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This study aimed to analyse population-based mortality attributed to rare congenital anomalies (CAs) and assess the associated time trends and geographical differences in Spain. Data on CA-related deaths were sourced from annual mortality databases kept by the National Statistics Institute of Spain (1999⁻2013). Based on the ICD-10, only CAs corresponding to rare diseases definition were included in this study. Annual age-adjusted mortality rates were calculated and time trends were evaluated by joinpoint regression analysis. Geographical differences were assessed using standardised mortality ratios and cluster detection. A total of 13,660 rare-CA-related deaths (53.4% males) were identified in the study period. Annual age-adjusted mortality rates decreased by an average of -5.2% (-5.5% males, -4.8% females, p &lt; 0.001). Geographical analysis showed a higher risk of rare-CA-related mortality in regions largely located in the south of the country. Despite their limitations, mortality statistics are essential and useful tools for enhancing knowledge of rare disease epidemiology and, by extension, for designing and targeting public health actions. Monitoring rare-CA-related mortality in Spain has shown a 15-year decline and geographical differences in the risk of death, all of which might well be taken into account by the health authorities in order to ensure equality and equity, and to adopt appropriate preventive measures.

A Nationwide Registry-Based Study on Mortality Due to Rare Congenital Anomalies