基于Cox比例风险模型探讨早发败血症新生儿早期死亡的影响因素

Exploring the risk factors for early death in neonates with early-onset sepsis based on the Cox proportional hazards model

摘要

目的 探讨早发败血症(EOS)新生儿早期死亡的影响因素,以期为后续质量改进提供依据。方法 选取2010年1月至2020年12月在南京医科大学附属苏州医院住院的EOS新生儿为研究对象,分为:死亡组(存活时间<生后7d),幸存组(存活时间≥生后7d).回顾性收集两组的临床资料,进行倾向性评分匹配后构建Cox比例风险模型分析EOS新生儿早期死亡的影响因素。结果 研究期间共纳入160例EOS新生儿,其中临床诊断34例,确诊126例,血培养检出致病菌中以无乳链球菌最常见(22.22%);幸存组133例,死亡组27例,病死率为16.88%.相较幸存组,死亡组的出生胎龄、出生体重更低(t=-7.86、-7.11,P<0.001).按出生胎龄、入院年份进行1∶1倾向性评分匹配后构建Cox回归模型,单因素分析提示影响EOS早期死亡的因素包括:胎膜早破>18h(HR=0.21,95%CI:0.05~0.88)、出生窒息(HR=2.45,95%CI:1.08~5.54)、入院体温<36.5℃(HR=2.85,95%CI:1.18~6.88)、入院需机械通气(HR=2.50,95%CI:1.03~6.06)、入院需血管活性药(HR=3.72,95%CI:1.65~8.38)、血培养阳性(HR=0.25,95%CI:0.11~0.59),P均<0.05;进一步行多因素分析发现:入院需血管活性药(HR=2.53,95%CI:1.07~5.99)、血培养阳性(HR=0.33,95%CI:0.13~0.83)与EOS早期死亡密切相关(P<0.05)。结论 入院时需血管活性药维持是EOS患儿发生早期死亡的危险因素,而血培养阳性则为保护因素.

Abstract

Objective To investigate the risk factors associated with early mortality in neonates with early-onset sepsis (EOS), with the aim of providing evidence for future quality improvement initiatives. Methods This retrospective cohort study included neonates diagnosed with EOS and hospitalized at The Affiliated Suzhou Hospital of Nanjing Medical University, between January 2010 and December 2020. The neonates were divided into two groups: the death group (survival time <7 days after birth) and the survival group (survival time ≥7 days). Clinical data were collected retrospectively for both groups. After 1:1 propensity score matching based on gestational age and year of admission, a Cox proportional hazards model was constructed to identify factors associated with early mortality. Results A total of 160 neonates with EOS were included, comprising 34 clinically diagnosed cases and 126 confirmed cases. Among the pathogens identified through blood culture, Streptococcus agalactiae was the most common (22.22%). Of the total cases, 133 survived and 27 died, resulting in a case fatality rate of 16.88%. Compared to the survival group, neonates in the death group had significantly lower gestational ages and birth weights (t=-7.86 and -7.11, respectively, both P<0.001). After propensity score matching, univariate Cox regression analysis revealed several factors associated with early mortality in EOS neonates: premature rupture of membranes >18 hours (HR=0.21, 95%CI: 0.05-0.88), birth asphyxia (HR=2.45, 95%CI: 1.08-5.54), admission temperature <36.5℃ (HR=2.85, 95%CI: 1.18-6.88), need for mechanical ventilation upon admission (HR=2.50, 95%CI: 1.03-6.06), use of vasopressors upon admission (HR=3.72, 95%CI: 1.65-8.38), and positive blood culture (HR=0.25, 95%CI: 0.11-0.59), all with P<0.05. Multivariate Cox analysis identified vasopressor use at admission (HR=2.53, 95%CI: 1.07-5.99) and positive blood culture (HR=0.33, 95%CI: 0.13-0.83) as independent factors significantly associated with early mortality (P<0.05). Conclusion The requirement for vasopressor support upon admission is an independent risk factor for early mortality in neonates with EOS, while a positive blood culture appears to be a protective factor.

关键词

新生儿 / 早发败血症 / Cox比例风险模型 / 预后

Key words

neonate / early-onset sepsis / Cox proportional hazards model / prognosis

参考文献

[1] Celik I H, Hanna M, Canpolat F E, et al. Diagnosis of neonatal sepsis: the past, present and future[J]. Pediatr Res, 2022, 91(2): 337-350.

[2] Glaser M A, Hughes L M, Jnah A, et al. Neonatal sepsis: a review of pathophysiology and current management strategies[J]. Adv Neonatal Care, 2021, 21(1): 49-60.

[3] Flannery D D, Puopolo K M. Neonatal early-onset sepsis[J]. Neoreviews, 2022, 23(11): 756-770.

[4] Tesfay N, Tariku R, Zenebe A, et al. Cause and risk factors of early neonatal death in Ethiopia[J]. PLoS One, 2022, 17(9): e0275475.

[5] 陈宇宏, 陆李珺, 杨祖铭, 等. 住院期间早期与晚期新生儿死亡的临床特征比较[J]. 中国病案, 2024, 25(5): 84-86.

[6] 中华医学会儿科学分会新生儿学组, 中国医师协会新生儿科医师分会感染专业委员会. 新生儿败血症诊断及治疗专家共识(2019年版)[J]. 中华儿科杂志, 2019, 57(4): 252-257.

[7] Stoll B J, Puopolo K M, Hansen N I, et al. Early-onset neonatal sepsis 2015 to 2017, the rise of escherichia coli, and the need for novel prevention strategies[J]. JAMA Pediatr, 2020, 174(7): e200593.

[8] Ogundare E, Akintayo A, Aladekomo T, et al. Presentation and outcomes of early and late onset neonatal sepsis in a Nigerian hospital[J]. Afr Health Sci, 2019, 19(3): 2390-2399.

[9] 王义, 田家豪, 唐小晶, 等. 基于logistic回归模型构建预测新生儿早发败血症预后的相关模型[J]. 中国医师杂志, 2022, 24(3): 415-419.

[10] Guo L, Han W, Su Y, et al. Perinatal risk factors for neonatal early-onset sepsis: a meta-analysis of observational studies[J]. J Matern Fetal Neonatal Med, 2023, 36(2): 2259049.

[11] 杨露, 孙晓红, 荆玉慧, 等. 妊娠晚期宫内感染B族链球菌对孕妇血清炎症因子的影响及妊娠结局分析[J]. 中国计划生育学杂志, 2022, 30(6): 1352-1356.

[12] Goldenberg R L, Dhaded S, Saleem S, et al. Birth asphyxia is under-rated as a cause of preterm neonatal mortality in low-and middle-income countries: a prospective, observational study from PURPOSe[J]. BJOG, 2022, 129(12): 1993-2000.

[13] Iribarren I, Hilario E, Álvarez A, et al. Neonatal multiple organ failure after perinatal asphyxia[J]. An Pediatr (Engl Ed), 2022, 97(4): 280.e1-280.e8.

[14] Dotters-Katz S. Antibiotics for prophylaxis in the setting of preterm prelabor rupture of membranes[J]. Obstet Gynecol Clin North Am, 2020, 47(4): 595-603.

[15] Malka E S, Solomon T, Kassa D H, et al. Time to death and predictors of mortality among early neonates admitted to neonatal intensive care unit of Addis Ababa public hospitals, Ethiopia: institutional-based prospective cohort study[J]. PLoS One, 2024, 19(6): e0302665.

[16] 朱晓洁, 王粉, 张君平, 等. 新生儿感染性休克的死亡危险因素分析[J]. 中华医院感染学杂志, 2017, 27(9): 2111-2113,2117.

[17] 詹实娜, 韩彤妍. 新生儿重症监护室血流动力学评估及血管活性药物选择[J]. 儿科药学杂志, 2023, 29(8): 57-63.

[18] 王义, 田家豪, 杨雪峰, 等. 乳酸浓度联合乳酸清除率对新生儿脓毒性休克预后的预测价值[J]. 中华儿科杂志, 2021, 59(6): 489-494.

基金资助

江苏省医学会科研专项基金资助项目(SYHG32034G0080(20230027))