SGEM#485: I Want a New Drug – One Not Associated with Neurodevelopmental Disorders

Date: Sept 16, 2025 Reference: Prada et al. Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology. Environ Health. August 2025 Guest Skeptic: Dr. Andrew Martin is an emergency physician practicing in Jacksonville, Florida.  Case: A 27-year-old at 24 weeks’ gestation presents to the emergency department (ED) with fever (38.6 °C), myalgias, and sore throat. She took 650 mg of acetaminophen (Tylenol) six hours ago with partial relief. She hesitated to repeat the dose after reading online posts about “Tylenol and autism.” She has no abdominal pain, no vaginal bleeding, and normal fetal movement. Vitals otherwise stable; pharynx erythematous, no exudate. She asks, “Is it safe to take another dose, or could this hurt my baby’s brain later?” Background: Acetaminophen (paracetamol) is the most used analgesic–antipyretic in pregnancy. A recent prospective cohort study suggests ~40 to 65% of pregnant people report using it. They are typically using acetaminophen for headache, myalgias, or fever, with most use being short and intermittent. Alternatives, particularly non-steroidal anti-inflammatory drugs (NSAIDs), carry well-described fetal risks in late gestation. This is one of the reasons why acetaminophen remains the default first-line choice [1,2]. Biologically, acetaminophen crosses the placenta and achieves fetal levels like maternal levels, making the developing brain theoretically exposed during critical windows [3]. This has motivated a large observational literature examining whether prenatal exposure is linked to later neurodevelopmental outcomes such as ADHD and autism. Meta-analyses generally report small associations (summary effects around 1.2 to 1.3) and signal stronger effects with longer duration of use, though heterogeneity in exposure measurement and outcome ascertainment is substantial.  Professional bodies, including the American College of Obstetricians and Gynecologists (ACOG) and the Society of Obstetricians and Gynecologists of Canada [SOGC], continue to recommend acetaminophen for appropriate indications at the lowest effective dose and shortest duration. At the same time, they do acknowledge ongoing research and the limitations of observational data (including confounding by indication). For emergency clinicians, the practical tension is familiar. The dilemma is that untreated maternal fever and significant pain can themselves harm pregnancy, yet patients are increasingly asking about possible long-term neurodevelopmental potential harms of using acetaminophen.  Clinical Question: Is acetaminophen exposure during pregnancy associated with ADHD, ASD, or other neurodevelopmental disorders (NDDs) in children? Reference: Prada et al. Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology. Environ Health. August 2025 Population: Observational studies assessing children of pregnant individuals for neurodevelopmental outcomes. Excluded: Postnatal exposures, non-human studies for the primary analysis, non-original publications, and duplicate reports from the same cohort. Exposure: Prenatal acetaminophen (maternal self-report, biomarkers such as meconium/cord blood, or medical records/prescription registries). Comparison: Children who were not exposed prenatally to acetaminophen, or those exposed to alternative analgesics. Outcome: Primary Outcome: NDDs (particularly ADHD and ASD) and related symptomatology measured by clinical diagnoses, medication use, or validated behavioural scales. Secondary Outcomes: Timing and dose–response patterns, broader cognitive/behavioural domains (language & executive function), and triangulation across design types. Type of Study: Systematic review using the Navigation Guide methodology with a qualitative synthesis (no meta-analysis) due to substantial heterogeneity.