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Objective To analyze the status of non-response to hepatitis B vaccine and its related factors in children born to mothers infected with hepatitis B virus (HBV). Methods The children born to mothers with HBV infection reported in Hunan Province from January to December 2022 were selected. All the children received hepatitis B immunoglobulin injection and 3 doses of hepatitis B vaccination and were followed up to 7-12 months of age for detection of hepatitis B surface antigen (HB-sAg) and anti-HBs. Both HBsAg and anti-HBs were negative, indicating that there was no response to hepatitis B vaccine in children. Unconditional binary logistic regression model was used to analyze the related factors of non-response to hepatitis B vaccine in children. Results A total of 9 792 children born to mothers infected with HBV were analyzed. Among 9 792 children, the non-response rate of hepatitis B vaccine was 9.5% (928/9 792). Non-conditional binary Logistic regression analysis showed that the risk of non-response to hepatitis B vaccine in children born to HBeAg-positive mothers was 1.62 times higher than that in children born to HBeAg-negative mothers (OR=1.62, 95% CI: 1.40-1.88). The risk of non-response to hepatitis B vaccine in children with macrosomia (birth weight ≥ 4 000g) was 1.41 times higher than that in children with normal birth weight (OR = 1.41, 95% CI: 1.08-1.85). Maternal antiviral therapy (OR=0.59, 95% CI: 0.48-0.73) and child HepB standard vaccination (OR=0.66, 95% CI: 0.57-0.78) were the protective factors of non-response to hepatitis B vaccine in children. Conclusion The non-response rate of hepatitis B vaccine in children born to HBV infected mothers is high, and it is affected by maternal HBeAg positive, antiviral therapy during pregnancy, birth weight, and standard vaccination. [ABSTRACT FROM AUTHOR]