新生儿使用中/长链脂肪乳与多种油脂肪乳安全性队列研究

目的 分析新生儿使用中/长链脂肪乳与多种油脂肪乳发生药物不良反应的差异，并探索潜在的危险因素。方法 采用回顾性队列研究方法，针对2020年1月—2023年6月使用中/长链脂肪乳或多种油脂肪乳的新生儿患者的数据，利用中国医院药物警戒系统(China Hospital Pharmacovigilance System，CHPS)，检索不良反应信息并做评价，纳入中/长链脂肪乳组新生儿患者499例，多种油脂肪乳组新生儿患者1 940例。利用Logistic回归及分层分析探索组间安全性差异及影响不良反应发生的危险因素。结果 中/长链脂肪乳组总不良反应发生率为19.24%，其中常见不良反应包括发热(5.81%)，血红蛋白减少(3.01%)，血压升高(2.40%)，低血糖(2.40%)等；多种油脂肪乳组总不良反应发生率为36.44%，其中十分常见的不良反应为发热(10.57%)；常见的不良反应为血红蛋白减少(8.97%)，血压降低(3.20%)，血压升高(3.09%)等；罕见的不良反应为肝功能异常(0.05%)，脾肿大(0.05%)，发绀(0.05%)。单因素分析中，多种油脂肪乳组发生发热，血红蛋白减少和血糖升高的风险均高于中/长链脂肪乳组(P<0.05)，但此关联在总体多因素分析中的差异无统计学意义，进一步以胎龄为分层因素进行多因素分析，发现极早产儿中多种油脂肪乳组发生发热和血红蛋白减少的风险显著高于中/长链脂肪乳组，相应的OR(95%CI)分别为6.437(1.327，31.227)和5.066(1.089，23.570)，其余胎龄分层中未见明显差异。结论 新生儿患者使用中/长链脂肪乳与多种油脂肪乳的风险相近，但在极早产儿中多种油脂肪乳发生发热、血红蛋白减少的风险高于中/长链脂肪乳，建议对体温、血红蛋白、血压等指标进行定期监测，做好药物警戒工作。

Cohort Study on the Safety of Medium/long Chain Fat Emulsions and Multiple Oil Fat Emulsions Used in Newborns

OBJECTIVE To analyze the differences in adverse drug reactions between newborns using medium/long chain fat emulsions and multiple types of oil fat emulsions, and to explore potential risk factors. METHODS A retrospective cohort study was conducted using data from newborns who used medium/long chain fat emulsions or multiple oil fat emulsions from January 2020 to June 2023. The China Hospital Pharmacovigilance System(CHPS) was used to retrieve adverse reaction information and evaluate it. Four hundred and ninety-nine newborns in the medium/long chain fat emulsion group and 1 940 newborns in the multiple oil fat emulsion group were included. Using logistic regression and stratified analysis to explore the safety differences between groups and the risk factors that affect the occurrence of adverse reactions. RESULTS The total incidence of adverse reactions in the medium/long chain fat emulsion group was 19.24%, with common adverse reactions including fever(5.81%), decreased hemoglobin(3.01%), increased blood pressure(2.40%) and hypoglycemia(2.40%); The total incidence of adverse reactions in the group of multiple oil fat emulsions was 36.44%, with a very common adverse reaction being fever(10.57%); common adverse reactions include decreased hemoglobin(8.97%), decreased blood pressure(3.20%), and increased blood pressure(3.09%); rare adverse reactions include liver dysfunction(0.05%), splenomegaly(0.05%) and cyanosis (0.05%). In univariate analysis, the risk of fever, decreased hemoglobin, and increased blood sugar in the group of multiple oil fat emulsions was higher than that in the medium/long chain fat emulsion group(P<0.05), but this association did not show statistical differences in the overall multivariate analysis. Furthermore, a stratified factor analysis based on gestational age found that the risk of fever and decreased hemoglobin in the group of multiple oil fat emulsions was significantly higher than that in the medium/long chain fat emulsion group in extremely premature infants. The corresponding OR(95%CI) were 6.437(1.327, 31.227) and 5.066(1.089, 23.570), respectively, with no significant differences observed in other gestational age stratification. CONCLUSION The risk of using medium/long chain fat emulsions in newborns is similar to that of using multiple types of oil fat emulsions. However, in extremely premature infants, the risk of fever and decreased hemoglobin in multiple types of oil fat emulsions is higher than that in medium/long chain fat emulsions. It is recommended to regularly monitor indicators such as body temperature, hemoglobin, and blood pressure, and do a good job in drug vigilance.