Prenatal Acetaminophen Exposure and Autism Risk: A Narrative Review of the Evidence, Mechanisms and Clinical Implications
Peter Aduvie Josiah
*
Department of Medicine and Surgery, College of Health Sciences, Niger Delta University, Bayelsa State, Nigeria.
Olukunle O. Akanbi
Department of Psychology and Behavioral Sciences, National Louis University, FL, USA.
Oluwabusayo Baliquees Salau
Department of Nursing, Bowie State University, MD, USA.
Peter Achem Shaibu
School of Graduate Studies, Lingnan University, Hong Kong.
Ava-Gay Annakaye Morgan
Department of Curriculum and Instruction, College of Education, Texas Southern University, Houston, TX, USA.
*Author to whom correspondence should be addressed.
Abstract
Acetaminophen (also known as paracetamol or Tylenol) is the most widely used analgesic and antipyretic during pregnancy and is globally recommended as the first-line treatment when needed. In recent years, observational studies and high-profile regulatory statements have linked prenatal acetaminophen exposure to neurodevelopmental disorders, such as autism spectrum disorder (ASD). These developments have created uncertainty among clinicians and pregnant individuals regarding established pain and fever management practices.
The aim of this narrative review is to synthesize evidence from large cohort studies, meta-analyses, and mechanistic research to evaluate the strength, consistency, and clinical relevance of these associations, with a view to providing clear guidance based on current evidence. Although some cohort studies report modestly increased relative risks, these associations are substantially weakened or eliminated in more rigorous study designs, particularly sibling-controlled analyses. This pattern strongly suggests that confounding factors, such as genetic predisposition, shared family traits, and indication bias related to the underlying reasons for acetaminophen use, may account for the observed associations.
Proposed biological mechanisms, including oxidative stress, prostaglandin inhibition, endocrine disruption, and epigenetic modifications leading to altered gene expression, are theoretically plausible but lack convincing evidence at therapeutic doses in humans. There are also indications that any potential risk may be associated primarily with excessive and/or prolonged use. In contrast, the risks of untreated maternal fever and pain during pregnancy are well established.
Overall, current evidence does not support avoiding acetaminophen when clinically indicated during pregnancy. Recommended practice includes judicious use at the lowest effective dose for the shortest possible duration, shared decision-making, and careful individualized risk–benefit assessment. Further research using robust designs, particularly sibling-comparison studies, is needed to better inform clinical practice and regulatory guidance.
Keywords: Acetaminophen, pregnancy, neurodevelopmental disorders, confounding, sibling-controlled analyses