Clinical analysis of risk factors of parenteral nutrition-associated cholestasis in very low birthweight infants

doi:10.3877/cma.j.issn.1673-5250.2015.05.002

Objective

To investigate the risk factors of parenteral nutrition-associated cholestasis (PNAC) in very low birth weight infants (VLBWI).

Methods

VLBWI who were accorded with inclusion and exclusion criteria of this study: treatment for parenteral nutrition (PN) for over 14 days in West China Second University Hospital of Sichuan University from May 2008 to May 2014 were chosen as study subjects. By retrospectively analyzed method, they were divided into PNAC group and non PNAC group according to whether suflered from PNAC or not. First of all, according to the clinical experience, the influence factors of PNAC were identified and carried on the single factor analysis, then comprehensively considered with statistically significant variables and professional knowledge, multiple factors unconditional logistic regression analysis method was used to further analyze the independent and risk factors of PNAC.

Results

①A total of 172 cases of VLBWI were chosen as study subjects finally. According to whether suffered from PNAC or not, they were divided into PNAC group (n=29) and non PNAC group (n=143), and the incidence of PNAC was 16.9%. There were no significant differences between two groups among gender ratio, gestational age at delivery and mode of delivery, etc. (P>0.05). ②According to clinical experience, the single factor analysis results about 27 clinical observation items and 19 nutritional factors which may lead to PNAC showed that 8 clinical observation items and 5 nutritional factors were influence factors of PNAC, such as VLBWI, less than appropriate for gestational age (SGA), long fasting time and longer duration of PN, higher amino acid and fat emulsion calories, milk lower calories, higher neonatal infections, such as infectious pneumonia, sepsis, neonatal necrotizing enterocolitis (NEC) and septic shock rate, lower breastfeeding and oral probiotics rate, and all the differences were statistically significant (t/χ²=3.306, 3.306, 1.790, 1.231, 3.193, 2.815, 2.519, 4.615, 3.949, 3.920, 3.861, 5.656, 5.535; P<0.05). The unconditioned and multi-factor of logistic regression analysis results of influence factors may cause PNAC showed that neonatal infections, SGA, VLBWI, long fasting time, long duration of PN, higher amino acid and fat emulsion calories were the risk factors of PNAC (OR=8.785, 8.785, 8.785, 3.851, 6.746, 7.113, 3.765; 95%CI: 3.603-25.236, 1.526-8.932, 2.534-19.651, 1.473-15.326, 1.219-12.471, 3.124-19.358, 3.230-26.246; P<0.05), milk high calorie, breastfeeding and oral probiotics were protective factors of PNAC (OR=0.016, 0.016, 0.016; 95%CI: 0.027-0.679, 0.076-0.531, 0.013-0.169; P<0.05).

Conclusions

Neonatal infections, SGA, low birth weight, long duration of PN, higher amino acid and fat emulsion calorie, long fasting time are significant risk factors of PNAC in our study. Protective factors are high milk calorie, breastfeeding and oral probiotics.

Key words: Parenteral nutrition-associated cholestasis, Risk factors, Birth weight, Very low birth weight, Infant, newborn

表1 可能导致PNAC的临床观察项目(27项)相关影响因素的单因素分析结果比较[例数(%)]

影响因素	PNAC组(n＝29)	非PNAC组(n＝143)	t值/χ²值	P值
产前应用糖皮质激素	21(74.4)	98(68.5)	0.171	0.157
母胆汁淤积症	8(27.6)	54(37.8)	1.083	0.102
胎龄(周，±s)	30.1±2.0	31.7±2.3	－1.524	0.762
出生体质量(g，±s)	1 228±219	1 240±231	－3.306	0.043
AGA儿	7(24.1)	35(26.6)	0.002	0.187
SGA儿	20(69.0)	68(47.6)	4.424	0.016
性别(男/女)	16/13	81/62	0.021	0.162
Apgar评分(分，±s)	8.5±1.5	9.0±1.0	0.987	0.715
分娩方式(自然分娩/剖宫产)	17/12	91/52	0.260	0.158
代谢性酸中毒	12(41.4)	69(48.3)	0.457	0.129
低氧血症	16(55.2)	71(49.7)	0.294	0.143
高碳酸血症	8(27.6)	56(39.2)	1.383	0.091
NRDS	11(37.9)	49(34.3)	0.143	0.156
新生儿吸入综合征	8(27.6)	57(39.9)	1.545	0.792
动脉导管未闭	4(13.8)	25(17.5)	0.045	0.214
贫血	3(10.3)	23(16.1)	0.252	0.178
呼吸衰竭	3(10.3)	19(13.3)	0.016	0.226
颅内出血	5(17.2)	22(15.4)	0.001	0.209
感染性肺炎	14(48.3)	40(28.0)	4.615	0.022
败血症	7(24.1)	13(9.1)	3.949	0.018
感染性休克	6(20.7)	10(5.6)	3.861	0.016
NEC	5(17.2)	7(4.9)	3.920	0.032
使用抗菌药物	15(51.7)	89(62.2)	1.115	0.091
吸氧	18(62.1)	91(63.6)	0.026	0.156
机械通气	15(51.7)	82(57.3)	0.310	0.096
口服益生菌	13(44.8)	97(67.8)	5.535	0.014
母乳喂养	9(31.0)	79(55.2)	5.656	0.012

表1 可能导致PNAC的临床观察项目(27项)相关影响因素的单因素分析结果比较[例数(%)]

影响因素	PNAC组(n＝29)	非PNAC组(n＝143)	t值/χ²值	P值
产前应用糖皮质激素	21(74.4)	98(68.5)	0.171	0.157
母胆汁淤积症	8(27.6)	54(37.8)	1.083	0.102
胎龄(周，±s)	30.1±2.0	31.7±2.3	－1.524	0.762
出生体质量(g，±s)	1 228±219	1 240±231	－3.306	0.043
AGA儿	7(24.1)	35(26.6)	0.002	0.187
SGA儿	20(69.0)	68(47.6)	4.424	0.016
性别(男/女)	16/13	81/62	0.021	0.162
Apgar评分(分，±s)	8.5±1.5	9.0±1.0	0.987	0.715
分娩方式(自然分娩/剖宫产)	17/12	91/52	0.260	0.158
代谢性酸中毒	12(41.4)	69(48.3)	0.457	0.129
低氧血症	16(55.2)	71(49.7)	0.294	0.143
高碳酸血症	8(27.6)	56(39.2)	1.383	0.091
NRDS	11(37.9)	49(34.3)	0.143	0.156
新生儿吸入综合征	8(27.6)	57(39.9)	1.545	0.792
动脉导管未闭	4(13.8)	25(17.5)	0.045	0.214
贫血	3(10.3)	23(16.1)	0.252	0.178
呼吸衰竭	3(10.3)	19(13.3)	0.016	0.226
颅内出血	5(17.2)	22(15.4)	0.001	0.209
感染性肺炎	14(48.3)	40(28.0)	4.615	0.022
败血症	7(24.1)	13(9.1)	3.949	0.018
感染性休克	6(20.7)	10(5.6)	3.861	0.016
NEC	5(17.2)	7(4.9)	3.920	0.032
使用抗菌药物	15(51.7)	89(62.2)	1.115	0.091
吸氧	18(62.1)	91(63.6)	0.026	0.156
机械通气	15(51.7)	82(57.3)	0.310	0.096
口服益生菌	13(44.8)	97(67.8)	5.535	0.014
母乳喂养	9(31.0)	79(55.2)	5.656	0.012

表2 可能导致PNAC的营养因素项目(19项)相关影响因素的单因素分析结果比较(±s)

影响因素	PNAC组(n＝29)	非PNAC组(n＝143)	t值	P值
PN起始时间(d)	3.1±2.3	4.1±2.9	0.301	0.691
PN持续时间(d)	30.1±15.9	25.6±10.9	1.790	0.041
葡萄糖累计用量(g)	369±142	299±128	0.710	0.052
氨基酸累计用量(g)	123±31	82±41	2.163	0.106
脂肪乳累计用量(g)	102±59	86±45	1.529	0.847
氨基酸每日最高用量[g/(kg·d)]	3.0±0.4	2.5±1.0	0.563	0.514
脂肪乳每日最高用量[g/(kg·d)]	3.0±0.5	2.6±0.9	0.582	0.570
禁食时间(d)	6.2±2.8	3.1±1.5	1.231	0.023
奶累积量(mL)	4 350±3 156	5 214±4 056	2.712	0.205
总热卡(kcal)	6 159±2 810	7 510±2 912	1.580	0.406
糖热卡比(%)	30.5±18.3	22.1±11.2	2.013	0.209
氨基酸热卡比(%)	8.2±3.8	5.1±2.5	3.193	0.037
脂肪乳热卡比(%)	19.0±7.3	12.1±4.5	2.815	0.012
奶热卡比(%)	42.5±26.3	64.8±18.1	2.519	0.023
住院天数(d)	42.1±19.5	39.4±17.3	0.873	0.127
每天总热卡[kcal/(kg·d)]	98.7±35.6	103.2±35.3	3.256	0.219
静脉每天热卡[kcal/(kg·d)]	45.6±23.8	46.2±19.7	1.592	0.501
PN持续第14天的静脉热卡(kcal/kg)	62±23	50±26	0.492	0.127
PN持续第14天的热氮比(kcal/kg)	142±57	153±59	3.139	0.212

表2 可能导致PNAC的营养因素项目(19项)相关影响因素的单因素分析结果比较(±s)

影响因素	PNAC组(n＝29)	非PNAC组(n＝143)	t值	P值
PN起始时间(d)	3.1±2.3	4.1±2.9	0.301	0.691
PN持续时间(d)	30.1±15.9	25.6±10.9	1.790	0.041
葡萄糖累计用量(g)	369±142	299±128	0.710	0.052
氨基酸累计用量(g)	123±31	82±41	2.163	0.106
脂肪乳累计用量(g)	102±59	86±45	1.529	0.847
氨基酸每日最高用量[g/(kg·d)]	3.0±0.4	2.5±1.0	0.563	0.514
脂肪乳每日最高用量[g/(kg·d)]	3.0±0.5	2.6±0.9	0.582	0.570
禁食时间(d)	6.2±2.8	3.1±1.5	1.231	0.023
奶累积量(mL)	4 350±3 156	5 214±4 056	2.712	0.205
总热卡(kcal)	6 159±2 810	7 510±2 912	1.580	0.406
糖热卡比(%)	30.5±18.3	22.1±11.2	2.013	0.209
氨基酸热卡比(%)	8.2±3.8	5.1±2.5	3.193	0.037
脂肪乳热卡比(%)	19.0±7.3	12.1±4.5	2.815	0.012
奶热卡比(%)	42.5±26.3	64.8±18.1	2.519	0.023
住院天数(d)	42.1±19.5	39.4±17.3	0.873	0.127
每天总热卡[kcal/(kg·d)]	98.7±35.6	103.2±35.3	3.256	0.219
静脉每天热卡[kcal/(kg·d)]	45.6±23.8	46.2±19.7	1.592	0.501
PN持续第14天的静脉热卡(kcal/kg)	62±23	50±26	0.492	0.127
PN持续第14天的热氮比(kcal/kg)	142±57	153±59	3.139	0.212

表3 可能导致PNAC的影响因素的非条件多因素logistic回归分析结果比较

变量	偏回归系数	偏回归系数标准误	Wald	P值	OR值	95%CI
新生儿感染	1.026	0.236	15.439	0.021	8.785	3.603～25.236
SGA儿	0.734	0.228	8.179	0.003	3.851	1.526～8.932
出生体质量	0.861	0.215	10.348	0.002	7.134	2.534～19.651
禁食时间	2.298	0.824	3.473	0.043	4.728	1.473～15.326
PN持续时间	1.356	0.361	14.527	0.021	6.746	1.219～12.471
氨基酸热卡比	16.289	0.927	9.266	0.002	7.113	3.124～19.358
脂肪乳热卡比	1.157	0.433	8.026	0.010	3.765	3.230～26.246
奶热卡比	1.972	0.316	8.017	0.031	0.016	0.027～0.679
母乳喂养	1.337	0.219	19.117	0.015	0.204	0.076～0.531
口服益生菌	0.679	0.139	26.132	0.043	0.078	0.013～0.169

表3 可能导致PNAC的影响因素的非条件多因素logistic回归分析结果比较

变量	偏回归系数	偏回归系数标准误	Wald	P值	OR值	95%CI
新生儿感染	1.026	0.236	15.439	0.021	8.785	3.603～25.236
SGA儿	0.734	0.228	8.179	0.003	3.851	1.526～8.932
出生体质量	0.861	0.215	10.348	0.002	7.134	2.534～19.651
禁食时间	2.298	0.824	3.473	0.043	4.728	1.473～15.326
PN持续时间	1.356	0.361	14.527	0.021	6.746	1.219～12.471
氨基酸热卡比	16.289	0.927	9.266	0.002	7.113	3.124～19.358
脂肪乳热卡比	1.157	0.433	8.026	0.010	3.765	3.230～26.246
奶热卡比	1.972	0.316	8.017	0.031	0.016	0.027～0.679
母乳喂养	1.337	0.219	19.117	0.015	0.204	0.076～0.531
口服益生菌	0.679	0.139	26.132	0.043	0.078	0.013～0.169

[1]	Willis TC, Cartler BA, Rogers SP, et al. High rates of mortality and mortality and morbidity occur in infants with parenteral nutrition-associated cholestasis[J]. J Parenter Enteral Nutr, 2010, 34(1):32-37.
[2]	孙梅. 早产儿胃肠外营养相关性胆汁淤积的研究进展[J]. 中华妇幼临床医学杂志：电子版，2008, 4(5):1-4.
[3]	中华医学会肠外肠内营养学分会儿科协作组，中华医学会儿科学分会新生儿组，中华医学会小儿外科分会新生儿组. 中国新生儿营养支持临床应用指南[J]. 中国当代儿科杂志，2006, 8(5):352-356.
[4]	Costa S, Maggio L, Sindico P, et al. Preterm small for gestational age infants are not at higher risk for parenteral nutrition-associated cholestasis[J]. J Pediatr, 2010, 156(4):575-579.
[5]	Peden VH, Witzleben CL, Skelton MA. Total parenteral nutrition[J]. J Pediatr, 1971, 78(1):180-181.
[6]	Arnold CJ, Miller GG, Zello GA. Parenteral nutrition-associated cholestasis in neonates the role of aluminum[J]. Nutr Rev, 2003, 61(9):306-310.
[7]	汤庆娅，王莹，冯一. 新生儿肠外营养相关性胆汁淤积因素612例分析[J]. 中华儿科杂志，2007, 45(1):838-842.
[8]	李卉，冯琪，王颖，等. 极低出生体质量儿肠道外营养相关性胆汁淤积的临床研究[J]．新生儿科杂志，2005, 20(2):57-61.
[9]	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):1152-1159.
[10]	朱明哲，单若冰，王培秋. 内毒素血症在新生儿全胃肠外营养相关性胆汁淤积中的作用[J]. 中国现代药物应用，2007, 1(8):21-23.
[11]	杨慧，王卫，刘晓红．早产儿胃肠外营养相关性胆汁淤积影响因素研究[J]．中国新生儿科杂志，2013，28(1):32-35.
[12]	Hsieh MH, Pai W, Tseng HI, et al. Parenteral nutrition-associated cholestasis in premature babies: risk factors and predictors[J]. Pediatr Neonatol , 2009, 50(5):202-207.
[13]	Christensen RD, Henry E, Wiedmeier SE, et al. Identifying patients, on eth first day of life, at high-risk of developing parenteral nutrition-associated liver disease[J]. J Perinatol, 2007, 27(5):284-290.
[14]	贝斐，孙建华，叶秀霞，等. 早期应用氨基酸对极低出生体质量儿胃肠外营养相关性胆汁淤积的影响[J]. 新生儿科杂志，2011, 26(2):83-86.
[15]	Shin JI, Namgung R, Park MS, et al. Could lipid infusion be a risk for parenteral nutrition-associated cholestasis in low birth weight neonates？[J]. Eur J Pediatr, 2008, 167(20):197-202.
[16]	母乳强化剂应用研究协作组. 母乳强化剂在早产儿母乳喂养中应用的多中心研究[J]．中华儿科杂志，2012, 50(5):336-341.
[17]	王翔，蔡威，洪莉，等. 双歧杆菌减轻肠外营养幼兔肝损害的实验研究[J]. 中华小儿外科杂志，2006, 27(3):155-158.
[18]	胡玉莲，黄志华，王晓东，等. 双歧杆三联活菌片对于胆淤幼鼠移行性机电复合波影响及其干预胆汁淤积的机制[J]. 实用儿科临床杂志，2007, 22(19):1487-1489.

[1]	Huanyan Liu, Yang Hua, Lingyun Jia, Xinyu Zhao, Beibei Liu. Lumen structure and hemodynamic characteristics of occluded internal carotid artery[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(08): 809-815.
[2]	Yanbo Ma, Yang Hua, Guimei Liu, Xiufeng Meng, Liping Cui. Risk factors for carotid atherosclerotic lesions in middle adults[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(08): 822-826.
[3]	Yingxiong Huang, Zi Ye, Peng Jiang, Hong Zhan, Chen Yao, Ji Cui. Clinical risk factors for transmural intestinal necrosis in acute mesenteric venous thrombosis[J]. Chinese Archives of General Surgery(Electronic Edition), 2023, 17(06): 413-421.
[4]	Zaibo Zhang, Bingyu Wang, Zhikai Jiao, Bibo Tan. Risk factors for lower extremity deep venous thrombosis after gastric cancer surgery: A Meta-analysis[J]. Chinese Archives of General Surgery(Electronic Edition), 2023, 17(06): 475-480.
[5]	Xu Tang, Bing Han, Wei Liu, Ruxing Chen. Analysis of risk factors for metachronous liver metastases after radical colorectal cancer surgery and construction of a predictive model[J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2024, 18(01): 16-20.
[6]	Fangyuan Wu, Xia Sun, Changfeng Lin, Zhensheng Zhang. Risk factors of HBV-associated cirrhosis complicated with acute upper gastrointestinal bleeding[J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2024, 18(01): 45-47.
[7]	Qingyan Yan, Xiaomei Yong, Hong Luo, Min Du. Prognostic factors and survival analysis of multicenter elderly patients with metastatic breast cancer[J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2023, 17(06): 636-638.
[8]	Xian Mo, Chuang Yang. Meta-analysis of risk factors for portal vein thrombosis in patients with cirrhosis[J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2023, 17(06): 678-683.
[9]	Yonghuan Mao, Hanwen Tong, Ji Miao, Xingzhou Wang, Xiaofei Shen, Chunzhao Yu. Analysis of risk factors and prediction model of parastomal hernia[J]. Chinese Journal of Hernia and Abdominal Wall Surgery(Electronic Edition), 2023, 17(06): 682-687.
[10]	Chao Hou, Meichen Pan, Wenming Wu, Xingguang Huang, Xiang Li, Lingxue Cheng, Yuxuan Zhu, Wenbo Li. Risk factors of esophageal stricture after endoscopic submucosal dissection for early esophageal carcinoma and intraepithelial neoplasia[J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2023, 13(06): 383-387.
[11]	Menggui Lu, Bin Huang, Qiulin Li, Yuanmei He. Risk factors for multiple organ dysfunction syndrome in patients with bee sting injury[J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(9): 1010-1015.
[12]	Da Li, Daya Zhang, Runxiang Chen, Xiaodong Zhang, Shimei Huang, Chen Chen, fan Zeng, Shiju Chen, Feihu Bai. Epidemiological characteristics and risk factors of Helicobacter pylori infection in Dongfang city of Hainan province[J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(08): 858-864.
[13]	Ke Meng, Yan Li, Jingshuang Yan, Bin Yan. Risk factors for prolonged gastric transit time in capsule endoscopy[J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(06): 671-675.
[14]	Yanli Yang, Yu Chen, Ruochen Zhao, Wei Du, Haijuan Ma, Ke Xu, Liyun Zhang. Bloodstream infection in patients with systemic lupus erythematosus: risk factors and bacteriological analysis[J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(06): 694-699.
[15]	Peipei Sun, Erming Zhang, Yanwei Shi, Chunyan Zhao, Pingping Song, Shuo Zhang, Ke Zhang, Yujiao Zhou, Can Zhao, Wei Yan, Rongju Wu, Liping Song, Weian Guo, Shitou Ma, Xinhua An, Caoxin Bao, Pingchao Xiang. Prevalence and risk factors of chronic obstructive pulmonary disease in residents aged 40 years and above in Shijingshan district of Beijing[J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(06): 711-719.

Viewed

Full text

Abstract

Please choose a citation manager

Content to export