Comment from Americans for Scientific Integrity

Americans for Scientific Integrity respectfully submits this comment in support of the request for a pregnancy warning regarding acetaminophen. We also wish to bring to the agency’s attention that our organization has filed a separate citizen petition addressing the need for a precautionary warning for pediatric use which can be viewed here https://www.regulations.gov/document/FDA-2025-P-6262-0001 and is also attached. These two petitions approach different parts of what is, biologically, a single exposure window that begins in pregnancy and continues through early childhood when antioxidant defenses and metabolic capacity are still developing. It is our view that evaluating pregnancy and pediatric use in isolation risks missing the cumulative and age specific vulnerabilities that arise across this full window. One reason this issue has remained unresolved for so long is that many pregnancy focused observational studies limit the exposure window to gestation alone. When a shortened window is used, analysts sometimes apply sibling control models to adjust for unmeasured confounding. This approach can attenuate or erase associations if the relevant exposure also occurs after birth during infancy and toddlerhood, because the sibling model assumes the exposure is confined to the measured period. If the true exposure window extends beyond pregnancy, applying a sibling comparison to a truncated window can give the appearance of no association even when exposure during early childhood remains relevant. For that reason, separating pregnancy and pediatric use methodologically has contributed to a fragmented understanding of risk. For these reasons, we request that the FDA consider reviewing the pregnancy petition and the pediatric petition together or in coordination so the agency can evaluate the full range of potential exposures relevant to neurodevelopment. We believe that an integrated review of the biological and epidemiologic evidence will provide the most accurate foundation for determining whether updated warnings are needed to inform caregivers and protect vulnerable children.