Hepatitis B virus (HBV) mother-to-child transmission (MTCT) remains a global health concern, with over 90% of perinatal infections leading to chronic HBV. To evaluate long-term trends in MTCT rates and associated factors within Korea's national program. Population-based cohort study using linked data from the Perinatal Hepatitis B Prevention Program (PHBPP) and National Health Insurance Services in Korea. The study included HBsAg-positive mother-infant pairs with post-vaccination serologic results from 2002 to 2021. Among the 154,478 mother-infant pairs, the overall MTCT rate after prophylaxis was 2.3%. Antiviral use lowered MTCT rates (0.9% vs 2.4%) particularly in HBeAg-positivity (1.0% vs 5.9%; aOR, 0.21; 95% CI, 0.14-0.32). Lower MTCT rates were observed for cesarean-section vs vaginal delivery (1.9% vs 2.6%; aOR, 0.78; 95% CI, 0.73-0.84) and breastfeeding vs formula feeding (1.8% vs 2.8%; aOR, 0.65; 95% CI, 0.56-0.76). Annual MTCT rates decreased from 3.6% (2002-2005) to 1.3% (2018-2021). Antivirals reduced MTCT rates; initiation at 14-27 weeks (0.39%), or 28-32 weeks (0.44%) vs ≥33 weeks (1.47%); postpartum continuation (0.55%) vs antepartum discontinuation (1.44%); use ≥61 days (0.51%) vs 1-60 days (1.67%). Lower MTCT risk was associated with maternal (old age, high income) and infant (female sex, pre-term birth) factors. This comprehensive analysis of the PHBPP in Korea demonstrates that the use of antivirals, breastfeeding, and cesarean section, combined with conventional immunoprophylaxis, has significantly reduced MTCT rates. These results are crucial for global HBV elimination and can help to guide HBV MTCT prevention strategies.
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