Abstract: Background：The Food and Drug Administration(FDA) Adverse Event Reporting System (FAERS) is an open database. After the outbreak of COVID-19, it is important to further evaluate the potential safety signals associated with the use of ibuprofen and acetaminophen. This is crucial for improving safety and protecting public health. Objective：To provide references for the clinical discovery, prevention, and management of adverse events (AEs) in children by performing signal detection of AEs related to ibuprofen and acetaminophen in children using the FAERS database. Design：Data mining analysis. Methods：The OpenVigil 2.1 software was used to extract AE reports with ibuprofen or acetaminophen as primary or secondary suspect drugs in patients aged ≤17 years, without restriction on gender or country. The reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) were used for signal detection. The AE reports were analyzed based on gender, country, year, and age groups (≤3 years, -11 years, and -17 years). The detected potential risk signals were classified according to SystemOrgan Classes (SOC) based on the Preferred Terms in the Medical Dictionary for Regulatory Activities. The changes in strong and mediumstrong potential risk signals were analyzed before and after the COVID-19 pandemic. Main outcome measures：Strong and mediumstrong potential risk signals before and after COVID-19. Results：A total of 7,552 (53.5 percent) reports were related to ibuprofen and 6,562 reports were related to acetaminophen in the FAERS database from the first quarter of 2004 to the third quarter of 2022. The number of AE reports for acetaminophen was higher in females, while the number of AE reports for ibuprofen was higher in males, with statistically significant differences. The number of AE reports for ibuprofen was higher than that for acetaminophen in the ≤3 years and -11 years age groups, while the number of AE reports for acetaminophen was higher than that for ibuprofen in the -17 years age group, with statistically significant differences. The United States accounted for 42.8% of ibuprofen-related AE reports and 41.7% of acetaminophen-related AE reports. Among the top 10 countries reporting AE, except for the United States and China, all were European countries. There were 358 potential risk signals for ibuprofen, including 2 strong signals, 58 medium-strong signals, and 298 weak signals. For acetaminophen, there were 283 potential risk signals, including 6 strong signals, 48 medium-strong signals, and 229 weak signals. Ibuprofen had more signals detected in the gastrointestinal system, skin and subcutaneous tissue, infectious and parasitic diseases, renal and urinary system, respiratory system, thorax, and mediastinum, and eye disorders by SOC compared to acetaminophen. Acetaminophen had more signals detected in the hepatobiliary system, psychiatric disorders, investigations, general disorders and administration site conditions, and nervous system disorders by SOC compared to ibuprofen. Three strong signals for ibuprofen were detected before the COVID-19 pandemic, including angioedema, extra dose administered, and accidental exposure to product. No strong signals were detected after the pandemic. However, attention should be paid to the change from weak to medium-strong signals in renal interstitial nephritis, acute kidney injury, nephrotic syndrome, toxic nephropathy, and membranous glomerulonephritis in the renal and urinary system disorders by SOC. Four strong signals for acetaminophen were detected before COVID-19, including liver necrosis, liver injury, acute liver failure, and liver failure. No strong signals were detected after the pandemic. However, attention should be paid to the medium-strong signals of suicide attempt, drug dependence, and drug abuse in the psychiatric disorders by SOC. Conclusion：Physicians, pharmacists, and patients are encouraged to actively report potential safety signals associated with the use of ibuprofen and acetaminophen, as there is an increased risk of renal adverse events with ibuprofen and an increased risk of intentional poisoning and suicide events with acetaminophen.

Key words: Ibuprofen, Acetaminophen, Adverse event, Drug safety, Signal detection, COVID-19, Antipyretic