Professor University of North Texas Denton, United States
Background: Acetaminophen [N-acetyl-p-aminophenol (APAP)] use is common worldwide, with 65% of US pregnant women reporting use. APAP is one of the major causes of pregnancy liver failure. Evidence is increasing for offspring neurodevelopmental effects. Few studies have reported on cancer outcomes, with conflicting findings, however the studies which collected medication use via medical record were more likely to observe increases in cancer risk, whereas the studies which relied on maternal recall more often found null results.
Objectives: To determine associations between maternal pregnancy APAP intake and risk for childhood cancers.
Methods: In Taiwan, all medications prescribed by a physician are free under the national health insurance plan; all medications, including both prescription and over-the-counter, can only be obtained at pharmacies. The Taiwan Maternal and Child Health Database (births 2004-2015; N=2,269,893 mother-child pairs) links the Taiwanese Birth Certificate Register and the Registry for Beneficiaries of the National Health Insurance Database, including the Pharmaceutical Register which records every prescription filled at a pharmacy in Taiwan. We linked these databases to the national Cancer Registry and ascertained all children with cancer diagnosed 2004-2016 (N=2143). Mothers who filled prescriptions for APAP during pregnancy were considered exposed (66.6%). We used Cox proportional hazards modeling to estimate hazard ratios (HR) and 95 confidence intervals (CI) for offspring cancer, adjusting for parental ages and socioeconomic status. We examined trimesters separately along with use across pregnancy.
Results: Maternal APAP use ever in pregnancy (HR=1.03, CI 0.93-1.13) and in all 3 trimesters (HR=1.08, 95% CI 0.94-1.23) was not associated with childhood cancer overall (all cancers combined). With regards to specific cancers, pregnancy APAP was associated with medulloblastoma (3rd trimester: HR=2.15, 95% CI 1.01-4.57; all three trimesters: HR=2.55, CI 1.16-5.58). Increases were also seen for hepatoblastoma (all three trimesters: HR=1.73, 95% CI 0.97-3.10) and bone tumors (all 3 trimesters: HR=1.89, 95% CI 0.95-3.78).
Conclusions: Results suggest increased risk for specific cancers with pregnancy APAP use, particularly for chronic use across trimesters. Although confounding by indication is a possibility, prior studies have not linked medulloblastoma, hepatoblastoma, or bone tumors with pregnancy infections. Our findings add to the debate regarding APAP safety in pregnancy.
