This study utilized data from the Global Burden of Disease (GBD) 2021 study, which provides comprehensive health metrics for 204 countries and territories from 1990 to 2021 (17). We focused on data specific to reproductive-age women of advanced maternal age (35–49 years) with hypertensive disorders in pregnancy. MHD were defined according to the International Classification of Diseases codes: 642–642.9 in ICD-9 and O10–O16.9 in ICD-10, encompassing chronic hypertension, gestational hypertension, preeclampsia, and eclampsia (18). We categorized each country and territory into one of five Socio-demographic Index (SDI) quintiles based on their SDI values (19). The SDI is a composite measure reflecting development status, incorporating income per capita, average educational attainment, and total fertility rate. This classification facilitated the analysis of trends in MHD incidence and mortality across varying levels of socioeconomic development.

The GBD 2021 study employs rigorous methodologies for data collection and processing, as described in detail elsewhere (20). The study synthesizes a large and growing number of data input sources including surveys, censuses, vital statistics, and other health-related data sources. These data sources and detailed methodological information are publicly accessible through the Global Health Data Exchange (GHDx) Sources Tool (http://ghdx.healthdata.org/gbd-2021/sources). This interactive tool allows users to access specific methodological details for different GBD components, causes, risks, and locations.

We extracted age-standardized incidence and mortality rates as the primary metrics for assessing the burden of MHD. To calculate these rates for the 35–49 age group, we employed the direct standardization method using the GBD 2021 standard population as the reference (21). Age-specific incidence and mortality rates were obtained from our study population and weighted by the corresponding proportion of the GBD 2021 standard population for each age group (22). This approach ensured comparability across different populations by accounting for variations in age distribution. The final age-standardized rates were calculated by multiplying the age-specific rates by the standard population weights and summing the results across the relevant age groups.

We conducted a descriptive analysis of the age-standardized incidence and mortality rates across regions and countries. To assess temporal trends from 1990 to 2021, we performed joinpoint regression analysis to calculate the average annual percentage change (AAPC) and 95% confidence intervals (CIs) for each metric (23). Trends were considered significant if the 95% CI of the AAPC did not include zero. Trends were classified as increasing (both CI limits positive), decreasing (both CI limits negative), or stable (CI includes zero).

To assess inequalities in the distribution of MHD across countries, we employed two complementary measures: the concentration index and the slope index of inequality (SII).

The concentration index was calculated using the Lorenz curve approach to evaluate the unequal distribution of incidence and mortality rates across countries ranked by their gross domestic product (GDP) per capita (24). The concentration index ranges from −1 to 1, with negative values indicating a concentration of the health outcome among poorer countries and positive values indicating a concentration among wealthier countries. A value of 0 represents perfect equality.

For the SII, we modeled the age-standardized mortality rates against a relative social position scale based on GDP per capita using weighted least squares regression to account for heteroskedasticity (25). The SII represents the absolute difference in the health outcome between the hypothetical countries at the bottom and top of the socioeconomic spectrum. Both inequality measures were calculated for each year from 1990 to 2021 to assess changes in health inequalities over time.

All statistical analyses were performed using the Health Equity Assessment Toolkit from the World Health Organization (WHO), R version 4.4.1, and Stata version 16.0. We adhered to the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) (26).

The primary outcome measures were the age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR). ASIR represents the number of new cases of maternal hypertensive disorders per 100,000 population, adjusted for differences in age structure across populations and time periods. ASDR represents the number of deaths from maternal hypertensive disorders per 100,000 population, similarly age-standardized to allow for valid comparisons across different populations and time periods. From 1990 to 2021, the global ASIR of MHD decreased from 568.10 (95% UI: 412.06–738.55) to 491.49 (95% UI: 368.78–619.84) per 100,000 population, with an average annual percentage change (AAPC) of −0.46% (95% CI: −0.54% to −0.38%) (Figure 1A, Table 1). During the same period, the ASDR declined from 2.57 (95% UI: 2.23–2.97) to 1.44 (95% UI: 1.19–1.76) per 100,000 population, with an AAPC of −1.83% (95% CI: −1.99% to −1.67%) (Figure 1B, Table 1).

Significant disparities in disease burden were observed across Socio-demographic Index (SDI) regions. For ASIR, the low SDI region consistently showed the highest burden, though decreasing from 2,486.09 (95% UI: 1,905.51–3,019.84) per 100,000 population in 1990 to 1,605.80 (95% UI: 1,240.79–1,939.66) per 100,000 population in 2021, with an annual average percent change (AAPC) of −1.41% (95% CI: −1.46 to −1.36) (Table 1). In contrast, both high SDI and high-middle SDI regions showed increasing trends, with their ASIRs rising from 170.29 to 351.63 (AAPC: 2.36%, 95% CI: 2.24 to 2.47) and from 153.77 to 237.83 (AAPC: 1.45%, 95% CI: 1.32 to 1.59), respectively (Table 1). The middle SDI and low-middle SDI regions experienced decreasing trends, with AAPCs of −0.95% (95% CI: −1.07 to −0.83) and −2.18% (95% CI: −2.23 to −2.13), respectively (Table 1).

For ASDR, all SDI regions showed declining trends, but with varying magnitudes. The low SDI region maintained the highest ASDR, despite decreasing from 13.44 (95% UI: 11.13–15.97) per 100,000 population in 1990 to 6.14 (95% UI: 4.90–7.68) per 100,000 population in 2021 (AAPC: −2.47%, 95% CI: −2.56 to −2.38) (Table 1). The high-middle SDI region showed the most substantial decline (AAPC: −5.13%, 95% CI: −5.50 to −4.76), while the high SDI region maintained the lowest ASDR throughout the period, decreasing from 0.09 to 0.05 (AAPC: −1.87%, 95% CI: −2.35 to −1.38) (Table 1).

At the Global Burden of Disease (GBD) regional level, Western Sub-Saharan Africa had the highest ASIR in 2021 at 2,234.25 (95% UI: 1,780.30–2,613.28) per 100,000 population, while East Asia had the lowest at 103.89 (95% UI: 69.45–150.93) (Supplementary Table S1). In 2021, the highest ASDR was observed in Central Sub-Saharan Africa at 8.86 (95% UI: 5.65–13.14) per 100,000 population, with Central Europe showing the lowest at 0.01 (95% UI: 0.01–0.02) (Supplementary Table S1). From 1990 to 2021, Eastern Europe experienced the fastest increase in ASIR with an AAPC of 3.17% (95% CI: 2.93% to 3.40%), while South Asia saw the most rapid decrease with an AAPC of −3.21% (95% CI: −3.40% to −3.03%) (Supplementary Table S1). East Asia demonstrated the most rapid decrease in ASDR with an AAPC of −6.35% (95% CI: −7.01% to −5.68%). High-income North America was the only region among the 21 GBD regions that showed an increase in ASDR, with an AAPC of 1.3% (95% CI: 0.49% to 2.12%) (Supplementary Table S1).

At the national level, South Sudan had the highest ASIR in 2021 (3,404.51; 95% UI: 2,744.38–3,945.33), while Canada had the lowest (48.80; 95% UI: 32.15–75.37) (Supplementary Table S2, Supplementary Figure S1B). The Central African Republic had the highest ASDR (14.41; 95% UI: 7.74–24.58), whereas Slovenia had the lowest (0.002; 95% UI: 0.001–0.003) (Supplementary Table S2, SupplementaryFigure S1D). Between 1990 and 2021, Nepal showed the most substantial annual decline in ASIR (AAPC: −5.88%; 95% CI: −6.04% to −5.72%), while Czechia demonstrated the most substantial annual increase (AAPC: 5.45%; 95% CI: 5.12% to 5.79%) (Supplementary Table S2). Jordan exhibited the most substantial decrease in ASDR (AAPC: −11.34%; 95% CI: −11.72% to −10.96%), whereas Guam demonstrated the highest increase in ASDR (AAPC: 3.97%; 95% CI: 2.65% to 5.31%) over the study period (Supplementary Table S2).

A significant negative correlation was observed between MHD and socio-demographic development for both ASIR and ASDR across countries throughout the study period (1990–2021). For ASIR, the strength of the negative correlation between ASIR and SDI has gradually decreased over time, from ρ = −0.85 in 1990 to ρ = −0.65 in 2021 (P < 0.001) (Figures 2A,B, E), indicating that while countries with lower SDI generally exhibited higher incidence rates, this relationship has become relatively less pronounced over the past three decades. The correlation between ASDR and SDI has remained consistently strong throughout the study period (ranging from ρ = −0.89 in 1990 to ρ = −0.87 in 2021, P < 0.001) (Figures 2C,D and E), suggesting that ASDR decreased more consistently with increasing socio-demographic development.The temporal trend analysis further revealed that the correlation coefficient for ASIR steadily weakened over time, while that for ASDR remained relatively stable throughout the study period (Figure 2E), highlighting the divergent patterns in the relationship between socio-demographic development and disease incidence vs. mortality.

From 1990 to 2021, trends in ASIR varied across different SDI regions (Figure 3A). High SDI regions showed a consistent increase (AAPC: 2.36%). The trend accelerated from 1990 to 2014, peaking with an annual percent change (APC) of 3.35% during 2011–2014, before slightly decelerating to 2.90% from 2014 to 2021. High-middle SDI regions experienced overall growth (AAPC: 1.45%) but with fluctuations. After an initial decline (APC: −5.07%) from 1990 to 1994, the trend reversed, reaching a 5.66% annual increase from 2006 to 2015, before stabilizing and slightly declining in recent years. Middle SDI regions showed a slight overall decrease (AAPC: −0.95%), characterized by periods of decline from 1990 to 2001, followed by an increase (APC: 1.41%) from 2006 to 2015, and then declining again. Low-middle SDI regions demonstrated a consistent decrease (AAPC: −2.18%), with the most rapid decline (APC: −3.10%) between 1996 and 2004. Low SDI regions also showed an overall decrease (AAPC: −1.41%), with varying rates over time and the most rapid decrease (APC: −2.26%) observed from 2011 to 2014.

The ASDR exhibited a decreasing trend across all SDI regions from 1990 to 2021 (Figure 3B). High SDI regions experienced the smallest decline (AAPC: −1.87%), with periods of slower decrease (APC: −0.40% from 1998 to 2008) and more rapid decline (APC: −4.40% from 2016 to 2021). High-middle SDI regions showed the most substantial decrease (AAPC: −5.13%), with rapid declines (APC: −7.68%) from 1990 to 1992 and (APC: −6.69%) from 2017 to 2021. Middle SDI regions demonstrated a consistent decline (AAPC: −2.80%), with the most rapid decrease (APC: −5.68%) observed from 1990 to 1992. Low-middle SDI regions showed a steady decrease (AAPC: −2.59%), with rapid declines from 1990 to 1992 (APC: −4.39%) and from 2017 to 2021 (APC: −4.11%). Low SDI regions experienced a consistent decline (AAPC: −2.47%), with the rate of decrease accelerating in recent years (APC: −4.12% from 2017 to 2021).

Significant inequalities in the burden of MHD among reproductive-age women of advanced maternal age were observed across different SDI levels from 1990 to 2021. The ASIR showed a consistent decrease, with notable disparities between countries at different SDI levels. In 1990, the SII for ASIR was −3,052.73 (95% CI: −3,329.55 to −2,775.91) per 100,000 women, indicating substantial absolute inequality between countries with the lowest and highest SDI (Figure 4A). By 2021, the SII had reduced to −1,209.36 (95% CI: −1,393.12 to −1,025.61) per 100,000 women, representing a 60.4% reduction (Figure 4A).

The SII for ASDR showed a similar trend. In 1990, the SII was −11.29 deaths per 100,000 women (95% CI: −12.38 to −10.20), indicating that countries with the lowest SDI experienced approximately 11 more deaths per 100,000 women compared to those with the highest SDI (Figure 4B). By 2021, the SII had decreased to −3.66 deaths per 100,000 women (95% CI: −4.13 to −3.20) (Figure 4B). Although inequality persisted, it decreased over time. The consistently negative SII values indicate that the burden among reproductive-age AMA women was consistently higher in countries with lower SDI levels.

The concentration index for ASIR among reproductive-age AMA women indicated a disproportionate burden among poorer populations, with slight improvement over time. The global concentration index for incidence was −0.46 (95% CI: −0.55 to −0.37) in 1990, improving to −0.34 (95% CI: −0.42 to −0.25) in 2021 (Figure 4C). For ASDR, the concentration index showed a marginal increase in inequality, from −0.62 (95% CI: −0.74 to −0.50) in 1990 to −0.66 (95% CI: −0.76 to −0.55) in 2021 (Figure 4D).