Could Tylenol During Pregnancy Be a Risk Factor for Autism? A Deeper Look at the Evidence and Hypotheses

Acetaminophen (also known as N-acetyl-para-aminophenol and paracetamol) is one of the most commonly used analgesic/antipyretic medications worldwide, including by pregnant individuals. Acetaminophen is mainly metabolized in the liver through three primary pathways: glucuronidation, sulfation, and oxidation. At therapeutic doses of acetaminophen, the first two pathways are most predominant, resulting in the formation of non-toxic, water-soluble metabolites that are easily excreted by the kidney. Only a small portion of acetaminophen is oxidized into toxic intermediate metabolites, which are also quickly neutralized in our body. ( Agrawalet al., 2025)

Standard Metabolic Routes

Roughly 90% of acetaminophen is processed by the liver via glucuronidation and sulfation, turning it into non‑toxic metabolites that are excreted in urine. A small portion (~5–10%) is metabolized by the cytochrome P450 enzyme system (notably CYP2E1, CYP1A2, CYP3A4) into a highly reactive metabolite called N‑acetyl‑p‑benzoquinone imine (NAPQI). At therapeutic doses, NAPQI is quickly neutralized by glutathione, an endogenous antioxidant, forming conjugates that are harmless.

The Risk: Glutathione Depletion and Mitochondrial Damage

If acetaminophen dose is high or glutathione reserves are low, NAPQI may accumulate. This leads to oxidative stress, as NAPQI is a strong prooxidant and forms reactive species. Mitochondria are especially sensitive to oxidative stress: NAPQI can damage electron transport chain complexes, mitochondrial DNA, and membrane integrity (Chu et al., 2025). In overdose situations, this mechanism is well known to cause hepatic necrosis. In clinical condition, N-acetylcysteine (NAC) is commonly used to replenish glutathione and prevent severe liver damage (Chiew et al., 2017; Licata et al., 2022)

Pregnancy as a Vulnerable State

During pregnancy, glutathione levels tend to decline (as the maternal body undergoes oxidative and metabolic stress). Some studies suggest ~20–30% reductions in glutathione or reduced antioxidant buffering capacity in pregnant women compared to non-pregnant women  (Chu et al., 2025). This makes pregnant individuals—and by extension the fetus—more vulnerable to oxidative insults. A given dose of acetaminophen might push the oxidative balance closer to the threshold of damage. Because of this, the usual safety margin may shrink in pregnancy, particularly under chronic use, coexisting oxidative stress (infection, inflammation, poor nutrition), or other environmental burdenors.

Beyond metabolism, what mechanisms might link prenatal acetaminophen exposure to neurodevelopmental disorders? The hypothesis is built on several overlapping threads.

Mitochondrial Dysfunction in ASD / ADHD

Many research studies (including in vivo animal and in vitro human tissue specific cell culture models) report mitochondrial abnormalities in individuals with autism or ADHD: altered oxidative phosphorylation, abnormal reactive oxygen species (ROS) production, mitochondrial DNA variants, and lower respiratory capacity (Chu et al., 2025). Because mitochondrial function is critical for high-energy utilizing tissues such as the brain. The damage or inefficiency in mitochondria early in development could ripple into structural and functional deficits of the brain.

Oxidative Stress and Neuroinflammation

Excessive ROS leads to lipid peroxidation, protein oxidation, and DNA damage. In the developing brain, these may disrupt synaptogenesis, neuronal migration, and network formation. Oxidative stress also triggers neuroinflammation—microglial activation, release of pro-inflammatory cytokines—which can further disturb neural development. Additionally, epigenetic changes may emerge, priming cells to alter gene expression patterns (e.g. methylation, histone modification) that persist.  (Chu et al., 2025).

Bridging to Acetaminophen

The NAPQI metabolite from acetaminophen is a direct source of oxidative insult. If not neutralized, it could impair mitochondrial membranes, complexes, and DNA (Chu et al., 2025). If this occurs during critical windows of fetal brain development (neurogenesis, migration, synaptic formation), even subtle mitochondrial impairments could alter developmental trajectories. Some authors propose that microglia become “primed” by early oxidative injury, making them hyperresponsive to later insults (e.g. infections, inflammation) across life (Chu et al., 2025). Acetaminophen crosses the placenta, exposing both the mother and fetus to its effects. As the fetal detoxification and antioxidant systems are still developing, this increases their vulnerability (Chu et al., 2025). A 2024 article titled “Acetaminophen’s Role in Autism and ADHD: A Mitochondrial Perspective” outlines this chain—from NAPQI to mitochondrial ROS to neurodevelopmental risk—as a unifying framework (Chu et al., 2025). Thus, although the mechanistic links are not proven in humans, the framework has biological plausibility and coherence with existing knowledge of mitochondrial vulnerability in ASD.

While mechanistic plausibility matters, ultimately the question is: do data from human populations support a link? The evidence is mixed but increasingly suggestive—though far from conclusive.

Key Findings Supporting a Link

A meta-analysis of six European birth cohorts (73,881 mother-child pairs) found that prenatal acetaminophen exposure was associated with ~19% higher odds of autism symptoms (ASC) and ~21% higher odds of ADHD symptoms in childhood (OR ~1.19 and 1.21, respectively). Postnatal exposure was not linked (Alemany et al., 2021). The recent review study, applying the rigorous Navigation Guide methodology to 46 studies, found that 27 of the 46 studies reported positive associations between prenatal acetaminophen use and neurodevelopmental disorders (ASD or ADHD)  (Mount Sinai Study Supports Evidence 2025 and Prada et al., 2025). This review examined study quality, bias risk, and consistency. The authors caution that causality cannot be established, but they suggest more caution in clinical use.  (Mount Sinai Study Supports Evidence 2025).

Some prospective cohort studies, cord blood metabolite analyses, and studies adjusting for maternal inflammation/fever have also found correlations between acetaminophen biomarkers and later ADHD/ASD risk. (Raghavan & Wang, 2024)

Contradictory or Null Evidence

A large Swedish registry-based study found that in sibling-controlled analyses, acetaminophen use during pregnancy was not significantly associated with later ASD, ADHD, or intellectual disability. That is, comparing siblings where one was exposed and one was not, the risk difference disappeared.  ( Ahlqvist et al., 2020) Critics argue that some studies cited by policy or media overstate the strength of evidence, or duplicate references, or fail to adequately control for confounding (e.g. maternal illness, genetics) (Green, 2025)

Limitations and Important Caveats

Confounding: Women take acetaminophen for pain, fever, or infections—each of which could independently affect fetal development. Is the drug the culprit, or the reason it was taken?

Exposure measurement: Many studies rely on self-reported acetaminophen use (yes/no), without precise dose, duration, or timing. OTC use is often underreported ( Ahlqvist et al., 2020).

Residual bias: Even controlling for known factors, unmeasured confounding is possible (e.g. lifestyle, nutrition, unknown exposures).

Reverse causation / familial factors: Genetic predispositions might lead to both increased pain/inflammation in pregnancy and higher neurodevelopmental risk.

Heterogeneity: Differences in diagnostic criteria, timing of exposure, population genetics, and study design make synthesis difficult.

Magnitude of risk: Even in studies showing associations, increases tend to be modest (e.g. ORs in the 1.1–1.3 range), not dramatic leaps.

Overall, epidemiological data suggest a signal—a consistent albeit relatively weak association—worthy of further study, but not proof.

An intriguing expansion of the hypothesis ties sunlight exposure, mitochondrial melatonin, and oxidative balance into the picture.

Mitochondrial Melatonin as Antioxidant

Beyond the well-known pineal gland source, melatonin is also generated within mitochondria in many cells, acting locally as a potent antioxidant and regulator of mitochondrial function (Chu et al., 2025). This intracellular melatonin is not strictly tied to circadian rhythms; instead, it may respond to the oxidant load (i.e. when ROS rises) (Chu et al., 2025).

Infrared / Near‑Infrared Light Stimulation

Some studies suggest near-infrared (NIR) light (a component of sunlight) may boost mitochondrial melatonin production and help reduce oxidative stress. The idea is that infrared photons penetrate tissue and stimulate mitochondrial responses. A recent (2025) article in Nature Scientific Reports reported that longer wavelengths in sunlight can pass through the human body and may have systemic mitochondrial effects (e.g. on remote cells) (Mount Sinai Study Supports Evidence 2025).

Modern Lifestyle & Light Deprivation

Over the past two centuries, human environments evolved toward enclosed indoor living, window glazing that blocks IR, LED and fluorescent lighting that emit little or no IR, and low time outdoors—all potentially reducing our exposure to beneficial IR. A forthcoming Department of Energy regulation (2028) will further raise lumens-per-watt standards for LED bulbs, likely eliminating any residual IR output—possibly exacerbating this deprivation. The hypothesis: in a low-IR, low-sunlight environment, mitochondrial antioxidant capacity is compromised; then when a stressor like acetaminophen is introduced, the system has less buffer and is more vulnerable. This sunlight-mitochondria hypothesis remains speculative and is not universally accepted—but it highlights the possibility that environmental light exposure is an underappreciated cofactor in neurodevelopmental outcomes.

If the associations and mechanistic hypotheses hold some truth, there are wide-ranging implications—not just for clinical practice, but for how we structure indoor environments and public health messaging.

Lighting Standards & Indoor Environments

The push for ever more energy-efficient lighting may inadvertently reduce infrared emission, removing a potential endogenous “antioxidant stimulant.” Buildings often use low-E glass, double glazing, tinted windows, etc., which block IR wavelengths. The cumulative effect may be subtle but widespread: chronic underexposure to beneficial IR in modern societies.

Public Health Messaging & Precautions

If acetaminophen in pregnancy carries even a modest risk, pregnant individuals should be informed and supported in weighing risks vs benefits. Guidelines might need updating to emphasize lowest effective dose, shortest duration, and only when necessary, particularly during critical windows of neural development. There is a need for environmental and lifestyle interventions: encouraging safe outdoor time, designing indoor lighting that includes beneficial spectra, and broader recognition of oxidative balance in maternal-fetal health.

Research Funding & Regulatory Attention

Agencies (NIH, FDA, CDC) and academic funders may need to prioritize prospective cohorts, biomarker studies, and interventional trials (where ethical) to clarify causation. Regulatory bodies should evaluate not only pharmaceutical safety but indoor environment safety (light spectra)—especially as lighting technology evolves. It may become necessary to revisit labeling of acetaminophen with clearer cautions regarding prenatal use, pending stronger evidence.

From a clinician’s or patient’s point of view, what do these data suggest in practical terms?

Balancing Risks: Pain, Fever, and Maternal

Untreated high fever or severe pain/inflammation in pregnancy carries its own risks (e.g. neural tube defects, preterm labor, fetal stress). For many pregnant individuals, acetaminophen remains one of the safer pharmacologic options available—especially compared to NSAIDs (which carry risks of closure of the ductus arteriosus, renal effects, etc.). Several coauthors of the cited review stress that acetaminophen should not be eliminated entirely; rather, its use should be judicious—lowest dose, shortest duration, under medical supervision ( Gardner, 2025)

Practical Recommendations (Pending More Evidence)

1. Before taking any medication, discuss with an obstetrician or maternal-fetal specialist.

2. If acetaminophen is needed:

   • Use lowest effective dose

   • Limit duration (avoid chronic use)

   • Avoid overlapping medications that also contain acetaminophen

   • Consider non-pharmacologic therapies (e.g. rest, hydration, non‑drug pain relief)

3. Encourage safe sunlight exposure (as weather and conditions permit), mindful of skin protection and comfort.

4. Monitor maternal health and inflammation, and avoid unnecessary oxidative stress (e.g. through good diet, antioxidant support, managing infections).

5. Remain updated on evolving guidelines—this field is active and subject to change.

No scientific debate is complete without acknowledging uncertainties. Here are key questions that need further resolution.

• Causality vs correlation: Are observed associations driven by unmeasured confounders (e.g. maternal illness, genetic liability, pain conditions)?

• Dose-response relationship: Is risk higher at higher doses or longer durations? Is there a threshold below which risk is negligible?

• Critical windows: Which gestational periods (e.g. first trimester neurogenesis vs later synaptogenesis) are most sensitive?

• Biomarker validation: Can we measure NAPQI, antioxidant depletion, or oxidative damage in maternal/fetal tissues in vivo and correlate with outcomes?

• Interventional studies: Ethical and methodological challenges exist, but is it possible to test reduced-acetaminophen protocols or antioxidant supplementation in cohorts?

• Population and genetic modifiers: Do genetic polymorphisms in detoxification enzymes, antioxidant capacity, or mitochondrial resilience modulate risk?

• Cross-species and mechanistic studies: Animal models with controlled acetaminophen exposure could help clarify causation pathways.

Until these gaps close, strong claims (especially by policy or media) should be treated cautiously.

The Role of NAC Supplementation in Combating Oxidative Stress from Tylenol Use

While Tylenol is generally safe when used as directed, excessive or prolonged use can lead to oxidative stress—a state where damaging free radicals overwhelm the body’s natural antioxidant defenses, particularly in the liver. This is where N-acetylcysteine (NAC) plays a crucial role (Chiew et al., 2017).

NAC is a powerful antioxidant and a precursor to glutathione, one of the body’s most important detoxifying molecules. When Tylenol is metabolized, especially at high doses, it produces a toxic byproduct called NAPQI. Under normal circumstances, glutathione neutralizes NAPQI. However, if glutathione levels are depleted, NAPQI builds up and can cause severe liver damage.

Supplementing with NAC helps replenish glutathione levels, allowing the body to safely process and eliminate harmful metabolites. In fact, NAC is the standard medical treatment for acetaminophen overdose for precisely this reason (Chiew et al., 2017; Licata et al., 2022)

For individuals who regularly use Tylenol—especially pregnant women or those with existing liver concerns—consulting a healthcare provider about  NAC supplementation may be beneficial. It’s a preventative step that can support the body’s antioxidant defenses and reduce potential risks associated with long-term acetaminophen use.

The idea that routine use of acetaminophen in pregnancy could contribute to autism or ADHD is provocative but not completely proven. The evidence to date offers:

• A plausible biological mechanism, rooted in oxidative stress, mitochondrial vulnerability, and fetal susceptibility

• Epidemiological signals: modest but consistent associations across multiple studies

• Hypotheses linking environment (especially light exposure) to antioxidant capacity and vulnerability

• Policy and lifestyle considerations that merit attention beyond just drug safety

• But also significant uncertainties: confounding, measurement biases, and lack of definitive causation

From a responsible perspective, the key is not alarmism, but informed caution. Clinicians and pregnant individuals should weigh the known benefits and risks of acetaminophen in context, using the minimal effective dose when needed, encouraging healthy antioxidant and environmental support, and staying current as science evolves.

LEGAL DISCLAIMER

1. Agrawal S, Murray BP, Khazaeni B. Acetaminophen Toxicity. [Updated 2025 Apr 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441917/)

2. 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):1205–1214. 

3. Alemany S, Avella-García C, Liew Z, García-Esteban R, Inoue K, Cadman T, López-Vicente M, González L, Riaño Galán I, Andiarena A, Casas M, Margetaki K, Strandberg-Larsen K, Lawlor DA, El Marroun H, Tiemeier H, Iñiguez C, Tardón A, Santa-Marina L, Júlvez J, Porta D, Chatzi L, Sunyer J. 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. 

4. Chu, S., Woodfin, S., Bayliss, E., Smith, M., Fulp, A., Mirabelli, E., & Moore, W. (2025). Acetaminophen’s Role in Autism and ADHD: A Mitochondrial Perspective. International Journal of Molecular Sciences, 26(17), 8585.

5. Chiew, A. L., Isbister, G. K., Kirby, K. A., Page, C. B., Chan, B. S. H., & Buckley, N. A. (2017). Massive paracetamol overdose: an observational study of the effect of activated charcoal and increased acetylcysteine dose (ATOM-2). Clinical toxicology (Philadelphia, Pa.), 55.(10), 1055–1065.

6. Du K, Ramachandran A, Jaeschke H. Oxidative stress during acetaminophen hepatotoxicity: Sources, pathophysiological role and therapeutic potential. Redox Biol. 2016 Dec;10:148-156. doi: 10.1016/j.redox.2016.10.001. Epub 2016 Oct 4. PMID: 27744120; PMCID: PMC5065645.

7. Green, H. H. (2025, October 2). How the White House spun ‘weak’ and ‘inconclusive’ studies to tie Tylenol to autism. The Guardian. https://www.theguardian.com/us-news/2025/oct/02/trump-tylenol-autism-expert-analysis?utm_source=chatgpt.com

8. Licata, A., Minissale, M. G., Stankevičiūtė, S., Sanabria-Cabrera, J., Lucena, M. I., Andrade, R. J., & Almasio, P. L. (2022). N-Acetylcysteine for Preventing Acetaminophen-Induced Liver Injury: A Comprehensive Review. Frontiers in pharmacology, 13, 828565. 

9. Mary Lynn Bajt, Tamara R. Knight, John J. Lemasters, Hartmut Jaeschke, Acetaminophen-Induced Oxidant Stress and Cell Injury in Cultured Mouse Hepatocytes: Protection by N-Acetyl Cysteine, Toxicological Sciences, Volume 80, Issue 2, August 2004, Pages 343–349, 

10. Mount Sinai Health System. (2025, August 13). Mount Sinai study supports evidence that prenatal acetaminophen use may be linked to increased risk of autism and ADHD [Press release]. Icahn School of Medicine at Mount Sinai. https://www.mountsinai.org/about/newsroom/2025/mount-sinai-study-supports-evidence-that-prenatal-acetaminophen-use-may-be-linked-to-increased-risk-of-autism-and-adhd?utm_source=chatgpt.com

11. Prada, D., Ritz, B., Bauer, A.Z. et al. Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology. Environ Health 24, 56 (2025 )

12. Politico. (2025, September 22). Pregnant women can still use Tylenol judiciously, says researcher.Politico.https://www.politico.com/news/2025/09/22/pregnant-women-can-still-use-tylenol-judiciously-says-researcher-005757

13. Raghavan, Ramkripa1; Wang, Xiaobin1,2. Early life origins of neurodevelopmental disabilities in the Boston Birth Cohort: research findings and future directions. Precision Nutrition 3(1):p e00062, March 2024.

14. Raghu G, Berk M, Campochiaro PA, Jaeschke H, Marenzi G, Richeldi L, Wen FQ, Nicoletti F, Calverley PMA. The Multifaceted Therapeutic Role of N-Acetylcysteine (NAC) in Disorders Characterized by Oxidative Stress. Curr Neuropharmacol. 2021;19(8):1202-1224.