Predictors of seronegativity to HBV vaccine in infants of HBsAg-positive mothers in a national prevention program.

Abstract

Background & aims: Seronegativity following perinatal hepatitis B prophylaxis increases the risk of horizontal infection. This study analyzed 20 years of data from the Korean Perinatal Hepatitis B Prevention Program (PHBPP) to identify factors associated with hepatitis B vaccine seronegativity after immunoprophylaxis in infants born to HBsAg-positive mothers.

Methods: The study population comprised 233,455 mother-infant pairs from 2002 to 2021, identified by linking the PHBPP database with National Health Insurance Service data. Among the 154,351 pairs with initial post-vaccination serologic testing (PVST) results, 150,709 pairs were analyzed, excluding 3,642 cases of mother-to-child transmission (immunoprophylaxis failure). Multivariable logistic regression was used to analyze factors associated with seronegativity.

Results: Overall, 11.3% of infants were seronegative at the initial PVST, with the proportion decreasing from 15.1% in 2002 to 4.2% in 2021. Higher seronegativity was associated with delayed PVST (7.8% at <10 months, 15.6% at 10-19 months, and 31.3% at ≥20 months post-vaccination), preterm birth, cesarean section, and maternal HBeAg-negative status without antiviral prophylaxis. Seronegativity varied by birth weight: 10.6% (≥3,000 g), 12.7% (2,500-2,999 g), 15.7% (2,000-2,499 g), and 14.5% (<2,000 g with four doses).

Conclusions: Timely PVST, full-term gestation, appropriate birth weight, vaginal delivery and maternal antiviral prophylaxis are associated with robust vaccine immunogenicity. To enhance program effectiveness, strict adherence to the recommended PVST timing is crucial, and extending the four-dose schedule to infants weighing 2,000-2,499 g warrants consideration.

Impact and implications: By analyzing a 20-year nationwide cohort of over 150,000 mother-infant pairs, this study establishes a robust scientific basis for the 9-15 month post-vaccination serologic testing window, demonstrating it as an optimal balance between clinical accuracy and practical healthcare access. Furthermore, we identified a specific immune vulnerability in infants weighing 2,000-2,499 g, suggesting that extending the four-dose vaccination schedule to this group is warranted to ensure optimal protection. These insights can directly inform global public health policies and optimize strategies toward achieving the WHO 2030 HBV elimination goals.