肺表面活性物质微创给药治疗早产儿呼吸窘迫综合征临床及随访研究

Clinical and follow-up study of premature infants with neonatal respiratory distress syndrome managed by the less invasive surfactant administration

目的探讨肺表面活性物质微创给药(LISA)技术与传统的气管插管-使用肺表面活性物质(PS)-拔管(INSURE)技术治疗早产新生儿呼吸窘迫综合征(NRDS)的临床治疗效果和预后效果。方法回顾性分析重庆医科大学附属妇女儿童医院新生儿科2019年3月至2021年2月收治的187例NRDS早产儿(胎龄24~31^(+6)周,且出生体重<1500 g)住院期间及出院后矫正年龄1岁内的随访资料,使用LISA注入PS的纳入LISA组,使用INSURE注入PS的纳入INSURE组,其中LISA组144例,INSURE组43例。采用倾向性评分匹配法对组间混杂因素进行矫正,获得组间协变量均衡样本(2组各39例)。采用t检验、χ^(2)检验等统计分析方法比较2组患儿临床治疗效果及体格发育、听力和视力发育、神经系统发育、呼吸系统疾病等预后情况。结果1.与INSURE组相比,LISA组支气管肺发育不良(BPD)[12例(33.3%)比23例(63.9%)]和视网膜病变(ROP)[13例(36.1%)比26例(72.2%)]发生率较低,差异均有统计学意义(χ^(2)=6.727,P=0.009;χ^(2)=9.455,P=0.002)。轻度BPD[8例(22.2%)比16例(44.4%)]和Ⅰ~Ⅱ期ROP[11例(30.6%)比22例(61.1%)]发生率差异均有统计学意义(χ^(2)=4.000,P=0.046;χ^(2)=6.769,P=0.009),而中重度BPD和≥Ⅲ期ROP差异均无统计学意义(均P>0.05)。2.两组患儿住院期间PS重复使用、72 h内机械通气率、气胸/肺出血、Ⅲ~Ⅳ度脑室周围-脑室内出血/脑白质软化、Ⅱ~Ⅲ期新生儿坏死性小肠结肠炎、败血症、异常振幅整合脑电图、矫正胎龄36周病死率、总吸氧时长、住院时长等差异均无统计学意义(均P>0.05)。3.出院后矫正年龄1岁内随访:宫外体质量、身长和头围发育、视力发育、听力发育、矫正胎龄40周新生儿行为神经评分、矫正月龄6个月及矫正年龄1岁时Bayley婴幼儿发育量表评分、肺炎、呼吸道疾病再住院等差异均无统计学意义(均P>0.05)。结论对胎龄24~31^(+6)周且出生体重<1500 g早产NRDS患儿进行治疗,采用LISA技术PS给药能够降低轻度BPD和Ⅰ~Ⅱ期ROP发生率,无增加其他并发症风险,2种技术远期预后效果相当。

Objective To explore the clinical therapeutic effect and follow-up prognosis of preterm infants with neonatal respiratory distress syndrome(NRDS)managed by less invasive surfactant administration(LISA)and traditional intubation-surfactant-extubation(INSURE)of pulmonary surfactant(PS).Methods Data during hospitalization and follow-up period of 187 NRDS preterm infants(gestational age 24 weeks to 31+6 weeks,and birth weight<1500 g)admitted to the Department of Neonatology,the Women and Children's Hospital of Chongqing Medical University from March 2019 to February 2021 were retrospectively analyzed.NRDS preterm infants who were injected with PS by LISA were included in the LISA group(144 cases),and those who were injected with PS by INSURE were included in the INSURE group(43 cases).The propensity score matching method was used to correct the confounding factors between groups,and the covariate equilibrium samples between groups were obtained(39 cases in each group).Clinical treatment effect and prognosis of physical development,hearing and vision development,nervous system development,respiratory system diseases and other conditions of the two groups of children were compared using the t test,Chi-square test and other statistical analysis methods as appropriate.Results(1)Compared with that of the INSURE group,the incidence of BPD[12 cases(33.3%)vs.23 cases(63.9%),χ^(2)=6.727,P=0.009]and ROP[13 cases(36.1%)vs.26 cases(72.2%),χ^(2)=9.455,P=0.002]in the LISA group were significantly lower.The incidence of mild BPD[8 cases(22.2%)vs.16 cases(44.4%),χ^(2)=4.000,P=0.046]and stage Ⅰ-Ⅱ ROP[11 cases(30.6%)vs.22 cases(61.1%),χ^(2)=6.769,P=0.009]in the LISA group was significantly lower than that of the INSURE group.There was no significant difference in the incidence of moderate and severe BPD and stage Ⅲ ROP and above between groups(all P>0.05).(2)There were no statistical differences in the repeated use of PS,mechanical ventilation rate within 72 h,pneumothorax/pulmonary hemorrhage,grade Ⅲ-Ⅳ periventricula-rintraventricular hemorrhage,stage Ⅱ-Ⅲ neonatal necrotizing enterocolitis,sepsis,abnormal amplitude integrated electroencephalogram,mortality in 36 weeks of corrected gestational age,total oxygen inhalation duration and hospitalization duration between the two groups(all P>0.05).(3)Follow-up within 1 year of corrected age after discharge.There were no significant differences in extrauterine body mass,body length and head circumference development,visual development,hearing development,Neonatal Behavioral Neurological Assessment score at corrected gestational age of 40 weeks,Bayley Scales of Infants Development score at corrected gestational age of 6 months and age of 1 year,pneumonia and re-hospitalization due to respiratory diseases between groups(all P>0.05).Conclusions PS administration with LISA technology can reduce the incidence of mild BPD and stage Ⅰ-Ⅱ ROP in premature infants with NRDS who had the gestational age of 24-31+6 weeks and birth weight<1500 g,without increasing the risk of other complications.The long-term prognosis of them treated with PS administration with LISA and INSURE is similar.