Demographic Transition and Maternal Ageing Are Associated with Increasing Mortality from Chromosomal Abnormalities in Brazil: A Nationwide Longitudinal Multilevel Time-Series Study (2004–2023)

Background : Brazil has undergone a rapid demographic transition marked by sustained fertility decline and progressive maternal ageing. Although advanced maternal age is a well-established risk factor for chromosomal abnormalities, the population-level implications of demographic ageing for mortality attributable to these conditions remain insufficiently explored, particularly in middle-income countries. Methods : We conducted a nationwide ecological longitudinal study using Brazilian mortality and demographic data from 2004 to 2023. Deaths attributed to chromosomal abnormalities (ICD-10: Q90–Q99) were analyzed in relation to trends in total fertility rate, age-specific fertility rates, and population ageing indicators. Mortality trends were assessed using time-series methods, including linear regression with autocorrelation diagnostics, Prais–Winsten regression, and ARIMA modeling. Population-adjusted analyses were performed using generalized linear models with log link and population offset, with negative binomial regression applied to account for overdispersion. Multilevel mixed-effects models were used to evaluate regional heterogeneity. Results : Between 2004 and 2023, 20 883 deaths were attributed to chromosomal abnormalities, corresponding to 0.08% of all deaths nationwide. Annual deaths increased by 114.5%, rising from 682 to 1 463 cases. Mortality exhibited a bimodal age distribution, with 58.25% of deaths occurring in the first year of life and a secondary peak between 50 and 64 years of age. Population-adjusted analyses demonstrated a significant increasing trend in mortality rates over time. In negative binomial models adjusted for population size, each additional calendar year was associated with an approximate 3.0% increase in mortality (incidence rate ratio ≈ 1.03; p < 0.001). Concurrently, total fertility declined, while age-specific fertility rates increased among women aged 30–44 years. Indicators of population ageing were strongly associated with mortality trends, and multilevel models identified demographic ageing as the principal driver of regional variation. Conclusions : During Brazil’s demographic transition, progressive maternal and population ageing were consistently associated with increasing mortality from chromosomal abnormalities at the population level. These findings suggest that demographic ageing may structurally influence the burden of chromosomal disorders in ageing societies. This study provides the first nationwide longitudinal evidence linking demographic ageing indicators to chromosomal abnormality mortality in a middle-income country.