Perinatal Risks of Neonatal and Infant Mortalities in a Sub-provincial Region of China: A Livebirth Population-based Cohort Study
Authors: Xu Yaling , Guo Xiaojing , Pan Zhaojun , Zheng Guofang , Li Xiaoqiong , Qi Tingting , Zhu Xiaoqin , Wang Hui , Ding Weijie , Tian Zhaofang , Wang Haijun , Yue Hongni , Sun Bo ,   on behalf of the Huai’an Perinatal-Neonatal Collaborative Study Group, Pan Zhaojun , Zheng Guofang , Ding Sufang , Li Xiaoqiong , Qi Tingting , Zhu Xiaoqin , Wang Hui , Ding Weijie , Yue Hongni , Tian Zhaofang , Zhang Muling , Wang Haijun , Yin Yaodong , Guan Honghua , Yang Juan , Wu Yongjian , Xu Tao , Tang Chunhong , Dong Maotian , Zhang Chunhua , Dong Chunqin , Zhou Sumei , Lei Yani , Li Shouzhong , Zhu Keyan , Zhao Xia , Xue Bi , Wang Zhaoxia , Wang Shucheng , Liu Hong , Xu Zhou , Yuan Chuntao , Cao Xihui , Zhang Jianya , Xu Bu , Lin Wenlong , Gao Cui , Heng Yongbo , Wang Lei , Wang Moqing 
Published: April 2022

Abstract
Background
Current vital statistics of birth population and neonatal outcome in China lacked information and definition of deaths at delivery and during hospitalization, especially for extreme preterm (EPT) birth. This study aims to delineate the prevalence of neonatal hospitalization, neonatal and infant mortality rates (NMR, IMR) and associated perinatal risks based on all livebirths in Huai’an, an evolving sub-provincial region in eastern China.

Methods
This retrospective cohort study established a comprehensive database linking information of whole regional livebirths and neonatal hospitalization in 2015, including deaths at delivery and EPT livebirths. The primary outcomes were NMR and IMR stratified by gestational age (GA) and birthweight (BW) with 95% confidence intervals. Causes of the neonatal and infant deaths were categorized according to the International Statistical Classification of Diseases 10th version, and population attributable fractions of GA and BW strata were analyzed. Perinatal risks of infant mortalities in continuum periods were estimated by Cox regression models.

Results
Among the whole livebirth population (59056), 7960 were hospitalized (prevalence 13.5%), with 168 (2.8‰) in-hospital deaths. The NMR was 3.6 (3.2, 4.1)‰ and IMR 4.9 (1.4, 4.5)‰, with additionally 35 (0.6‰) deaths at delivery. The major causes of infant deaths were perinatal conditions (2.6‰, mainly preterm-related), congenital anomalies (1.5‰), sudden unexpected death in infancy (0.6‰) and other causes (0.2‰). The deaths caused by preterm and low BW (LBW) accounted for 50% and 40% of NMR and IMR, with 20-30% contributed by EPT or extremely LBW, respectively. Multivariable Cox regression analysis revealed that peripartum factors and LBW strata had strong association with early- and late-neonatal deaths, whereas those of GA < 28 weeks were highly associated with postneonatal deaths. Congenital anomalies and neonatal hospitalization remained high death risks over the entire infancy, whereas maternal co-morbidities/complications were modestly associated with neonatal but not postneonatal infant mortality.

Conclusions
The NMR, IMR, major causes of deaths and associated perinatal risks in continuum periods of infancy, denote the status and quality improvement of the regional perinatal-neonatal care associated with socioeconomic development. The study concept, applicability and representativeness may be validated in other evolving regions or countries for genuine comparison and better maternal-infant healthcare.