FDA Starts an Acetaminophen-in-Pregnancy Label Change (2025)

Table of Contents

1. What the FDA Did
2. What the Label Change Is Meant to Reflect
3. What the Notice to Physicians Says
4. Causation Not Established: The FDA’s Own Caveats
5. The Two Studies the FDA Names
6. Other Published Research on the Question
7. Fever in Pregnancy and the Other Pain Relievers the FDA Mentions
8. What the Action Does Not Do
9. Dates and Status as of 11 October 2026
10. How It Fits Other FDA Actions of 2025
11. Primary Documents
12. Key Research Papers
13. Connections

1. What the FDA Did

The FDA took two steps on 22 September 2025:

• A press release titled “FDA Responds to Evidence of Possible Association Between Autism and Acetaminophen Use During Pregnancy,” with the subtitle “Agency initiates safety label change and notifies physicians of possible link.” It states that the FDA “today initiated the process for a label change for acetaminophen” covering acetaminophen and similar products.
• A letter to physicians, the “Notice to Physicians on the Use of Acetaminophen During Pregnancy,” dated 22 September 2025 and signed by Martin A. Makary, M.D., M.P.H., Commissioner of Food and Drugs. The press release describes it as “a related letter alerting physicians nationwide.”

Neither step was published in the Federal Register, the U.S. government’s daily journal of proposed and final rules, and neither opened a public docket (a numbered file that collects public comments). The action is a safety communication plus the start of a labeling process, not a rulemaking.

The press release quotes the Commissioner: “The FDA is taking action to make parents and doctors aware of a considerable body of evidence about potential risks associated with acetaminophen. Even with this body of evidence, the choice still belongs with parents. The precautionary principle may lead many to avoid using acetaminophen during pregnancy, especially since most low-grade fevers don’t require treatment. It remains reasonable, however, for pregnant women to use acetaminophen in certain scenarios.”

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2. What the Label Change Is Meant to Reflect

A drug’s label is the official text that travels with it: for an over-the-counter (OTC) medicine, the “Drug Facts” panel on the package; for a prescription drug, the prescribing information written for clinicians. Changing it is how the FDA puts safety information in front of everyone who buys or prescribes the product.

According to the press release, the label change is meant to reflect “evidence suggesting that the use of acetaminophen by pregnant women may be associated with an increased risk of neurological conditions such as autism and ADHD in children.” Autism (autism spectrum disorder) is a developmental condition affecting social communication and behaviour; ADHD (attention-deficit/hyperactivity disorder) affects attention, activity and impulse control. Both are described on the site’s Autism, Autism Spectrum Disorder and ADHD pages.

The press release does not give the proposed label wording, does not say which acetaminophen products or which parts of the label would change, and does not give a timetable for completing the change. It says only that the process was initiated.

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3. What the Notice to Physicians Says

The letter has three short paragraphs. In order, it states:

1. The concern. “In recent years, evidence has accumulated suggesting that the use of acetaminophen by pregnant women may be associated with an increased risk of neurological conditions such as autism and ADHD in children.” It adds that some studies “have described that the risk may be most pronounced when acetaminophen is taken chronically throughout pregnancy to childbirth,” and that the concerns “may be magnified by the fact that a very young child’s liver may still be developing and thus a child’s ability to metabolize the drug may be limited.”
2. The limits of the evidence. “To be clear, while an association between acetaminophen and autism has been described in many studies, a causal relationship has not been established and there are contrary studies in the scientific literature.” The letter calls the association “an ongoing area of scientific debate” and says clinicians should be aware of the issue in their decision-making, “especially given that most short-term fevers in pregnant women and young children do not require medication.”
3. The FDA’s guidance to clinicians. “In the spirit of patient safety and prudent medicine, clinicians should consider minimizing the use of acetaminophen during pregnancy for routine low-grade fevers.” The letter says this consideration “should also be balanced with the fact that acetaminophen is the safest over-the-counter alternative in pregnancy among all analgesics and antipyretics; aspirin and ibuprofen have well-documented adverse impacts on the fetus.”

Analgesics are pain relievers and antipyretics are fever reducers. The letter is addressed to clinicians and frames its guidance as something for them to weigh; it sets no dose limit and no number of days.

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4. Causation Not Established: The FDA’s Own Caveats

The difference between an association and a cause is the centre of this debate. An association means two things are found together more often than chance would predict — for example, children whose mothers reported taking acetaminophen in pregnancy being diagnosed with ADHD somewhat more often. A cause means one thing actually produces the other. An association can arise without causation when a third factor drives both: the illness, fever, pain or infection that led a mother to take the medicine, or genes and family circumstances shared by mother and child. Researchers call this confounding.

Both FDA documents make the same three statements on this point:

• a causal relationship “has not been established” (press release and letter);
• “there are contrary studies in the scientific literature” (press release and letter);
• the association is “an ongoing area of scientific debate” (letter).

The press release adds that “while an association between acetaminophen and neurological conditions has been described in many studies,” causation has not been shown. The FDA therefore describes a possible risk under study, not a demonstrated harm.

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5. The Two Studies the FDA Names

The press release says “multiple large-scale cohort studies, including the Nurses’ Health Study II and the Boston Birth Cohort, find this association,” and links each name to a PubMed record. A cohort study follows a group of people over time and compares outcomes between those who were and were not exposed to something. The two linked papers, as their own abstracts describe them:

• Nurses’ Health Study II (Liew and colleagues, 2019). Among 8,856 children born 1993–2005 to women in this long-running U.S. cohort, with acetaminophen use collected prospectively in questionnaires every two years, 721 children (8.1%) had an ADHD diagnosis reported by their mothers. Acetaminophen use at the time of pregnancy was associated with ADHD (odds ratio 1.34, 95% confidence interval 1.05–1.72). The paper used a “negative control” design: use in the periods about four years before and four years after the pregnancy showed no association, which the authors say provides assurance that unchanging family factors do not explain the finding. The outcome studied was ADHD, not autism.
• Boston Birth Cohort (Ji and colleagues, 2020). In 996 mother–infant pairs followed at a Boston hospital from 1998 to 2018, the researchers measured acetaminophen and its breakdown products in umbilical-cord blood collected at birth, rather than relying on mothers’ recall. Compared with the lowest third of cord acetaminophen levels, the highest third was associated with higher odds of a physician-diagnosed ADHD (odds ratio 2.86) and autism spectrum disorder (odds ratio 3.62). The authors concluded that the findings “support previous studies” and “warrant additional investigations.”

An odds ratio above 1 means the outcome was more common in the exposed group; it does not by itself show the exposure caused it. Both papers are observational, as the FDA’s own caveat about causation reflects.

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6. Other Published Research on the Question

The FDA documents refer to “contrary studies” without naming them, and name only the two studies above as supporting the association. The papers below are not cited in the FDA documents; they are included here, each with its own stated conclusion, because they are among the most-cited analyses on both sides of the debate.

• Meta-analysis of cohort studies (Masarwa and colleagues, 2018). Pooling seven cohorts with 132,738 mother–child pairs, the authors found pooled risk ratios of 1.34 for ADHD and 1.19 for autism spectrum disorder. They wrote that the findings “are concerning” but that results “should be interpreted with caution” because the evidence is observational and “susceptible to several potential sources of bias.”
• Consensus statement (Bauer and colleagues, 2021). An international group of scientists and clinicians summarised experimental and epidemiological evidence that prenatal exposure “might alter fetal development” and called for “precautionary action” through focused research and greater awareness, while stating that acetaminophen “is an important medication and alternatives for treatment of high fever and severe pain are limited.” The statement was followed by several published letters in reply in the same journal.
• Swedish nationwide sibling study (Ahlqvist and colleagues, 2024). In 2,480,797 children born in Sweden 1995–2019, with acetaminophen use recorded during pregnancy in antenatal and prescription records, standard models showed a marginally higher risk of autism (hazard ratio 1.05) and ADHD (1.07). When the researchers compared full siblings — one exposed in pregnancy, one not — to account for shared genes and family environment, there was no association with autism (0.98), ADHD (0.98) or intellectual disability (1.01), and no dose–response pattern. The authors concluded that associations seen in other models “may have been attributable to familial confounding.”
• Navigation Guide review (Prada and colleagues, 2025). Applying a structured evidence-rating method to 46 studies, the authors counted 27 reporting positive associations, 9 null and 4 negative, and wrote that higher-quality studies were more likely to show positive associations. They concluded that the evidence is “consistent with an association” and called for steps to advise limiting use in pregnancy.

The studies differ in how they measured exposure (mothers’ reports, prescription records or cord blood), in which outcome they studied, and in how they handled confounding. That disagreement is the “ongoing area of scientific debate” the FDA letter describes.

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7. Fever in Pregnancy and the Other Pain Relievers the FDA Mentions

Both FDA documents set the possible risk against the risks of the alternatives:

• The press release states that acetaminophen “is the only over-the-counter drug approved for use to treat fevers during pregnancy, and high fevers in pregnant women can pose a risk to their children.”
• Both documents state that “aspirin and ibuprofen have well-documented adverse impacts on the fetus.”
• The letter calls acetaminophen “the safest over-the-counter alternative in pregnancy among all analgesics and antipyretics.”
• The letter notes that “most short-term fevers in pregnant women and young children do not require medication,” and the Commissioner’s quoted statement says “most low-grade fevers don’t require treatment.”

The FDA’s focus, as worded in the letter, is “routine low-grade fevers.” Neither document defines a low-grade fever by temperature. Background on fever itself is on the site’s Fever page.

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8. What the Action Does Not Do

• It does not remove acetaminophen from sale or restrict over-the-counter purchase.
• It does not state a causal finding: the FDA says causation “has not been established.”
• It does not itself change any label. The press release says the label-change process was initiated; no completed label revision was found in an FDA primary document as of 11 October 2026.
• It is not a rule. Nothing was published in the Federal Register and no public comment docket was opened.
• It does not say acetaminophen cannot be used in pregnancy. The Commissioner’s quoted statement says it “remains reasonable … for pregnant women to use acetaminophen in certain scenarios,” and the letter’s guidance concerns “routine low-grade fevers.”
• It makes no statement about acetaminophen given to children after birth, beyond the letter’s remark about the developing liver of a very young child and that most short-term fevers in young children do not require medication.

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9. Dates and Status as of 11 October 2026

• 22 September 2025: press release announces that the label-change process has been initiated; Notice to Physicians issued the same day.
• Status as of 11 October 2026: label change initiated. No FDA primary document was found confirming that the label change has been finalized or approved, and no Federal Register document exists for it. This page therefore reports the change as initiated only.

The legal status of acetaminophen itself is unchanged: it remains an approved over-the-counter and prescription medicine.

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10. How It Fits Other FDA Actions of 2025

The acetaminophen action was announced on the same day, 22 September 2025, as a separate FDA action on leucovorin for cerebral folate deficiency, which the FDA describes as a neurological condition affecting folate transport into the brain. That action is reported on its own page, FDA Moves to Approve Leucovorin for Cerebral Folate Deficiency (2025).

Neither acetaminophen document refers to earlier FDA statements on acetaminophen in pregnancy, so this page does not describe any. Among the agency’s other 2025 labeling actions, a July 2025 change concerned extended-release ADHD stimulants in children under 6 (FDA Label Change for Extended-Release ADHD Stimulants Under Age 6 (2025)). The full year is listed on the FDA Actions of 2025 hub.

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11. Primary Documents

1. U.S. Food and Drug Administration (2025). FDA Responds to Evidence of Possible Association Between Autism and Acetaminophen Use During Pregnancy. FDA News Release, 22 September 2025. Not published in the Federal Register; no docket — fda.gov press announcement
2. U.S. Food and Drug Administration (2025). Notice to Physicians on the Use of Acetaminophen During Pregnancy. Letter signed by Martin A. Makary, M.D., M.P.H., Commissioner of Food and Drugs, 22 September 2025. Not published in the Federal Register; no docket — fda.gov letter (PDF)

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Key Research Papers

1. Liew Z, Kioumourtzoglou MA, Roberts AL, O’Reilly ÉJ, Ascherio A, Weisskopf MG (2019). Use of negative control exposure analysis to evaluate confounding: an example of acetaminophen exposure and attention-deficit/hyperactivity disorder in Nurses’ Health Study II. American Journal of Epidemiology 188(4):768-775 — PubMed PMID: 30923825
2. Ji Y, Azuine RE, Zhang Y, Hou W, Hong X, Wang G, Riley A, Pearson C, Zuckerman B, Wang X (2020). 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 77(2):180-189 — PubMed PMID: 31664451
3. Masarwa R, Levine H, Gorelik E, Reif S, Perlman A, Matok I (2018). Prenatal exposure to acetaminophen and risk for attention deficit hyperactivity disorder and autistic spectrum disorder: a systematic review, meta-analysis, and meta-regression analysis of cohort studies. American Journal of Epidemiology 187(8):1817-1827 — PubMed PMID: 29688261
4. Bauer AZ, Swan SH, Kriebel D, Liew Z, Taylor HS, Bornehag CG, Andrade AM, Olsen J, Jensen RH, Mitchell RT, Skakkebaek NE, Jégou B, Kristensen DM (2021). Paracetamol use during pregnancy — a call for precautionary action. Nature Reviews Endocrinology 17(12):757-766 — PubMed PMID: 34556849
5. Ahlqvist VH, Sjöqvist H, Dalman C, Karlsson H, Stephansson O, Johansson S, Magnusson C, Gardner RM, Lee BK (2024). Acetaminophen use during pregnancy and children’s risk of autism, ADHD, and intellectual disability. JAMA 331(14):1205-1214 — PubMed PMID: 38592388
6. Prada D, Ritz B, Bauer AZ, Baccarelli AA (2025). Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology. Environmental Health 24(1):56 — PubMed PMID: 40804730

Papers 1 and 2 are the two studies linked from the FDA press release; papers 3–6 are not cited in the FDA documents.

PubMed Topic Searches

1. PubMed: prenatal acetaminophen and autism
2. PubMed: prenatal acetaminophen and ADHD
3. PubMed: paracetamol in pregnancy, neurodevelopment and sibling analyses
4. PubMed: maternal fever in pregnancy and neurodevelopmental outcomes

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Connections

• FDA Actions of 2025
• FDA and Regulation
• FDA Moves to Approve Leucovorin for Cerebral Folate Deficiency (2025)
• FDA Label Change for Extended-Release ADHD Stimulants Under Age 6 (2025)
• Acetaminophen Overdose
• Autism
• Autism Spectrum Disorder (ASD)
• ADHD (Attention-Deficit/Hyperactivity Disorder)
• Fever (Pyrexia)

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