Exposure to acetaminophen (paracetamol) during pregnancy and childhood cancer: a population-based cohort study in Taiwan

Background: The safety of using acetaminophen (paracetamol) during pregnancy has been questioned due to concerns about its potential negative impact on fetal development and the risk of adverse pediatric outcomes. We aimed to investigate whether maternal prescriptions of acetaminophen during pregnancy are associated with childhood cancer. Methods: We conducted a population-based cohort study in Taiwan using data from the Maternal and Child Health Database linked to additional registries to identify children diagnosed with cancer between 2004-2017. Cox proportional hazard models were used to estimate effects. Probabilistic bias analysis was conducted to address potential biases and validate our findings. Results: The cohort consisted of 2,269,384 mother-child pairs, among whom 2,754 childhood cancer cases were identified. The main analysis did not yield sufficient evidence to conclude that acetaminophen exposure during pregnancy increases the risk of all childhood cancer. However, regular use of acetaminophen throughout all trimesters suggested an increase in the risk of medulloblastoma (adjusted hazard ratio [HR]=2.43; 95% confidence interval [CI] 1.10-5.39), hepatoblastoma (adjusted HR=1.73; 95% CI 0.97-3.10), and bone tumors (adjusted HR=1.85; 95% CI 0.92-3.72). Probabilistic bias analysis supported positive effects. Conclusions: Although this study did not show a strong association between acetaminophen prescription during pregnancy and many childhood cancers, the results for regular use and three types of rare childhood cancer raise concern. Impact: Further research is needed to replicate these findings and to explore potential underlying mechanisms.