The epidemiological trends of multiple sclerosis among women of child-bearing age: a global analysis from 1990 to 2021 and forecasts to 2040

Introduction: Multiple sclerosis (MS) shows marked female predominance, particularly among women of childbearing age (WCBA, 15-49 years), yet their specific disease burden remains under characterized. Using Global Burden of Disease (GBD) 1990-2021 data, we conducted the first comprehensive analysis of MS trends in WCBA globally, with projections to 2040, to guide targeted interventions for this vulnerable population. Methods: We analyzed age-standardized incidence (ASIR), prevalence (ASPR), mortality (ASMR), and disability-adjusted life years (ASDR) rates across 204 countries using GBD 2021 data. Our analytical approach incorporated Pearson correlation to examine Socio-demographic Index (SDI) relationships, decomposition analysis to identify burden drivers, and frontier analysis to assess disease control efficiency gaps. We employed Bayesian Age-Period-Cohort modeling alongside ARIMA for 20-year projections, with joinpoint regression analyzing temporal trends through annual percentage changes. Age-period-cohort effects were further disentangled through APC modeling, with stratification by age group, SDI level, and geographic region. Results: Between 1990-2021, WCBA experienced a 48% rise in MS incidence and 66% increase in prevalence, with mortality growing by 17% despite a 7% DALYs reduction. Age-standardized rates improved (ASMR:-0.35; ASDR:-0.3), though burden varied regionally: Australasia showed greatest incidence growth versus East Asia's decline, while Central Latin America led prevalence increases. High-SDI countries (>0.4) carried disproportionate burden, peaking at ages 45-49 (incidence:30-34 years). Projections indicate rising crude rates but falling ASDR. Low-SDI nations (e.g., Cambodia) demonstrated optimal control versus high-SDI underperformers (e.g., Sweden). Birth cohorts revealed generally declining risk (RR1.146→0.805) except 2002-2006(RR1.413), with elevated DALYs(20-25y) and prevalence(30-35y) warranting targeted action. Discussion: This study reveals key disparities in MS burden among WCBA, with high-SDI countries showing paradoxical high burden yet improvement potential. The 2002-2006 cohort rebound and persistent burdens in 30-49-year-olds highlight critical intervention windows. While low-SDI countries demonstrate unexpected control efficiency, rising crude rates globally underscore the growing women's health challenge of MS, particularly given projected prevalence increases. These findings advocate for tailored, age-specific management strategies.