Abstract
Background:
Neonatal encephalopathy (NE) due to birth asphyxia and trauma has become the second leading cause of global neonatal and under-5 deaths. However, comprehensive data on the global NE burden are scarce. This study aimed to determine the global, regional, and national trends in NE burden from 1990 to 2019, utilizing the 2019 Global Burden of Disease (GBD) study data.
Methods:
Annual incident cases, deaths, disability-adjusted life years (DALYs), and age-standardized rates (incidence [ASIR], mortality [ASMR], DALYs) of NE were collected from the 2019 GBD study. The percentage of relative changes and estimated annual percentage changes (EAPCs) were calculated to assess temporal trends.
Results:
NE global incident cases increased from 1.33 million in 1990 to 1.38 million in 2019, with a 4.87% rise in ASIR. Global NE deaths remained at 0.57 million in 2019, despite a 29.88% reduction from 1990. Significant annual reductions in ASMR and DALYs were observed post-2005. South Asia and sub-Saharan Africa accounted for 80.00% of global NE cases, with South Asia, Eastern and Western sub-Saharan Africa contributing to 81.42% of global deaths and 79.50% of DALYs. NE-related deaths comprised 22.76% and 11.24% of neonatal and under-5 mortality. There were 3.91 million epilepsy, 4.23 million developmental intellectual disability, and 0.57 million blindness cases caused by NE globally in 2019.
Conclusions:
Despite a significant reduction in NE mortality from 1990 to 2019, the ongoing rise in incidence, particularly in South Asia and sub-Saharan Africa, is alarming. Targeted initiatives to prevent NE are needed, especially tailored to high-burden regions.
Keywords: Global Burden of Disease Study, Neonatal encephalopathy, Birth asphyxia, Neonate, Mortality
Introduction
Neonatal encephalopathy (NE) is a clinically defined syndrome of disturbed neurologic function in the earliest days of life in term neonates, often resulting from intrapartum injury.[1] NE due to birth asphyxia and trauma has emerged as the second leading cause of global neonatal and under-5 deaths, with survivors facing a high risk of long-term neuro-developmental impairments.[2–4] Despite its significant impact on neonatal and childhood mortality and morbidities, concurrent global data on NE trends and outcomes is lacking. The most recent estimation reported 1.15 million global cases of NE, with 0.29 million associated deaths in 2010.[5] However, in the past decade, multiple global initiatives have been launched to reduce neonatal mortality.[6,7] The Sustainable Development Goal 3.2 calls to end preventable newborn deaths, with a specific emphasis on preventing intrapartum injury, including NE.[6–9] Understanding the current burden of NE, as well as tracking its trend, is crucial to assess progress and to inform future targeted interventions and policies. To this end, we utilized data from the 2019 Global Burden of Disease (GBD) study, focusing on NE due to birth asphyxia and trauma. We aimed to provide a comprehensive analysis of the global, regional, and national incidence, mortality, and long-term impairments associated with NE from 1990 to 2019. The analysis placed particular emphasis on the current burden, temporal trends, and the identification of regions in need of significant improvement in NE prevention.
Methods
Data source
This study collected data from the Global Health Data Exchange query tool (https://vizhub.healthdata.org/gbd-results/). The GBD 2019 study estimated global burden of 369 diseases and injuries across 204 countries/territories from 1990 to 2019.[10] Data modeling was performed using DisMod-MR version 2.1 meta-analysis tool, a Bayesian meta-regression tool developed by the Institute for Health Metrics and Evaluation (Seattle, WA, USA). For countries without data, the GBD imputes region-specific averages, assuming these averages contain modest bias and that no systematic differences exist between the missing and observed values.[11] For data reported using alternative case definitions or measurement methods, strict exclusion criteria were applied and network meta-regression was used to ensure consistency and comparability.[12,13] For deaths classified under unspecified codes, redistribution algorithms were employed to reassign them to more specific disease categories. Detailed descriptions of overall GBD 2019 methodologies have been provided elsewhere.[10,13]
Definition
In the GBD 2019 study, NE was defined as injury to the brain in the first days of life in full-term infants, causing abnormal neurological function due to hypoxia and birth injury, according to the International Classification of Diseases-10 (ICD-10).[10,14] The GBD Collaborator Network used strict exclusion criteria to ensure consistency and reliability in case definitions. Studies were excluded if they: (1) did not limit the NE definition to full-term infants; (2) lacked a clearly defined selection of the birth cohort or cases; (3) exhibited substantial selection biases or drew cases from a specialized subpopulation; (4) reported the same data from a previously included cohort; or (5) had a median birth year of the study cohort before 1980. Epilepsy was defined as active epilepsy with at least one seizure in the previous five years, regardless of treatment.[15] Developmental intellectual disability was defined as a condition of below-average intelligence or mental ability.[16,17]
To facilitate regional comparisons, the GBD study employed age-standardized rate, an approach that adjusted age-specific rates for each location, year, and gender based on a GBD world standard population. This method eliminates potential confounding of age structure and makes statistical indicators comparable.[18] Age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life years (DALYs) rate were used in this study.
Regions were divided by two ways, geographically and by the sociodemographic index (SDI).[10,13,19] The SDI, a composite indicator of development status strongly linked to health outcomes, is calculated as the geometric mean of 0–1 indices of lag distributed income per capita, mean education of those ages 15 years and older, and total fertility rate under the age of 25 years. A location with an SDI of 0 would have a theoretical minimum level of development status relevant to health, while a location with an SDI of one indicates a theoretical maximum level. A total of 204 countries and territories are categorized into five SDI regions.
Statistical analysis
The annual numbers of incident cases, deaths, DALYs, ASIR, ASMR, age-standardized DALYs rate, and their corresponding 95% uncertainty intervals (UIs) were used to describe the burden. The percentage of relative change in these figures from 1990 to 2019 was calculated by the equation: percentage of relative change = (values in 2019–values in 1990)/values in 1990 × 100%. To quantify the temporal trends of age-standardized estimates of NE, we calculated the estimated annual percentage changes (EAPCs). This involved fitting a regression line to the natural logarithm of the age-standardized rate, that is, y = α + βx + ε, where y = ln (age-standardized rate) and x = calendar year. EAPCs were calculated as 100 × (eβ−1) with their 95% confidence intervals (CIs) determined by linear modeling. EAPC and the lower boundary of its 95% CI being greater than 0 indicated an upward trend, whereas those being less than 0 indicated a downward trend. Model validation involves checking the assumptions of the line regression model (normality, independence, and homoscedasticity of residuals) to ensure the model’s accuracy and appropriateness. Additionally, the correlations of ASIR, ASMR, and age-standardized DALYs rates with SDI values (2019) in 21 regions were assessed by Pearson correlation analyses. A P value less than 0.05 was considered statistically significant. All analyses were conducted using R 4.2.1 (R Foundation for Statistical Computing, Vienna, Austria).
Results
Global burden of NE: incidence, mortality, and DALYs
Globally, the total incident cases of NE increased from 1,335,110 (95% UI, 907,226–2,086,317) in 1990 to 1,378,698 (95% UI, 963,701–2,024,055) in 2019, representing a 3.26% increase [Table 1]. ASIR also increased by 4.87% from 1990 to 2019 [Figure 1A]. Over the three decades, the EAPC of ASIR had an initial annual increase of 0.49% (95% CI, 0.47–0.52%) from 1990 to 2005 and a subsequent annual decrease of −0.23% (95% CI, −0.39% to –0.07%) from 2006 to 2019 [Table 1].
Table 1.
Incident cases and ASIR of NE in 2019 and their change trends from 1990 to 2019.
| Characteristic | Incident cases | ASIR | |||||
|---|---|---|---|---|---|---|---|
| Number (95% UI) | Percentage change, % (95% UI) | Rate (95% UI) per 100,000 population | Percentage change (%) | EAPC (95% CI) | |||
| 1990–2019 | 1990–2005 | 2006–2019 | |||||
| Overall | 1,378,698 (963,701–2,024,055) | 3.26 (–2.98 to 6.23) | 21.29 (14.87–31.25) | 4.87 (–1.48 to 7.90) | 0.07 (–0.01 to 0.15) | 0.49 (0.47–0.52) | –0.23 (–0.39 to –0.07) |
| Sex | |||||||
| Female | 636,262 (448,706–916,258) | 5.74 (–1.40 to 10.02) | 20.35 (14.35–29.30) | 7.56 (0.27–11.93) | 0.13 (0.07–0.20) | 0.50 (0.47–0.53) | 0.03 (–0.14–0.21) |
| Male | 742,436 (318,207–1,098,556) | 1.23 (–4.86 to 4.38) | 22.16 (15.47–32.80) | 2.64 (–0.56 to 5.89) | 0.01 (–0.09 to 0.11) | 0.49 (0.45–0.53) | –0.45 (–0.63 to –0.26) |
| SDI region | |||||||
| High SDI | 32,309 (23,509–43,553) | –19.30 (–21.78 to –17.93) | 6.51 (4.73–8.77) | –7.79 (–10.58 to –6.20) | –0.31 (–0.36 to –0.25) | –0.57 (–0.60 to –0.54) | 0.02 (–0.05 to 0.08) |
| High-middle SDI | NA | NA | 7.57 (5.47–10.40) | –25.86 (–33.33 to –20.29) | –1.24 (–1.36 to –1.12) | –0.62 (–0.72 to –0.51) | –1.41 (–1.73 to –1.1) |
| Middle SDI | NA | NA | 10.60 (7.22–15.94) | –22.90 (–29.65 to –16.28) | –1.08 (–1.19 to –0.98) | –0.54 (–0.62 to –0.47) | –1.45 (–1.68 to –1.22) |
| Low-middle SDI | NA | NA | 22.95 (15.27–35.52) | –4.35 (–12.13 to 0.20) | –0.20 (–0.26 to –0.14) | 0.06 (–0.01 to 0.12) | –0.46 (–0.60 to –0.31) |
| Low SDI | NA | NA | 39.70 (28.30–56.99) | –5.13 (–5.03 to –4.52) | –0.11 (–0.15 to –0.08) | –0.08 (–0.20 to 0.03) | –0.13 (–0.23 to –0.04) |
| GBD region | |||||||
| Central Europe | 4113 (2997–5230) | –36.38 (–41.28 to –36.13) | 7.98 (5.81 to 10.4) | –0.86 (–8.50 to –0.49) | –0.17 (–0.26 to –0.08) | –0.30 (–0.43 to –0.17) | 0.46 (0.31–0.62) |
| Eastern Europe | 10,277 (6900–10,277) | –50.30 (–53.23 to –48.99) | 9.48 (6.37 to 12.59) | –35.55 (–39.19 to –33.33) | –1.63 (–1.89 to –1.36) | –2.42 (–2.62 to –2.23) | 0.09 (–0.45 to 0.62) |
| Central Asia | 18,004 (14,489–21,728) | –9.26 (–11.09 to –9.06) | 19.90 (16.01–24.01) | –6.12 (–8.05 to –5.88) | –0.15 (–0.27 to –0.02) | 0.47 (0.41–0.53) | –0.82 (–0.91 to –0.73) |
| Australasia | 919 (693–1178) | –12.21 (–18.01 to –6.67) | 5.20 (3.92–6.67) | –24.35 (–30.36 to –19.28) | –1.50 (–1.76 to –1.23) | –1.65 (–2.31 to –0.97) | 0.07 (–0.06 to 0.20) |
| High-income Asia Pacific | 5664 (4021–7770) | –34.55 (–35.48 to –34.24) | 8.55 (6.07–11.7) | –6.55 (–7.58 to –6.40) | –0.17 (–0.27 to –0.06) | –0.47 (–0.72 to –0.22) | 0.02 (–0.29 to 0.32) |
| High-income North America | 13,252 (8792–18,991) | –12.15 (–12.47 to –11.96) | 6.57 (4.35–9.41) | –4.20 (–4.35 to –4.08) | –0.09 (–0.17 to –0.01) | –0.45 (–0.59 to –0.31) | 0.27 (0.18–0.36) |
| Southern Latin America | 2846 (2104–3683) | 5.49 (–5.33 to 13.88) | 6.13 (4.53–7.94) | 14.15 (2.27–23.44) | 0.67 (0.51–0.84) | 1.05 (0.69–1.40) | –0.32 (–0.50 to –0.14) |
| Caribbean | 4272 (3426–5204) | –1.95 (–4.19 to 0.17) | 10.94 (8.77–13.32) | 8.86 (7.32–10.83) | 0.20 (0.17–0.24) | 0.29 (0.24–0.34) | 0.19 (0.06–0.33) |
| Western Europe | 10,686 (7990–13,664) | –8.36 (–12.86 to –6.4) | 5.16 (3.86–6.60) | –1.34 (–4.88–0.76) | –0.09 (–0.12 to –0.07) | –0.20 (–0.22 to –0.17) | –0.02 (–0.08 to 0.04) |
| Andean Latin America | 8491 (6474–10,846) | 3.41 (–2.49 to 7.13) | 13.50 (10.29–17.25) | –4.99 (–10.43 to –1.14) | –0.34 (–0.50 to –0.17) | 0.54 (0.42–0.67) | –0.94 (–1.19 to –0.69) |
| Central Latin America | 9158 (6765–13,141) | –48.50 (–54.28 to –42.69) | 4.34 (3.20–6.23) | –42.01(–48.76 to –36.00) | –1.71 (–1.86 to –1.56) | –2.12 (–2.45 to –1.79) | –1.41 (–1.90 to –0.93) |
| Tropical Latin America | 24,157 (15,933–34,985) | –25.60 (–34.36 to –21.29) | 15.63 (10.31–22.64) | –17.60 (–27.33 to –12.71) | –0.69 (–0.75 to –0.62) | –0.58 (–0.74 to –0.42) | –0.73 (–0.96 to –0.50) |
| North Africa and Middle East | 88,554 (65,491–118,253) | –5.39 (–9.79 to –1.06) | 20.32 (11.25–20.32) | –8.82 (–12.40 to –4.69) | –0.56 (–0.65 to –0.46) | –0.20 (–0.36 to –0.04) | –0.30 (–0.51 to –0.09) |
| South Asia | 316,904 (170,644–597,493) | –17.65 (–18.53 to –16.89) | 19.75 (10.64–37.25) | –11.78 (–12.40 to –11.65) | –0.50 (–0.60 to –0.41) | –0.17 (–0.29 to –0.05) | –0.92 (–1.18 to –0.65) |
| East Asia | 25,920 (15,202–46,081) | –76.73 (–78.96 to 72.33) | 3.49 (2.05–6.21) | –62.24 (–65.93 to –54.35) | –3.90 (–4.20 to –3.60) | –2.36 (–2.81 to –1.90) | –4.30 (–4.91 to –3.68) |
| Oceania | 1454 (1137–1807) | 62.62 (58.61–66.74) | 7.38 (5.77–9.18) | –12.06 (–13.43 to –9.80) | –0.57 (–0.60 to –0.53) | –0.58 (–0.66 to –0.50) | –0.38 (–0.45 to –0.30) |
| Southeast Asia | 30,000 (18,522–51,071) | –54.39 (–56.04 to –53.09) | 5.73 (3.54–9.76) | –47.36 (–48.96 to –46.15) | –2.48 (–2.59 to –2.37) | –2.26 (–2.37 to –2.15) | –1.98 (–2.35 to –1.62) |
| Central sub-Saharan Africa | 114,118 (77,934–159,041) | 75.58 (68.73–83.59) | 53.59 (36.60–74.69) | 5.23 (1.10–10.01) | 0.71 (0.49–0.94) | 1.18 (0.73–1.64) | –0.51 (–0.97 to –0.04) |
| Eastern sub-Saharan Africa | 287,605 (213,804–387,789) | 35.95 (34.77–36.16) | 42.63 (31.69–57.49) | –14.19 (–15.78 to –13.94) | –0.54 (–0.60 to –0.48) | –0.42 (–0.48 to –0.36) | –0.38 (–0.62 to –0.13) |
| Western sub-Saharan Africa | 384,337 (268,190–549,780) | 63.03 (59.41–66.92) | 49.04 (34.22–70.15) | –11.02 (–12.98 to –8.83) | –0.51 (–0.58 to –0.44) | –0.76 (–0.86 to –0.65) | –0.15 (–0.29 to –0.02) |
| Southern sub-Saharan Africa | 17,958 (12,697–24,757) | 3.70 (3.04–4.22) | 22.55 (15.95–31.10) | –4.02 (–4.61 to –3.42) | –0.02 (–0.11 to 0.06) | 0.13 (0.01–0.25) | –0.61 (–0.74 to –0.47) |
ASIR: Age-standardized incidence rate; CI: Confidence interval; EAPC: Estimated annual percentage change; GBD: Global Burden of Disease; NA: Not applicable; NE: Neonatal encephalopathy; SDI: Sociodemographic index; UI: Uncertainty interval.
Figure 1.
The trends of NE globally and by SDI regions, from 1990 to 2019. (A) ASIR. (B) ASMR. (C) Age-standardized DALYs rates. (D) NE contribution in NMR. (E) NE contribution in U5MR. ASIR: Age-standardized incidence rate; ASMR: Age-standardized mortality rate; DALYs: Disability-adjusted life years; NE: Neonatal encephalopathy; NMR: Neonatal mortality rate; SDI: Sociodemographic index; U5MR: Under-5 mortality rate.
Global deaths due to NE significantly decreased from 808,681 (95% UI, 726,796–903,200) in 1990 to 566,976 (95% UI, 477,535–672,551) in 2019, representing a 29.88% reduction [Table 2]. The ASMR also decreased by 28.92% from 1990 to 2019 [Figure 1B]. The EAPC of ASMR had a decrease of −2.35% (95% CI, −2.44% to −2.25%) per year from 2006 to 2019 [Table 2].
Table 2.
Death number and ASMR of NE in 2019 and their change trends from 1990 to 2019.
| Characteristics | Death number | ASMR per 100,000 population | |||||
|---|---|---|---|---|---|---|---|
| Number (95% UI) | Percentage change, % (95% UI) | Rate (95% UI) per 100,000 population | Percentage change (%) | EAPC (95% CI) | |||
| 1990–2019 | 1990–2005 | 2006–2019 | |||||
| Overall | 566,976 (475,535–672,551) | –29.88 (–34.57 to –25.54) | 8.75 (7.33–10.38) | –28.92 (–33.69 to –24.50) | –1.16 (–1.38 to –0.94) | 0 (–0.09 to 0.09) | –2.35 (–2.44 to –2.25) |
| Sex | |||||||
| Female | 236,443 (199,832–27,7814) | –32.29 (–35.42 to –30.50) | 7.56 (6.39–8.88) | –31.21 (–34.39 to –29.47) | –1.29 (–1.49 to –1.09) | –0.25 (–0.37 –to –0.14) | –2.35 (–2.46 to –2.25) |
| Male | 330,533 (268,751–401,902) | –28.07 (–33.59 to –23.07) | 9.87 (8.02–12.00) | –27.16 (–32.77 to –22.00) | –1.06 (–1.29 to –0.82) | 0.18 (0.10–0.26) | –2.34 (–2.43 to –2.25) |
| SDI region | |||||||
| High SDI | 3636 (3161–4174) | –61.96 (–64.41 to –59.84) | 0.72 (0.63–0.83) | –56.56 (–62.50 to –55.56) | –2.82 (–2.94 to –2.70) | –3.25 (–3.35 to –3.16) | –2.02 (–2.15 to –1.88) |
| High-middle SDI | 12,880 (10,636–15,188) | –77.91 (–79.59 to –76.78) | 1.69 (1.40–2.00) | –71.07 (–73.08 to –69.70) | –4.53 (–4.90 to –4.15) | –2.36 (–2.77 to –1.95) | –5.90 (–6.02 to –5.77) |
| Middle SDI | 68,350 (56,376–81,914) | –64.42 (–67.23 to –62.36) | 3.97 (3.27–4.76) | –57.27 (–60.24 to –54.29) | –2.99 (–3.32 to –2.66) | –1.22 (–1.43 to –1.00) | –4.70 (–4.83 to –4.57) |
| Low-middle SDI | 189,168 (156,159–225,490) | –38.06 (–41.83 to –35.63) | 11.13 (9.19–13.27) | –33.97 (–37.84 to –31.09) | –1.27 (–1.53 to –1.02) | –0.03 (–0.11 to 0.06) | –2.74 (–2.89 to –2.60) |
| Low SDI | 292,662 (232,636–356,110) | 20.49 (9.30–28.07) | 16.22 (12.89–19.74) | –24.73 (–31.75 to –20.24) | –0.77 (–0.88 to –0.66) | –0.39 (–0.44 to –0.33) | –1.47 (–1.66 to –1.27) |
| GBD region | |||||||
| Central Europe | 315 (242–403) | –88.60 (–90.21 to –86.78) | 0.60 (0.46–0.77) | –82.27 (–83.87 to –78.95) | –6.36 (–6.56 to –6.15) | –6.02 (–6.42 to –5.61) | –5.28 (–5.69 to –4.87) |
| Eastern Europe | 1335 (1073–1648) | –84.78 (–86.21 to –83.56) | 1.22 (0.98–1.50) | –80.31 (–81.82 to –78.87) | –6.15 (–6.40 to –5.90) | –5.52 (–6.27 to –4.75) | –6.06 (–6.52 to –5.59) |
| Central Asia | 5922 (4881– 7183) | –52.26 (–53.94 to –49.97) | 6.53 (5.38–7.92) | –50.69 (–52.21 to –48.37) | –2.60 (–3.17 to –2.03) | 0.33 (0.02–0.64) | –5.71 (–6.05 to –5.37) |
| Australasia | 179 (141–224) | –34.12 (–42.73 to –26.60) | 1.01 (0.79–1.26) | –43.23 (–50.00 to –35.00) | –1.81 (–2.02 to –1.60) | –0.78 (–1.19 to –0.37) | –2.46 (–2.61 to –2.32) |
| High-income Asia Pacific | 178 (151–205) | –81.20 (–82.04 to –80.84) | 0.26 (0.22–0.30) | –73.28 (–77.78 to –72.73) | –4.38 (–4.60 to –4.17) | –5.03 (–5.50 to –4.56) | –3.26 (–3.44 to –3.07) |
| High-income North America | 1814 (1606–2031) | –43.25 (–46.24 to –40.31) | 0.89 (0.79–1.00) | –38.23 (–42.86 to –33.33) | –1.49 (–1.57 to –1.41) | –1.89 (–2.00 to –1.77) | –1.14 (–1.25 to –1.03) |
| Southern Latin America | 528 (393–691) | –72.78 (–77.03 to –68.32) | 1.13 (0.84–1.48) | –70.64 (–76.47 to –65.12) | –4.36 (–4.52 –to –4.20) | –4.84 (–5.00 to –4.68) | –3.20 (–3.36 –to –3.04) |
| Caribbean | 2722 (1911–3722) | –25.81 (–34.75 to –18.68) | 6.96 (4.89–9.52) | –17.73 (–27.94 to –10.38) | –0.49 (–0.61 to –0.36) | –1.16 (–1.30 to –1.03) | –0.16 (–0.36 to 0.05) |
| Western Europe | 1427 (1149–1741) | –63.19 (–68.74 to –58.32) | 0.68 (0.55–0.83) | –60.42 (–62.5 to –57.89) | –2.94 (–3.23 to –2.65) | –4.48 (–4.64 to –4.32) | –1.43 (–1.66 to –1.20) |
| Andean Latin America | 2305 (1638–3151) | –61.25 (–65.55 to –56.39) | 3.65 (2.60–5.00) | –64.54 (–68.29 to –60.00) | –3.32 (–3.50 to –3.15) | –2.62 (–2.70 to –2.55) | –4.43 (–4.70 to –4.17) |
| Central Latin America | 5045 (3860–6460) | –74.51 (–77.16 to –71.35) | 2.38 (1.82–3.05) | –71.39 (–74.65 to –67.37) | –4.22 (–4.34 to –4.10) | –4.87 (–5.04 to –4.70) | –3.85 (–3.91 to –3.80) |
| Tropical Latin America | 6780 (5362–8508) | –60.85 (–64.32 to –57.88) | 4.37 (3.45–5.48) | –56.82 (–60.23 to –53.39) | –2.63 (–2.83 to –2.42) | –1.85 (–2.05 to –1.64) | –4.01 (–4.12 to –3.90) |
| North Africa and Middle East | 11,330 (8121–15,147) | –65.58 (–69.82 to –63.58) | 1.94 (1.39–2.59) | –67.34 (–70.83 to –64.86) | –3.77 (–3.87 to –3.67) | –3.32 (–3.41 to –3.23) | –4.37 (–4.48 to –4.27) |
| South Asia | 204,537 (168,433–245,327) | –33.78 (–35.43 to –32.35) | 12.75 (10.50–15.30) | –29.21 (–30.92 to –27.49) | –0.98 (–1.19 to –0.76) | 0.05 (–0.06 to 0.16) | –2.23 (–2.43 to –2.03) |
| East Asia | 15,170 (12,818–17,762) | –84.49 (–85.01 to –84.18) | 2.03 (1.71–2.37) | –75.01 (–76.06 to –74.19) | –5.42 (–6.30 to –4.52) | –0.21 (–0.97 to 0.55) | –8.87 (–9.41 to –8.32) |
| Oceania | 1083 (648–1681) | 53.23 (43.19–60.83) | 5.51 (3.29–8.56) | –17.26 (–23.26 to –13.13) | –0.56 (–0.62 to –0.49) | –0.30 (–0.47 to –0.13) | –0.73 (–0.81 to –0.65) |
| Southeast Asia | 25,027 (19,614–31,754) | –59.93 (–61.04 to –56.65) | 4.77 (3.74–6.06) | –53.85 (–55.42 to –50.00) | –2.60 (–2.79 to –2.41) | –1.67 (–1.78 to –1.56) | –3.70 (–3.85 to –3.56) |
| Central sub-Saharan Africa | 17,917 (12,686–24,499) | 14.75 (14.29 –18.04) | 8.41 (5.96–11.50) | –31.49 (–31.95 to –29.41) | –1.03 (–1.24 to –0.82) | –0.15 (–0.26 to –0.03) | –2.38 (–2.59 to –2.17) |
| Eastern sub-Saharan Africa | 107,298 (83,476–136,553) | 12.11 (1.51–24.66) | 15.91 (12.38–20.25) | –29.50 (–36.08 to –21.32) | –0.95 (–1.12 to –0.78) | –0.41 (–0.46 to –0.36) | –2.16 (–2.39 to –1.92) |
| Western sub-Saharan Africa | 149,818 (118,097–184,510) | 38.85 (34.19–41.03) | 19.13 (15.08–23.56) | –24.30 (–26.70 to –22.69) | –0.86 (–0.94 to –0.77) | –0.52 (–0.60 to –0.44) | –1.32 (–1.49 to –1.14) |
| Southern Sub-Saharan Africa | 6245 (4641–8116) | –1.3 (–11.83 to 5.07) | 7.74 (5.90–10.32) | –8.83 (–19.44 to –2.86) | 0.35 (–0.11 to 0.81) | 1.55 (1.00–2.10) | –2.91 (–3.20 to –2.62) |
ASMR: Age-standardized mortality rate; CI: Confidence interval; EAPC: Estimated annual percentage change; GBD: Global Burden of Disease; NE: Neonatal encephalopathy; SDI: Sociodemographic index; UI: Uncertainty interval.
Global DALYs for NE decreased from 72,555,078 (95% UI, 65,080,037–81,070,340) in 1990 to 53,356,613 (95% UI, 45,101,596–62,832,902) in 2019, with a reduction of 26.46% [Table 3]. The age-standardized DALYs also decreased from 1990 to 2019 [Figure 1C]. The annual reduction in age-standardized DALYs was significant from 2006 [Table 3].
Table 3.
Number and age-standardized rates of DALYs of NE in 2019, their change trends from 1990 to 2019, number of YLDs and proportion of YLDs in DALYs.
| Characteristics | DALYs number | Age-standardized DALY rate | YLDs | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Number (95% UI) | Percentage change, % (95% UI) | Rate (95% UI) per 100,000 population | Percentage change (%) | EAPC (95% CI) | Number (95% UI) | Proportion of YLDs in DALYs | |||
| 1990–2019 | 1990–2005 | 2006–2019 | |||||||
| Overall | 53,356,613 (45,101,596–62,832,902) | –26.46 (–30.70 to –22.50) | 817.02 (691.12 to 964.38) | –26.16 (–30.37 to –21.99) | –1.03 (–1.23 to –0.83) | 0.03 (–0.06 to 0.11) | –2.04 (–2.12 to –1.96) | 2,988,362 (1,979,868–4,323,882) | 5.60 |
| Sex | |||||||||
| Female | 22,412,430 (19,204,300–26,113,571) | –28.57 (–30.98 to –27.41) | 709.27 (607.04–829.12) | –28.33 (–30.83 to –26.92) | –1.15 (–1.32 to –0.98) | –0.21 (–0.32 to –0.10) | –2.03 (–2.11 to –1.94) | 1,407,318 (924,829–2,050,474) | 6.28 |
| Male | 30,944,182 (25,509,823–37,075,101) | –24.84 (–29.80 to –20.75) | 917.65 (755.28–1101.42) | –24.53 (–29.65 to –20.21) | –0.93 (–1.15 to –0.72) | 0.20 (0.12–0.28) | –2.05 (–1.97 to –2.12) | 1,581,043 (1,053,393–2,291,209) | 5.11 |
| SDI region | |||||||||
| High SDI | 650,343 (553,385–765,765) | –39.10 (–42.07 to –36.98) | 100.61 (87.27–115.41) | –43.19 (–45.61 to –41.63) | –1.88 (–2.02 to –1.73) | –2.47 (–2.57 to –2.38) | –0.95 (–1.09 to –0.81) | 327,588 (243,233–431,209) | 50.37 |
| High-middle SDI | 1,553,900 (1,327,500–1,813,571) | –71.20 (–72.47 to –69.98) | 181.84 (154.65–212.48) | –66.29 (–67.93 to –64.85) | –4.03 (–4.34 to –3.72) | –2.20 (–2.58 to –1.82) | –4.91 (–5.06 to –4.76) | 410,640 (290,101–548,015) | 26.42 |
| Middle SDI | 6,774,339 (5,654,903–8,022,408) | –60.68 (–63.32 to –58.9) | 383.09 (319.08–455.96) | –54.12 (–57.28 to –51.79) | –2.76 (–3.06 to –2.46) | –1.13 (–1.34 to –0.92) | –4.21 (–4.31 to –4.12) | 703,439 (464,445–1,013,603) | 10.38 |
| Low-middle SDI | 17,597,424 (14,537,533–21,037,461) | –35.32 (–39.21 to –32.50) | 1032.59 (853.30–1234.14) | –31.33 (–35.44 to –28.33) | –1.14 (–1.37 to –0.92) | 0 (–0.08 to 0.08) | –2.43 (–2.57 to –2.29) | 792,178 (490,545–1,204,489) | 4.50 |
| Low SDI | 26,754,443 (21,550,028–32,482,849) | –23.73 (13.81–31.15) | 1499.89 (1209.72–1819.91) | –21.90 (–28.05 to –17.26) | –0.64 (–0.73 to –0.56) | –0.37 (–0.43 to –0.31) | –1.14 (–1.33 to –0.94) | 752,944 (440,109–1,207,548) | 2.81 |
| GBD region | |||||||||
| Central Europe | 71,208.56 (58,055–85,974) | –73.96 (–76.23 to –71.92) | 96.51 (79.61–115.80) | –70.56 (–72.93 to –68.16) | –4.58 (–4.85 to –4.32) | –5.05 (–5.36 to –4.74) | –2.67 (–3.05 to –2.30) | 43,260 (32,126–55,922) | 60.75 |
| Eastern Europe | 198,981 (165,913–235,154) | –76.81 (–77.98 to –76.13) | 151.80 (125.01–180.97) | –74.18 (–76.02 to –73.07) | –5.23 (–5.46 to –5.00) | –5.18 (–5.83 to –4.52) | –4.25 (–4.64 to –3.85) | 80,550 (57,744–107,023) | 40.48 |
| Central Asia | 599,975 (509,570–720,210) | –46.36 (–46.96 to –44.17) | 656.94 (557.43–788.37) | –45.21 (–45.97 to –42.92) | –2.24 (–2.74 to –1.74) | 0.40 (0.11–0.69) | –4.90 (–5.14 to –4.65) | 73,939 (51,497–103,035) | 12.32 |
| Australasia | 23,900.76 (19,610–28,518) | –19.94 (–25.87 to –16.71) | 119.45 (98.11–143.71) | –36.18 (–41.40 to –32.22) | –1.54 (–1.71 to –1.38) | –0.77 (–1.18 to –0.36) | –1.69 (–1.80 to –1.57) | 8022 (5776–10,575) | 33.56 |
| High-income Asia Pacific | 96,000 (75,226–122,004) | –37.94 (–38.52 to –37.50) | 73.50 (60.26–89.52) | –43.59 (–44.98 to –43.07) | –1.72 (–1.95 to –1.50) | –2.69 (–3.13 to –2.25) | –0.67 (–0.84 to –0.51) | 80,202 (59,497–105,673) | 83.54 |
| High-income North America | 271,320 (234,864–314,367) | –23.85 (–25.63 to –22.38) | 112.95 (99.76–128.34) | –27.60 (–28.92 to –26.43) | –0.95 (–1.05 to –0.85) | –1.45 (–1.55 to –1.35) | –0.41 (–0.55 to –0.27) | 110,291 (79,189–149,372) | 40.65 |
| Southern Latin America | 67,226 (53,498–83,841) | –62.52 (–66.19 to –58.44) | 132.22 (104.11–166.16) | –62.97 (–66.95 to –58.63) | –3.53 (–3.73 to –3.33) | –4.23 (–4.36 to –4.10) | –2.14 (–2.32 to –1.95) | 20,433 (14,284–27,859) | 30.39 |
| Caribbean | 256,616 (183,859–343,934) | –22.43 (–30.66 to –16.55) | 651.09 (465.06–876.41) | –14.97 (–24.28 to –8.23) | –0.39 (–0.52 to –0.25) | –1.10 (–1.23 to –0.97) | 0.09 (–0.13 to 0.31) | 14,819 (10,063–21,345) | 5.77 |
| Western Europe | 246,484 (203,671–291,259) | –42.24 (–47.10 to –39.38) | 91.85 (77.02–107.84) | –48.17 (–52.99 to –44.52) | –2.04 (–2.30 to –1.78) | –3.42 (–3.59 to –3.25) | –0.72 (–0.9 to –0.53) | 119,755 (89,037–158,095) | 48.59 |
| Andean Latin America | 237,476 (176,434–312,208) | –55.35 (–58.64 to –51.66) | 375.79 (278.71–494.18) | –59.35 (–62.39 to –55.93) | –2.88 (–3.00 to –2.76) | –2.41 (–2.49 to –2.34) | –3.58 (–3.81 to –3.35) | 32,821 (22,305–45,990) | 13.82 |
| Central Latin America | 494,263 (383,750–623,395) | –72.12 (–74.55 to –69.14) | 230.32 (178.74–291.82) | –69.25 (–71.91 to –65.81) | –3.98 (–4.11 to –3.84) | –4.70 (–4.88 to –4.52) | –3.46 (–3.52 to –3.4) | 46,326 (28,721–69,972) | 9.37 |
| Tropical Latin America | 727,245 (591,090–888,138) | –53.60 (–56.64 to –51.35) | 445.57 (360.07–548.79) | –51.41 (–54.82 to –48.59) | –2.24 (–2.40 to –2.08) | –1.65 (–1.86 to –1.45) | –3.25 (–3.31 to –3.2) | 125,429 (84,091–179,844) | 17.25 |
| North Africa and Middle East | 1,357,820 (1,055,786–1,718,303) | –54.68 (–56.42 to –54.30) | 228.28 (177.03–288.16) | –57.74 (–59.35 to –57.62) | –2.95 (–3.00 to –2.89) | –2.91 (–2.98 to –2.85) | –2.72 (–2.92 to –2.53) | 352,730 (257,006–462,799) | 25.98 |
| South Asia | 18,895,487 (15,637,384–22,485,498) | –31.31 (–32.91 to –30.27) | 1172.16 (970.12–1396.43) | –27.01 (–28.71 to –25.77) | –0.88 (–1.08 to –0.68) | 0.08 (–0.03 to 0.19) | –1.99 (–2.19 to –1.79) | 724,008 (425,882–1,147,549) | 3.83 |
| East Asia | 1,537,258 (1,314,658–1,791,268) | –82.50 (–82.93 to –82.27) | 194.22 (165.49–226.50) | –73.38 (–74.12 to –72.99) | –5.21 (–6.06 to –4.35) | –0.17 (–0.91 to 0.57) | –8.46 (–9.01 to –7.91) | 190,825 (117,331–285,728) | 12.41 |
| Oceania | 99,404 (61,112–153,169) | 56.68 (49.01–64.24) | 511.22 (317.85–786.19) | –14.85 (–17.98 to –10.75) | –0.46 (–0.52 to –0.40) | –0.29 (–0.46 to –0.13) | –0.46 (–0.57 to –0.34) | 3197 (2011–4807) | 3.22 |
| Southeast Asia | 2,332,081 (1,827,308–2,926,767) | –58.16 (–59.36 to –55.23) | 440.62 (345.83–553.40) | –52.37 (–53.65 to –48.97) | –2.50 (–2.68 to –2.33) | –1.63 (–1.75 to –1.52) | –3.49 (–3.62 to –3.35) | 1,089,534 (66,202–165,069) | 46.72 |
| Central sub-Saharan Africa | 1,725,921 (1,261,824–2,305,704) | 23.76 (20.63–31.68) | 835.39 (612.00–1109.84) | –24.09 (–26.38 to –19.51) | –0.68 (–0.81 to –0.54) | –0.11 (–0.24 to 0.01) | –1.41 (–1.66 to –1.16) | 134,101 (74,025–216,225) | 7.77 |
| Eastern sub-Saharan Africa | 9,916,452 (7,756,178–12,552,915) | 16.31 (5.88–28.66) | 1495.28 (1174.67–1887.05) | –25.77 (–32.21 to –18.06) | –0.78 (–0.91 to –0.65) | –0.38 (–0.44 to –0.33) | –1.69 (–1.92 to –1.47) | 383,732 (227,073–596,382) | 3.87 |
| Western sub-Saharan Africa | 13,604,441 (10,761,173–16,685,665) | 42.75 (37.37–40.78) | 1756.10 (1391.91–2150.57) | –22.76 (–24.28 to –21.84) | 0.51 (0.11–0.92) | –0.51 (–0.59 to –0.43) | –1.03 (–1.21 to –0.86) | 292,738 (155,750–495,456) | 2.15 |
| Southern Sub-Saharan Africa | 597,047 (455,790–766,462) | 4.60 (–4.2 to 11.24) | 747.93 (570.75–959.36) | –3.80 (–11.93 to 2.39) | –0.76 (–0.82 to –0.69) | 1.52 (0.99–2.05) | –2.36 (–2.61 to –2.11) | 42,226 (27,279–62,451) | 7.07 |
CI: Confidence interval; DALY: Disability Adjusted Life Year; Estimated annual percentage change; GBD: Global Burden of Disease; NE: Neonatal encephalopathy; SDI: Sociodemographic index; UI: Uncertainty interval; YLD: The years lived with a disability.
Regional and national burden of NE
Among 21 geographical regions, South Asia and regions across sub-Saharan Africa (Central, Eastern, and Western) were regions with the largest number of cases of NE, accounting for 80.00% of global cases in 2019 [Table 1]. South Asia, and Eastern and Western sub-Saharan Africa also contributed to the largest number of deaths and DALYs, accounting for 81.42% and 79.50% of global totals in 2019 [Tables 2 and 3]. Notably, the number of NE cases increased in Sub-Saharan Africa from 1990 to 2019, accompanied by rising deaths and DALYs in its central, eastern, and western regions. Sub-Saharan Africa and South Asia also exhibited the highest ASIR, ASMR, and age-standardized DALY rates in 2019 [Tables 1–3]. In contrast, East Asia had the lowest ASIR, and high-income Asia Pacific had the lowest AMSR and age-standardized DALY rate [Tables 1–3]. Between 1990 and 2019, the ASIR of NE decreased in all regions except Southern Latin America, Caribbean, and central sub-Saharan Africa [Table 1]. During the same time period, there was a significant reduction in ASMR and age-standardized DALY across all regions [Tables 2 and 3].
There was a significant negative correlation between regional SDI and age-standardized incidence (R = −0.56), mortality (R = −0.77), and DALY rate (R = −0.76) for NE (all P values <0.01, Figure 2). In SDI-stratified regions, low-middle- and low-SDI regions constituted 84.98% and 83.12% of global deaths and DALY in 2019 [Tables 2 and 3]. Low-middle or low SDI regions also experienced the smallest reductions in ASIR, ASMR, and age-standardized DALY rates from 1990 to 2019 compared to other regions [Figure 1, Tables 1–3]. The most notable declines were observed in high-middle and middle SDI regions [Figure 1, Tables 1–3]. Post-2005, all regions, except those with high SDI, saw an accelerated reduction in ASIR, ASMR, and age-standardized DALY rates, with the greatest EAPCs in high-middle and middle SDI regions [Tables 1–3].
Figure 2.
Age-standardized incidence, mortality and DALYs rates of NE vs. SDI by region, 1990–2019. The black line, a LOWESS (locally weighted smoothing) smoother, shows the expected value only on the SDI values of the global regions between 1990 and 2019, trends in incident cases and ASIR. (A) Age-standardized incidence vs. SDI. (B) Age-standardized mortality vs. SDI. (C) Age-standardized DALYs rates vs. SDI. ASIR: Age-standardized incidence rate; DALYs: Disability-adjusted life years; NE: Neonatal encephalopathy; SDI: Sociodemographic index.
National level analyses [Supplementary Tables 1–3, http://links.lww.com/CM9/C461] showed that Nigeria, India, Pakistan, and Ethiopia had the highest burden of NE in 2019, contributing to 82.75% of cases, 52.93% of deaths, and 51.60% of DALYs globally. The most pronounced increase in incidence was observed in Qatar (183.47%), followed by Afghanistan (183.47%), both of which are located in North Africa and Middle East. The country with the most pronounced decrease in incident cases was China (−76.84%), followed by Democratic People’s Republic of Korea (−75.78%), both of which are located in East Asia. The country with the most pronounced decrease in deaths and DALYs was Cook Islands (−96.77% in deaths and −93.35% in DALYs), followed by Hungary (−96.39% in deaths and −88.44% in DALYs). In sub-Saharan Africa, Gabon (13.17%) and Congo (12.04%) had the largest increases in ASIR, while Liberia had the largest decreases in ASIR (−29.26%) and ASMR (−58.59%).
Contribution of NE in neonatal and under-5 mortality rate (U5MR)
In 2019, the distribution of NE-related deaths was 90.10% in early neonatal period (0–6 days), 7.11% in late neonatal period (7–28 days), 2.33% in post-neonatal infancy, and 0.47% in children aged 1–4 years [Supplementary Figure 1, http://links.lww.com/CM9/C461]. NE-related death comprised 22.76% of global all-cause neonatal mortality and 11.24% of under-5 mortality. From 1990 to 2019, the proportion of NE-related deaths in both neonatal and under-5 mortality demonstrated a significant increase, while the rate of increase slowed down after 2005 [Figure 1D,E]. NE-related death showed the highest contribution to neonatal and under-5 mortality in low (25.94% of neonatal, 10.96% of under-5 mortality) and low-middle SDI regions (21.85% of neonatal, 12.74% of under-5 mortality) in 2019.
Long-term impairment caused by NE
In terms of impairment, global number of NE-related years lived with a disability (YLDs) increased significantly from 722,356 in 1990 to 2,988,362 in 2019, representing an increase of 313.70% [Table 3]. The global proportion of NE-related YLDs in DALYs rose from 1.00% in 1990 to 5.60% in 2019, with the highest share in high (50.37%) and high-middle (26.43%) regions [Supplementary Figure 2, http://links.lww.com/CM9/C461].
For specific impairment, in 2019, an estimated 3,911,702 cases of epilepsy were caused by NE, representing 7.44% of all epilepsy cases. Of these, 2,078,377 (53.13%) were moderate epilepsy and 1,833,325 (46.87%) were severe. A total of 4,233,436 cases of developmental intellectual disability were caused by NE, accounting for 2.38% of all such disability globally. Among these, 1,471,049 (34.75%) had moderate and 1,739,173 (41.08%) severe disability. Furthermore, NE led to 566,291 cases of blindness, constituting 0.07% of global blindness cases. Notably, the impact of NE-related impairments spanned the entire lifespan [Supplementary Figure 3, http://links.lww.com/CM9/C461].
Discussion
Main findings
This study presents the most extensive assessment to date of the global and regional burden of NE. Despite a 30% reduction in deaths and a 26% decrease in DALYs since 1990, global NE cases have risen by 3% over three decades. In 2019, the world still faced 1.38 million NE cases, 0.57 million NE-related deaths, and 5.34 million NE-related DALYs. Notably, NE’s proportion of neonatal and U5MR has grown, accounting for 23% of neonatal and 11% of U5MR in 2019 globally. The study also highlights the substantial risk of long-term impairment, with 3.91 million epilepsy and 4.23 million developmental intellectual disability cases attributable to NE. The highest NE burden was concentrated in South Asia and sub-Saharan Africa, contributing to over 80% of global burden. A significant acceleration in the decline of NE incidence and mortality rates post-2005 marks another key finding.
High incidence of NE
The persistent high incidence of NE, with 1.38 million cases in 2019, underscores an urgent need for targeted interventions. Our findings are consistent with previous research, which estimated 1.15 million global NE cases in 2010.[5] More importantly, in the spectrum of critical events caused by birth asphyxia, around 60% of fetuses or neonates present with stillbirth or early neonatal death before the onset of NE.[5] Therefore, with NE as an indicator, the actual burden of birth asphyxia could be double those of reported cases. Another critical concept is that the majority of NE are preventable. The ASIR in East Asia was as low as 3.49/100,000, only 1/6 of the global rate and 1/15 of that in central sub-Saharan Africa. This significant difference confirms that most NE could potentially be prevented. Aligning with the Sustainable Development Goals and the Every Newborn Action Plan, prioritizing the prevention of NE and birth asphyxia could prevent over a million NE cases annually and even more birth asphyxia-related deaths.[6,7]
Increased total number of cases
The 3% global increase in absolute NE cases from 1990 to 2019 is also concerning. The global increase was caused by the increasing incident cases in sub-Saharan Africa, which may be largely attributed to the region’s significant birth rate increase.[20] Despite a general decrease in ASIR in sub-Saharan Africa (except the central region), the sheer number of births has led to a substantial rise in NE cases. An accelerated reduction in incidence is essential to counteract this trend. On the other hand, improved neonatal care might also have contributed to this increase, as it reduces stillbirths and early neonatal deaths, leading to more NE diagnoses. However, our aim is not merely to shift the outcome from early death to NE, but to prevent the entire spectrum of birth asphyxia-related injuries.
High mortality of NE
The near 30% global decrease in NE’s ASMR over the past three decades is a commendable achievement, reflecting progress across all regions. Yet, the burden of mortality remained significant with 0.57 million NE deaths in 2019. While a prior study estimated lower NE deaths in 2010, it likely underrepresented global NE mortality, drawing heavily on data from areas with advanced neonatal care.[5] Our study could not provide case fatality rate directly. However, the 41% rate derived from dividing 0.57 million deaths by 1.38 million incident cases may reflect NE’s high fatality rate, because 97% of NE deaths occurred within the neonatal period. Therefore, NE remains a critically fatal condition globally, underscoring the need for more comprehensive data to refine case-fatality rate estimations.
Increased share in neonatal and under-5 mortality
Also, the growing share of NE deaths in neonatal and U5MR is a critical concern. In 2019, NE was responsible for about one-fourth of all neonatal deaths and one-ninth of under-5 deaths. Recent studies corroborate this trend, showing an increasing proportion of neonatal deaths in overall under-5 mortality, with NE emerging as the second leading cause of death in these age groups.[2,21,22] Despite experiencing decreases, the progress for reducing mortality due to NE was relatively much slower compared with various communicable diseases.[2] Intensifying efforts to lower NE-related deaths should be a priority, offering significant potential to improve overall neonatal and U5MR.
Long-term impairment
Beyond mortality, survivors of NE face a high risk of long-term neuro-developmental impairments.[3,4] We found a threefold increase in impairment burden from 1990 to 2019, as shown by the rising absolute numbers and age-adjusted rates of YLDs, signaling an emerging urgency in preventing disabilities. Regionally, high and high-middle SDI regions are facing growing challenges. Importantly, NE is also a significant preventable contributor to global epilepsy and developmental intellectual disability burden, with over 40% of NE-related cases classified as severe with a lifelong impact. However, our findings should be interpreted with caution. Our data may underestimate the true burden of NE-related impairment, as GBD data did not include impairments such as cerebral palsy, hearing loss, and behavioral problems.[23–25] The reliance on prevalence data also means the effect of recent interventions might not be immediately evident, emphasizing the need for incidence data on NE-related impairments.
Regions with the highest NE burden
Over 80% of global NE burden is concentrated in south Asia and sub-Saharan Africa, regions characterized by high baseline burden with relatively slow progress in reducing incidence and mortality. Key factors contributing to NE in these areas include low rates of skilled birth attendance and facility births, poor intrapartum care and emergency obstetric care, and limited access to essential neonatal resuscitation.[7] For example, only about 50% of births in sub-Saharan Africa and some South Asian countries receive skilled birth attendance.[7,26] The absence of reliable vital registration data further hampers progress by impeding targeted and timely responses.[27] Therefore, primary prevention, through skilled care at birth, facility births, and scaling up at-risk and emergency obstetric care, is vital and priority.[28–30] Enhancing community mobilization and implementing financial strategies can significantly improve access to these essential services. Additionally, basic and simplified neonatal resuscitation, as secondary prevention of NE, is sufficient for most babies in low-resource settings.[28,30,31] Post-resuscitation management includes managing serum glucose levels, fluid management, the use of anticonvulsants, and thermal management to reduce the risk of further brain damage. Enhancing data collection and surveillance systems will help monitor NE trends more accurately, identify high-risk areas, and allocate resources effectively. Our data also showed considerable variation in progress among countries within the same regions, highlighting the potential for benchmarking and mutual learning among countries.
Acceleration of improvement since 2005
The most encouraging finding in our study is the accelerated reduction in the global burden of NE since 2005. The acceleration was particularly notable in high-middle and middle SDI regions. This temporal trend also parallels the reported faster decline in U5MR from 2005.[22] Such marked reduction coincides with the intensified global health initiatives that launched around 2000, focusing on improving child and neonatal health—a focus previously overlooked in global health policy.[32–34] The improvement in neonatal care has also accelerated the decline in NE mortality. For instance, hypothermia was proven in 2005 to be a valuable treatment for infants with moderate or severe hypoxic-ischemic encephalopathy and has since rapidly developed.[35,36] Complementing these efforts, enhanced data availability has also played a critical role. Initiatives like “Countdown to 2015” have been pivotal in raising awareness of the problem and tracking progress.[26,32,33] Additionally, the introduction of the World Health Organization’s newborn resuscitation guidelines in 1998 may also have been crucial, especially in resource-limited settings, offering essential clinical guidance for basic neonatal resuscitation.[37] Notably, the remarkable progress observed in high-middle and middle SDI regions presents a crucial opportunity for future research. Investigating these regions in depth can help identify the most effective strategies and interventions. The lessons learned post-2005 are indispensable for shaping future strategies and sustaining the momentum in reducing NE globally.
While our study fills a crucial gap in concurrent NE burden data, it is important to recognize its limitations. Firstly, while GBD methodologies are state-of-the-art, the estimates rely on the availability and quality of existing data. In regions where data are scarce, especially those with the highest NE burden, estimates are based on mathematical modeling. This approach could introduce biases. Secondly, though strict inclusion and exclusion criteria were applied and ICD-10 diagnosis was used to define NE in the GBD data, there was a lack of standardized diagnostic criteria for NE in the included studies. Therefore, misclassification errors could arise from varying definitions and diagnostic criteria for NE across various studies. The absence of data on NE severity also precluded analysis across different stages of severity. Also, in the GBD database, confounding factors are not available, and thus we cannot directly produce results accounting for such factors. Additionally, our study could not provide specific metrics like incidence rates in birth or live-birth populations, case-fatality rates, or detailed date on the incidence of impairments. This underscores the need for data from multiple sources to gain a more complete understanding of NE’s burden. Lastly, the GBD data does not capture all types of impairments associated with NE, potentially leading to an underestimation of the overall impairment burden.
In conclusion, there have been significant strides in reducing NE mortality from 1990 to 2019, particularly since 2005. However, the persistent and escalating incidence and absolute number of cases of NE remains a critical concern, especially in South Asia and sub-Saharan Africa. These results underscore the urgent need for targeted interventions and robust initiatives specifically tailored to high-burden regions.
Conflicts of interest
None.
Funding
This study was funded by grants from the National Key Research and Development Program of China (No. 2024YFC2707700) and the Shanghai Science and Technology Commission’s Scientific and Technological Innovation Action Plan (No. 21Y21900800).
Supplementary Material
Footnotes
How to cite this article: Ji XS, Xiong ZM, Peng T, Hu LY, Cheng GQ, Qian LL, Zhang P, Zhao XF, Lee HC, Zhou WH, Jiang SY. Global, regional, and national burden of neonatal encephalopathy due to birth asphyxia and trauma, 1990–2019. Chin Med J 2026;139:2597–2607. doi: 10.1097/CM9.0000000000003642
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