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

doi:10.3877/cma.j.issn.1673-5250.2021.05.007

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(%)]
组别	例数	顺产	剖宫产	清亮	浑浊/血性	胎龄(周，±s )	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 )
组别	例数	出生体重(g，±s )	出生时窒息[例数(%)]	小于胎龄儿[例数(%)]	母乳	配方奶	PN持续时间(d，±s )	氨基酸开始输注时间(生后h，±s )
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(%)]
组别	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(%)]
组别	例数	顺产	剖宫产	清亮	浑浊/血性	胎龄(周，±s )	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 )
组别	例数	出生体重(g，±s )	出生时窒息[例数(%)]	小于胎龄儿[例数(%)]	母乳	配方奶	PN持续时间(d，±s )	氨基酸开始输注时间(生后h，±s )
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(%)]
组别	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

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.

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