From past patterns to future preparedness: a secondary analysis of the Global Burden of Disease Study 2021 on neonatal communicable disease burden in China and the Asia-Pacific region, 1990–2035

Introduction

In 2021, coronavirus disease 2019 (COVID-19) was the primary contributor to disability-adjusted life years (DALYs) globally, followed by ischemic heart disease, neonatal diseases, and stroke (1). The neonatal period (0–28 days after birth) is the most vulnerable and critical stage for children’s survival, with nearly 47% of under-five child deaths occurring in this period worldwide in 2022, and neonatal infections being the leading cause of these deaths (2). Neonatal communicable diseases (CDs), a major subset of neonatal infections, are closely associated with immature immune systems, suboptimal perinatal care, and adverse environmental factors (3). Additionally, unhygienic delivery conditions, preterm birth, low birth weight and inadequate postnatal care further exacerbate the risk of neonatal CDs in low-and middle-income countries (LMICs) (4). Although global neonatal CDs mortality has declined with advances in medical care and public health interventions, the disease burden remains disproportionately distributed across regions (5), posing a major barrier to achieving the Sustainable Development Goal (SDG) 3.2 target of ending preventable neonatal deaths (6).

At the national level (China), previous studies have documented the declining trend of neonatal CD burden since the 1990s, attributing the reduction to the implementation of national maternal and child health programs (7). However, these studies are limited by single-site or provincial-level data coverage, lack of long-term continuous trend analysis, and insufficient quantification of disease burden indicators (8). Local surveillance studies in China also suffer from inconsistent diagnostic criteria and incomplete reporting systems across different regions, especially in rural and remote areas, leading to underreporting of neonatal CD cases and difficulty in reflecting the true disease burden (9).

At the Asia-Pacific regional level, existing research has identified the region as a global hotspot for neonatal CD burden, with high disease burden concentrated in South Asian and Southeast Asian LMICs such as India, Indonesia, and Bangladesh (10). These studies have analyzed short-term trends of neonatal CD mortality and identified preterm birth and low birth weight as key risk factors (11), but most lack cross-country comparative analysis of age-standardized disease burden rates and fail to capture the heterogeneous temporal trends across countries with different economic and health development levels.

Previous iterations of the Global Burden of Disease (GBD) study have provided a global framework for quantifying neonatal CD burden, but they have critical limitations. First, earlier GBD iterations lacked stratification of neonatal CDs by sub-disease categories, making it impossible to identify the dominant CD subtypes driving the regional disease burden (12). Second, the earlier versions had insufficient refinement of age stratification for neonates, failing to distinguish between early (0–6 days) and late (7–27 days) neonatal periods (13). Third, previous GBD studies did not fully link neonatal CD burden to Socio-demographic Index (SDI) at the national level, which limits the analysis of the association between socioeconomic development and disease burden disparities (12). The GBD 2021 study, as the latest iteration of the GBD series, has addressed the limitations of previous versions by refining disease classification, age stratification, and SDI linkage. According to statistics, many countries, including China, Brazil, India, Japan, New Zealand and the United Kingdom, have applied the relevant results of the GBD Study to support their national project planning (14). A key issue in global neonatal health is the severe health inequity in neonatal services, correlated with SDI values and especially prominent in the Asia-Pacific region (15). This vast SDI disparity directly leads to extreme inequity in neonatal service access and quality (15).

This study evaluates the burden of neonatal CDs in China and the Asia-Pacific region from 1990 to 2021 using GBD 2021 data and projects trends through 2035. These findings will elucidate key epidemiological challenges and inform targeted public health strategies to improve patient outcomes and reduce health inequity. Specific objectives include: (I) quantifying the incidence, prevalence, mortality, and DALYs burden levels of CDs during 1990–2021, along with their evolving trends at the national and regional levels; (II) identifying critical turning points, phased trends and gender/age disparities in neonatal CDs burden and its primary risk factors across China and the Asia-Pacific region from 1990 to 2021; (III) predicting the trajectory of CDs in China and the Asia-Pacific region from 2022 to 2035 by gender and population subgroup; (IV) analyzing the association between neonatal CD burden disparities and SDI values in the Asia-Pacific region to provide evidence for SDI-adapted regional neonatal health interventions. We present this article in accordance with the STROBE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0049/rc).

Methods

Data sources

We used the data of GBD 2021 (https://ghdx.healthdata.org/gbd-2021), led by the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in the United States. GBD 2021 adopted a uniform and comparable approach to assess the disease burden data for 371 diseases/injuries and 88 risk factors across 204 countries/regions, with strict quality control and standardized processing to ensure cross-temporal and cross-regional comparability (1). We have provided more detailed information of GBD 2021 in the Appendix 1. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

For China, GBD 2021 integrated multi-source data to address the heterogeneity of data availability across periods. Disease Surveillance Points (DSP) system launched in 1980s, covered 145 surveillance points across 31 provinces by 1990s. It collected routine data on infectious disease incidence, mortality, and demographic information via hierarchical reporting (16). The supplementary materials are sourced from the National Health Statistics Yearbooks, vital registration data, hospital discharge records from key tertiary hospitals, and epidemiological surveys (17). DSP system provided continuous, standardized data for key infectious diseases with clear diagnostic criteria aligned with the 9th/10th edition of the International Classification of Diseases (ICD) (ICD-9/ICD-10) (18). To address under-reporting and miscoding, GBD 2021 applied two key calibration strategies: under-reporting adjustment (19) and miscoding correction (20).

The Asia-Pacific region integrated data from national vital registration systems, disease registries, WHO regional reports, and academic studies (21). For LMICs in the region, GBD 2021 supplemented with verbal autopsy data and demographic and health surveys to address data scarcity.

Despite being in 2026, the 1990–2035 timeframe was selected for three key reasons. First, regarding data availability and continuity, GBD 2021 offers the most comprehensive and standardized data from 1990 onwards for China and the Asia- Pacific region (10). Second, for long-term trend analysis, a 31-year retrospective period [1990–2021] helps capture secular trends, critical turning points, and the impact of major public health interventions (22). Third, in terms of policy relevance, the 10- year projection [2022–2035] aligns with the SDG 3.2 target timeline, providing actionable evidence for long-term policy planning (23).

GBD 2021’s national-level estimates for neonatal CDs are highly reliable, achieved through three validation mechanisms: internal cross-validation (R²>0.8 for mortality and incidence) (24), external validation against independent surveys (mortality deviation <15%) (22) and uncertainty quantification via 95% uncertainty intervals (UIs) from Monte Carlo simulations (25).

Analysis index

Disease burden indicators: incidence, prevalence, death and DALYs of neonatal CDs in China and the Asia-Pacific region [1990–2021], including absolute numbers and age-standardized rates [age-standardized incidence rate (ASIR); age-standardized prevalence rate (ASPR); age-standardized mortality rate (ASMR); age-standardized DALYs rate (ASDR)]. Age-standardization was performed using the GBD 2021 world standard population to eliminate age structure differences across regions.

Trend of change: (I) estimated annual percentage change (EAPC) quantifies the average annual trend of disease burden rates over a period. We calculated EAPC and 95% CIs for ASIR/ASPR/ASMR/ASDR using R’s lm function, based on 100 × (exp(β) − 1), where β is the annual change in the natural logarithm of the age-standardized rate (26). The trends were considered a decrease when the upper boundary of the 95% CI of EAPC was less than 0; whereas if the lower boundary was greater than 0, the upward trends of the burden were defined; otherwise, the trends were stable (27,28). (II) Joinpoint regression (version 5.2.0, https://surveillance.cancer.gov/joinpoint) identifies “joinpoints” and quantifies trend changes in segments (29). The model can calculate annual percentage change (APC), average annual percent change (AAPC), and their 95% CI. APC indicates the description of the alteration in data within a particular period; AAPC represents the average annual rate of change of data throughout the entire time span to reflect the overall trend of data variance over an extended period (10). (III) The autoregressive integrated moving average (ARIMA) possesses excellent predictive capability, and its predictive accuracy is relatively high within the 10-year forecasting period. To ensure a high level of predictability, accordingly, this article predicted the burden of CDs in China and the Asia-Pacific region employing the data from 1990 to 2021 as the test set, the ARIMA was utilized to predict the variations in diseases burden for different genders and the entire population.

For non-statistical audiences: Joinpoint regression identifies significant turning points in trends. It splits the long-term trend into connected linear segments, with the optimal number of segments selected by the Bayesian Information Criterion (BIC) (lower = better fit). APC describes the annual change in each segment; AAPC summarizes the overall average trend. Significance is verified by Monte Carlo permutation tests (10,000 permutations, P<0.05). We have provided the detailed calculation formulas in the Appendix 2.

Statistical analysis

All statistical analyses and the visualization of results were accomplished through the R software (version 4.4.2), with the following packages: joinpoint (for Joinpoint regression), Epi (for APC analysis), forecast (for ARIMA modeling), and ggplot2 (for visualization) (30). A two-tailed P value<0.05 was deemed statistically significant.

Results

Overall burden

The numbers and rates of incidence, prevalence, mortality, and DALYs of CDs in China and the Asia-Pacific region, along with the EAPC from 1990 to 2021, was presented in Table 1. In 2021, the incident cases, prevalent cases, deaths and DALYs cases of CDs among neonates decreased to 3,741,300.85 (3,225,740.06; 4,336,353.39); 324,827.41 (285,469.40; 370,668.75); 10,443.43 (9,249.43; 11,680.64); 943,933.69 (836,631.68; 1,054,860.03) in China and 9,506,181.04 (8,231,390.93; 10,912,289.76); 907,884.72 (864,617.13; 952,117.81); 139,795.68 (120,557.20; 161,328.99); 12,601,800.32 (10,867,306.15; 14,540,210.20) in the Asia-Pacific region. The age-standardized rates showed a statistically significant declining trend However, the incidence rate and prevalence rate showed a trend of exhibited a trend of initial decline followed by a gradual increase in the Asia-Pacific region. (Figure 1). Among the ASIR, ASMR and ASDR, the burden diseases among males were higher than that among females in China and the Asia-Pacific region (Figure 1A,1C,1D,1E,1G,1H).

Figure 1 Trends in rates of incidence, prevalence, death and DALYs of neonatal CDs in China and the Asia-Pacific region from 1990 to 2021. (A-D) The changing trends of the incidence rate, prevalence rate, death rate and DALYs rate of neonatal CDs in China. (E-H) The changing trends of the incidence rate, prevalence rate, death rate and DALYs rate of neonatal CDs in the Asia-Pacific region. The solid red line, the dotted blue line and the dotted green line represent the overall population, females and males respectively. CDs, communicable diseases; DALYs, disability-adjusted life years.

Analysis of AAPC

Between 1990–2021, the ASIR (AAPC =−1.997, 95% CI: −2.042, −1.951), the ASPR (AAPC =−1.693, 95% CI: −1.723, −1.663), ASMR (AAPC =−9.295, 95% CI: −9.574, −9.015), ASDR (AAPC =−9.283, 95% CI: −9.563, −9.004) of CDs decreased in China. In the Asia-Pacific region, the ASPR took 2015 as a turning point and showed a trend of first decreasing and then increasing, with the AAPC of −0.623 (95% CI: −0.707, −0.539) and the ASIR took 2016 as a turning point with the AAPC of −0.980 (95% CI: −1.069, −0.891). The ASMR (AAPC =−3.408, 95% CI: −3.554, −3.263) and the ASDR (AAPC =−3.402, 95% CI: −3.548, −3.256) of CDs in the Asia-Pacific region were decreased (P<0.05, Figure 2).

Figure 2 Time trends of incidence, prevalence, death and DALYs rate of neonatal CDs in China and the Asia-Pacific region from 1990 to 2021. (A) The AAPC changes of China’s incidence rate can be divided into four stages: 1990–1996, APC was −0.87%; 1996–2003, APC was −3.44%; 2003–2009, APC was −4.16%; 2009–2021, APC was −0.64%. (B) The AAPC changes of China’s prevalence rate can be divided into six stages: 1990–1995, APC was −1.34%; 1995–2000, APC was −1.75%; 2000–2004, APC was −3.40%; 2004–2009, APC was −1.29%; 2009–2015, APC was −1.47%; 2015–2021, APC was 1.37%. (C) The AAPC changes of China’s death rate can be divided into five stages: 1990–1995, APC was −2.56%; 1995–2023, APC was −6.58%; 2003–2008, APC was −9.90%; 2008–2014, APC was −11.92%; 2014–2021, APC was −14.52. (D) The AAPC changes of China’s DALYs rate can be divided into five stages: 1990–1995, APC was −2.56%; 1995–2003, APC was −6.58%; 2003–2008, APC was −9.90%; 2008–2014, APC was −11.91%; 2014–2021, APC was −14.48. (E) The AAPC changes of the Asia-Pacific region’s incidence rate can be divided into four stages: 1990–1998, APC was −0.70%; 1998–2012, APC was −1.54%; 2012–2016, APC was −2.27%; 2016–2021, APC was 1.17%. (F) The AAPC changes of the Asia-Pacific region’s prevalence rate can be divided into five stages: 1990–1998, APC was −0.87%; 1998–2005, APC was −1.78%; 2005–2012, APC was −0.70%; 2012–2015, APC was −1.92%; 2015–2021, APC was 1.80%. (G) The AAPC changes of the Asia-Pacific region’s death rate can be divided into five stages:1990–1992, APC was −0.97%; 1992–2000, APC was −2.52%; 2000–2011, APC was −4.19%; 2011–2016, APC was −5.32%; 2016–2021, APC was −2.17%. (H) The AAPC changes of the Asia-Pacific region’s DALYs rate can be divided into five stages: 1990–1992, APC was −0.94%; 1992–2000, APC was −2.52%; 2000–2011, APC was −4.18%; 2011–2016, APC was −5.31%; 2016–2021, APC was −2.17%. All of the above were P<0.05 and were statistically significant. AAPC, average annual percent change; APC, annual percentage change; CDs, communicable diseases; DALYs, disability-adjusted life years.

The composition and temporal trend of CDs in neonates

The CDs in the GBD database covered a wide range and mainly included the following categories: human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and sexually transmitted infections, respiratory infections and tuberculosis, enteric infections, neglected tropical diseases and malaria, other infectious diseases. Figure 3 presented the changing trends of the burden of 5 sub-diseases of neonatal CDs in China and in the Asia-Pacific region from 1990 to 2021.The ASIR, ASPR, ASMR and ASDR of CDs by disease category, as well as the relative ranking were showed in Figure S1. Overall, respiratory infections and tuberculosis still had high endemic levels. The ASIR of respiratory infections and tuberculosis has not shown significant improvement. The changing of the ASPR is rather complex, showing a trend of first decreasing and then increasing both in China and the Asia-Pacific region. The remaining four sub-diseases, after effective prevention and control, have dropped to a relatively low level in 2021, and the disease burden has been significantly reduced.

Figure 3 Trends in the disease burden of five sub-diseases of neonatal CDs in China and the Asia-Pacific region from 1990 to 2021. (A-D) The changing trends of the incidence rate, prevalence rate, death rate and DALYs rate of five sub-diseases of neonatal CDs in China. (E-H) The changing trends of the incidence rate, prevalence rate, death rate and DALYs rate of five sub-diseases of neonatal CDs in the Asia-Pacific region. The five different colored lines respectively represent five sub-diseases. AIDS, acquired immunodeficiency syndrome; CDs, communicable diseases; DALYs, disability-adjusted life years; HIV, human immunodeficiency virus.

The temporal trends in age, gender of neonatal CDs

The neonatal period, within 28 days after birth, can be divided into the early neonatal period (0–6 days) and the late neonatal period (7–27 days). As can be seen in Figure 4, from 1990 to 2021, the overall neonatal CDs showed a downward trend in China. In the Asia-Pacific region, the ASIR and ASPR showed a trend of first decreasing and then increasing, while the ASMR and ASDR is continuously declining. Neonatal CDs mainly occurred in the early stage of neonates. During this period, the improvement of indicators was the greatest, suggesting the effectiveness of early intervention strategies.

Figure 4 Trends in the burden of neonatal CDs in different periods in China and the Asia-Pacific region from 1990 to 2021. These eight figures illustrate the changing trends of the incidence rate, prevalence rate, death rate and DALYs rate of CDs in neonates (A-H). The three lines in figures represent three different age groups. CDs, communicable diseases; DALYs, disability-adjusted life years.

By gender stratification, we have drawn a gender two-coordinate graph. Figure 5 showed the gender stratification trend analysis of neonatal CDs in China and the Asia-Pacific region from 1990 to 2021. These figures presented the differences in indicators and the temporal evolution characteristics of different gender groups through the dual indicators of “number” and “rate”. From 1990 to 2021, the disease burden has shown a continuous downward trend, and the gender gap has narrowed, reflecting the balanced effectiveness of disease prevention and control measures for both male and female. Especially after 2010, gender equity has improved.

Figure 5 The gender stratification trend of neonatal CDs in China and the Asia-Pacific region from 1990 to 2021. These eight figures are based on the time axis of “year (year, horizontal axis, 1990–2021)”, and each graph contains two types of data dimensions: the left vertical axis: absolute number, right vertical axis: rate per 100,000 population. Each figure contains three lines, corresponding respectively to “female”, “male”, and “total”. (A-D) The disease burdens in China. (E-H) The disease burdens in the Asia-Pacific region. CDs, communicable diseases.

Analysis of risk factors

We summarized the main risk factors of neonatal CDs in China and the Asia-Pacific region and plotted the changing trends of relevant indicators of the 7 key risk factors, as shown in Figure 6. The risk factors mainly included: (I) high temperature; (II) ambient particulate matter (PM) pollution; (III) low birth weight and short gestation; (IV) low temperature; (V) secondhand smoke; (VI) suboptimal breastfeeding; (VII) unsafe water, sanitation, and handwashing. The disease burden caused by risk factors mainly includes: death rate and DALYs rate. It can be seen from the figure that the disease burden of the 7 risk factors all show a continuous downward trend. Among them, the death rate and DALYs rate of “Low birth weight and short gestation” is the highest. In 2021, the death rate and DALYs rate of the “Low birth weight and short gestation” decreased to 2,148.60 and 193,394.45 per 100,000 in China, 5,515.23 and 496,355.59 per 100,000 in the Asia-Pacific region. The death and DALYs rate of “Low birth weight and short gestation” decreased the fastest, reflecting the significant effectiveness of perinatal care (such as preterm birth prevention and neonatal resuscitation).

Figure 6 Trends in the death rate (A,C) and DALYs rate (B,D) of 7 key risk factors. The 7 solid lines of different colors are respectively used to represent 7 risk factors. The disease burden of all 7 types of risk factors has shown a continuous downward trend. Among them, the death rate and DALYs rate of “low birth weight and short gestation” and “ambient particulate matter pollution” accounted for the highest proportion. DALYs, disability-adjusted life years.

Overall burden of neonatal CDs in the Asia-Pacific region by SDI

Across the Asia-Pacific region, as shown in Figure 7, the age-standardized rates of death, DALYs, prevalence, and incidence of neonatal CDs all exhibited strong inverse associations with the SDI. As SDI increased, all four burden indicators declined monotonically, with the most rapid reductions observed at low-to-middle SDI levels. Regions with lower SDI, such as South Asia, carried substantially higher disease burden, whereas high-SDI regions including Australia and New Zealand maintained consistently low rates. The steepest decline was seen for mortality and DALYs, suggesting that improvements in socio-economic development and health care access predominantly reduce fatal outcomes. In contrast, prevalence and incidence declined more gradually, and residual burden persisted even at high SDI levels, indicating a continued need for preventive interventions beyond mortality reduction. These findings highlight a pronounced health equity gradient across the Asia-Pacific, whereby socio-economic development is strongly linked to reductions in neonatal infectious disease burden.

Figure 7 Overall burden of neonatal CDs in the Asia-Pacific region classified by SDI. For each region, points from left to right depict estimates from each year from 1990 to 2021. The figure contains 4 core indicators: deaths, DALYs, prevalence and incidence. All are plotted with the “age-standardized rate” as the vertical axis and “SDI” as the horizontal axis. CDs, communicable diseases; DALYs, disability-adjusted life years; LOESS, locally estimated scatterplot smoothing; SDI, Socio-Demographic Index.

Prediction of CDs burden in China and the Asia-Pacific region in the next 10 years

By employing ARIMA, the burden of CDs in China and the Asia-Pacific region were predicted until 2035 by sex, and the results were presented in Figure 8. Based on the data of CDs among neonates in China from 1990 to 2021, the ARIMA model predicted that the number of incidence, prevalence, death and DALYs will drop to 1,987,828, 175,075, 947 and 86,057.30 person-years in China by 2035. It is suggested that the disease burden of neonates in China will show a downward trend in the future. Gender analysis showed that the disease burden was consistently higher in male than in female, but the unfair gender gap is narrowing. In the Asia-Pacific region, the incidence, prevalence, death and DALYs number will drop to 6,920,272.98, 684,508.80, 72,668.08 and 65,53370.45 person-years by 2035 and the unfair gender gap is narrowing.

Figure 8 Long-term trends and future predictions of CDs in China and the Asia-Pacific region of different genders from 1990 to 2035. Horizontal axis: year, covering 1990 to 2035, where 1990 to 2021 are actual monitoring data and 2020 to 2035 are predicted data. Longitudinal axis: health indicators values (number of incidence, prevalence, deaths and DALYs). Each figure contains three line breaks, corresponding to “female”, “male”, and “both” respectively, focusing on gender differences and overall trends. (A) China incidence number; (B) China prevalence number; (C) China mortality number; (D) China DALYs number; (E) Asia-Pacific region incidence number; (F) Asia-Pacific region prevalence number; (G) Asia-Pacific region mortality number; (H) Asia-Pacific region DALYs number. CDs, communicable diseases; DALYs, disability-adjusted life years.

Discussion

This is the first study to systematically estimate the long-term burden of neonatal CDs in China and the Asia-Pacific region using GBD 2021 data. Our findings demonstrate a substantial and sustained decline in the burden of neonatal CDs over the past three decades, with further reductions projected through 2035.

The decline in neonatal CDs burden is due to enhanced antenatal care, hospital delivery, neonatal resuscitation, vaccination, and antibiotic access-reducing pathogen exposure, improving host defense, and enabling timely treatment. Mortality has fallen more sharply than incidence, highlighting the impact of better case management. Respiratory infections and tuberculosis remain leading causes, with slower progress indicating ongoing challenges in infection control and maternal respiratory health.

The higher burden of CDs in male neonates, linked to biological factors (immature immunity, weaker barriers, androgen effects), narrowed post-2010. This trend reflects improved health equity through universal care and gender-equitable policies, reducing disparities in treatment and support, rather than a change in inherent biological vulnerability.

The burden of neonatal CDs in Asia-Pacific shows a clear inverse gradient with SDI. High-SDI countries saw early, rapid declines. Middle-SDI nations like China accelerated progress post-2000. Low-SDI countries face persistently high burdens. Importantly, as SDI improved, the epidemiological pattern shifted from high mortality due to severe systemic infections to higher prevalence due to milder, recurrent, or persistent infections. This transition reflects a shift from mortality reduction to morbidity control, requiring targeted strategies for infection prevention rather than just emergency treatment (31). Key dimensions of neonatal health inequity analyzed in this study: (I) inequity in access to skilled birth attendants and facility-based delivery: low-SDI and lower-middle-SDI countries in the Asia-Pacific region have much lower coverage of facility deliveries and skilled birth attendants, leading to higher risks of intrapartum infection and early-onset neonatal sepsis (15); (II) inequity in infection prevention and control: hygienic delivery practices, clean surface, clean cord care, hand hygiene, and access to safe water and sanitation are far less consistent in low-SDI settings, directly increasing neonatal CD transmission (6); (III) inequity in timely and effective treatment: access to emergency newborn care, appropriate antibiotics, neonatal resuscitation, and supportive care is severely limited in low-SDI regions, causing higher case fatality despite similar incidence patterns (13); (IV) inequity in public health infrastructure and preventive policies: high-SDI regions benefit from stronger maternal and child health programs, routine immunization, perinatal quality improvement, and surveillance systems, whereas low-SDI regions lack sustained investment and implementation capacity (21); (V) inequity driven by socioeconomic disadvantage: poverty, maternal education, household nutrition, and environmental pollution further widen the gap in neonatal health outcomes between SDI subgroups within the Asia-Pacific (2).

Stratified analysis of age suggested that neonates aged 0–6 days is in a “critical window period” for disease prevention and control. Early detection, early diagnosis, and early treatment can effectively reduce the disease burden. Gender stratification analysis showed that the health indicators of neonatal CDs have been effectively improved and the gender gap has gradually narrowed in the past 30 years.

In the risk factor analysis, we found that with the intensification of global climate change, high-temperature events have become more frequent and severe, posing significant health risks to pregnant women and neonates. Neonates exposed to heat are more likely to develop low birth weight (32), jaundice (33), respiratory distress syndrome, etc. (34). In addition to high temperatures, low temperatures also have adverse effects on neonates, which is consistent with the findings of this study that high and low temperatures are risk factors for CDs (35). Ambient PM a key risk factor for neonatal CDs through multiple biological pathways: it induces maternal oxidative stress and placental dysfunction, disrupts fetal respiratory barriers, alters neonatal microbiomes, and increases preterm birth. These pathways collectively suppress innate and adaptive immunity, providing a mechanistic link between air pollution and the burden of neonatal infections. In the future, it is necessary to strengthen the formulation and implementation of strict environmental protection regulations and emission standards, and strictly control the PM emissions from industrial enterprises (36). Breastfeeding is significant in enhancing feeding tolerance, reducing the occurrence of infections, promoting the development of the nervous system, and improving long-term prognosis, which is consistent with the finding of this study that suboptimal breastfeeding is a risk factor for CDs (37). Unsafe water, sanitation, and handwashing is also the risk factor of CDs. The role of rural drinking water projects, hygiene habit education should be emphasized (38). Low birth weight and short gestation remained the predominant risk factor, acting through immature organogenesis, impaired immunity, and weakened barrier function (39).

Our mechanistic findings support region-specific, SDI-tailored interventions: (I) strengthen perinatal care to reduce preterm birth and low birth weight; (II) mitigate air pollution through stricter environmental regulations to protect neonatal immune development; (III) promote gender-equitable access to neonatal care to sustain the narrowing gender gap; (IV) scale up hygiene, safe water, sanitation, and breastfeeding programs in low-SDI settings; (V) prioritize respiratory infection prevention and early treatment given its persistent contribution to the burden.

This article has standardized the writing by referring to the STROBOD statement, improving its overall quality and the comparability of research results, thereby providing a high-quality evidence basis for formulating scientific and effective public health policies (40).

There are some limitations in this study. Firstly, due to the fact that the definitions of neonatal CDs may vary in different regions, there may be incorrect classification or coding in the statistical sources, which affects the results (24). Secondly, the GBD database cannot clearly define the causal relationship between the risk factors and the disease burden. At the same time, the lag of GBD data should also be noted. Thirdly, the GBD database relies on the public health systems and reporting mechanisms of various countries. Low-income countries or regions with scarce medical resources often encounter problems such as insufficient collection of data and incomplete health reports. There may be under reporting or misreporting of diseases in these regions, which can lead to deviations in the accuracy of the data on a global scale.

Conclusions

Our study showed that the burden of CDs among neonates in China and the Asia-Pacific region are in a dynamic downward trend, confirming the remarkable achievements in public health prevention and medical treatment over the past 30 years. Nevertheless, considering the vast population base in China, the disease burden remains profoundly severe. Male neonates have always been a high-risk group in disease burden, but the gender gap has gradually narrowed, reflecting that the coverage and effectiveness of intervention measures for different gender groups tend to be balanced, and health equity continues to improve among different genders. A comprehensive grasp of the burden of CDs and the temporal variation patterns in China and the Asia-Pacific region will facilitate the formulation of customized and adjustable intervention strategies.

Acknowledgments

We sincerely thank all the members of the Global Burden of Disease 2021 Collaborative Group for their commitment. Based on their work, we have analyzed and deepened our understanding of the burden of disease.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0049/rc

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0049/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0049/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The GBD project team desensitised all patient information used for the study, and the University of Washington’s Institutional Review Board approved a waiver of informed consent and ethical review. Therefore, the Ethics Committee of Children’s Hospital of Nanjing Medical University exempted this study from ethical review. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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