新生儿期后以便血起病的坏死性小肠结肠炎病因及预后影响因素分析

Etiology and prognostic factors of necrotizing enterocolitis in infants after neonatal period with hematochezia

目的:分析新生儿期后以便血起病的坏死性小肠结肠炎(NEC)病因及预后的影响因素。方法:回顾性分析2016年1月至2021年12月首都医科大学附属北京儿童医院消化科收治的62例起病年龄大于28 d、以便血起病的临床诊断NEC患儿的临床资料,总结此年龄段NEC的病因,并分析影响预后的因素。按食物过敏源IgE检测结果分为:牛奶蛋白阳性组,牛奶蛋白阴性组;按外周血嗜酸性粒细胞绝对值水平分为:嗜酸细胞增多组(≥0.5×10^(9)/L),嗜酸细胞正常组(<0.5×10^(9)/L);按是否合并感染分为:单纯NEC组(无合并感染),NEC+艰难梭菌相关腹泻(CDAD)组,NEC+其他感染组(合并沙门菌感染或败血症等);按不同喂养方式分为:普通氨基酸组(渗透压310 mOsm/L),稀释氨基酸组(渗透压233 mOsm/L),深度水解组(渗透压185 mOsm/L);比较各组临床症状缓解时间、肠壁积气恢复时间、达到生理需要量的喂养时间、住院时间等。结果:62例患儿中男27例,女35例,发病年龄中位数1.4(1.2,2.3)个月,出生体重中位数为3.2(2.9,3.4)kg,足月儿占87.1%,剖宫产占62.9%。53例(85.5%)存在过敏症状,13例(21.0%)有过敏家族史,29例(46.8%)存在牛奶蛋白过敏,32例(51.6%)外周血嗜酸性粒细胞增多;牛奶蛋白阳性组的住院时间长于阴性组(P=0.047);嗜酸细胞增多组低敏配方喂养1 d临床缓解率高于嗜酸细胞正常组(100.0%比65.0%,P=0.002)。10例(16.1%)患儿合并艰难梭菌感染,2例(3.2%)沙门菌肠炎、4例(6.5%)败血症;NEC+其他感染组患儿平均住院时间以及达到生理需要量的喂养时间更长(P<0.05),NEC+CDAD组患儿反复住院的几率更高(40%,P=0.004)。62例患儿肠壁积气消失时间平均为(4.5±2.9)d,平均禁食(3.9±3.0)d后开始低敏配方喂养,喂养后1 d的临床缓解率为79.0%,平均(5.8±3.2)d可加量至满足生理需要。稀释氨基酸组患儿临床症状缓解时间更短(H=10.208,P=0.006),不同喂养方案患儿达到生理需要量的喂养时间和住院时间之间差异无统计学意义(P>0.05)。结论:以便血起病、年龄大于28 d的NEC患儿,牛奶蛋白过敏、感染(尤其是CDAD)与NEC的发生发展关系密切,给予接近母乳渗透压的稀释氨基酸配方粉及针对性抗感染治疗,能够缩短NEC的临床缓解时间,降低反复住院风险。

Objective To analyze the etiology and prognostic factors of necrotizing enterocolitis(NEC)in infants after neonatal period with hematochezia.Methods The clinical data of 62 infants older than 28 days with NEC and hematochezia diagnosed at Beijing Children′s Hospital,Capital Medical University from January 2016 to December 2021 were retrospectively analyzed,summarizing the etiology of NEC in this age group and analyze the factors affecting the prognosis of NEC.According to IgE detection results of food allergens,the infants were divided into milk protein positive group and milk protein negative group.According to the absolute value level of peripheral blood eosinophils,they were divided into increased eosinophils group(≥0.5×10^(9)/L)and normal eosinophils group(<0.5×10^(9)/L).They were divided into three groups according to co-infection:NEC group(no co-infection),NEC+clostridium difficile associated diarrhea(CDAD)group,and NEC+other infection group(salmonella infection or sepsis).According to different feeding methods,they were divided into normal amino acid group(osmotic pressure 310 mOsm/L),diluted amino acid group(osmotic pressure 233 mOsm/L),and deep hydrolysis group(osmotic pressure 185 mOsm/L).The relief time of clinical symptoms,the recovery time of intestinal gas accumulation,feeding time to achieve physiological requirements,and the length of hospital stay in each group were compared.Results Among 62 cases,there were 27 males and 35 females.The median age of onset was 1.4(1.2,2.3)months.The median birth weight was 3.2(2.9,3.4)kg.Full-term infants accounted for 87.1%.Cesarean accounted for 62.9%.Fifty-three patients(85.5%)had allergic symptoms.Thirteen patients(21.0%)had family history of allergy.Cow milk protein allergy was diagnosed in 29 cases.Thirty-two cases(51.6%)had elevated peripheral blood eosinophils.The hospitalization time of milk protein positive group was longer than that of negative group(P=0.047).The clinical remission rate after hypoallergenic formula feeding for 1 day of increased eosinophils group was higher than that of normal eosinophil group(100.0%vs.65.0%,P=0.002).Ten patients(16.1%)were complicated with clostridium difficile infection,two patients(3.2%)with salmonella enteritis,and four patients(6.5%)with sepsis.Both the hospital stay and feeding time to achieve physiological requirements of NEC+other infection group were longer than the other two groups(P<0.05).NEC+CDAD group had a higher rate of repeated hospitalizations(40.0%,P=0.004).The mean recovery time of intestinal gas accumulation was(4.5±2.9)days.After(3.9±3.0)days,hypoallergenic formula feeding started.After one day of feeding,the clinical remission rate was 79.0%.The average time to achieve physiological requirements was(5.8±3.2)days.The clinical symptom relief time of diluted amino acid group was shorter(P=0.006),but there was no statistical difference in feeding time to achieve physiological requirements and hospitalization time between each group(P>0.05).Conclusion Cow′s milk protein allergy and infection(especially CDAD)are closely related to the occurrence and development of NEC after neonatal period with hematochezia.The administration of diluted amino acid-based formulae close to the osmotic pressure of breast milk and targeted anti-infective therapy could shorten the clinical remission time of NEC and reduce the risk of repeated hospitalization.