Global, regional and national burden of infections among pregnant women, 1990–2021: a prospective cohort study
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* Siqiao Wang
* Shun Chen
* Meiyi Chen
* Wei Xu
* Zhourui Wu
* Xiao Hu
* Chen Li
* Zhihui Xiao
* Bei Ma
* Liming Cheng

## Abstract

**Objectives** We aimed to analyse the trends, age distribution and disease burden of maternal sepsis and other maternal infections (MSMI) to improve management strategies.

**Design** We extracted data from the global burden of disease (GBD) 2021 database to evaluate MSMI burden with different measures for the whole world, 21 GBD regions and 204 countries from 1990 to 2021.

**Setting** Studies from the GBD 2021 database generated by population-representative data sources identified through a literature review and research collaborations were included.

**Participants** Patients with an MSMI diagnosis.

**Outcomes** Total numbers, age-standardised rates (ASRs) of incidence, prevalence, mortality and disability-adjusted life years (DALYs) on MSMI from the GBD 2021 study and their estimated annual percentage changes (EAPCs) were the primary outcomes.

**Results** There were 19 047 404 (95% uncertainty interval (UI) 14 608 563 to 24 086 486) annual incident cases, 2 376 876 (95% UI 1 678 868 to 3 421 377) prevalent cases at a single time point, 17 665 (95% UI 14 628 to 21 191) death cases and 1 144 233 (95% UI 956 988 to 1 352 034) DALYs of total MSMI in 2021. From 1990, the case number and ASRs of incidences and prevalence showed decreasing trends, while the case number and ASRs of mortality and DALYs gradually increased with time, reaching the peak in 2001, and then declined. In 2021, the ASRs of incidence, prevalence, mortality and DALYs sharply increased with age, which reached the peak in the 20–24 age group. The ASRs were decreased with increasing sociodemographic index (SDI). In 2021, it showed a positive correlation between EAPC and ASR of DALYs (r=0.3398, p<0.001).

**Conclusions** The disease burden in low-SDI regions far exceeded that of regions with higher SDI. The persistent disparities in the burden of MSMI between low- and high-SDI regions underscore the urgent need for context-specific interventions, including targeted healthcare infrastructure investments in central and western sub-Saharan Africa, integration of WHO’s Maternal Sepsis Guidelines into national policies, and prioritisation of antenatal care access for women aged 20–24 years. These strategies align with sustainable development goals to reduce maternal mortality and achieve universal health coverage by 2030.

*   Prevalence
*   Mortality
*   Maternal medicine

### STRENGTHS AND LIMITATIONS OF THIS STUDY

*   This is the most updated estimate on maternal sepsis and other maternal infections epidemiology worldwide, 21 regions and 204 countries, some of which have not been evaluated before.

*   This study used data from the global burden of disease 2021 database, which incorporated more studies, adjusted diagnostic criteria and further improved data reliability.

*   This study relied on modelled estimates, which may affect accuracy in regions with limited data collection.

*   The variability in data collection and study design may affect the precision of our estimates.

*   The results for several geographical locations were limited by the data paucity, which should be treated with caution.

## Introduction

Maternal infections represent a diverse group of diseases, such as urinary tract infections, cervicitis, chorioamnionitis and postpartum uterine infections. Maternal infections may cause life-threatening complications, such as sepsis, multiorgan failure and even death.1 Maternal sepsis is a particularly severe form of infection during pregnancy, childbirth, postpartum or postabortion, characterised by organ dysfunction resulting from the body’s response to infection.2

A systematic review by the WHO reported that infections related to obstetric complications are a major contributor to maternal mortality, responsible for around 10.7% of maternal deaths globally.3 This issue is especially pronounced in low-income countries (LICs), where the maternal mortality rate due to infections is more than double that in high-income countries, at 10.7% compared with 4.7%. Findings from the global maternal sepsis study (GLOSS) revealed that, approximately, 70 out of every 1000 live births involved maternal infections requiring hospital care. Furthermore, severe maternal complications related to infections were observed in 10.9 out of every 1000 live births.4 In 2016, the WHO and partners launched the Global Maternal and Neonatal Sepsis Initiative to standardise care protocols and strengthen health systems in low-resource settings. This initiative contributed to the development of the GLOSS in 2017, which was implemented across 52 countries with the aim of enhancing surveillance and early intervention strategies to mitigate the burden of maternal sepsis and other maternal infections (MSMI).5 Parallel initiatives, such as the African Union’s Campaign for Accelerated Reduction of Maternal Mortality in Africa (CARMMA), have emphasised the importance of infection prevention by enhancing antenatal care coverage and providing training for community health workers.6 These programmes underscored the essential role of coordinated policy actions in addressing health disparities.

Herein, we investigated the epidemiology and global MSMI burden using the data from the global burden of diseases (GBD) study 2021. We also explored their links to sociodemographic index (SDI). Our findings were intended to equip policymakers and healthcare providers with insights to optimise resource allocation and implement effective prevention strategies for maternal infections.

## Methods

### Data acquisition and sources

The data for this study were obtained from the GBD 2021 dataset ([http://ghdx.healthdata.org/gbd-results-tool](http://ghdx.healthdata.org/gbd-results-tool)). Specifically, data on MSMI were extracted, including prevalence, incidence, mortality and disability-adjusted life years (DALYs).

### Definition of key measurements

MSMI consists of two different components. Maternal sepsis is characterised by deviations in body temperature (> 38 °C or<36 °C) and clinical indicators of shock, including tachycardia (>120 beats per minute) and systolic blood pressure (< 90 mm Hg). Other maternal infections include non-sexually transmitted or non-HIV infections, which do not have epidemiological associations with pregnancy. This category encompasses conditions, including mastitis, urinary tract infections, bacterial vaginosis and candidiasis during pregnancy.

We obtained annual data on its incident cases, incident rate (per 100 000), prevalent cases, prevalent rate (per 100 000), deaths (mortality) and DALYs (per 100 000) between 1990 and 2021. Incidence reflects the annual count of new MSMI cases, while prevalence captures active cases at a single time point (midyear 2021). For acute infections, such as sepsis, prevalent cases do not accumulate over time due to rapid resolution (via treatment) or fatal outcomes.7 The DALY, a composite metric encompassing years lived with disability and years of life lost, is an important indicator of population health. Specific definition of these measures was shown in online supplemental table S1. SDI was used for representing the impact of economic and social conditions on patients’ outcomes.8

### Supplementary data

[[bmjopen-2024-096746supp001.pdf]](pending:yes)

### Global and regional burden analysis

To analyse the global distribution and regional differences in the burden of MSMI, we generated global maps and regional comparative analyses. The data were aggregated by geographical regions as defined by the GBD study, and maps were created using R software with the ‘ggplot2’ and ‘sf’ packages to visualise the distribution of disease burden.

### Temporal trend analysis

Temporal trends in the incidence, prevalence, mortality and DALYs of MSMI between 1990 and 2021 were assessed using joinpoint regression analysis based on the ‘Joinpoint’ R package. The annual percentage change was evaluated, with 95% uncertainty intervals (95% UIs) used to identify the statistical significance of the trends.

### Population analysis

Population-level analyses were performed to investigate the distribution of MSMI across different demographic groups, such as age and specific subpopulations. The data were stratified by seven age groups (eg, 65–69 years and 70–74 years) for females.

### Analysis of regions by SDI

The relationship between SDI and the burden of MSMI was analysed by calculating SDI-specific disease rates. The ‘dplyr’ and ‘ggplot2’ R packages were used for data manipulation and visualisation.

### Patient and public involvement

Patients and/or the public were not involved in our study design, manuscript drafting, data interpretation and dissemination plans of the present study.

### Statistical analysis

The Bayesian-based tool DisMod-MR 2.1 was chosen to estimate 95% UIs due to its capacity to synthesise heterogeneous data sources, adjust for covariates, such as age and geography, and address issues of underreporting or missing data through hierarchical modelling.9 This tool uses Markov chain Monte Carlo methods to iteratively update parameter distributions, thereby ensuring robust quantification of uncertainty. Specifically, DisMod-MR 2.1 incorporates prior distributions informed by epidemiological literature and adjusts for variability between studies, which enhances the reliability of estimates in settings with limited data. Its application is consistent with the standardised methodology of the GBD study for comparative risk assessment.10 11 We adjusted the DisMod-MR 2.1 model to account for variations in data quality and availability across different regions and time periods. Specifically, we incorporated adjustments for data sources with high uncertainty, used smoothing techniques for addressing irregularities in the data and used covariates, such as SDI, to improve the precision of our estimates. The evolutionary trends of the age-standardised rates (ASRs) were revealed by using estimated annual percentage change (EAPC). The EAPC was explored using a linear regression model of the ASRs, and we also calculated the 95% UI for EAPC. Spearman’s rank correlation was applied to evaluate monotonic associations between SDI and ASRs (age standardised incidence rate (ASIR), age standardised prevalence rate (ASPR), age standardised mortality rate (ASMR) and age standardised disability-adjusted life years rate (ASDR)) across regions and countries. Prior to applying Spearman’s correlation, we formally tested the monotonicity assumption using Kendall’s tau-b statistic, which is robust to non-linear but monotonic trends. This two-step approach ensured robustness, as Kendall’s tau-b is less sensitive to outliers and non-linear but monotonic trends.12 A *p* value<0.05 was considered statistically significant (online supplemental file 14).

### Supplementary data

[[bmjopen-2024-096746supp014.pdf]](pending:yes)

## Results

### The global disease burden of MSMI in 2021

Globally, there were 19 047 404 (95% UI 14 608 563 to 24 086 486) incident patients with MSMI in 2021, with an ASIR of 494.19 (95% UI 377.34 to 623.90) per 100 000. The ASIR was steadily declining from 764.03 in 1990 to 494.19 per 100 000 live births in 2021 (EAPC = −1.18%; 95% UI −1.25% to −1.12%) (online supplemental table S2). The global prevalence number of MSMI in 2021 was about 2 376 876 (95% UI 1 678 868 to 3 421 377), with an ASPR of 60.38 (95% UI 42.19 to 87.24) per 100 000, which showed a decreasing trend from 1990 (ASPR 85.40; 95% UI 56.75 to 127.67) to 2021 (EAPC = −1.02%; 95% UI −1.07% to −0.97%) (online supplemental table S3). The annual incidence of MSMI (19 047 404 cases) exceeded point prevalence (2 376 876 cases), consistent with the acute nature of maternal sepsis, where most cases resolve within days through treatment or result in mortality, thereby limiting prolonged prevalence.8

### Supplementary data

[[bmjopen-2024-096746supp002.pdf]](pending:yes)

### Supplementary data

[[bmjopen-2024-096746supp003.pdf]](pending:yes)

The global case number of mortalities of MSMI in 2021 was about 17 665 (95% UI 14 628 to 21 191), with an ASMR of 0.45 (95% UI 0.37 to 0.54) per 100 000, which slightly declined from 1990 (ASMR 0.92; 95% UI 0.81 to 1.05) to 2021 (EAPC = −2.03%; 95% UI −2.33% to −1.74%) (online supplemental table S4). The global case number of DALYs of MSMI in 2021 was approximately 1 144 233 (95% UI 956 988 to 1 352 034), with an ASDR of 29.46 (95% UI 24.63 to 34.77) per 100 000, which declined from 1990 (ASDR 59.33; 95% UI 51.24 to 67.09) to 2021 (EAPC = −2.46%; 95% UI −2.89% to −2.02%) (online supplemental table S5). Overall, from 1990 to 2021, the case number and ASRs of incidences and prevalence exhibited slightly decreasing trends. However, the case number and ASRs of mortality and DALYs gradually increased with time, reaching their peak in 2001, and then declined (figure 1A–D). Global distribution maps of ASIR, ASPR, ASMR and ASDR for MSMI in 2021 were also presented (figure 2). Incidence, prevalence, mortality, DALYs and related percentage alterations in ASRs for MSMI changed among different regions between 1990 and 2021. In the regional level, of the 21 GBD regions, the negative EAPCs of ASIR were identified in almost all regions, ranging from −2.45% in South Asia to −0.24% in western Europe, except eastern Europe (EAPC = 0.36%; 95% UI −0.07% to 0.79%) and Australasia (EAPC = 0.71%; 95% UI 0.52% to 0.90%) (figure 2).

### Supplementary data

[[bmjopen-2024-096746supp004.pdf]](pending:yes)

### Supplementary data

[[bmjopen-2024-096746supp005.pdf]](pending:yes)

![Figure 1](http://bmjopen.bmj.com/https://bmjopen.bmj.com/content/bmjopen/15/6/e096746/F1.medium.gif)

[Figure 1](http://bmjopen.bmj.com/content/15/6/e096746/F1)

Figure 1 
Global numbers and ASRs of incidence, prevalence, mortality and DALYs for MSMI from 1990 to 2021. (A) Trend of case number and ASR of incidence of MSMI in the global from 1990 to 2021. (B) Trend of case number and ASR of prevalence of MSMI in the global from 1990 to 2021. (C) Trend of case number and ASR of mortality of MSMI in the global from 1990 to 2021. (D) Trend of case number and ASR of DALYs of MSMI in the global from 1990 to 2021. ASRs, age-standardised rates; DALYs, disability-adjusted life years; MSMI, maternal sepsis and other maternal infections.

![Figure 2](http://bmjopen.bmj.com/https://bmjopen.bmj.com/content/bmjopen/15/6/e096746/F2.medium.gif)

[Figure 2](http://bmjopen.bmj.com/content/15/6/e096746/F2)

Figure 2 
Global age-standardised incidence, prevalence, mortality and DALYs rates per 10 000 for MSMI in 2021. (A) Age-standardised incidence rate of MSMI in 2021 in 204 countries and territories. (B) Age-standardised prevalence rate of MSMI in 2021 in 204 countries and territories. (C) Age-standardised mortality rate of MSMI in 2021 in 204 countries and territories. (D) Age-standardised DALYs rate of MSMI in 2021 in 204 countries and territories. DALYs, disability-adjusted life years; MSMI, maternal sepsis and other maternal infections.

### Age-standardised incidence, prevalence, mortality and DALYs rates for MSMI at regional and national level

Andean Latin America showed the highest ASIR in 2021 with 938.27 (95% UI 747.74 to 1163.11) per 100 000, followed by 770.44 (95% UI 590.83 to 999.44) per 100 000 in eastern sub-Saharan Africa (online supplemental table S2). East Asia (275.07 (95% UI 201.43 to 361.64) per 100 000) and high-income Asia Pacific (123.05 (95% UI 99.79 to 150.96) per 100 000) showed the lowest ASIRs (online supplemental table S2). The highest ASPRs in 2021 were observed in central sub-Saharan Africa (123.09 (95% UI 94.40 to 166.88) per 100 000) and western sub-Saharan Africa (117.09 (95% UI 89.73 to 158.60) per 100 000) (online supplemental table S3). In contrast, East Asia, with 25.57 (95% UI 15.06 to 40.67) per 100 000, and high-income Asia Pacific, with 15.52 (95% UI 11.18 to 22.40) per 100 000, showed the lowest ASPRs (online supplemental table S3). The highest ASMRs in 2021 were observed in central sub-Saharan Africa, with 3.70 (95% UI 2.43 to 5.15) per 100 000, followed by western sub-Saharan Africa (2.42 (95% UI 1.84 to 3.18) per 100 000) and eastern sub-Saharan Africa (1.61 (95% UI 1.26 to 2.05) per 100 000) (online supplemental table S4). The lowest ASMRs were for central Europe, high-income Asia Pacific, western Europe and Australasia (all ASMRs and 95% UIs=0) (online supplemental table S4). The highest ASDRs in 2021 were observed in central sub-Saharan Africa (214.38 (95% UI 141.43 to 298.51) per 100 000) and western sub-Saharan Africa (147.8 (95% UI 114.03 to 192.57) per 100 000). East Asia with 1.40 (95% UI 0.79 to 2.37) per 100 000 and high-income Asia Pacific with 0.60 (95% UI 0.32 to 0.96) per 100 000 showed the lowest ASDRs (online supplemental table S5).

ASIR of MSMI in 2021 widely varied among countries, with the highest ASIRs identified in Afghanistan (1180.19 (95% UI 856.22 to 1538.13) per 100 000) as compared with the lowest ASIR in the Republic of Singapore (47.82 (95% UI 36.92 to 60.44) per 100 000). The ASPR of MSMI in 2021 varied from 5.28 (95% UI 3.45 to 7.76) per 100 000 in Republic of Singapore and 6.59 (95% UI 4.33 to 10.30) per 100 000 in Republic of Korea to 171.72 (95% UI 139.90 to 217.20) per 100 000 in Pakistan and 144.28 (95% UI 116.91 to 185.60) per 100 000 in Zimbabwe. The highest ASMRs of MSMI in 2021 were for Somalia, with 8.26 (95% UI 5.02 to 12.58) per 100 000, and Chad, with 7.57 (95% UI 4.79 to 11.37) per 100 000. In contrast, the lowest ASMRs were identified in the Republic of Slovenia and Republic of Iceland (all ASMRs and 95% UIs<0.001). The ASDR of MSMI in 2021 varied from 471.77 (95% UI 293.21 to 702.75) per 100 000 in Somalia and 447.44 (95% UI 286.77 to 671.15) per 100 000 in Chad to 0.21 (95% UI 0.08 to 0.43) per 100 000 in Republic of Singapore and 0.40 (95% UI 0.23 to 0.64) per 100 000 in Republic of Korea.

### Age-specific distribution of MSMI in 2021

The incidence, prevalence, mortality and DALYs of MSMI across age groups separately in 2021 were shown in figure 3A,B. In 2021, the ASIR, ASPR, ASMR and ASDR of MSMI sharply increased with age, which reached its peak in the 20–24 age group (ASIR 2098.90; 95% UI 1356.23 to 2919.64; ASPR 187.12; 95% UI 101.25 to 309.58; ASMR 1.36; 95% UI 1.10 to 1.66 and ASDR 100.78; 95% UI 83.43 to 119.94). Subsequently, the incidence rate by age decreased gradually after the 25–29 age group (figure 3A). Specifically, the ASIRs of 15–39 age groups were higher than the global average level in 2021; the ASPRs of 15–49 age groups were higher than the global average level in 2021 and the ASMRs and ASDRs of 15–44 age groups were higher than the global average level in 2021 (online supplemental figure S1A). Likewise, the case number of incidence, prevalence, mortality and DALYs first increased with age, reaching its peak in the 20–24 age group (incident case 6 165 567; 95% UI 3 983 962 to 8 576 508; prevalence case 549 662; 95% UI 297 435 to 909 405; mortality case 4007; 95% UI 3241 to 4884 and DALYs case 296 055; 95% UI 245 085 to 352 332), and then declined (figure 3B and online supplemental figure S1B).

### Supplementary data

[[bmjopen-2024-096746supp006.pdf]](pending:yes)

### Supplementary data

[[bmjopen-2024-096746supp007.pdf]](pending:yes)

![Figure 3](http://bmjopen.bmj.com/https://bmjopen.bmj.com/content/bmjopen/15/6/e096746/F3.medium.gif)

[Figure 3](http://bmjopen.bmj.com/content/15/6/e096746/F3)

Figure 3 
Numbers and ASRs of MSMI for different age groups, sex and SDI regions in 2021. (A) Age-standardised incidence, prevalence, mortality and DALYs of MSMI for different age groups in 2021. (B) The absolute case numbers of incidence, prevalence, mortality and DALYs of MSMI for different age groups in 2021. ASRs, age-standardised rates; DALYs, disability-adjusted life years; MSMI, maternal sepsis and other maternal infections; SDI, sociodemographic index.

### Relationship between MSMI burden and SDI

Generally, the ASRs of incidence, prevalence, mortality and DALYs were decreased with rising SDI level. In the SDI region level, the low-SDI region showed the highest ASIR (793.64; 95% UI 610.12 to 1026.92) per 100 000, ASPR (111.93; 95% UI 83.08 to 154.80) per 100 000, ASMR (2.22; 95% UI 1.79 to 2.76) per 100 000 and ASDR (133.02; 95% UI 108.27 to 163.35) per 100 000 (figure 4A; online supplemental figure S2A). As for the case number of mortality and DALYs, the distribution of regions by SDI was the same as that of ASRs, with the highest case number in the low-SDI region (mortality 12 062; 95% UI 9735 to 14 937 and DALYs 746 867; 95% UI 609 519 to 920 320). As for the case number of incidence and prevalence, there was an inverted U shape with the peak in low-middle SDI region (incidence 5 878 472; 95% UI 4 402 325 to 7 500 139 and prevalence 829 751; 95% UI 615 733 to 1 147 388) (figure 4B; online supplemental figure S2B).

### Supplementary data

[[bmjopen-2024-096746supp008.pdf]](pending:yes)

![Figure 4](http://bmjopen.bmj.com/https://bmjopen.bmj.com/content/bmjopen/15/6/e096746/F4.medium.gif)

[Figure 4](http://bmjopen.bmj.com/content/15/6/e096746/F4)

Figure 4 
Numbers and ASRs of MSMI for different SDI regions in 2021. (A) Age-standardised incidence, prevalence, mortality and DALYs rates of MSMI for different SDI regions in 2021. (B) The absolute case numbers of incidence, prevalence, mortality and DALYs of MSMI for different SDI regions in 2021. ASRs, age-standardised rates; DALYs, disability-adjusted life years; MSMI, maternal sepsis and other maternal infections; SDI, sociodemographic index.

Andean Latin America demonstrated the highest ASIR (938.27; 95% UI 747.74 to 1163.11) per 100 000; central sub-Saharan Africa showed the highest ASPR (123.09; 95% UI 94.40 to 166.88) per 100 000 and central Africa showed the highest ASMR (3.89; 95% UI 2.71 to 5.30) per 100 000 and ASDR (226.58; 95% UI 158.02 to 306.35) per 100 000 in 2021 (figure 5A). The lowest ASMR (0.0004; 95% UI 0.0003 to 0.0005) was identified in Australasia in 2021 (figure 5A). High-income Asia Pacific showed the lowest ASIR (123.05; 95% UI 99.79 to 150.96), ASPR (13.38; 95% UI 10.09 to 18.60) and ASDR (0.60; 95% UI 0.32 to 0.96) (figure 5A). However, in 2021, Asia showed the greatest number of incident cases at 9 385 429 (95% UI 6 944 033 to 12 156 608) and prevalent cases at 1 260 460 (95% UI 915 733 to 1 772 101). Africa had the highest number of mortalities at 12 151 (95% UI 9786 to 15 251) and DALYs cases at 755 439 (95% UI 617 384 to 945 670) (figure 5B). By contrast, the lowest case number of incidence (55 512; 95% UI 44 860 to 67 998), prevalence (5054; 95% UI 3072 to 7872), mortality (0.06; 95% UI 0.04 to 0.08) and DALYs (226; 95% UI 105 to 400) was observed in Australasia (figure 5B).

![Figure 5](http://bmjopen.bmj.com/https://bmjopen.bmj.com/content/bmjopen/15/6/e096746/F5.medium.gif)

[Figure 5](http://bmjopen.bmj.com/content/15/6/e096746/F5)

Figure 5 
Numbers and ASRs of MSMI for different GBD regions in 2021. (A) Age-standardised incidence, prevalence, mortality and DALYs rates of MSMI for 50 GBD regions in 2021. (B) The absolute case numbers of incidence, prevalence, mortality and DALYs of MSMI for 50 GBD regions in 2021. ASRs, age-standardised rates; DALYs, disability-adjusted life years; GBD, global burden of disease; MSMI, maternal sepsis and other maternal infections.

Spearman’s rank order correlation analysis demonstrated a negative association between ASIR and SDI (online supplemental figure S3A), a negative association between ASPR and SDI (online supplemental figure S3B), a negative association between ASMR and SDI (online supplemental figure S3C) and a negative association between ASDR and SDI (online supplemental figure S3D). Additionally, Kendall’s tau-b tests revealed strong negative associations between SDI and ASMR (Kendall’s τ=−0.710, p<0.001, online supplemental figure S4A), ASDR (Kendall’s τ=−0.700, p<0.001, online supplemental figure S4B), ASPR (Kendall’s τ=−0.657, p<0.001, online supplemental figure S4C) and ASIR (Kendall’s τ=−0.552, p<0.001, online supplemental figure S4D) at the regional level. With the growth of SDI, the decreasing trends of ASMR and ASDR gradually slowed down. The national-level analysis also showed a generally negative relationship between SDI and ASIR (online supplemental figure S5A), ASPR (online supplemental figure S5B), ASMR (online supplemental figure S5C) and ASDR (online supplemental figure S5D). Furthermore, Kendall’s tau-b tests showed strong negative associations between SDI and ASMR (Kendall’s τ=−0.702, p<0.001, online supplemental figure S6A), ASDR (Kendall’s τ=−0.693, p<0.001, online supplemental figure S6B), ASPR (Kendall’s τ=−0.604, p<0.001, online supplemental figure S6C) and ASIR (Kendall’s τ=−0.541, p<0.001, online supplemental figure S6D) at the national level. The results of Spearman’s rank order correlation analysis align with the monotonicity confirmed by Kendall’s tau-b tests (p<0.001 for all metrics), indicating consistent reductions in MSMI burden with higher SDI.

### Supplementary data

[[bmjopen-2024-096746supp009.pdf]](pending:yes)

### Supplementary data

[[bmjopen-2024-096746supp010.pdf]](pending:yes)

### Supplementary data

[[bmjopen-2024-096746supp011.pdf]](pending:yes)

### Supplementary data

[[bmjopen-2024-096746supp012.pdf]](pending:yes)

### The influential factors for EAPC

In 1990, obviously negative correlations were identified between EAPCs and ASIR, ASPR, ASMR and ASDR (online supplemental figure S7A). However, in 2021, positive correlations were identified between EAPCs and ASRs (online supplemental figure S7B). Specifically, significant positive associations were identified between EAPCs and ASDRs (r=0.3398, p<0.001).

### Supplementary data

[[bmjopen-2024-096746supp013.pdf]](pending:yes)

## Discussion

This study integrated the epidemiology and disease burden of MSMI in the whole world, 21 GBD regions and 204 countries from 1990 to 2021, investigating the secular trends, regional variations and relationships with SDI. The EAPCs of ASIRs, ASPRs, ASMRs and ASDRs in the vast majority of GBD regions exhibited decreasing trends, whereas there were several exceptions. Herein, we observed that the decreased ASIRs and ASPRs were identified in almost all regions, except eastern Europe and Australasia. The observed disparity between annual incidence and point prevalence reflected the transient nature of maternal sepsis. Unlike chronic conditions, acute infections, such as sepsis, are characterised by short duration (median 7–14 days) and high case-fatality rates, leading to limited accumulation of prevalent cases over time. This pattern aligned with previous GBD analyses of acute infectious diseases.10 However, all the regions showed downwards trends in ASMRs. Only Oceania and Australasia showed increased ASDRs, whereas other regions showed decreased ASDRs. Between 1990 and 2021, the ASIRs, ASPRs, ASMRs and ASDRs of low-SDI regions were much higher than those of other regions with higher SDI, although they all continued to decrease. Both the case numbers and ASRs of incidence, prevalence, mortality and DALYs of MSMI increased first until 20–24 years and then declined with age both in 2021. With the growth of SDI in 2021, the downwards trends of ASIR, ASPR, ASMR and ASDR gradually slowed down.

MSMI was one of the triumvirates of principal causes underpinning maternal mortality.4 Chen *et al.* revealed a continuous decrease in the ASIRs, ASMRs and ASDRs of MSMI on the global level, which spanned the temporal continuum from 1990 to 2021.8 Notably, these descending trends were most pronounced in regions characterised by high MSMI burden, which were fastest in lower SDI regions. A previous scrutiny performed by the UN Maternal Mortality Estimation Interagency Group reported a significant decrease in the global mortality rates, which plummeted from about 385 deaths per 100 000 live births in 1990 to 216 deaths per 100 000 live births in 2015, approximately 44% relative decrease over the course of 3 decades.13 Furthermore, advancements in diminishing mortality rates exhibited regional differences, which manifested as an annualised decrement ranging from about 2.0% in the Caribbean to 5.0% in east Asia since 1990.13 In addition, the discernments provided by the GLOSS accentuated higher incidence and mortality of maternal sepsis in regions characterised by diminished fiscal affluence.4

Maternal deaths have long played an apprehension-inducing role in the ambit of global health concerns, with an emphasis on mortality entwined with infections.4 14 Various scholarly inquiries have reported a discernible decline in the mortality rates and incidence rates of MSMI over the past years, emblematic of strides made in improving maternal outcomes.15 This study revealed that, despite a consistent annual decrease in the ASIRs, ASPRs, ASMRs and ASDRs, low-SDI regions manifested markedly higher ASRs than high-SDI regions and middle-high SDI regions, with the slowest downtrends. Additionally, LICs showed an ASMR of 42.31 per 100 000 in 2019, significantly deviating from the benchmarks of sustainable development goals (SDGs).16 Although efforts have been devoted to mitigating the MSMI burdens of regions with low-SDI levels, the deficiencies in healthcare systems have exacerbated the gap across lower-middle SDI regions in the treatment of maternal infections.17 Lower-middle SDI regions, including Liberia, Central African Republic and Haiti, persisted in grappling with formidable challenges in overcoming maternal health problems.6 The obvious burden disparity necessitated targeted managements and resource allocation for addressing the huge challenges confronted by lower-middle SDI regions. The epidemiological landscapes of MSMI showed substantial heterogeneity among 204 countries in 2021, with Afghanistan registering the highest estimated national-level ASIR (1180.19 per 100 000) and Somalia exhibiting the highest ASMRs (8.26 per 100 000). Importantly, the high incidence of maternal sepsis was intimately associated with the ubiquity of healthcare services and sanitation facilities, with these conditions being specifically accentuated in Somalia.18 19 Those regions grappling with conflicts and pollution were confronted with resource constraints for addressing the deficiency of healthcare resources.19–21

The distribution of ASRs of MSMI exhibited consistent patterns, characterised by increased ASRs in the young age groups (20–24 age group) within low-SDI regions, which might be attributable to the heightened susceptibility of females in these age brackets to maternal infections post childbirth.22 In recent years, the prevailing trends of delayed childbearing in various regions and countries have directly resulted in the increased average age of parturient.23 Several policies aiming at encouraging birth have augmented the occurrence of advanced maternal age pregnancies, to a certain extent, especially the pregnancies in females aged above 35.24 Advanced maternal age status has been widely acknowledged as one of the risk factors for adverse maternal events.25 Additionally, the majority of all age groups of MSMI burdens in low-SDI regions showed downwards trends over the past 3 decades. The gradual shifts in sexual attitudes in several low-SDI regions might explain the trends partially; however, there are deeper underlying causes that warrant more investigation.

Our findings showed inverse correlations between the SDI and MSMI burdens across 21 GBD regions and 204 countries. These associations underscored those regions or countries with lower SDI levels and insufficient awareness in females tended to have higher burdens of MSMI, which was consistent with previous epidemiological surveys.6 These correlations might be partially explained by the limited access to healthcare resources in low-SDI regions, leading to increased ASRs of incidence, prevalence and mortality.6 Fundamental disease burdens of MSMI persisted, especially the pervasive inequalities of healthcare coverage, even in countries devoting much more effort to improving healthcare service coverage.4

To alleviate the MSMI burdens and improve maternal outcomes in low-SDI regions, multifaceted and comprehensive managements are critical. It is of vital importance to promote antenatal healthcare and infection control interventions, especially focusing on early diagnosis and treatments of maternal infections.5 14 In addition, enhancing postpartum healthcare and follow-up is equally important, which can ensure timely detection and management for postpartum infections.5 Furthermore, addressing the socioeconomic risk factors of health, such as gender inequality and poverty, via gender-equitable policies as well as females’ empowerment initiatives, may have substantial impacts on MSMI burdens in low-SDI regions.16

This study had several limitations. First, some data of unavailable location or year may underestimate the real burdens of MSMI. Second, our findings were presented in limited depth because of the characteristics of GBD 2021, which could not be subdivided into the aetiology and pathogens of MSMI. Third, application of the EAPC for each ASR and the corresponding percent change in the case number for assessing secular trends from 1990 to 2021 might have obscured dynamic processes because of several preventive measures.

### Conclusions

The persistent disparities in the burden of MSMI between low- and high-SDI regions underscored the urgent necessity for context-specific interventions. Our findings delineated priority areas for resource allocation, particularly the enhancement of healthcare infrastructure in central and western sub-Saharan Africa, where ASMRs and age-standardised disability rates ASDRs remain the highest. Policymakers should prioritise the expansion of access to antenatal care, the implementation of early sepsis detection tools and the training of community health workers in low-SDI regions, especially for women aged 20–24 years, who experience the greatest burden. Global initiatives, such as the WHO’s Maternal Sepsis Guidelines, should be adapted to incorporate region-specific barriers and use SDI-driven data to ensure equitable distribution of funding. Furthermore, international collaborations, modelled after the African Union’s CARMMA, could facilitate resource sharing and capacity building to mitigate preventable maternal deaths. These strategies are consistent with the targets set forth by the SDGs regarding maternal health and universal healthcare coverage.

## Data availability statement

Data are available on reasonable request.

## Ethics statements

### Patient consent for publication

Not applicable.

### Ethics approval

This study involves human participants and were based on public datasets. No ethical approval and patient consent were required for all analyses. This study was exempted by ethics committee of the Tongji Hospital Affiliated to Tongji University. Participants gave informed consent to participate in the study before taking part.

## Footnotes

*   SW, SC and MC are joint first authors.

*   SW, SC and MC contributed equally.

*   Contributors Study concept and design: SW, SC, BM and LC. Acquisition of data: SW and SC. Data analysis and interpretation: SW, SC, MC, WX, ZW, XH, CL and ZX. Drafting the manuscript: SW, SC and MC. Critical revision of manuscript: all authors. LC accepted full responsibility for the work and the conduct of the study, had access to the data, and controlled the decision to publish as the guarantor. All authors had full access to all the data in the study and had final responsibility for the decisions to submit for publication.

*   Funding This work was supported by a grant from the National Key Research and Development Programme of China (2024YFA1108200), International (Regional) Cooperation and Communication Program of the National Natural Science Foundation of China (81820108013), Shanghai Key Discipline Clinical Research Center Construction Program (No. 2023ZZ02016), the National Key Clinical Specialty Discipline Construction Program of China (No. Z155080000004), the Key Program of National Natural Science Foundation of China (No. 82330062), the Scientific Research Project of Shanghai Municipal Health Committee (202040075) and the General Program of National Natural Science Foundation of China (82071370, 82371378, 82371380). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

*   Map disclaimer The depiction of boundaries on this map does not imply the expression of any opinion whatsoever on the part of BMJ (or any member of its group) concerning the legal status of any country, territory, jurisdiction or area or of its authorities. This map is provided without any warranty of any kind, either express or implied.

*   Competing interests None declared.

*   Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

*   Provenance and peer review Not commissioned; externally peer reviewed.

*   Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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