Persistence of antibody to hepatitis b surface antigen and reported post-vaccination symptoms in young children with glucose-6-phosphate dehydrogenase deficiency: a comparative cross-sectional study

We compared persistence of antibody to hepatitis B surface antigen (anti-HBs) and retrospectively reported post-vaccination symptoms between young children with glucose-6-phosphate dehydrogenase (G6PD) deficiency and healthy controls. This comparative cross-sectional study was conducted in Heyuan, China, from March 2024 to January 2025. G6PD deficiency was enzymatically confirmed. Controls were frequency-matched by sex, with body mass index used for group-level balancing. Vaccination histories were obtained from records; parents retrospectively reported six common symptoms within 30 days after each hepatitis B vaccine dose. Anti-HBs was measured at enrolment. Primary persistence analyses included children sampled at least 6 months after dose 3. Risk differences and risk ratios with 95% confidence intervals (CIs) were estimated. Modified Poisson and linear regression used robust standard errors and adjusted for age, sex, body mass index, time since dose 3, and vaccine product. The study included 505 children (55 with G6PD deficiency; 450 controls); 98.2% were aged 1–4 years. The mean interval from dose 3 to sampling was approximately 30 months. Primary analyses included 54 and 438 children, respectively. Seroprotection (anti-HBs ≥10 mIU/mL) was 87.0% versus 82.2% (risk difference, 4.8 percentage points; 95% CI, −7.1 to 12.4; adjusted risk ratio, 1.07; 95% CI, 0.96–1.19). The adjusted association between G6PD deficiency and log2(anti-HBs concentration+1) was not statistically significant (β = −0.04; 95% CI, −0.68 to 0.59; P = 0.90). At least one symptom was reported in 5/55 (9.1%) versus 19/450 (4.2%) children (P = 0.17). No statistically detectable differences in anti-HBs seroprotection, antibody concentrations, or retrospectively reported common post-vaccination symptoms were observed. These findings do not establish equivalence. The long recall interval and lack of systematic ascertainment of hemolysis-related and serious clinical outcomes preclude conclusions regarding G6PD-specific vaccine safety. Larger prospective multicentre cohorts incorporating genotype, quantitative G6PD activity, standardized serological follow-up, and active safety surveillance are needed.