Objectives: To evaluate the trends in mortality for early- and late-onset neonatal sepsis, as well as the attributable risk factors at global, regional and national levels from 1990 to 2021. Early-onset sepsis occurs within 0-6 days after birth, whereas, late-onset sepsis occurs between 7 and 27 days of life.

Methods: Data on deaths from early- and late-onset neonatal sepsis, as well as the proportion attributable to risk factors, was sourced from the Global Burden of Disease Study (GBD) 2021. Temporal trends in mortality rates were assessed using estimated annual percentage changes.

Results: In 2021, global deaths from early- and late-onset neonatal sepsis totalled 136 040 and 70 411, respectively, corresponding to mortality rates of 5549.9 and 965.3 per 100 000 population. Both early- and late-onset neonatal sepsis mortality declined from 1990 to 2021, with a more pronounced reduction in late-onset sepsis. However, total deaths increased in low-SDI regions, driven by early-onset sepsis. The highest mortality rates were observed in Sub-Saharan Africa, particularly in Western and Eastern Sub-Saharan Africa. In 2021, short gestation (gestational age < 38 weeks) and low birth weight (< 2500 g) were responsible for 29.6% and 66.3% of neonatal sepsis deaths globally. Mortality rates showed an inverse correlation with SDI, with higher-SDI regions experiencing faster reductions in mortality.

Conclusions: Neonatal sepsis remains a major global health challenge, particularly in low-SDI regions. Interventions targeting preterm birth, low birth weight and healthcare infrastructure are urgently needed.