Acetaminophen, widely recognized under the brand name Tylenol®, is the most commonly recommended over-the-counter (OTC) analgesic and antipyretic for pregnant women. For decades, both regulatory agencies and medical professionals have considered it the safest option for managing pain and fever during pregnancy, especially given the well-documented risks associated with alternatives such as NSAIDs and opioids. In recent years, however, reports suggesting a possible link between prenatal acetaminophen use and autism spectrum disorder (ASD)-along with attention-deficit/hyperactivity disorder (ADHD)-have generated both scientific investigation and public concern. Heightened media attention and policy debates, culminating in recent government advisories, have led some patients and even professionals to second-guess long-held medical guidance.

This comprehensive review synthesizes decades of scientific research, including the largest and most methodologically rigorous studies to date, and presents a clear, fact-based argument: There is no credible evidence that acetaminophen use during pregnancy causes autism. The article will detail the breadth and quality of research, analyze biological plausibility and confounding factors, discuss regulatory and professional guidelines, and provide practical information for patients-including warnings, potential side effects, and a review of alternative OTC pain relievers during pregnancy.

---

The Evidence: Quantity, Quality, and Findings of the Research

Questions about acetaminophen’s safety in pregnancy have catalyzed an expansive research effort. As of 2025, systematic reviews and meta-analyses have cataloged at least 46 original studies analyzing the relationship between prenatal acetaminophen exposure and neurodevelopmental outcomes-including autism-encompassing over 100,000 participants across global, multiethnic cohorts.^{1 2 3} The largest, most definitive study conducted by researchers at Drexel University and Sweden’s Karolinska Institutet analyzed nearly 2.5 million children born between 1995 and 2019, making it the most comprehensive evaluation to date.^{4 5}

---

Key Studies:

Study/Review	Sample Size	Design/type	Main Finding	Dose-Response Analysis	Causal Conclusion
Ahlqvist et al. 2024 (JAMA)	2,480,797 children	Population-based cohort (sibling analysis)	No association between acetaminophen and autism, ADHD, or intellectual disability when confounders controlled	No dose-response in controlled design	No causal link
Prada et al. 2025 (Environ Health)	46 studies; >100,000 participants	Systematic review (navigation guide, incl. biomarkers, sibling studies)	Slight association in some studies, but not causal; confounding likely.	No robust dose-response	No proven causation
Masarwa et al. 2018 (Meta-analysis)	132,738 pairs	Meta-analysis	Small increased risk in pooled unadjusted data; no proof of causation.	Dose findings inconsistent	Association only
Okubo et al. 2025 (Japan, sibling study)	203,000+ children	Large cohort with sibling analysis	No association between prenatal acetaminophen and autism	Not found	No causal link
European Collaborative Cohorts (2021)	73,881 pairs	Multi-cohort meta-analysis	~19% higher risk of clinical ASD symptoms, but effect size small; confounding not fully controlled	Not clear	Association, not causation

Adapted from JAMA 2024,  Environmental Health 2025, and others as cited.

---

Each of these major studies provides unique insights into the topic, but crucially, the weight of the evidence does not substantiate a causal relationship between acetaminophen use during pregnancy and increased autism risk. Instead, the best-designed research, using advanced statistical controls for familial and genetic confounding, repeatedly finds no increased autism risk.

---

Sibling-Control Studies: The Gold Standard for Causality

Sibling-control studies are especially powerful in medicine because they compare outcomes among siblings in the same family, thus controlling for genetics, socioeconomic background, parental health behaviors, and environment. The landmark 2024 Swedish cohort, which followed over 2.4 million children and included nearly 1.8 million sibling pairs, found that any small statistical association between acetaminophen and autism disappeared completely when using the sibling-control design. Hazard ratios for autism in the sibling analysis were essentially 1.00, meaning no increased risk.^{14 6}

Similarly, very large Japanese and Norwegian studies employing sibling design reported no risk increase, even with high-quality diagnostic data and careful control for confounding variables.³

---

Systematic Reviews and Meta-Analyses: Associations Without Proof

A widely publicized 2025 systematic review collated 46 studies and concluded the majority observed a “small association” between prenatal acetaminophen and neurodevelopment disorders (including ADHD and, less commonly, autism). ^{2 3 7} However, even the authors caution that these are associations and not proof of causation-a distinction that is both scientifically and clinically crucial. Many included studies suffered from exposure misclassification, self-report bias, limited outcome validation, and, most critically, insufficient control for confounding variables such as maternal illness, genetics, and co-medication use. When only the most robust, prospectively controlled, or sibling-controlled designs are considered, the associations largely disappear.^{5 8 9}

Recent meta-analyses confirm this. For example, the 2018 Masarwa et al. study with 132,738 pairs found a 19% increased risk for autism, but this was based on statistical association, not causal effect, and the clinical significance was minimal in absolute terms.³

---

Why Associations Are Not Causation: Confounders, Biases, and Statistical Realities

One must carefully separate association (a relationship found in statistical data) from causation (a direct, biologically plausible, and reproducible mechanism). Most early positive studies assessed by recent reviews were observational and therefore susceptible to bias from:

• Confounding by indication (i.e., the reason acetaminophen was used-such as infection or chronic pain-may itself be associated with increased autism risk).^{1 10}.
• Genetic and familial factors (e.g., hereditary neurodevelopmental risk or parental traits associated both with acetaminophen usage and child neurodevelopment issues). ¹¹
• Recall and self-report bias (parents who have a child with autism may be more likely to recall and report medication use). ¹
• Publication bias (positive findings are more likely to be published than null results).¹²

Famously, the Ahlqvist 2024 study demonstrated that adjusting for these factors-via sibling comparison and extensive statistical modeling-rendered all associations null. This finding was robust across all levels of exposure, including the highest daily doses recorded.^{4 6}

---

Absolute Risk: Numbers Put in Perspective

Across the largest studies, absolute differences in autism rates between acetaminophen-exposed and unexposed children are extremely small, and when familial and indication-related confounders are controlled for, the risk difference becomes statistically and clinically insignificant.

For example, in the Swedish cohort:

1.33% in non-exposed children, 1.53% in exposed children (crude difference: 0.2 percentage points; disappears with robust controls).⁵

This should be compared to background increases in autism diagnoses, which have risen due to changes in diagnostic criteria and greater public awareness, not due to changes in acetaminophen use.^{6 10}

---

Biological Plausibility: Is There a Mechanism?

A critical element of assigning causality is understanding whether a plausible biological mechanism exists. Some animal and cellular studies suggest acetaminophen may have weak endocrine-disrupting properties, can cross the placental barrier, and alter prostaglandin or neurotransmitter pathways.² However, translating findings from animal exposure (often at higher doses or during different developmental windows) to meaningful human clinical harm is fraught.

Importantly, epidemiological data does not support a consistent, dose-dependent risk for human neurodevelopmental disorders when considering real-world use at recommended doses. Nor have potential immune, hormonal, or epigenetic changes been robustly linked to clinically significant autism risk at population scale.⁵

---

Regulatory Guidelines and Professional Consensus

Statements from Leading Organizations

With rumors and controversy swirling, what do the major medical organizations say?

• American College of Obstetricians and Gynecologists (ACOG): “In more than two decades of research on the use of acetaminophen in pregnancy, not a single reputable study has successfully concluded that the use of acetaminophen in any trimester of pregnancy causes neurodevelopmental disorders in children. In fact, the two highest-quality studies on this subject-one published in JAMA last year-found no significant associations.”⁸
• Society for Maternal-Fetal Medicine (SMFM): “The weight of scientific evidence that acetaminophen use during pregnancy causes an increased risk for autism or ADHD is simply inconclusive.” The SMFM continues to recommend acetaminophen as an appropriate medication for fever and pain during pregnancy.¹³
• Society of Obstetricians and Gynaecologists of Canada (SOGC): “The SOGC recommends the use of acetaminophen as a first-line therapeutic option for fever and pain in pregnancy when medically indicated at recommended doses for the shortest duration required”.¹⁴
• FDA and CDC: The US FDA continues to state that acetaminophen is the only OTC analgesic/antipyretic with sufficient safety for pregnancy-NSAIDs and aspirin carry higher known risks for the fetus, especially after 20 weeks gestation.^{15 16}

---

Response to Recent Government Advisories

The September 2025 FDA statement, catalyzed by a White House announcement, notes that “a correlation” between acetaminophen and autism has been described in some studies, but explicitly says, “a causal relationship has not been established and there are contrary studies in the scientific literature.” ^{17 18} Experts and leading organizations are critical of any change in public messaging not reflecting robust, high-quality data.^{14 19}

Key takeaway: Despite increased scrutiny, regulatory and professional bodies worldwide continue to support acetaminophen as the safest analgesic/antipyretic during pregnancy when clinically indicated.

---

Limitations and Nuances in the Science

Quality and Limitations of the Evidence

Many published studies reporting associations suffered from significant methodological weaknesses, including:

• Heavy reliance on self-reported acetaminophen usage, resulting in recall biases.¹²
• Lack of standardized outcome definitions for diagnosis of ASD or neurodevelopmental disorders.
• Varied timing, dosage, and duration of prenatal exposure not reliably tracked/
• Insufficient adjustment for medication use, genetics, co-occurring conditions, socioeconomic status.
• Publication bias and selective outcome reporting.

In contrast, the highest-quality studies-large, prospective cohorts with registry-based data and sibling analyses-do not demonstrate an increased risk and, in fact, suggest that previously observed associations are artifacts of confounding.^{4 8 10}

Mechanistic Obstacles

Even the most rigorous reviews that discuss potential toxicology and experimental effects on fetal neurodevelopment in animals consistently acknowledge that such findings cannot be directly extrapolated to human developmental outcomes at approved doses.²

---

Autism: Causes and Diagnostic Trends Are Much Broader

Autism is a complex neurodevelopmental condition, with hundreds of genetic loci now identified as contributing risk. Heritability remains >70% for autism in most modern twin studies. Environmental risk factors-such as advanced parental age, preterm birth, prenatal infections, and metabolic disorders-have been implicated, often in conjunction with genetic risk.¹⁰

Current consensus among autism researchers is that the rising incidence of ASD worldwide is fueled primarily by broadened diagnostic criteria, earlier and better screening, increased awareness, and changes in societal attitudes, rather than shifts in environmental toxin or pharmaceutical exposure.^{1 10}

---

Warnings and Maternal-Fetal Side Effects of Acetaminophen Use During Pregnancy

Known Warnings

• Hepatotoxicity: Acetaminophen is generally well-tolerated at recommended doses. However, chronic overdose, intentional misuse, or accidental ingestion of large amounts can cause severe liver damage in the pregnant person, with secondary risk for the fetus.⁶
• Allergic reactions and skin reactions: Rare but possible.
• Medication interactions: Acetaminophen is an ingredient in many combination OTC cold and flu preparations; total daily intake should be monitored to avoid accidental overdose.
• Maternal risks: No increased risk observed for congenital anomalies, preeclampsia, or other common obstetric complications at normal doses.⁸
• Fetal risks: Current evidence does not suggest increased risk of birth defects, miscarriage, or neurodevelopmental disorders when acetaminophen is used appropriately during pregnancy. ^{4 16 20}
• Overdose risk: As with all populations, overdose can be life-threatening and should be managed as a medical emergency.

Pros and Cons of Acetaminophen Use During Pregnancy

Pros	Cons
Safest OTC pain/fever medication in pregnancy	Liver toxicity if overdosed
No known increased risk of congenital malformation at recommended doses	Possible weak association (not causation) with neurodevelopmental issue in smaller or less-controlled studies
Rapidly reduces fever (prevents maternal and fetal complications from hyperthermia)	May mask symptoms of more serious illness
No increased risk of preeclampsia, miscarriage, or stillbirth in large studies	Potential for accidental overdose with combination drugs
Well-tolerated for routine indications	Extremely rare hypersensitivity/alergic reactions

Clinical Context: The risk to mother and fetus from untreated fever or severe pain is well-documented and exceeds any theoretical risk from prudent acetaminophen use.^{6 8 16}

---

Alternatives to Acetaminophen for Pain Relief During Pregnancy

For readers seeking additional or alternative OTC pain relief options during pregnancy, several considerations must be noted:

NSAIDs (e.g., ibuprofen, naproxen, diclofenac, aspirin)

• Not recommended after 20 weeks of gestation, as all major regulatory and professional bodies warn of risks including decreased amniotic fluid, fetal kidney problems, and risk of premature closure of the ductus arteriosus.^{1 2 6}
• Aspirin: Low-dose aspirin (typically 81mg) is prescribed in specific clinical scenarios (e.g., preeclampsia prevention) and under close medical supervision.
• High-dose NSAIDs/aspirin: Associated with miscarriage, cardiac, renal, gastrointestinal, and bleeding risk for fetus/mother.

Opioids

• Strictly limited to specific indications; associated with fetal dependency, withdrawal symptoms in newborn, and increased risk for stillbirth and preterm delivery when used inappropriately.²¹

Topical Treatments

• Some topical analgesics (menthol, lidocaine, capsaicin) may be used in limited circumstances, but always under medical guidance due to limited human data.²¹

Non-pharmacological Approaches

• Physical/cooling methods for fever.
• Physical therapy, support garments, gentle stretching, and heat/cold compresses for pain.
• Rest, hydration, and sleep optimization.

---

Media, Public Discourse, and Unwarranted Anxiety

Recent media announcements and government guidance linking Tylenol® to autism have created anxiety and confusion among pregnant individuals and their providers. However, experts emphasize that such warnings are not supported by the totality of the scientific evidence. Communication should reflect nuance and accuracy, emphasizing the established safety of acetaminophen when used appropriately, the absence of proven causality, and the risks of untreated pain and fever during pregnancy.^{8 10 18}

Numerous autism research and advocacy groups-including the Autism Science Foundation and SARRC-continue to state there is no proven causal link between acetaminophen and autism, and that expectant parents should not be unduly alarmed by recent headlines.^{10 19}

---

Data backed recommendation

Acetaminophen should remain the first-line treatment for fever and pain relief during pregnancy when indicated, at the lowest effective dose and shortest necessary duration. Non-drug approaches and consultation with obstetrical care providers are always advised before using any medication.²¹

---

References (24)

1. Evaluation of the evidence on acetaminophen use ehjournal.biomedcentral.com
2.  Acetaminophen During Pregnancy: What the Research Really Says autismcenter.org
3. Using acetaminophen during pregnancy hsph.harvard.edu
4.  Mount Sinai Study www.mountsinai.org
5.  Prenatal and postnatal exposure to acetaminophen in relation to autism link.springer.com
6. Acetaminophen Use During Pregnancy and Children’s Risk of Autism jamanetwork.com
7.  No link between acetaminophen use during pregnancy drexel.edu
8.  Acetaminophen Use During Pregnancy and Children’s Risk Of Autism thesgem.com
9. Is Tylenol Safe During Pregnancy? health.clevelandclinic.org
10. Research doesn’t show using Tylenol during pregnancy causes autism www.pbs.org
11.  Systematic review: associations between acetaminophen during pregnancy   www.ehn.org
12.  Acetaminophen in Pregnancy  www.acog.org
13.  Acetaminophen (Tylenol) in Pregnancy: Relief or Risk? www.acsh.org
14.  Author of Study Linking Tylenol to Autism Says More Research Still Needed www.newsweek.com
15.  What the research says about autism and Tylenol use during pregnancy ysph.yale.edu
16.  ACOG Affirms Safety Benefits Acetaminophen Pregnancy www.acog.org
17.  SMFM Statement on Acetaminophen Use During Pregnancy and Autism  www.smfm.org
18.  SOGC Position Statement on the use of Acetaminophen sogc.org
19.  FDA recommends avoiding use of NSAIDs in pregnancy at 20 weeks or later  www.fda.gov
20.  FDA Responds to Evidence of Possible Association Between Autism and  Acetaminophen www.fda.gov
21.  Evidence Suggests Link Between Acetaminophen, Autism  www.whitehouse.gov
22.  Does Tylenol Cause Autism? Here’s What the Science Says www.healthline.com
23.  White House links Tylenol in pregnancy to autism; experts say evidence falls short  www.wtae.com
24.  What OTC Pain Relievers Are Safe to Take When Pregnant? www.verywellhealth.com

Chart References:

1. https://jamanetwork.com/journals/jama/fullarticle/2817406

2. SMFM Statement on Acetaminophen Use During Pregnancy and Autism. https://www.smfm.org/news/smfm-statement-on-acetaminophen-use-during-pregnancy-and-autism-

3. SOGC Position Statement on the use of Acetaminophen for Analgesia and …. https://sogc.org/common/Uploaded%20files/Position%20Statements/SOGC%20Position%20Statement%20Acetamenophin_EN_20250911.pdf

4. FDA Responds to Evidence of Possible Association Between Autism and …. https://www.fda.gov/news-events/press-announcements/fda-responds-evidence-possible-association-between-autism-and-acetaminophen-use-during-pregnancy

5. FACT: Evidence Suggests Link Between Acetaminophen, Autism. https://www.whitehouse.gov/articles/2025/09/fact-evidence-suggests-link-between-acetaminophen-autism/