Evaluation of Anti-HBs Levels in Children Who Received Three Doses of Hepatitis B Vaccine According to Age Groups and Gestational Age: A Retrospective Single-Center Cross-Sectional Study

Background Anti-HBs levels decline after infant hepatitis B vaccination, especially during school age and adolescence, but data evaluating both age and gestational age-related effects in a large pediatric cohort remain limited. Methods In this retrospective, single-center, cross-sectional study, we included 6,510 children aged 9 months–18 years who had completed three hepatitis B vaccine doses and had at least one quantitative anti-HBs measurement between 2021 and 2023. Seronegativity was defined as anti-HBs < 10 mIU/mL. Children were grouped by age (9 months–5 years, 6–11 years, 12–18 years) and gestational age (early preterm < 32 weeks, late preterm 32–36⁺⁶ weeks, term ≥ 37 weeks). Comparisons used Kruskal–Wallis, chi-square, ANCOVA, and logistic regression. Results Overall seronegativity was 30.6% (1,989/6,510), and the median anti-HBs level was 34.30 mIU/mL (IQR 6.72–143.23). Anti-HBs levels decreased significantly with age (medians 99.17, 23.94, and 12.55 mIU/mL for the 9 months–5 years, 6–11 years, and 12–18 years groups; p < 0.001), while seronegativity increased (14.4%, 33.9%, and 45.5%; p < 0.001). Age group was the strongest independent predictor of seronegativity (6–11 years: OR 3.218, 95% CI 2.521–4.108; 12–18 years: OR 5.348, 95% CI 4.183–6.839). Among 4,242 children with gestational age data, gestational age was not independently associated with seronegativity after adjustment (p = 0.109), and seronegativity rates were comparable across groups (34.5% early preterm, 25.8% late preterm, 36.9% term; p = 0.168). In children born at term, mean anti-HBs was 525.05 ± 401.31 mIU/mL at ≤ 3 years versus 74.99 ± 143.60 mIU/mL at ≥ 4 years. Conclusion Anti-HBs levels decline significantly with age after three-dose hepatitis B vaccination, whereas gestational age is not an independent predictor of seronegativity. Targeted serological follow-up and individualized booster strategies, particularly for high-risk groups, may be warranted.