Trends in Neonatal and Postneonatal Respiratory-Related Mortality in the United States, 1999–2020: A National Analysis by Sex, Urbanization, and Region

Background Respiratory conditions are a leading cause of infant mortality in the United States, particularly during the first year of life. Distinct etiologies underlie respiratory-related deaths in neonatal (0–27 days) versus post-neonatal (28–364 days) periods, necessitating age-specific analyses. Despite overall declines in infant mortality, disparities in respiratory-related deaths persist across demographic and geographic subgroups. Methods This retrospective observational study used CDC WONDER mortality data from 1999 to 2020 to examine trends in respiratory-related deaths among U.S. infants. Crude mortality rates (CMRs) per 100,000 live births were calculated separately for neonates and post-neonates. Joinpoint regression analysis was employed to evaluate temporal trends, with stratification by sex, urbanization level (metropolitan vs. non-metropolitan), and U.S. Census region. Results Over the 22-year period, 96,165 neonatal and 53,623 post-neonatal respiratory deaths were reported. Neonatal CMR declined from 1.33 to 1.01 (AAPC: − 1.25%, p < 0.001), with the most significant reduction from 2006–2011. Post-neonatal mortality fell more steeply from 0.83 to 0.47 (AAPC: − 2.77%, p < 0.000001). Males consistently exhibited higher mortality than females in both age groups. While mortality declined across all urbanization levels, non-metropolitan areas exhibited persistently higher rates. Geographic disparities were also evident, with the South showing the highest mortality burden throughout. Conclusion Respiratory-related infant mortality in the U.S. significantly declined from 1999 to 2020, with more pronounced improvements in post-neonatal than neonatal populations. Persistent disparities by sex, geography, and urbanization highlight the need for targeted public health interventions to further reduce preventable infant deaths. These findings underscore the importance of stratified surveillance and intervention strategies to address underlying socio demographic inequities.