Acetaminophen remains first-line medication for pain, fever in pregnancy

In an updated clinical guidance statement published on June 1, 2026, in Pregnancy, the Society for Maternal-Fetal Medicine (SMFM) reaffirmed that acetaminophen remains the recommended first-line medication for managing pain and fever during pregnancy. Following a comprehensive review of recent and historical scientific literature, the Society concluded that the available data do not establish a causal relationship between prenatal acetaminophen exposure and an increased risk of autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD) in children.^1,2

Acetaminophen is often utilized during pregnancy, with large surveys indicating that up to 65% of pregnant individuals take the medication at some point, primarily to treat headaches and fevers. It serves as the active ingredient in numerous over-the-counter and prescription formulations, including Tylenol. While some observational studies have flagged small potential associations with childhood neurodevelopmental issues, SMFM emphasized that these papers feature substantial design limitations that preclude drawing conclusions about direct causality.

Limitations in observational research

The updated statement noted that the broader body of epidemiological evidence is complicated by widespread heterogeneity in how child outcomes are measured, varying from parent-reported behavioral checklists to clinician-verified registry data. Furthermore, studies face significant exposure misclassification because they rely on maternal recall collected postpartum, which rarely tracks the exact dosage, frequency, or trimester timing of medication use.

A primary challenge in this research is confounding by indication, meaning that the underlying maternal illnesses prompting the use of the drug—such as active infections, high fevers, or severe migraines—can independently impact fetal neurodevelopment through inflammatory or metabolic pathways. When studies attempt to employ stricter sibling-comparison models or genetically informed cohort designs that account for shared family environments and parental polygenic risk scores, the previously observed links to ADHD and ASD generally disappear. This indicates that heritable genetic traits and familial factors, rather than the medication itself, drive the modest relative risk increases (which average 1.2 to 1.3 for ADHD and 1.1 to 1.2 for ASD in pooled meta-analyses), according to data published in Pregnancy.
“These modest associations are accompanied by moderate-to-substantial heterogeneity and persistent residual confounding, particularly by maternal illness, fever, infection, and genetic predisposition,” wrote the statement authors. “These findings emphasize the broader limitations of meta-analyses, which remain constrained by the methodological weaknesses of the included studies.”

“After another careful review of the existing research, we continue recommending acetaminophen as a safe treatment for our pregnant patients who need it for pain relief and to reduce fever,” said Judette M. Louis, MD, MPH, chair of the SMFM Publications Committee.

Documented risks of untreated clinical conditions

The guidance emphasizes that avoiding necessary treatment carries severe, well-documented fetal and maternal health risks.

"Both untreated fever and pain during pregnancy carry potential health risks, so you shouldn’t just ‘tough it out’," Louis said. "Untreated fever, particularly in the first trimester, is known to be linked to birth defects and miscarriage. We also know that maternal fever during labor can be associated with poor neonatal outcomes." In addition to miscarriage and congenital anomalies, maternal fever during labor is linked to:

• Low Apgar scores
• Neonatal sepsis
• Neonatal intensive care unit (NICU) admission.

SMFM advised against utilizing common alternative systemic medications like nonsteroidal anti-inflammatory drugs (NSAIDs) or opioids as first-line options due to their distinct safety profiles. NSAIDs are known to increase the risk of fetal renal impairment, oligohydramnios, premature closure of the fetal ductus arteriosus, and maternal bleeding. Meanwhile, opioid use during pregnancy is linked to neonatal abstinence syndrome, maternal sedation, and addiction.

Counseling pregnant patients on acetaminophen use

For optimal clinical practice, the statement recommends that patients use the lowest effective dose of acetaminophen for the shortest duration necessary. Clinicians are urged to counsel patients to carefully review ingredient labels on multi-symptom cold and flu products to avoid accidentally exceeding the maximum safe adult threshold of 4000 mg per day. Finally, the Society noted that nonpharmacological strategies, such as physical therapy, rest, and hydration, should be integrated alongside frontline pharmaceutical therapies to holistically manage maternal pain.

This article was originally published by our sister publication Contemporary OB/GYN.

References:

1. SMFM reaffirms acetaminophen as first-line medication for treating pain and fever during pregnancy. Society for Maternal-Fetal Medicine. News release. Published June 1, 2026. Accessed June 1, 2026. https://www.smfm.org/news/smfm-reaffirms-acetaminophen-as-first-line-medication-for-treating-pain-and-fever-during-pregnancy

2. SMFM Publications Committee (2026). Society for Maternal-Fetal Medicine Statement: Acetaminophen use during pregnancy. Pregnancy. doi:10.1002/pmf2.70318