Urban–Rural Disparity in Preterm Neonatal Mortality in China: A Retrospective Study

Urban–Rural Disparity in Preterm Neonatal Mortality in China: A Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Urban–Rural Disparity in Preterm Neonatal Mortality in China: A Retrospective Study Yuxi Liu, Leni Kang, Yanna Zou, Xue Yu, Chunhua He, Yiyong Su, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6210926/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Oct, 2025 Read the published version in BMC Pediatrics → Version 1 posted 10 You are reading this latest preprint version Abstract Background The neonatal mortality rate (NMR) is a vital indicator for assessing maternal and child health, and preterm birth is one of the leading causes of neonatal mortality. Since 2010, China has implemented multiple maternal and child health policies aimed at reducing neonatal mortality. However, systematic research on urban-rural disparities in neonatal mortality among preterm births remains relatively scarce. In this study, we analyzed the national and subnational cause-specific death rates of preterm neonates in mainland China during 2010 to 2021 to provide data support for the further elimination of neonatal deaths. Methods In this retrospective study, we analyzed empirical data on levels and causes of preterm neonatal mortality data from the China Maternal and Child Health Surveillance System to show the cause-specific death rates, birthplaces and treatment levels at the national and subnational levels. Results Between 2010 and 2021, the top three causes of death in preterm neonates were preterm birth, birth asphyxia and congenital malformations in both urban and rural areas. From 2010 to 2021, the mortality rate among preterm neonates born at 28 to 31 gestational weeks was significantly higher than that among preterm neonates born at 32 to 33 gestational weeks and 34 to 36 gestational weeks in both urban and rural areas. We also found that in urban areas, 95.5% of preterm neonates were born at provincial (or municipal)-level hospitals in 2021, while this proportion was 60.2% in rural areas. Regarding the treatment level, the proportion of preterm neonates in rural areas who were diagnosed at district (or county)-level health facilities decreased from 46.7–21.8% from 2010 to 2021. In contrast, this proportion in urban areas was 6.5% in 2010 and 2.3% in 2021. Conclusions This study reveals the remarkable achievements China has made in reducing preterm neonatal mortality and narrowing the urban-rural disparity, while the gap between urban and rural preterm neonatal mortality is not negligible. Policy interventions have been the primary driving force behind the reduction of the urban-rural gap, while resource scarcity in remote western regions and the economic pressures faced by rural households remain significant challenges. Preterm neonates neonatal death urban–rural disparity Figures Figure 1 Figure 2 Figure 3 Background Preterm neonates are defined as babies born alive before 37 weeks of gestation. Preterm birth complications remain the leading cause of under-5 mortality worldwide. Approximately 13.4 million premature babies are born in 2020 and were responsible for approximately 900 thousand deaths in 2019 1 2 . Premature births are on the rise worldwide in recent decade 1 3 – 6 .The incidence of preterm birth may increase the financial burden for both families and society, since surviving preterm infants have higher risks of neonatal complications and adulthood diseases than infants born at term 7 8 . As neonatal deaths accounted for approximately half of the total deaths in children under 5 years old worldwide in 2020 9 , and direct complications caused by preterm birth were the main cause of children under 5 mortalities in 2019 2 . Therefore, to achieve the SDG 3.2 (Sustainable Development Goal 3.2) 10 , it is necessary to pay more attention to the management of preterm birth and its complications to reduce children under 5 mortalities. A total of 7.8% of the total preterm births worldwide in 2014 were estimated to have occurred in China, placing it second in the world 3 11 . China began to implemented family planning policy since 1980, encouraging couples to have only one child (or the ‘One Child Policy’ for short). 12 In order to promote the long-term balanced development of population and alleviate the pressure of population aging, the Chinese government officially implemented the Universal Two Child Policy on January 1st 2016. 13 Since the Universal Two Child Policy closely related to the increased proportion of maternal age, multipara, and the assisted reproductive technologies. 14 – 16 The implementation of the two-child policy may increase demand for basic public health services. To advance neonatal survival in China, the classification of preterm neonates’ causes of death would help policy-makers better target interventions to prevent neonatal deaths. Due to the difference of social development between urban and rural areas in China, there are significant urban-rural disparity in neonatal health in China 17 – 19 . Since the recent analysis of different causes of death among preterm newborns in urban and rural areas in mainland China is lacking. In this study, we analyzed the national and subnational cause-specific death rates of preterm neonates in mainland China from 2010 to 2021 to provide data support for the further elimination of neonatal deaths. Methods Study subjects All study subjects were drawn from the Maternal and Child Health Surveillance System (MCHSS). The MCHSS is a sample registration system collecting vital statistics on levels and causes of maternal and child mortality and data on congenital abnormalities. Further details about the MCHSS have been described in another study 15 . All 327 National Maternal and Child Health Surveillance Districts (with 130 urban districts and 197 rural districts) in the 31 provinces, autonomous regions and municipalities of China were covered. The urban or rural classification was derived from criteria used in the 1993 National Health Services Survey and the 2006 administrative division codes published by the National Bureau of Statistics 20 21 . All children under five from the 327 surveillance districts were involved in the MCHSS, there were no exclusion criteria. The study subjects also involved adopted children and children of nonlocal household residents whose mothers have been living in the surveillance districts for over one year. A livebirth was defined as a fetus of at least 28 weeks’ gestation (or with birthweight of more than 1000g if the gestational age was unknown), and who had one of the four life indicators after birth—heartbeat, breathing, umbilical cord pulsation, and voluntary muscle contraction. Community health workers and village doctors of surveillance districts were recorded and reported livebirths’ number to the local district (or county) Maternal and Child Health Centers (MCHCs) monthly, and the district (or county) MCHCs were uploaded livebirths’ information quarterly. Data collection and quality control All children under five of surveillance districts who died after birth and had one of the four life indicators (including heartbeat, breathing, umbilical cord pulsation, and voluntary muscle contraction) were involved in the MCHSS. For children who died in home or communities (or villages), community health workers (or village doctors) were confirmed the child's survival status and report to the township MCHCs within 3 days. Then township MCHCs health workers were collected the death information (including the last clinical diagnosis, the causes of accidental injury types or signs and symptoms experienced by the child before death) and sent to the local district (or county) MCHCs within 7 days. Based on the collected death information, the surveillance staff of the district (or county) MCHCs were determined the cause and classification of death, then uploaded the Under Five Child Death Report Card in the MCHSS. The classification of diseases was performed according to the International Classification of Diseases-10. For children who died in health facilities of the surveillance districts, the cause ascertainment was based on death certificates and last clinical diagnosis. Skilled health care workers of health facilities were completed the Under Five Child Death Report Card, then sent regularly to the local district (or county) MCHCs every month. All child mortality data were uploaded into the MCHSS and checked level by level. The district (or county) MCHCs check the accuracy and completeness of all local child death report cards. If any errors were found, the district (or county) MCHCs provide feedback to the township (or street) MCHCs for correction. The district (or county) MCHCs complete checks regularly and send feedback to the local municipal and provincial MCHCs every season. The National Office of Maternal and Child Health summarizes and analyses the data annually. Annually, the National Office of Maternal and Child Health randomly chooses fourteen to eighteen districts (or counties) of six to seven provinces for level-to-level quality control. According to the requirements of the Chinese Maternal and Child Health Surveillance Work Manual, the quality control method of cross-checking multisource data is adopted to recheck the original data of the hospitals and MCHCs at all levels. The aim of quality control is to find missed data and guide the daily work of the township (or street) and district (or county) MCHCs. Statistics The data were analyzed by SPSS 22.0 (IBM, Armonk, NY, USA), and the annual percent change (APC) were analyzed by the Join point Regression Program (version 4.8.0.1, Statistical Research and Applications Branch, National Cancer Institute, Bethesda, MD, USA). Based on the standard of World Health Organization (1977), we categorized preterm births into very preterm (born between 28 and 31 weeks), moderate preterm (born between 32 and 33 weeks), and late preterm (born between 34 and 36 weeks). 22 Results Preterm neonatal mortality rates of neonates at different gestational ages in urban and rural areas from 2010 to 2021 The preterm neonatal mortality rates of all groups showed decreasing trends from 2010 to 2021. In 2010, the mortality rates for extremely preterm neonates in urban and rural areas were 171.6 per 100000 live births and 94.7 per 100000 live births respectively, which decreased to 119.2 per 100000 live births and 68.4 per 100000 live births by 2021. For the moderate preterm neonates, the mortality rates were 82.6 per 100000 live births and 36.4 per 100000 live births in urban and rural areas in 2010, declining to 28.1 per 100000 live births and 15.2 per 100000 live births in 2021. Similarly, the late preterm neonates mortality rates showed a significant reduction from 128.0 per 100000 live births (urban) and 74.8 per 100000 live births (rural) in 2010 to 45.0 per 100000 live births and 28.7 per 100000 live births respectively in 2021. The neonatal mortality rate of the very preterm group was significantly higher than those of the other groups in both urban and rural areas.[ Figure 1 ] Cause-specific of preterm neonatal deaths in China from 2010 to 2021 The cause-specific mortality rate of preterm neonates in China from 2010 to 2021 is summarized in Table 1a to 1c . Since 2016 marks the official implementation of the two-child policy, we consider 2016 as a time node to analyze the APC. At the national level, the top causes of preterm neonatal deaths from 2010 to 2021 were preterm birth, birth asphyxia, and congenital malformations. The mortality rate of preterm neonates fell from 245.8 (230.3 to 261.4) per 100000 live births in 2010 to 75.8 (65.7 to 85.9) per 100000 live births in 2021, and the APC was showed a faster downward trend since 2016, which was decreased from -7.8% (-9.2 to -6.4) to -12.9% (-19.9 to -7.4). The mortality rate of birth asphyxia fell from 31.8 (26.2 to 37.4) per 100000 live births in 2010 to 28.5 (22.3 to 34.7) per 100000 live births in 2021, and the APC was 6.8% (0.1 to 14.8) in 2010 to 2015, but was not statistically significant in 2016 to 2021, with an APC of -3.0%. On the contrast, the mortality rate of congenital malformations at national level was fluctuated from 2010 to 2021, with 22.4 (17.7 to 27.1) per 100000 live births and 21.5 (16.1 to 26.9) per 100000 live births, respectively. The APC of congenital malformations were both not statistically significant during study period. [ Table 1a ] From 2010 to 2021, the top three causes of preterm neonatal deaths in urban and rural areas were same, but the urban‒rural variation was observed in cause-specific mortality rates and APC. The proportion of preterm births and birth asphyxia of urban and rural areas in 2021 were closed, while the mortality rate of rural areas was almost twice that of those in urban areas. Between 2010 and 2015, the decline trend of preterm births in rural areas was higher than that in urban areas, while the urban-rural gap narrowed significantly from 2016 to 2021, with the APC were -12.2% and -13.1%, respectively. In both urban and rural areas, the death rate of congenital malformations fluctuated and showed no obvious downward trend, with the APC were not statistically significant. It is worth noting that neonatal sepsis was not serious in either urban or rural areas in 2010, but in 2021, the death rate of neonatal sepsis increased to 10.1 per 100000 live births and 12.4 per 100000 live births. Moreover, from 2016 to 2021, the increase was more prominent and has statistically significant in rural areas, with an APC of 27.6% [ Table 1b & 1c ] Preterm neonates’ birthplaces and treatment levels in China between 2010 and 2021 The percentages of preterm neonatal birthplaces and the last treatment health facilities level in China from 2010 to 2021 was represented in Figure 2. The proportion of birth at provincial (or municipal) level hospitals increased from 35.0% in 2010 to 75.7% in 2021, and that at district (or county) level hospitals dropped from 45.5% in 2010 to 18.8% in 2021. For treatment level, 79.9% of preterm neonates were treated in provincial (or municipal) level hospitals in 2021, which was almost doubled the proportion in 2010. There were still 13.2% of preterm neonates last treated at district (or county) level hospitals. [ Figure 2 ] Referral of preterm neonates in rural China from 2010 to 2021 In this study, the referral was defined as preterm neonates who born at other level health facilities and treated at the provincial (or municipal) level hospitals. After we calculated the referral rate in rural areas by three preterm birth groups, the results showed that the referral rates of all groups showed a fluctuating upward trend during 2010 to 2021. The gap in referral rates of the very preterm groups versus the other two groups peaks in 2021. The referral rate of the very preterm group was 15.8% in 2021, which was significantly lower than that of other groups. The referral rate of the moderate preterm group was increased from 6.2% in 2010 to 33.3% in 2021. Moreover, the referral rate of the late preterm group was the highest among three groups, which have almost quadrupled from 9.9% in 2010 to 38.1% in 2021. [ Figure 3 ] Discussion In this study, we analyzed urban-rural disparities in preterm neonatal mortality rates in China from 2010 to 2021, highlighted that while persistent urban-rural gaps remain, it also reflects China's remarkable progress in reducing neonatal mortality over this period. China has emerged as one of 10 'high-performing' countries in achieving MDGs (Millennium Development Goals) 4 and 5, with significant improvements in maternal and child health over the past decade 23 . In order to promote the healthy growth of children, the State Council of PRC issued the Outline of China's Child Development (2011–2020) and the Healthy China 2030 24 25 . These policies emphasize strengthening the construction of the maternal and child health service system and improving the service capacity of medical and health institutions. By strengthening personnel training, equipment allocation and referral mechanism construction, the survival rate of premature newborns in rural areas has been significantly improved. To our knowledge, this study of preterm neonatal deaths in the 327 National Maternal and Child Health Surveillance Districts is the first national-level assessment of different gestational weeks in urban and rural areas, which serves to fill a gap in our knowledge of the current status of preterm neonatal deaths in China. It may enable to prioritize and target specific areas of care practices for change. The results of our study showed that the difference between urban and rural preterm neonates was still obvious. The disparity in the preterm neonatal mortality rate between urban and rural areas of the moderate preterm group and the late preterm group were become narrowing during 2010 to 2021. Moreover, the gap of the very preterm group was particularly larger when compared to the other two groups. [ Figure 1 ] These results may be related to several factors. Firstly, this may relate to the increased maternal age and proportion of multiparous mothers during the Universal Two Child Policy period 16 26 27 . Since the China's new family planning policy (the Three-child Policy) was officially implemented since May 2021 28 , the rate of preterm birth increased significantly from after the two-child policy. After the implementation of the Two-child policy, the preterm birth rate of second children increased significantly 29 , and the proportion of elderly mothers increased from 14.6–34.6%, and the risk of fetal distress also increased 30 . The increased maternal age and the proportion of multiparous mothers may continue to be important factors for preterm birth. Moreover, the relative lack of health care resources per capita and the economic burden in rural areas. The medical resources in rural areas are relatively scarce and impose asignificant economic burden. In 2021, the number of medical practitioners per 1,000 population and the number of hospital beds per 1,000 population of urban areas were significantly higher than that of rural areas, while the percentage healthcare expenditure of consumer expenditure in rural areas was higher than urban areas, with 10.3% and 8.0%, respectively. 19 Furthermore, the awareness of prenatal care among pregnant women in rural areas is relatively weak, and the screening and management of risk factors for preterm birth are not timely enough. The hospital delivery rate in urban and rural China increased from 73.5% and 50.8% in 1996 to both 99.9% in 2021, respectively 31 32 . China issued guidelines and regulations on standardizing prenatal care services in 2011 and 2016 respectively, which were implemented nationwide. The guidelines recommend that all pregnant women receive prenatal care services at medical institutions no less than five times 33 34 and all pregnant women can receive five free health services at primary health care institutions. However, the proportion of pregnant women receiving prenatal care five or more times in rural areas is significantly lower than that in urban areas 35 until 2015, and the early warning ability of premature birth is weak. In view of the above challenges, the measures to reduce preterm neonatal deaths in China should focus on the following measures. Firstly, the local RNTN (Reginal neonatal transport network) in rural areas must be enhanced. The National Health Commission of China released the Regulations on pregnancy risk assessment and management 36 and the Guidelines for neonatal transport in China in 2017 37 , which serve as guidelines for intrauterine referral and neonatal transport. The implementation of the Universal Two Child Policy in China in 2016, the number of the second children has occupied near 50% of the total number of new births 38 , and the neonatal care resources (NCR) is highly related to neonatal deaths 39 . Therefore, continuous efforts need to be made to strengthen the construction and coverage of Neonatal Intensive Care Unit (NICU) in rural area to ensure that premature newborns can receive timely treatment. Simultaneously, the discharge against medical advice (DAMA) constitutes a significant contributing factor to neonatal survival and morbidity in preterm infants 40 . Given that financial constraints represent a primary factor influencing parental decisions to discontinue medical treatment for preterm infants, incorporating neonatal intrauterine transport into medical insurance reimbursement coverage could effectively alleviate the healthcare burden in rural areas. Furthermore, it is imperative to enhance maternal health education campaigns in rural regions, particularly emphasizing the importance of ensuring completion of five complimentary prenatal check-ups. This preventive strategy facilitates early identification of preterm delivery risks and consequently improves survival outcomes for premature infants. Limits The MCHSS does not contain maternal information for deceased children, such as parity, number of fetuses, age, and educational level, which have been proven to be directly related to neonatal deaths. 41 42 Therefore, this study cannot determine the impact on survival of preterm newborns by analyzing maternal factors. Moreover, the MCHSS have not collected the number of livebirths at different gestational weeks before 2022, so the mortality of different gestational weeks was calculated by total livebirths. In 2022, we started to collect livebirths’ number with gestational weeks, the mortality of different gestational weeks would be more accurate in further studies. Conclusion In conclusion, there were significant disparities between urban and rural areas in the cause-specific mortality rate and different gestational ages among preterm neonates during 2010 to 2021. It is important to focus on preterm neonatal survival, especially for neonates born at 28 to 31 gestational weeks. This study has shown the preterm neonatal death status in rural areas, which may help local governments further reduce the total neonatal mortality rate. Abbreviations NMR Neonatal Mortality Rate SDG Sustainable Development Goal MCHSS Maternal and Child Health Surveillance System MCHC Maternal and Child Health Center APC Annual Percent Change MDG Millennium Development Goal NICU Neonatal Intensive Care Unit DAMA Discharge Against Medical Advice Declarations Clinical trial number Not applicable. Ethics approval and consent to participate This study was approved by the Ethics Committee of West China Second University Hospital, Sichuan University, China. Our analysis is based on the national Maternal and Child Health Surveillance System, for which we have obtained a waiver of informed consent from the parents of the died children. Additionally, our report does not contain any personal information of the patients. This study was performed in accordance with the principles of the Declaration of Helsinki. Consent for publication Not applicable. Availability of data and materials This study used data from the NMCHSS. This system is co-established by the National Health Commission of the People Republic of China and Sichuan University, and finally owned by National Health and Family Planning Commission of the People Republic of China. The researchers did not obtain consent to publicly share data. The de-identified data set is available upon request to interested researchers. For data requests, please contact the Department of Science and Technology of West China Second University Hospital, Sichuan University, at: [email protected] . This department is in charge of all the programs in the hospital, including the data management. One staff from the department monitors this email. Competing interests None. Funding The study was supported by the National Key Research and Development Program of China (2022YFC2704605). Author Contributions Concept: Yanping Wang Design: Yuxi Liu Definition of intellectual content: Leni Kang, Yanna Zou, Xue Yu, Chunhua He Literature search: Yiyong Su, Chongmei Huang, Data analysis: Juan Liang, Cheng Wan Manuscript preparation: Yuxi Liu Manuscript editing & review: Cheng Wan Acknowledgments The authors would like to thank all health workers in this surveillance system for providing the data and investigating the cause of death. References Ohuma EO, Moller, A. 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Notice on the issuance of the National Basic Public Health Service Regulations. (Third Edition) 2016 [Available from: http://www.nhc.gov.cn/cms-search/xxgk/getManuscriptXxgk.htm?id=d20c37e23e1f4c7db7b8e25f34473e1b accessed February 27th 2025. National Health Commission of the People’s Republic of China. Administration of health care during pregnancy and childbirth, Guideline for Maternal Health Care Service 2011 [Available from: http://www.nhc.gov.cn/wjw/ywfw/201306/61f0bee3af344623a566ab099fffbf34.shtml accessed February 27th 2025. National Health Commission of the People’s Republic of China. Regulations on pregnancy risk assessment and management (2017 No.35) 2017 [Available from: http://www.nhc.gov.cn/fys/s3581/201711/9c3dc9b4a8494d9a94c02f890e5085b1.shtml accessed Mar. 27th 2024. Liu Y & Feng X. Status and relative changes of equality of antenatal cares among women in 15 provinces in China. Chinese Journal of Reproductive Health 2022;5(33):401-06. National Health Commission of the People’s Republic of China. Regulations on pregnancy risk assessment and management (2017 No.35) 2017 [Available from: http://www.nhc.gov.cn/fys/s3581/201711/9c3dc9b4a8494d9a94c02f890e5085b1.shtml accessed Mar. 27th 2024. Chinese Physicians Association Neonatal Specialty Committee. Guidelines for neonatal transport in China (2017 edition) Electronic Journal of Developmental Medicine 2017;4(5):193-97. National Health Commission of the People’s Republic of China . Statistical bulletin of health development 2022 in China 2023 [Available from: http://www.nhc.gov.cn/guihuaxxs/s3585u/202309/6707c48f2a2b420fbfb739c393fcca92.shtml accessed February 27th 2025. Li Q, Li X, Zhang Q, Zhang Y, Liu L, Cheng X, Yi B, Mao J, Chen C, He S, Liu L, Zhou X, Lu X, Lin Z, Zheng J, Chen X, Xia S, Li Y, Yue S, Yan C, Lin X, Wang Z, Tang J, Wang Y, Zhong D, Ma L, Chen Y, Li M, Mei H, Liu K, Yang L, Wang X, Wu H, Shi Y, Feng Z. A Cross-Sectional Nationwide Study on Accessibility and Availability of Neonatal care Resources in Hospitals of China: Current Situation, Mortality and Regional Differences: Neonatal Care Resources and Newborn Mortality in China. Lancet Reg Health West Pac 2021;14:100212. PMID: 34528000 doi: 10.1016/j.lanwpc.2021.100212 Cao Y, Jiang S, Sun J, Hei M, Wang L, Zhang H, Ma X, Wu H, Li X, Sun H, Zhou W, Shi Y, Wang Y, Gu X, Yang T, Lu Y, Du L, Chen C, Lee SK, Zhou W. Assessment of Neonatal Intensive Care Unit Practices, Morbidity, and Mortality Among Very Preterm Infants in China. JAMA Netw Open 2021;4(8):e2118904. PMID: 34338792 doi: 10.1001/jamanetworkopen.2021.18904 Liyew EF, Yalew AW, Afework MF, Essén B. Maternal near-miss and the risk of adverse perinatal outcomes: a prospective cohort study in selected public hospitals of Addis Ababa, Ethiopia. BMC Pregnancy Childbirth 2018;18(1):345. PMID: 30134858 doi: 10.1186/s12884-018-1983-y Carolan M, Frankowska D. Advanced maternal age and adverse perinatal outcome: A review of the evidence. Midwifery 2011;6(27):793-801. PMID: 20888095 doi: 10.1016/j.midw.2010.07.006 Table Table 1 is available in the Supplementary Files section Additional Declarations No competing interests reported. Supplementary Files Table1.docx Cite Share Download PDF Status: Published Journal Publication published 09 Oct, 2025 Read the published version in BMC Pediatrics → Version 1 posted Editorial decision: Revision requested 28 Apr, 2025 Reviews received at journal 27 Apr, 2025 Reviewers agreed at journal 31 Mar, 2025 Reviews received at journal 22 Mar, 2025 Reviewers agreed at journal 21 Mar, 2025 Reviewers invited by journal 21 Mar, 2025 Editor assigned by journal 21 Mar, 2025 Editor invited by journal 21 Mar, 2025 Submission checks completed at journal 20 Mar, 2025 First submitted to journal 20 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6210926","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":435586561,"identity":"9263566d-2f51-4a23-a3d9-1862c95d76e2","order_by":0,"name":"Yuxi Liu","email":"","orcid":"","institution":"West China Second University Hospital of Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Yuxi","middleName":"","lastName":"Liu","suffix":""},{"id":435586564,"identity":"db7d7fbe-5c6a-4303-b252-a4ca52fda2c5","order_by":1,"name":"Leni Kang","email":"","orcid":"","institution":"West China Second University Hospital of Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Leni","middleName":"","lastName":"Kang","suffix":""},{"id":435586565,"identity":"65f3af66-64be-4975-a45a-4301a82e1c7f","order_by":2,"name":"Yanna Zou","email":"","orcid":"","institution":"Changyi Maternal and Child care Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yanna","middleName":"","lastName":"Zou","suffix":""},{"id":435586566,"identity":"a0d964dd-941e-419e-9b12-e7f5680ac028","order_by":3,"name":"Xue Yu","email":"","orcid":"","institution":"West China Second University Hospital of Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Xue","middleName":"","lastName":"Yu","suffix":""},{"id":435586567,"identity":"170ac3d7-e30c-4252-8213-cbfcbd77afa8","order_by":4,"name":"Chunhua He","email":"","orcid":"","institution":"West China Second University Hospital of Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Chunhua","middleName":"","lastName":"He","suffix":""},{"id":435586568,"identity":"8c05b6b6-42b6-4787-9deb-938394c449b6","order_by":5,"name":"Yiyong Su","email":"","orcid":"","institution":"Maternity and child health hospital of Yanting County","correspondingAuthor":false,"prefix":"","firstName":"Yiyong","middleName":"","lastName":"Su","suffix":""},{"id":435586569,"identity":"4630d3ec-bd7a-4ca7-82a0-bc614911c6b3","order_by":6,"name":"Chongmei Huang","email":"","orcid":"","institution":"China MCC5 Group Corp. Ltd. Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chongmei","middleName":"","lastName":"Huang","suffix":""},{"id":435586571,"identity":"836a659f-9947-4037-8059-4f018314ed90","order_by":7,"name":"Juan Liang","email":"","orcid":"","institution":"West China Second University Hospital of Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Juan","middleName":"","lastName":"Liang","suffix":""},{"id":435586573,"identity":"ca2cd4af-8865-4f8a-9280-f0446cb46f25","order_by":8,"name":"Yanping Wang","email":"","orcid":"","institution":"West China Second University Hospital of Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Yanping","middleName":"","lastName":"Wang","suffix":""},{"id":435586574,"identity":"8f0dc83f-d4b9-4548-8a4f-9006337737fb","order_by":9,"name":"Cheng Wan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA50lEQVRIiWNgGAWjYJACZhDBxsz/8cEHAxs74rXwszcYG84oSEsmXotkzwEzaZ4PhxgbCCk3OH724OeCijt2G24kpEnbGBxgZmA/fHQDXi1n8pKlZ5x5lgzUctg6x+AOHwNPWtoNfFrMDuSYMfO2HU42uJHYeDvH4BkzgwSPGX4t598AtfwDaUlmkLYwOMzYQFDLDZAtDYftJHuOMUkzEKPF/sYbY2meY4cT+Nl7mA17DNKS2Qj5RbI/x/AzT81hezZmHsYHP/7Y2PGzHz6GVwsMJDbAWGzEKAc7kFiFo2AUjIJRMAIBAIq1TGd2whM3AAAAAElFTkSuQmCC","orcid":"","institution":"West China Second University Hospital of Sichuan University","correspondingAuthor":true,"prefix":"","firstName":"Cheng","middleName":"","lastName":"Wan","suffix":""}],"badges":[],"createdAt":"2025-03-12 09:53:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6210926/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6210926/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12887-025-06042-4","type":"published","date":"2025-10-09T15:57:16+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":79662078,"identity":"b47e032e-f062-49db-97cf-5b4791ebcd22","added_by":"auto","created_at":"2025-04-01 09:50:44","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":175087,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version.\u003c/p\u003e","description":"","filename":"Figure1.ThepretermneonatalmortalityrateindifferentgestationalweeksofChinafrom2010to2021.png","url":"https://assets-eu.researchsquare.com/files/rs-6210926/v1/9202bdf175c134110f731f7e.png"},{"id":79662074,"identity":"850bade3-5269-4edc-b54d-9fc4cb8f1999","added_by":"auto","created_at":"2025-04-01 09:50:44","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":69052,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version.\u003c/p\u003e","description":"","filename":"Figure2.ThebirthplacesandtreatmenthospitalsofpretermneonatesinChinafrom2010to2021.png","url":"https://assets-eu.researchsquare.com/files/rs-6210926/v1/11ef33e50f07b69b46e98916.png"},{"id":79662072,"identity":"b311f715-1d06-40cd-a339-42f02de3f202","added_by":"auto","created_at":"2025-04-01 09:50:44","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":36585,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version.\u003c/p\u003e","description":"","filename":"Figure3.TheproportionofreferralofpretermneonatesinChinafrom2010to2021.png","url":"https://assets-eu.researchsquare.com/files/rs-6210926/v1/1b94ec336b1b5d861eb047c2.png"},{"id":93419637,"identity":"f13a36c7-1307-4ddb-99ff-4fc29816c95d","added_by":"auto","created_at":"2025-10-13 16:04:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":909890,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6210926/v1/5a159da1-e326-40ce-8c6f-71f2cc36703b.pdf"},{"id":79662071,"identity":"6cdad267-d1be-4794-8cc4-25d67d6ae532","added_by":"auto","created_at":"2025-04-01 09:50:44","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":403967,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-6210926/v1/f63c088ee35e635609980a95.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Urban–Rural Disparity in Preterm Neonatal Mortality in China: A Retrospective Study","fulltext":[{"header":"Background","content":"\u003cp\u003ePreterm neonates are defined as babies born alive before 37 weeks of gestation. Preterm birth complications remain the leading cause of under-5 mortality worldwide. Approximately 13.4\u0026nbsp;million premature babies are born in 2020 and were responsible for approximately 900 thousand deaths in 2019\u003csup\u003e1 2\u003c/sup\u003e. Premature births are on the rise worldwide in recent decade\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e \u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e.The incidence of preterm birth may increase the financial burden for both families and society, since surviving preterm infants have higher risks of neonatal complications and adulthood diseases than infants born at term\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. As neonatal deaths accounted for approximately half of the total deaths in children under 5 years old worldwide in 2020\u003csup\u003e9\u003c/sup\u003e, and direct complications caused by preterm birth were the main cause of children under 5 mortalities in 2019\u003csup\u003e2\u003c/sup\u003e. Therefore, to achieve the SDG 3.2 (Sustainable Development Goal 3.2)\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e, it is necessary to pay more attention to the management of preterm birth and its complications to reduce children under 5 mortalities.\u003c/p\u003e \u003cp\u003eA total of 7.8% of the total preterm births worldwide in 2014 were estimated to have occurred in China, placing it second in the world\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. China began to implemented family planning policy since 1980, encouraging couples to have only one child (or the \u0026lsquo;One Child Policy\u0026rsquo; for short).\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e In order to promote the long-term balanced development of population and alleviate the pressure of population aging, the Chinese government officially implemented the Universal Two Child Policy on January 1st 2016.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e Since the Universal Two Child Policy closely related to the increased proportion of maternal age, multipara, and the assisted reproductive technologies.\u003csup\u003e\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e The implementation of the two-child policy may increase demand for basic public health services. To advance neonatal survival in China, the classification of preterm neonates\u0026rsquo; causes of death would help policy-makers better target interventions to prevent neonatal deaths.\u003c/p\u003e \u003cp\u003eDue to the difference of social development between urban and rural areas in China, there are significant urban-rural disparity in neonatal health in China\u003csup\u003e\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Since the recent analysis of different causes of death among preterm newborns in urban and rural areas in mainland China is lacking. In this study, we analyzed the national and subnational cause-specific death rates of preterm neonates in mainland China from 2010 to 2021 to provide data support for the further elimination of neonatal deaths.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy subjects\u003c/h2\u003e \u003cp\u003eAll study subjects were drawn from the Maternal and Child Health Surveillance System (MCHSS). The MCHSS is a sample registration system collecting vital statistics on levels and causes of maternal and child mortality and data on congenital abnormalities. Further details about the MCHSS have been described in another study\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. All 327 National Maternal and Child Health Surveillance Districts (with 130 urban districts and 197 rural districts) in the 31 provinces, autonomous regions and municipalities of China were covered. The urban or rural classification was derived from criteria used in the 1993 National Health Services Survey and the 2006 administrative division codes published by the National Bureau of Statistics \u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. All children under five from the 327 surveillance districts were involved in the MCHSS, there were no exclusion criteria. The study subjects also involved adopted children and children of nonlocal household residents whose mothers have been living in the surveillance districts for over one year. A livebirth was defined as a fetus of at least 28 weeks\u0026rsquo; gestation (or with birthweight of more than 1000g if the gestational age was unknown), and who had one of the four life indicators after birth\u0026mdash;heartbeat, breathing, umbilical cord pulsation, and voluntary muscle contraction. Community health workers and village doctors of surveillance districts were recorded and reported livebirths\u0026rsquo; number to the local district (or county) Maternal and Child Health Centers (MCHCs) monthly, and the district (or county) MCHCs were uploaded livebirths\u0026rsquo; information quarterly.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData collection and quality control\u003c/h3\u003e\n\u003cp\u003eAll children under five of surveillance districts who died after birth and had one of the four life indicators (including heartbeat, breathing, umbilical cord pulsation, and voluntary muscle contraction) were involved in the MCHSS. For children who died in home or communities (or villages), community health workers (or village doctors) were confirmed the child's survival status and report to the township MCHCs within 3 days. Then township MCHCs health workers were collected the death information (including the last clinical diagnosis, the causes of accidental injury types or signs and symptoms experienced by the child before death) and sent to the local district (or county) MCHCs within 7 days. Based on the collected death information, the surveillance staff of the district (or county) MCHCs were determined the cause and classification of death, then uploaded the Under Five Child Death Report Card in the MCHSS. The classification of diseases was performed according to the International Classification of Diseases-10. For children who died in health facilities of the surveillance districts, the cause ascertainment was based on death certificates and last clinical diagnosis. Skilled health care workers of health facilities were completed the Under Five Child Death Report Card, then sent regularly to the local district (or county) MCHCs every month.\u003c/p\u003e \u003cp\u003eAll child mortality data were uploaded into the MCHSS and checked level by level. The district (or county) MCHCs check the accuracy and completeness of all local child death report cards. If any errors were found, the district (or county) MCHCs provide feedback to the township (or street) MCHCs for correction. The district (or county) MCHCs complete checks regularly and send feedback to the local municipal and provincial MCHCs every season. The National Office of Maternal and Child Health summarizes and analyses the data annually.\u003c/p\u003e \u003cp\u003eAnnually, the National Office of Maternal and Child Health randomly chooses fourteen to eighteen districts (or counties) of six to seven provinces for level-to-level quality control. According to the requirements of the Chinese Maternal and Child Health Surveillance Work Manual, the quality control method of cross-checking multisource data is adopted to recheck the original data of the hospitals and MCHCs at all levels. The aim of quality control is to find missed data and guide the daily work of the township (or street) and district (or county) MCHCs.\u003c/p\u003e\n\u003ch3\u003eStatistics\u003c/h3\u003e\n\u003cp\u003eThe data were analyzed by SPSS 22.0 (IBM, Armonk, NY, USA), and the annual percent change (APC) were analyzed by the Join point Regression Program (version 4.8.0.1, Statistical Research and Applications Branch, National Cancer Institute, Bethesda, MD, USA). Based on the standard of World Health Organization (1977), we categorized preterm births into very preterm (born between 28 and 31 weeks), moderate preterm (born between 32 and 33 weeks), and late preterm (born between 34 and 36 weeks).\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePreterm neonatal mortality rates of neonates at different gestational ages in urban and rural areas from 2010 to 2021\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe preterm neonatal mortality rates of all groups showed decreasing trends from 2010 to 2021. In 2010, the mortality rates for extremely preterm neonates in urban and rural areas were 171.6 per 100000 live births and 94.7 per 100000 live births respectively, which decreased to 119.2 per 100000 live births and 68.4 per 100000 live births by 2021. For the moderate preterm neonates, the mortality rates were 82.6 per 100000 live births and 36.4 per 100000 live births in urban and rural areas in 2010, declining to 28.1 per 100000 live births and 15.2 per 100000 live births in 2021. Similarly, the late preterm neonates mortality rates showed a significant reduction from 128.0 per 100000 live births (urban) and 74.8 per 100000 live births (rural) in 2010 to 45.0 per 100000 live births and 28.7 per 100000 live births respectively in 2021. The neonatal mortality rate of the very preterm group was significantly higher than those of the other groups in both urban and rural areas.[\u003cstrong\u003eFigure 1\u003c/strong\u003e]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCause-specific of preterm neonatal deaths in China from 2010 to 2021\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe cause-specific mortality rate of preterm neonates in China from 2010 to 2021 is summarized in \u003cstrong\u003eTable 1a to 1c\u003c/strong\u003e. Since 2016 marks the official implementation of the two-child policy, we consider 2016 as a time node to analyze the APC. At the national level, the top causes of preterm neonatal deaths from 2010 to 2021 were preterm birth, birth asphyxia, and congenital malformations. The mortality rate of preterm neonates fell from 245.8 (230.3 to 261.4) per 100000 live births in 2010 to 75.8 (65.7 to 85.9) per 100000 live births in 2021, and the APC was showed a faster downward trend since 2016, which was decreased from -7.8% (-9.2 to -6.4) to -12.9% (-19.9 to -7.4). The mortality rate of birth asphyxia fell from 31.8 (26.2 to 37.4) per 100000 live births in 2010 to 28.5 (22.3 to 34.7) per 100000 live births in 2021, and the APC was 6.8% (0.1 to 14.8) in 2010 to 2015, but was not statistically significant in 2016 to 2021, with an APC of -3.0%. On the contrast, the mortality rate of congenital malformations at national level was fluctuated from 2010 to 2021, with 22.4 (17.7 to 27.1) per 100000 live births and 21.5 (16.1 to 26.9) per 100000 live births, respectively. The APC of congenital malformations were both not statistically significant during study period. [\u003cstrong\u003eTable 1a\u003c/strong\u003e]\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFrom 2010 to 2021, the top three causes of preterm neonatal deaths in urban and rural areas were same, but the urban‒rural variation was observed in cause-specific mortality rates and APC. The proportion of preterm births and birth asphyxia of urban and rural areas in 2021 were closed, while the mortality rate of rural areas was almost twice that of those in urban areas. Between 2010 and 2015, the decline trend of preterm births in rural areas was higher than that in urban areas, while the urban-rural gap narrowed significantly from 2016 to 2021, with the APC were -12.2% and -13.1%, respectively. In both urban and rural areas, the death rate of congenital malformations fluctuated and showed no obvious downward trend, with the APC were not statistically significant. It is worth noting that neonatal sepsis was not serious in either urban or rural areas in 2010, but in 2021, the death rate of neonatal sepsis increased to 10.1 per 100000 live births and 12.4 per 100000 live births. Moreover, from 2016 to 2021, the increase was more prominent and has statistically significant in rural areas, with an APC of 27.6% [\u003cstrong\u003eTable 1b \u0026amp; 1c\u003c/strong\u003e]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePreterm neonates’ birthplaces and treatment levels in China between 2010 and 2021\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe percentages of preterm neonatal birthplaces and the last treatment health facilities level in China from 2010 to 2021 was represented in \u003cstrong\u003eFigure 2.\u0026nbsp;\u003c/strong\u003eThe proportion of birth at provincial (or municipal) level hospitals increased from 35.0% in 2010 to 75.7% in 2021, and that at district (or county) level hospitals dropped from 45.5% in 2010 to 18.8% in 2021. For treatment level, 79.9% of preterm neonates were treated in provincial (or municipal) level hospitals in 2021, which was almost doubled the proportion in 2010. There were still 13.2% of preterm neonates last treated at district (or county) level hospitals. [\u003cstrong\u003eFigure 2\u003c/strong\u003e]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eReferral of preterm neonates in rural China from 2010 to 2021\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, the referral was defined as preterm neonates who born at other level health facilities and treated at the provincial (or municipal) level hospitals. After we calculated the referral rate in rural areas by three preterm birth groups, the results showed that the referral rates of all groups showed a fluctuating upward trend during 2010 to 2021. The gap in referral rates of the very preterm groups versus the other two groups peaks in 2021. The referral rate of the very preterm group was 15.8% in 2021, which was significantly lower than that of other groups. The referral rate of the moderate preterm group was increased from 6.2% in 2010 to 33.3% in 2021. Moreover, the referral rate of the late preterm group was the highest among three groups, which have almost quadrupled from 9.9% in 2010 to 38.1% in 2021. [\u003cstrong\u003eFigure 3\u003c/strong\u003e]\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we analyzed urban-rural disparities in preterm neonatal mortality rates in China from 2010 to 2021, highlighted that while persistent urban-rural gaps remain, it also reflects China's remarkable progress in reducing neonatal mortality over this period. China has emerged as one of 10 'high-performing' countries in achieving MDGs (Millennium Development Goals) 4 and 5, with significant improvements in maternal and child health over the past decade\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. In order to promote the healthy growth of children, the State Council of PRC issued the Outline of China's Child Development (2011\u0026ndash;2020) and the Healthy China 2030\u003csup\u003e24 25\u003c/sup\u003e. These policies emphasize strengthening the construction of the maternal and child health service system and improving the service capacity of medical and health institutions. By strengthening personnel training, equipment allocation and referral mechanism construction, the survival rate of premature newborns in rural areas has been significantly improved.\u003c/p\u003e \u003cp\u003eTo our knowledge, this study of preterm neonatal deaths in the 327 National Maternal and Child Health Surveillance Districts is the first national-level assessment of different gestational weeks in urban and rural areas, which serves to fill a gap in our knowledge of the current status of preterm neonatal deaths in China. It may enable to prioritize and target specific areas of care practices for change. The results of our study showed that the difference between urban and rural preterm neonates was still obvious. The disparity in the preterm neonatal mortality rate between urban and rural areas of the moderate preterm group and the late preterm group were become narrowing during 2010 to 2021. Moreover, the gap of the very preterm group was particularly larger when compared to the other two groups. [\u003cb\u003eFigure 1\u003c/b\u003e] These results may be related to several factors. Firstly, this may relate to the increased maternal age and proportion of multiparous mothers during the Universal Two Child Policy period\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. Since the China's new family planning policy (the Three-child Policy) was officially implemented since May 2021\u003csup\u003e28\u003c/sup\u003e, the rate of preterm birth increased significantly from after the two-child policy. After the implementation of the Two-child policy, the preterm birth rate of second children increased significantly\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e, and the proportion of elderly mothers increased from 14.6\u0026ndash;34.6%, and the risk of fetal distress also increased\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. The increased maternal age and the proportion of multiparous mothers may continue to be important factors for preterm birth. Moreover, the relative lack of health care resources per capita and the economic burden in rural areas. The medical resources in rural areas are relatively scarce and impose asignificant economic burden. In 2021, the number of medical practitioners per 1,000 population and the number of hospital beds per 1,000 population of urban areas were significantly higher than that of rural areas, while the percentage healthcare expenditure of consumer expenditure in rural areas was higher than urban areas, with 10.3% and 8.0%, respectively.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Furthermore, the awareness of prenatal care among pregnant women in rural areas is relatively weak, and the screening and management of risk factors for preterm birth are not timely enough. The hospital delivery rate in urban and rural China increased from 73.5% and 50.8% in 1996 to both 99.9% in 2021, respectively\u003csup\u003e31 32\u003c/sup\u003e. China issued guidelines and regulations on standardizing prenatal care services in 2011 and 2016 respectively, which were implemented nationwide. The guidelines recommend that all pregnant women receive prenatal care services at medical institutions no less than five times\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e33\u003c/span\u003e \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e and all pregnant women can receive five free health services at primary health care institutions. However, the proportion of pregnant women receiving prenatal care five or more times in rural areas is significantly lower than that in urban areas\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e until 2015, and the early warning ability of premature birth is weak.\u003c/p\u003e \u003cp\u003eIn view of the above challenges, the measures to reduce preterm neonatal deaths in China should focus on the following measures. Firstly, the local RNTN (Reginal neonatal transport network) in rural areas must be enhanced. The National Health Commission of China released the Regulations on pregnancy risk assessment and management \u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e and the Guidelines for neonatal transport in China in 2017\u003csup\u003e37\u003c/sup\u003e, which serve as guidelines for intrauterine referral and neonatal transport. The implementation of the Universal Two Child Policy in China in 2016, the number of the second children has occupied near 50% of the total number of new births\u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e, and the neonatal care resources (NCR) is highly related to neonatal deaths\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e. Therefore, continuous efforts need to be made to strengthen the construction and coverage of Neonatal Intensive Care Unit (NICU) in rural area to ensure that premature newborns can receive timely treatment.\u003c/p\u003e \u003cp\u003eSimultaneously, the discharge against medical advice (DAMA) constitutes a significant contributing factor to neonatal survival and morbidity in preterm infants\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e. Given that financial constraints represent a primary factor influencing parental decisions to discontinue medical treatment for preterm infants, incorporating neonatal intrauterine transport into medical insurance reimbursement coverage could effectively alleviate the healthcare burden in rural areas. Furthermore, it is imperative to enhance maternal health education campaigns in rural regions, particularly emphasizing the importance of ensuring completion of five complimentary prenatal check-ups. This preventive strategy facilitates early identification of preterm delivery risks and consequently improves survival outcomes for premature infants.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eLimits\u003c/h2\u003e \u003cp\u003eThe MCHSS does not contain maternal information for deceased children, such as parity, number of fetuses, age, and educational level, which have been proven to be directly related to neonatal deaths.\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e41\u003c/span\u003e \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e Therefore, this study cannot determine the impact on survival of preterm newborns by analyzing maternal factors. Moreover, the MCHSS have not collected the number of livebirths at different gestational weeks before 2022, so the mortality of different gestational weeks was calculated by total livebirths. In 2022, we started to collect livebirths\u0026rsquo; number with gestational weeks, the mortality of different gestational weeks would be more accurate in further studies.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, there were significant disparities between urban and rural areas in the cause-specific mortality rate and different gestational ages among preterm neonates during 2010 to 2021. It is important to focus on preterm neonatal survival, especially for neonates born at 28 to 31 gestational weeks. This study has shown the preterm neonatal death status in rural areas, which may help local governments further reduce the total neonatal mortality rate.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eNMR \u0026nbsp;Neonatal Mortality Rate\u003c/p\u003e\n\u003cp\u003eSDG \u0026nbsp;Sustainable Development Goal\u003c/p\u003e\n\u003cp\u003eMCHSS \u0026nbsp;Maternal and Child Health Surveillance System\u003c/p\u003e\n\u003cp\u003eMCHC \u0026nbsp;Maternal and Child Health Center\u003c/p\u003e\n\u003cp\u003eAPC \u0026nbsp;Annual Percent Change\u003c/p\u003e\n\u003cp\u003eMDG \u0026nbsp;Millennium Development Goal\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNICU \u0026nbsp; Neonatal Intensive Care Unit\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDAMA \u0026nbsp;Discharge Against Medical Advice\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of West China Second University Hospital, Sichuan University, China. Our analysis is based on the national Maternal and Child Health Surveillance System, for which we have obtained a waiver of informed consent from the parents of the died children. Additionally, our report does not contain any personal information of the patients. This study was performed in accordance with the principles of the Declaration of Helsinki.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study used data from the NMCHSS. This system is co-established by the National Health Commission of the People Republic of China and Sichuan University, and finally owned by National Health and Family Planning Commission of the People Republic of China. The researchers did not obtain consent to publicly share data. The de-identified data set is available upon request to interested researchers. For data requests, please contact the Department of Science and Technology of West China Second University Hospital, Sichuan University, at: [email protected]. This department is in charge of all the programs in the hospital, including the data management. One staff from the department monitors this email.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was supported by the National Key Research and Development Program of China (2022YFC2704605).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConcept: Yanping Wang\u003c/p\u003e\n\u003cp\u003eDesign: Yuxi Liu\u003c/p\u003e\n\u003cp\u003eDefinition of intellectual content: Leni Kang, Yanna Zou, Xue Yu, Chunhua He\u003c/p\u003e\n\u003cp\u003eLiterature search: Yiyong Su, Chongmei Huang,\u003c/p\u003e\n\u003cp\u003eData analysis: Juan Liang, Cheng Wan\u003c/p\u003e\n\u003cp\u003eManuscript preparation: Yuxi Liu\u003c/p\u003e\n\u003cp\u003eManuscript editing \u0026amp; review: Cheng Wan\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all health workers in this surveillance system for providing the data and investigating the cause of death.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eOhuma EO, Moller, A. 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Changes in the characteristics and outcomes of high-risk pregnant women who delivered prior to and after China\u0026apos;s universal two-child policy: a real-world retrospective study, 2010-2021. \u003cem\u003eBMC Public Health\u003c/em\u003e 2024;24(1):336. PMID: 38297279 doi: 10.1186/s12889-024-17810-9\u003c/li\u003e\n \u003cli\u003eTura G, Fantahun M, Worku A. The effect of health facility delivery on neonatal mortality: systematic review and meta-analysis. \u003cem\u003eBMC Pregnancy Childbirth\u003c/em\u003e 2013;13:18. PMID: 23339515 doi: 10.1186/1471-2393-13-1832. China NHCotPsRo. China Health Statistics Yearbook 2020. Beijing, 2021:421.\u003c/li\u003e\n \u003cli\u003eNational Health Commission of the People\u0026rsquo;s Republic of China. Notice on the issuance of the National Basic Public Health Service Regulations. 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PMID: 34528000 doi: 10.1016/j.lanwpc.2021.100212\u003c/li\u003e\n \u003cli\u003eCao Y, Jiang S, Sun J, Hei M, Wang L, Zhang H, Ma X, Wu H, Li X, Sun H, Zhou W, Shi Y, Wang Y, Gu X, Yang T, Lu Y, Du L, Chen C, Lee SK, Zhou W. Assessment of Neonatal Intensive Care Unit Practices, Morbidity, and Mortality Among Very Preterm Infants in China. \u003cem\u003eJAMA Netw Open\u003c/em\u003e 2021;4(8):e2118904. PMID: 34338792 doi: 10.1001/jamanetworkopen.2021.18904\u003c/li\u003e\n \u003cli\u003eLiyew EF, Yalew AW, Afework MF, Ess\u0026eacute;n B. Maternal near-miss and the risk of adverse perinatal outcomes: a prospective cohort study in selected public hospitals of Addis Ababa, Ethiopia. \u003cem\u003eBMC Pregnancy Childbirth\u003c/em\u003e 2018;18(1):345. PMID: 30134858 doi: 10.1186/s12884-018-1983-y\u003c/li\u003e\n \u003cli\u003eCarolan M, Frankowska D. Advanced maternal age and adverse perinatal outcome: A review of the evidence. \u003cem\u003eMidwifery\u003c/em\u003e 2011;6(27):793-801. PMID: 20888095 doi: 10.1016/j.midw.2010.07.006\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Preterm neonates, neonatal death, urban–rural disparity","lastPublishedDoi":"10.21203/rs.3.rs-6210926/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6210926/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe neonatal mortality rate (NMR) is a vital indicator for assessing maternal and child health, and preterm birth is one of the leading causes of neonatal mortality. Since 2010, China has implemented multiple maternal and child health policies aimed at reducing neonatal mortality. However, systematic research on urban-rural disparities in neonatal mortality among preterm births remains relatively scarce. In this study, we analyzed the national and subnational cause-specific death rates of preterm neonates in mainland China during 2010 to 2021 to provide data support for the further elimination of neonatal deaths.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eIn this retrospective study, we analyzed empirical data on levels and causes of preterm neonatal mortality data from the China Maternal and Child Health Surveillance System to show the cause-specific death rates, birthplaces and treatment levels at the national and subnational levels.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eBetween 2010 and 2021, the top three causes of death in preterm neonates were preterm birth, birth asphyxia and congenital malformations in both urban and rural areas. From 2010 to 2021, the mortality rate among preterm neonates born at 28 to 31 gestational weeks was significantly higher than that among preterm neonates born at 32 to 33 gestational weeks and 34 to 36 gestational weeks in both urban and rural areas. We also found that in urban areas, 95.5% of preterm neonates were born at provincial (or municipal)-level hospitals in 2021, while this proportion was 60.2% in rural areas. Regarding the treatment level, the proportion of preterm neonates in rural areas who were diagnosed at district (or county)-level health facilities decreased from 46.7\u0026ndash;21.8% from 2010 to 2021. In contrast, this proportion in urban areas was 6.5% in 2010 and 2.3% in 2021.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis study reveals the remarkable achievements China has made in reducing preterm neonatal mortality and narrowing the urban-rural disparity, while the gap between urban and rural preterm neonatal mortality is not negligible. Policy interventions have been the primary driving force behind the reduction of the urban-rural gap, while resource scarcity in remote western regions and the economic pressures faced by rural households remain significant challenges.\u003c/p\u003e","manuscriptTitle":"Urban–Rural Disparity in Preterm Neonatal Mortality in China: A Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-01 09:50:39","doi":"10.21203/rs.3.rs-6210926/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-28T06:56:47+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-27T11:23:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"141387503814822440636272067415929883876","date":"2025-04-01T01:40:40+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-03-23T01:47:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"75377248432352033397971844246277719543","date":"2025-03-21T21:16:48+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-21T21:05:32+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-21T21:00:21+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-03-21T06:58:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-20T09:59:08+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2025-03-20T09:58:01+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"258c6d80-5bf3-42b9-a88d-2fdd76f0679b","owner":[],"postedDate":"April 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-13T15:59:51+00:00","versionOfRecord":{"articleIdentity":"rs-6210926","link":"https://doi.org/10.1186/s12887-025-06042-4","journal":{"identity":"bmc-pediatrics","isVorOnly":false,"title":"BMC Pediatrics"},"publishedOn":"2025-10-09 15:57:16","publishedOnDateReadable":"October 9th, 2025"},"versionCreatedAt":"2025-04-01 09:50:39","video":"","vorDoi":"10.1186/s12887-025-06042-4","vorDoiUrl":"https://doi.org/10.1186/s12887-025-06042-4","workflowStages":[]},"version":"v1","identity":"rs-6210926","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6210926","identity":"rs-6210926","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}