support, including discredited claims about vaccines. His approach to seeking single environmental causes for autism runs counter to the scientific consensus that the condition arises from complex gene-environment interactions.

The timing of a potential HHS report linking acetaminophen to autism has raised concerns among autism advocates and researchers.

This political backdrop risks turning a legitimate scientific discussion into a polarized debate, potentially undermining public health messaging and unnecessarily frightening pregnant women away from a medication that may be medically necessary.

Future Directions: What Science Needs to Know

The acetaminophen question highlights important gaps in our understanding of prenatal influences on neurodevelopment. Future research would benefit from objective exposure assessment through repeated biomarkers across pregnancy, rigorous control for confounding through sibling designs and negative control studies, standardized outcome measures that distinguish clinical diagnoses from behavioral symptoms, and diverse cohorts with long-term follow-up (Damkier et al., 2025).

Particularly valuable would be studies using Mendelian randomization—a technique that uses genetic variants to simulate randomized trials—to better establish causal relationships. Research into safer alternatives for pregnancy pain management could also provide additional options for women facing difficult treatment decisions.

The emergence of biomarker studies measuring acetaminophen metabolites in cord blood represents a promising avenue for overcoming the limitations of maternal self-report, though these approaches need larger sample sizes and better control for confounding by acute illness.

The Bottom Line: Evidence, Uncertainty, and Clinical Wisdom

The current state of acetaminophen research illustrates medicine's ongoing struggle with uncertainty in the face of incomplete evidence. While some studies suggest possible associations between prenatal acetaminophen exposure and neurodevelopmental outcomes, the highest-quality research, particularly the large Swedish sibling study, finds no evidence for causal relationships when proper controls are applied.

The pattern across study designs points toward a coherent conclusion: conventional observational studies detect small associations that are substantially attenuated or disappear entirely in methodologically stronger designs that better address confounding (Damkier et al., 2025).

The acetaminophen story also serves as a reminder of autism's complexity. As researchers increasingly recognize, autism likely represents multiple conditions with varied genetic and environmental contributors rather than a single disorder with a single cause. Simple explanations, however politically appealing, are unlikely to capture this biological reality.

As science continues to refine our understanding of prenatal influences on neurodevelopment, the acetaminophen question will undoubtedly evolve. For now, clinical wisdom suggests maintaining current practices while remaining open to new evidence, a stance that serves both maternal health and fetal wellbeing in the face of uncertainty.

Key Takeaways

1. The strongest scientific evidence finds no causal link: the largest and most rigorous study to date, involving over 2 million children, found no association between acetaminophen use during pregnancy and autism or ADHD when properly controlling for family factors.

   
   

2. Medical organizations maintain safety recommendations: major professional groups including ACOG and the Society for Maternal-Fetal Medicine continue to recommend acetaminophen as safe for pregnancy use when medically necessary.

   
   

3. Untreated maternal conditions pose established risks: fever, pain, and infections during pregnancy carry well-documented risks including birth defects, preterm birth, and maternal complications that often outweigh theoretical medication risks.

   
   

4. Research limitations create uncertainty: observational studies suggesting associations between acetaminophen and autism suffer from methodological problems including confounding by the underlying conditions that prompt medication use.

   
   

5. Autism has complex, multifactorial causes: hundreds of genes contribute to autism risk, and environmental factors interact in complicated ways, making single-cause explanations scientifically implausible.

Glossary

ACOG: the American College of Obstetricians and Gynecologists, a professional organization that provides clinical guidelines for pregnancy care and women's health.

acetaminophen: a common over-the-counter pain reliever and fever reducer, also known as paracetamol outside North America, found in medications like Tylenol.

ADHD: attention-deficit/hyperactivity disorder, a neurodevelopmental condition characterized by persistent patterns of inattention, hyperactivity, and impulsivity.

ASD: autism spectrum disorder, a complex developmental condition affecting social communication, interaction, and behavior, with symptoms ranging from mild to severe.

blood-brain barrier: a protective membrane that controls which substances can pass from the bloodstream into brain tissue, incompletely developed during fetal growth.

broader autism phenotype: the presence of mild or subclinical autistic traits in individuals who do not meet the diagnostic threshold for autism spectrum disorder (ASD).

confounding: a research problem where an unmeasured factor influences both the exposure being studied and the outcome, making it difficult to determine true cause-and-effect relationships.

confounding by indication: a specific type of bias where the medical condition being treated, rather than the treatment itself, may cause the observed outcome.

endocannabinoid signaling: a biological communication system involving naturally occurring compounds similar to those found in cannabis, important for brain development and function.

epigenetic modifications: changes in gene expression that don't alter DNA sequence but can affect how genes are turned on or off, potentially influencing development.

epidemiology: the study of how diseases and health conditions are distributed in populations and what factors influence their occurrence.

meta-analysis: a statistical technique that combines results from multiple independent studies to provide a more precise estimate of treatment effects or associations.

Mendelian randomization: a research method that uses genetic variants as natural experiments to better establish causal relationships between exposures and outcomes.

Navigation Guide Systematic Review: a specialized methodology for evaluating environmental health evidence that assesses studies across humans, animals, and cells while rating evidence quality.

NDDs: neurodevelopmental disorders, conditions that result from impaired growth and development of the brain, typically manifesting in childhood.

NSAIDs: nonsteroidal anti-inflammatory drugs such as ibuprofen and naproxen, which reduce pain and inflammation but carry risks during pregnancy.

oxidative stress: cellular damage caused by an imbalance between harmful molecules called free radicals and the body's ability to neutralize them.

paracetamol: the international name for acetaminophen, commonly used outside North America for the same pain-relieving medication.

placental barrier: the membrane between maternal and fetal blood that regulates which substances can pass from mother to developing baby.

prostaglandins: hormone-like substances that play important roles in inflammation, pain, and various bodily functions including brain development.

relative risk: a statistical measure comparing the likelihood of an outcome occurring in exposed versus unexposed groups, expressed as a ratio.

sibling-comparison studies: research designs that compare outcomes between siblings within the same family, helping control for shared genetic and environmental factors.

Society for Maternal-Fetal Medicine: a professional organization focused on high-risk pregnancies and the health of pregnant women and their babies.

umbilical cord blood biomarkers: measurable substances in cord blood that can indicate fetal exposure to medications or other compounds during pregnancy.

References

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About the Author

Fred Shaffer earned his PhD in Psychology from Oklahoma State University. He earned BCIA certifications in Biofeedback and HRV Biofeedback. Fred is an Allen Fellow and Professor of Psychology at Truman State University, where has has taught for 50 years. He is a Biological Psychologist who consults and lectures in heart rate variability biofeedback, Physiological Psychology, and Psychopharmacology. Fred helped to edit Evidence-Based Practice in Biofeedback and Neurofeedback (3rd and 4th eds.) and helped to maintain BCIA's certification programs.

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