切换至 "中华医学电子期刊资源库"
高级检索
中华妇幼临床医学杂志(电子版)

中华妇幼临床医学杂志(电子版) ›› 2021, Vol. 17 ›› Issue (05) : 545 -551. doi: 10.3877/cma.j.issn.1673-5250.2021.05.007

论著

极/超低出生体重儿胃肠外营养相关性胆汁淤积的临床特点分析
龙丽娟1,1, 闭宏娟1,†,1(), 黄谊思2,2, 韦秋芬1,1, 姚丽平1,1   
  • 收稿日期:2020-04-21 修回日期:2021-07-19 出版日期:2021-10-01
  • 通信作者: 闭宏娟

Analysis of clinical characteristics of parenteral nutrition associated cholestasis in very/extremely low birth weight infants

Lijuan Long1,1, Hongjuan Bi1,1,†(), Yisi Huang2,2, Qiufen Wei1,1, Liping Yao1,1   

  • Received:2020-04-21 Revised:2021-07-19 Published:2021-10-01
  • Corresponding author: Hongjuan Bi
  • Supported by:
    Medical and Health Technology Development and Application Project of Guangxi Zhuang Autonomous Region(S2018115)
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

龙丽娟, 闭宏娟, 黄谊思, 韦秋芬, 姚丽平. 极/超低出生体重儿胃肠外营养相关性胆汁淤积的临床特点分析[J]. 中华妇幼临床医学杂志(电子版), 2021, 17(05): 545-551.

Lijuan Long, Hongjuan Bi, Yisi Huang, Qiufen Wei, Liping Yao. Analysis of clinical characteristics of parenteral nutrition associated cholestasis in very/extremely low birth weight infants[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2021, 17(05): 545-551.

目的

探讨对极低出生体重儿/超低出生体重儿(VLBWI/ELBWI)采取胃肠外营养(PN)治疗后，发生胃肠外营养相关性胆汁淤积(PNAC)的影响因素。

方法

选择2017年7月至2019年7月，于广西壮族自治区妇幼保健院诊治的88例胎龄<32周的VLBWI/ELBWI为研究对象。根据住院期内是否发生PNAC，将其分为PNAC组(n＝42，发生PNAC)及非PNAC组(n＝46，未发生PNAC)。回顾性分析2组患儿临床病例资料。采用t检验及χ2检验，对2组患儿一般临床资料，PN及肠内营养(EN)支持及并发症情况进行比较，并对差异具有统计学意义的指标，采用多因素非条件logistic回归分析，对VLBWI/ELBWI采取PN治疗后发生PNAC的独立影响因素进行分析。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。

结果

①单因素分析结果显示：2组患儿胎龄、母乳喂养比例、PN持续时间、败血症及喂养不耐受发生率比较，差异均有统计学意义(P<0.05)。②多因素非条件logistic回归分析结果显示：PN持续时间长(OR＝1.423，95%CI：1.151~1.758，P＝0.001)，合并败血症(OR＝5.067，95%CI：1.355~18.951，P＝0.016)，喂养不耐受(OR＝7.258，95%CI：2.659~19.816，P<0.001)，均为VLBWI/ELBWI给予PN后发生PNAC的独立危险因素；而母乳喂养(OR＝0.149，95%CI：0.048~0.458，P＝0.001)则为独立保护因素。

结论

对VLBWI/ELBWI采用PN持续时间长，发生喂养不耐受及感染等，更易发生PNAC。同时，应重视对VLBWI/ELBWI的母乳喂养，以降低PNAC发生率。

关键词: 胃肠外营养, 胆汁淤积, 脓毒症, 母乳喂养, 营养支持, 婴儿，极低出生体重, 婴儿，超低出生体重
Objective

To investigate the influencing factors of parenteral nutrition associated cholestasis (PNAC) in very-/extremely-low birth weight infant (VLBWI/ELBWI) after parenteral nutrition (PN) treatment.

Methods

From July 2017 to July 2019, a total of 88 VLBWI/ELBWI (gestational age<32 weeks) hospitalized in Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region were selected as research objects. According to whether PNAC occurred or not during hospitalization period, they were divided into PNAC group (n=42, complicated with PNAC) and non-PNAC group (n=46, without PNAC). Clinical data of subjects of two groups were retrospectively analyzed. The general clinical data, PN and enteral nutrition (EN) supports treatment and their related complications were compared between two groups by t test and chi-square test. And for indicators with statistical significance, multivariate unconditional logistic regression analysis was performed to analyze independent influencing factors of PNAC occurrence in VLBWI/ELBWI after PN treatment. The procedures followed in this study was in line with the World Medical Association Declaration of Helsinki revised in 2013.

Results

① Univariate analysis showed that there were significant differences in gestational age, breast feeding ratio, PN duration, incidence of sepsis and feeding intolerance between two groups (P<0.05). ② Multivariate unconditional logistic regression analysis showed that long duration of PN (OR=1.423, 95%CI: 1.151-1.758, P=0.001), complicated with sepsis (OR=5.067, 95%CI: 1.355-18.951, P=0.016) and feeding intolerance (OR=7.258, 95%CI: 2.659-19.816, P<0.001) were independent risk factors of PNAC occurrence in VLBWI/ELBWI after given PN, on the contrary, breast feeding (OR=0.149, 95%CI: 0.048-0.458, P=0.001) was an independent protective factor.

Conclusions

When VLBWI/ELBWI with long duration of PN, feeding intolerance and infection, etc., are more prone to PNAC. At the same time, attention should be paid to breast feeding of VLBWI/ELBWI to reduce PNAC complication.

Key words: Parenteral nutrition, Cholestasis, Sepsis, Breast feeding, Nutritional support, Infant, very low birth weight, Infant, extremely low birth weight
表1 2组VLBWI/ELBWI一般情况，PN及EN支持及并发症发生率比较
组别 例数 娩出方式[例数(%)] 孕母羊水性质[例数(%)] 胎龄(周，±s ) 性别[例数(%)]
顺产 剖宫产 清亮 浑浊/血性 男 女
PNAC组 42 20(47.6) 22(52.4) 37(88.1) 5(11.9) 28.4±2.1 27(64.3) 15(35.7)
非PNAC组 46 17(37.0) 29(63.0) 38(82.6) 8(17.4) 29.4±1.5 25(54.3) 21(45.7)
检验值   χ2＝1.024 χ2＝0.525 t＝2.677 χ2＝0.897
P值   0.388 0.556 0.009 0.390
组别 例数 出生体重(g，±s ) 出生时窒息[例数(%)] 小于胎龄儿[例数(%)] 喂养方式[例数(%)] PN持续时间(d，±s ) 氨基酸开始输注时间(生后h，±s )
母乳 配方奶
PNAC组 42 1 042±188 9(21.4) 10(23.8) 7(16.7) 35(83.3) 55.3±15.0 13.5±8.6
非PNAC组 46 1 097±209 6(13.0) 15(32.6) 35(76.1) 11(23.9) 34.0±7.2 12.2±6.6
检验值   t＝1.275 χ2＝1.092 χ2＝0.836 χ2＝31.070 t＝-8.581 t＝-0.803
P值   0.206 0.397 0.479 <0.001 <0.001 0.424
组别 例数 最大输入量[g/(kg·d)，±s] 并发症[例数(%)]
氨基酸 脂肪乳 PDA NEC 败血症 喂养不耐受 PPHN
PNAC组 42 2.9±0.6 3.0±0.4 14(33.3) 8(19.0) 14(33.3) 27(64.3) 8(2.4)
非PNAC组 46 2.9±0.3 2.8±0.3 19(41.3) 9(19.6) 4(8.7) 9(19.6) 2(4.3)
检验值   t＝-0.669 t＝-1.881 χ2＝0.440 χ2＝0.004 χ2＝8.191 χ2＝18.163 χ2＝3.364
P值   0.505 0.064 0.511 0.950 0.007 <0.001 0.067
表2 对VLBWI/ELBWI采取PN治疗后，导致发生PNAC影响因素的多因素非条件logistic回归分析变量含义及赋值情况
自变量/因变量 变量名 赋值
PNAC y1 y1＝0表示发生，y1＝1表示未发生
胎龄(周) x1 x1为连续变量
PN持续时间(d) x2 x2为连续变量
喂养方式 x3 x3＝0表示配方奶喂养，x3＝1表示母乳喂养
败血症 x4 x4＝0表示未发生，x4＝1表示发生
喂养不耐受 x5 x5＝0表示未发生，x5＝1表示发生
表3 对VLBWI/ELBWI采取PN治疗后，导致发生PNAC影响因素的多因素非条件logistic回归分析结果
影响因素 B SE Wald值 P值 OR值 OR值95%CI
胎龄 0.033 0.220 0.023 0.880 1.034 0.672~1.591
PN持续时间 0.353 0.108 10.674 0.001 1.423 1.151~1.758
母乳喂养 -1.905 0.573 11.053 0.001 0.149 0.048~0.458
败血症 1.623 0.673 5.812 0.016 5.067 1.355~18.951
喂养不耐受 1.982 0.512 14.963 <0.001 7.258 2.659~19.816
[1]
Fawaz R, Baumann U, Ekong U, et al. Guideline for the evaluation of cholestatic jaundice in infants: Joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition[J]. J Pediatr Gastroenterol Nutr, 2017, 64(1): 154-168. DOI: 10.1097/MPG.0000000000001334.
[2]
孙梅. 早产儿胃肠外营养相关性胆汁淤积的研究进展[J/CD]. 中华妇幼临床医学杂志(电子版), 2008, 4(5): 397-401. DOI: 10.3877/cma.j.issn.1673-5250.2008.05.101.
[3]
Alkharfy TM, Ba-Abbad R, Hadi A, et al. Total parenteral nutrition-associated cholestasis and risk factors in preterm infants[J]. Saudi J Gastroenterol, 2014, 20(5): 293-296. DOI: 10.4103/1319-3767.141688.
[4]
詹江华，冯杰雄. 胆道闭锁何时完成Kasai[J]. 中华小儿外科杂志，2016, 37(5): 321-326. DOI: 10.3760/cma.j.issn.0253-3006.2016.05.001.
[5]
General Assembly of the World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects[J]. J Am Coll Dent, 2014, 81(3): 14-18.
[6]
夏世文. 早产儿胃肠外营养相关性胆汁淤积[J]. 中国新生儿科杂志，2011, 26(5): 289-292. DOI: 10.3969/j.issn.1673-6710.2011.05.001.
[7]
中华医学会儿科学分会新生儿学组. 早产儿管理指南(英文)[J]. 中国当代儿科杂志，2005, 7(1): 1-7.
[8]
庄思齐. 中国新生儿营养支持临床应用指南(2013年更新版)解读[J]. 临床儿科杂志，2014, 32(9): 801-803. DOI: 10.3969/j.issn.1000-3606.2014.09.001.
[9]
Teng J, Arnell H, Bohlin K, et al. Impact of parenteral fat composition on cholestasis in preterm infants[J]. J Pediatr Gastroenterol Nutr, 2015, 60(6): 702-707. DOI: 10.1097/MPG.0000000000000739.
[10]
Lauriti G, Zani A, Aufieri R, et al. Incidence, prevention, and treatment of parenteral nutrition-associated cholestasis and intestinal failure-associated liver disease in infants and children: a systematic review[J]. JPEN J Parenter Enteral Nutr, 2014, 38(1): 70-85. DOI: 10.1177/0148607113496280.
[11]
Willis TC, Carter BA, Rogers SP, et al. High rates of mortality and morbidity occur in infants with parenteral nutrition-associated cholestasis[J]. JPEN J Parenter Enteral Nutr, 2010, 34(1): 32-37. DOI: 10.1177/0148607109332772.
[12]
Agostoni C, Buonocore G, Carnielli VP, et al. Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition[J]. J Pediatr Gastroenterol Nutr, 2010, 50(1): 85-91. DOI: 10.1097/MPG.0b013e3181adaee0.
[13]
Wales PW, Brindle M, Sauer CJ, et al. Percutaneous cholangiography for the treatment of parenteral nutrition-associated cholestasis in surgical neonates: preliminary experience[J]. J Pediatr Surg, 2007, 42(11): 1913-1918. DOI: 10.1016/j.jpedsurg.2007.07.022.
[14]
Ananth R. Neonatal cholestasis: a primer of selected etiologies[J]. Pediatr Ann, 2018, 47(11): e433-e439. DOI: 10.3928/19382359-20181018-01.
[15]
钟美娇，薛辛东. 早产儿胃肠外营养相关性胆汁淤积的研究现状[J/CD]. 中华妇幼临床医学杂志(电子版), 2017, 13(3): 249-255. DOI: 10.3877/cma.j.issn.1673-5250.2017.03.001.
[16]
Sharef SW, Al-Sinani S, Al-Naamani K, et al. Incidence and risk factors of parenteral nutrition-associated cholestasis in Omani neonates: single centre experience[J]. Sultan Qaboos Univ Med J, 2015, 15(2): e234-e240.
[17]
Teitelbaum DH, Tracy TF Jr, Aouthmany MM, et al. Use of cholecystokinin-octapeptide for the prevention of parenteral nutrition-associated cholestasis[J]. Pediatrics, 2005, 115(5): 1332-1340. DOI: 10.1542/peds.2004-1014.
[18]
Yildizdas HY, Poyraz B, Atli G, et al. Effects of two different lipid emulsions on antioxidant status, lipid peroxidation and parenteral nutrition-related cholestasis in premature babies, a randomized-controlled study[J]. Pediatr Neonatol, 2019, 60(4): 359-367. DOI: 10.1016/j.pedneo.2018.07.012.
[19]
Carter BA, Taylor OA, Prendergast DR, et al. Stigmasterol, a soy lipid-derived phytosterol, is an antagonist of the bile acid nuclear receptor FXR[J]. Pediatr Res, 2007, 62(3): 301-306. DOI: 10.1203/PDR.0b013e3181256492.
[20]
Hoang V, Sills J, Chandler M, et al. Percutaneously inserted central catheter for total parenteral nutrition in neonates: complications rates related to upper versus lower extremity insertion[J]. Pediatrics, 2008, 121(5): e1152-e1159. DOI: 10.1542/peds.2007-1962.
[21]
Fell JM, Reynolds AP, Meadows N, et al. Manganese toxicity in children receiving long-term parenteral nutrition[J]. Lancet, 1996, 347(9010): 1218-1221. DOI: 10.1016/s0140-6736(96)90735-7.
[22]
Gupta K, Wang H, Amin SB. Parenteral nutrition-associated cholestasis in premature infants: role of macronutrients[J]. JPEN J Parenter Enteral Nutr, 2016, 40(3): 335-341. DOI: 10.1177/0148607114555161.
[23]
Lee HH, Jung JM, Nam SH, et al. Risk factor analysis of parenteral nutrition-associated cholestasis in extremely low birth weight infants[J]. Acta Paediatr, 2016, 105(7): e313-e319. DOI: 10.1111/apa.13441.
[24]
邵肖梅，叶鸿瑁，丘小汕. 实用新生儿学[M]. 4版. 北京：人民卫生出版社，2011: 365-370.
[25]
Cao S, Niu S, Wang X, et al. Sepsis and bronchopulmonary dysplasia as potential risk factors for parenteral nutrition-associated cholestasis in neonates: a Meta-analysis of retrospective studies[J]. Minerva Pediatr, 2019. DOI: 10.23736/S0026-4946.19.05337-4.
[26]
Johnson TJ, Patel AL, Bigger HR, et al. Cost savings of human milk as a strategy to reduce the incidence of necrotizing enterocolitis in very low birth weight infants[J]. Neonatology, 2015, 107(4): 271-276. DOI: 10.1159/000370058.
[27]
Madnawat H, Welu AL, Gilbert EJ, et al. Mechanisms of parenteral nutrition-associated liver and gut injury[J]. Nutr Clin Pract, 2020, 35(1): 63-71. DOI: 10.1002/ncp.10461.
[28]
Parm Ü, Metsvaht T, Ilmoja ML, et al. Gut colonization by aerobic microorganisms is associated with route and type of nutrition in premature neonates[J]. Nutr Res, 2015, 35(6): 496-503. DOI: 10.1016/j.nutres.2015.04.006.
[29]
曹春英，王丽珠，易美宏，等. 微量喂养护理对早产儿肠道菌群平衡的影响观察[J]. 中国当代医药，2019, 26(8): 192-194. DOI: 10.3969/j.issn.1674-4721.2019.08.060.
[30]
韩树萍. 母乳喂养对新生儿重症监护病房早产儿的益处[J]. 中国新生儿科杂志，2015, 30(3): 161-163. DOI: 10.3969/j.issn.1673-6710.2015.03.001.
[31]
刘凤，韩树萍，余章斌，等. 持续母乳喂养质量改进对极/超低出生体重儿的影响[J]. 中华围产医学杂志，2019, 22(7): 451-456. DOI: 10.3760/cma.j.issn.1007-9408.2019.07.005.
[1] 孟建标, 张庚, 焦燕娜. 脓毒症合并心功能障碍患者早期肠道微生态改变的探讨[J]. 中华危重症医学杂志(电子版), 2023, 16(04): 279-285.
[2] 陈宇, 冯芳, 张露, 刘健. 基于生物信息学分析筛选脓毒症心肌病关键致病基因[J]. 中华危重症医学杂志(电子版), 2023, 16(04): 286-291.
[3] 韩媛媛, 热孜亚·萨贝提, 冒智捷, 穆福娜依·艾尔肯, 陆晨, 桑晓红, 阿尔曼·木拉提, 张丽. 组合式血液净化治疗对脓毒症患者血清炎症因子水平和临床预后的影响[J]. 中华危重症医学杂志(电子版), 2023, 16(04): 272-278.
[4] 张晓燕, 肖东琼, 高沪, 陈琳, 唐发娟, 李熙鸿. 转录因子12过表达对脓毒症相关性脑病大鼠大脑皮质的保护作用及其机制[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 540-549.
[5] 魏徐, 张鸽, 伍金林. 新生儿脓毒症相关性凝血病的监测和治疗[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(04): 379-386.
[6] 李敏, 熊菲. 母乳成分及其影响因素的研究现状[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(03): 267-272.
[7] 李聪, 徐艳, 吴铭, 丁瑞东, 王军. 极低出生体重儿出生时血清25-羟维生素D水平与其生后早期喂养不耐受关系的临床分析[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(03): 309-314.
[8] 姚咏明. 如何精准评估烧伤脓毒症患者免疫状态[J]. 中华损伤与修复杂志(电子版), 2023, 18(06): 552-552.
[9] 黄翠君, 张喜玲, 刘思嘉, 刘云建. 重症急性胰腺炎营养支持治疗研究进展[J]. 中华普通外科学文献(电子版), 2023, 17(05): 385-390.
[10] 窦上文, 邓欢, 刘邦锋, 岳高远志, 朱华财, 刘永达. 术前复查尿培养在预测微通道经皮肾镜取石术相关感染并发症中的作用[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(04): 361-366.
[11] 李伟, 卓剑, 黄川, 黄有攀. Lac、HO-1、sRAGE、CRP/ALB表达及脓毒症并发ARDS危险因素分析[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 514-516.
[12] 苗软昕, 乔晞. Toll样受体在脓毒症性急性肾损伤中的作用[J]. 中华肾病研究电子杂志, 2023, 12(04): 210-214.
[13] 张雯, 宋牡丹, 邓雪婷, 张云. 强化营养支持辅助奥曲肽治疗肝硬化合并食管胃底静脉曲张破裂出血的疗效及再出血危险因素[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 456-460.
[14] 谭睿, 王晶, 於江泉, 郑瑞强. 脓毒症中高密度脂蛋白、载脂蛋白A-I和血清淀粉样蛋白A的作用研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(06): 749-753.
[15] 蔡荇, 郑瑞强. 肝素结合蛋白在脓毒症中的应用及研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(04): 487-490.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号