Analyzing the Data: Does Acetaminophen in Pregnancy Cause Autism?

By: Amanda Kastel, PharmD Candidate c/o 2027

On September 22, 2025, President Donald Trump and HHS Secretary Robert F. Kennedy Jr. held a press conference that sparked widespread confusion among medical professionals and the public. Roughly three minutes into the briefing, President Trump announced that the FDA would notify physicians about a “very increased risk” of autism associated with acetaminophen use during pregnancy. He further urged expectant mothers not to take the medication due to this alleged risk. As current and future medical professionals, it is crucial to understand the actual evidence behind this claim – especially since it concerns the health of a particularly vulnerable population: pregnant patients.

What the Data Says

To make their claim, RFK and his team cited a systematic review of 46 studies.¹ Of the 46 studies included, only 8 studied an association between acetaminophen and autism spectrum disorder (ASD). It is important to note that all studies included in the review were observational – either cohort or case control designs – which means causation cannot be established. Moreover, the studies demonstrated significant heterogeneity in several key areas such as how acetaminophen exposure was defined, the timing of exposure during pregnancy, and the dose and duration of use.

Out of the 8 studies, 5 utilized self-reported maternal data^2,3,4,5,6 to define acetaminophen exposure, while others measured maternal cord blood⁷. Liew et al² used a retrospective recall method to collect data. In this study, 6-month postpartum mothers were asked whether they had used acetaminophen during pregnancy, when they took it, and how long they took it for. This is a weak method of data collection, as it depends entirely on maternal memory, opening the door for recall bias and potential exposure misclassification.

Ji, et al⁷ determined acetaminophen exposure by measuring maternal cord blood for acetaminophen and its metabolites. While this approach eliminates recall bias, there are still significant concerns with this study design. Being that the half-life of acetaminophen is only 2-3 hours long and the cord blood is measured at birth, this method only accounts for exposure very late in pregnancy and does not account for any acetaminophen exposure early in pregnancy (1^st and 2^nd trimesters), a time much more crucial for fetal neurodevelopment.

These inconsistencies make it difficult to pool the data to draw a definitive, single conclusion. The authors of the systematic review acknowledge this substantial heterogeneity and therefore correctly choose not to perform a quantitative meta-analysis. While the decision makes sense, without a meta-analysis, the magnitude of association between acetaminophen use and autism cannot be quantified using statistics, resulting in a much weaker, more subjective conclusion.

A Sibling Control Analysis Refutes the Claim

Numerous reliable studies have demonstrated that autism spectrum disorder has a genetic component attached to it.^8,9 Therefore, in a study attempting to establish an association between ASD and acetaminophen use, it is crucial to account for this genetic confounder to ensure legitimate, unbiased results.

In the systematic review cited by RFK Jr. and his team, the only study to control for genetics was a large-scale cohort study¹⁰ conducted in Sweden between 1995-2019. This study examined over 2.4 million births to evaluate the risk of acetaminophen exposure during pregnancy and the development of various neurodevelopmental disorders including ASD, ADHD, and intellectual disability. Acetaminophen exposure was determined through midwife interviews starting at 8-10 weeks gestation, supplemented by prescription data (2005 onward). The study accounted for numerous confounders, including genetics, using a sibling-controlled design. In the analysis where they did not account for sibling relationships, the results showed a small but statistically significant increase in the risk of autism with prenatal acetaminophen exposure (HR, 1.05 [95% CI, 1.02-1.08]; e-value, 1.28). However, once the genetic component was considered, the association was no longer observed (HR, 0.98 [95% CI, 0.93-1.04]), with similar results observed for ADHD and intellectual disability. These findings indicate that apparent associations between prenatal acetaminophen exposure and autism are likely attributable to genetic factors, rather than causal effects of the medication.

Clinical Implications

Even before the September 22 press conference, it has always been clinical practice for expectant mothers to use any medication, including acetaminophen, only when necessary and at the lowest effective dose and shortest possible duration, due to the delicate biological state of pregnancy and risk-benefit considerations. Organizations such as the American College of Obstetricians and Gynecologists (ACOG), the American Academy of Pediatrics (AAP), and the World Health Organization (WHO), have emphasized this principle for decades.

During the press conference, President Trump stated there is “no downside” to not taking acetaminophen in pregnancy. However, prolonged or uncontrolled maternal fever can pose real risks to the fetus, including neural tube defects¹¹, congenital heart defects¹², and even neurodevelopmental disorders such as autism.¹³ The language used in the press conference may generate unnecessary fear in expectant mothers, potentially leading to serious damage as a result of avoiding acetaminophen when medically needed.

Conclusion

Based on the evidence, the medical consensus regarding acetaminophen use in pregnancy remains unchanged. Acetaminophen continues to be considered the first-line, safest option for treating maternal pain and fever. As with all medications in pregnancy, expectant mothers should consult with their doctor or pharmacist to ensure the safety of both mother and baby.

References

1. Prada D, Ritz B, Bauer AZ, et al. Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology. Environ Health. 2025;24:56. doi:10.1186/s12940-025-01208-0
2. Liew Z, Ritz B, Rebordosa C, Lee P-C, Olsen J. Acetaminophen use during pregnancy, behavioral problems, and hyperkinetic disorders. JAMA Pediatrics. 2014;168(4):313-320. doi:10.1001/jamapediatrics.2013.4914
3. Alemany S, Avella-García C, Liew Z, 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. Eur J Epidemiol. 2021;36(10):993-1004. doi:10.1007/s10654-021-00754-
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7. Ji Y, Azuine RE, Zhang Y, et al. Association of cord plasma biomarkers of in utero acetaminophen exposure with risk of attention-deficit/hyperactivity disorder and autism spectrum disorder in childhood. JAMA Psychiatry. 2020;77(2):180–189. doi:10.1001/jamapsychiatry.2019.3259
8. Sandin S, Lichtenstein P, Kuja-Halkola R, Larsson H, Hultman CM, Reichenberg A. The heritability of autism spectrum disorder. JAMA. 2017;318(12):1182–1184. doi:10.1001/jama.2017.12161
9. Gaugler T, Klei L, Sanders SJ, et al. Most genetic risk for autism resides with common variation. Nat Genet. 2014;46(8):881–885. doi:10.1038/ng.3039
10. Ahlqvist V, 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;331(14):1205-1214. doi:10.1001/jama.2024.3172
11. Organization of Teratology Information Specialists (OTIS). MotherToBaby Fact Sheets. Fever/Hyperthermia. Brentwood, TN: OTIS; 1994–. Updated February 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK582757/
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13. Antoun S, Ellul P, Peyre H, et al. Fever during pregnancy as a risk factor for neurodevelopmental disorders: results from a systematic review and meta-analysis. Mol Autism. 2021;12(1):60. Published 2021 Sep 18. doi:10.1186/s13229-021-00464-4