Objective: In 1985, the hepatitis B (HB) vaccination strategy against mother-to-child HB virus infection was introduced in Japan, involved HB vaccinations at 2, 3, and 5 months of age (delayed method). From December 2013, the schedule was changed to those at birth, 1, and 6 months of age (infants weighing <2000 g at birth receive an additional dose at 2 months of age, non-delayed method). Our objective was to compare the immunogenicity and mother-to-child HB virus infection rates between these methods in infants born to mothers with positive test results for serum hepatitis B surface antigen (HBsAg).
Subjects and Methods: This multicenter observational cohort study with Institutional Review Board approval included 264 infants born to mothers with positive test results for serum HBsAg between 2008 and 2017. We excluded 42 infants with lack of parental consent for HB vaccinations or those lost to follow-up. Finally, we investigated 222 infants. Notably, 136 and 86 infants received delayed and non-delayed HB vaccinations, respectively. Seropositive immunogenic response was defined as serum anti-HBs titers ?10 mIU/mL. Positive serum HBsAg status was decided using a cut-off value that each manufacturer recommended (considered positive mother-to-child HB virus infection). 
Results: No significant intergroup difference was observed in the clinical background of mothers and infants, except the age at which the serum anti-HBs titer and HBsAg were evaluated (median age 192 and 333 days, respectively, p<0.001). Seropositive immunogenic response rates were 136/136(100%) and 84/86 (98%) in the delayed and non-delayed groups, respectively (p=0.87). Post-vaccination serum HBsAg positivity rates did not differ significantly (0/136 [0%] and 2/86 [2.3%] in the delayed and non-delayed groups, respectively, p=0.88).
Conclusions: Seropositive immunogenic response and mother-to-child HB virus infection rates were similar between the delayed and non-delayed methods. Two infants did not prevent a mother-to-child HB virus infection in the non-delayed method.