🧭 REBEL Rundown
👉 Bottom Line Up Top
Acetaminophen is the safest choice for the treatment of pain and/or fever in pregnancy. There is no clear evidence of a relationship between acetaminophen use in any trimester of pregnancy and fetal developmental issues.
🤕 Case
A 25 year old G1P0 woman at 27 weeks gestation presents with 2 days of fever, cough and nasal congestion. Vital signs are significant for a temperature of 101.2 °F and the patient’s exam is otherwise unremarkable. You diagnose her with a viral syndrome and recommend rest, fluids and acetaminophen for fever. However, the patient expresses reluctance in taking acetaminophen due to reported links with the development of autism for her fetus.
🗣️ What Your Gut Says
Acetaminophen is fine in pregnancy, right?
📝 Introduction
In the first trimester, fever is associated with increased risk of birth defects such as cleft lip and palate, as well as serious neural-tube defects such as spina bifida and anencephaly. In late pregnancy, fevers can boost the risk of miscarriage, stillbirth, and preterm birth (Antoun 2021). Acetaminophen is the most commonly used antipyretic/analgesic medications with up to 62% of women using it during pregnancy (Bandli 2020). The drug does cross the placenta making it important to research fetal effects, particularly neurodevelopmental disorders (NDDs) including autism, ADHD and intellectual disability. For decades, the American College of Obstetrics and Gynecology (ACOG) has recommended acetaminophen as the safest antipyretic/analgesic during pregnancy (ACOG 2021).
📈 What The Evidence Says
Unfortunately, the majority of data available on the topic is of low to moderate quality. Because it would be unethical to perform a randomized controlled trial, we are left with observational cohort studies. Regardless of how well designed these studies are, they cannot show a causal link.
Pearl #1: There is NO data showing a causal relationship between acetaminophen exposure and the development of NDDs.
A recent publication combining data from observational studies touted a consistent association between acetaminophen exposure and NDDs. However, this publication contains a number of methodological flaws that bias the results (The SGEM).
The best data available comes from a Swedish national database (Ahlqvist 2024). The study looked at over 185,000 children who were exposed to acetaminophen during pregnancy and found a small increase in NDDs in that group. However, after comparing exposed patients to siblings (sibling control analysis) the association disappeared. Additionally, the researchers did not find any association between increasing doses of acetaminophen exposure and NDDs. The authors conclude,
“Acetaminophen use during pregnancy was not associated with children’s risk of autism, ADHD, or intellectual disability in sibling control analysis. This suggests that associations observed in other models may have been attributable to familial confounding.”
A large Japanese birth cohort study (> 217,000 children) echoes these findings noting that small differences in NDDs are likely attributable to confounding and misclassification (Okubo 2025).
Based on this data, ACOG continues to recommend acetaminophen in pregnancy as the safest treatment for pain and fever (ACOG 2025).
💬 Our Conclusion
The best available data shows no association between acetaminophen exposure in pregnancy and neurodevelopmental disorders including autism.
🚨 Clinical Bottom Line
Clinicians should continue to feel safe in treating pregnant patients with acetaminophen and pregnant patients should feel safe taking acetaminophen for pain or fever during any phase of pregnancy.
📚 References
- Antoun S 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. PMID: 34537069
- Bandoli G, Palmsten K, Chambers C. Acetaminophen use in pregnancy: Examining prevalence, timing, and indication of use in a prospective birth cohort. Paediatr Perinat Epidemiol. 2020; 34(3):237-246. PMID: 31696962
- Prada D et al. Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology. Environ Health 2025; 24(1); 56. PMID: 40804730
- Ahlqvist VH et al. Acetaminophen Use During Pregnancy and Children’s Risk Of Autism, ADHD, And Intellectual Disability. JAMA 2024; 331 (14): 1205-14. PMID: 38592388
- Okubo Y et al. Maternal Acetaminophen Use and Offspring’s Neurodevelopmental Outcome: A Nationwide Birth Cohort Study. Pediatr perinat epidemiol 2025. PMID: 40898607
Post Peer Reviewed By: Mark Ramzy, DO (X: @MRamzyDO), and Marco Propersi, DO (X: @Marco_Propersi)
👤 Associate Editor
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