Acetaminophen (Paracetamol) in Pregnancy and Child Neurodevelopment: What the Latest “Gold-Standard” Review Means for Practice

Acetaminophen (Paracetamol) remains the most commonly used OTC analgesic/antipyretic worldwide and is frequently taken during pregnancy for fever and pain. In September 2025, U.S. federal messaging reignited concerns about a potential association between prenatal acetaminophen exposure and neurodevelopmental disorders (NDDs), particularly autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD).

A newly published systematic review and meta-analysis in The Lancet Obstetrics, Gynaecology & Women’s Health re-examined this question using a methodologically stricter approach than many prior observational syntheses. The bottom line: when the evidence base is restricted to the most robust designs — especially sibling-comparison studies and analyses with stronger bias control — there is no credible signal supporting a causal link between Acetaminophen use in pregnancy and ASD, ADHD, or intellectual disability.

Why this review is considered “gold-standard”?

Earlier studies suggesting associations were largely conventional observational cohorts and are highly vulnerable to confounding by indication (i.e., the reason acetaminophen was used—fever, infection, inflammation, pain—may itself be associated with adverse outcomes) and to familial/genetic confounding.

To address these limitations, the review:

• Prioritized cohort designs with defined exposure assessment (biomarkers, medical records, or self-report) and validated outcome ascertainment.
• Extracted adjusted estimates where available.
• Included sibling-comparison studies, which help control for shared familial factors (genetics, socioeconomic context, home environment).
• Assessed study quality with the QUIPS tool and stratified results by risk of bias.

This analytic strategy directly targets the core weakness of earlier syntheses: residual confounding and heterogeneity that can exaggerate apparent risk signals.

Key findings (clinically relevant summary)

Across the strongest evidence strata—particularly:

• Sibling-comparison analyses,
• Studies rated low risk of bias,
• Studies reporting adjusted estimates,
• Cohorts studies with longer follow-up (e.g., >5 years),

The review found no association between prenatal acetaminophen exposure and ASD, ADHD or Intellectual disability. In practical terms, the more rigorously the analysis controlled for familial and clinical confounding, the more the purported “signal” attenuated toward null.

Why the public message became contentious in late 2025 ?

U.S. health communications in September 2025 publicly emphasized “mounting evidence” and signaled possible new cautionary guidance. These statements drew criticism because they appeared to move beyond what the best causal-inference evidence could support at the time, while major professional groups reiterated that acetaminophen has an important role in pregnancy when used appropriately.

What should we talk to our patients?

A balanced counseling script for antenatal care:

• Reassure on neurodevelopmental risk (based on best current evidence):The most methodologically rigorous human evidence does not support a causal relationship between acetaminophen in pregnancy and ASD/ADHD/intellectual disability.  
• Do not encourage fear-driven avoidance—untreated fever matters: Fever and significant pain in pregnancy are not benign; risk–benefit discussions should account for harms of undertreatment as well as medication exposure.
• Use remains “prudent, not prohibited.”: Consistent with common professional guidance: use only when clinically indicated, at the lowest effective dose for the shortest necessary duration, and avoid inadvertent duplication from combination cold/flu products. (This is particularly important because acetaminophen appears in many OTC and Ethical combinations.

Conclusion

In late 2025,  messaging amplified concern, but high-quality evidence does not support a causal link between prenatal acetaminophen exposure and ASD/ADHD/intellectual disability. The “signal” seen in some older observational studies is plausibly explained by residual confounding, particularly underlying maternal illness prompting acetaminophen use. To improve clinical practice and patient safety:  reassure, contextualize, and counsel on prudent use—and do not overlook the risks of untreated maternal fever/pain.

Source

MedicalNewsToday - access January 2026