左旋肉碱在超未成熟儿脂类及胆红素代谢中的作用

doi:10.12372/jcp.2022.21e0730

摘要/Abstract

摘要：

目的探讨左旋肉碱在超未成熟儿（EPI）脂类及胆红素代谢中的作用。方法回顾分析2016年8月至2019年12月住院的胎龄<28周早产儿的临床资料。根据入院72小时内有无预防性使用左旋肉碱将早产儿分为左旋肉碱组和非左旋肉碱组,比较两组间血脂及胆红素水平。结果纳入261例EPI,男151例、女110例,平均胎龄（26.5±1.3）周,平均出生体质量（907.3±175.9）g。左旋肉碱组139例、非左旋肉碱组122例。左旋肉碱组1分钟Apgar评分以及产前使用地塞米松比例均高于非左旋肉碱组,差异有统计学意义（P<0.05）。与非左旋肉碱组相比,左旋肉碱组住院第1和第2周总胆红素水平均较低,第2周胆汁酸水平较高,第4周直接胆红素水平较低,第1周三酰甘油水平较高,第1和第2周BUN和Cr均较低、ALT较高,差异均有统计学意义（P<0.05）。261例患儿中,肠外营养相关胆汁淤积症（PNAC）共发生66例,其中左旋肉碱组33例（23.7%）,非左旋肉碱组33例（27.0%）。二元logistic回归分析发现,住院4周时三酰甘油水平是PNAC发生的危险因素（P<0.05）。是否预防性使用左旋肉碱与PNAC的发生无显著相关性（P>0.05）。结论 EPI早期预防性使用左旋肉碱可调节胆红素及脂类代谢,但不会降低PNAC的发生率,也不会影响肝肾功能。

关键词: 左旋肉碱, 脂类代谢, 胆红素代谢, 超未成熟儿

Abstract:

Objective To investigate the effect of L-carnitine on lipid and bilirubin metabolism in extremely premature infants (EPI). Methods The clinical data of preterm infants with gestational age <28 weeks hospitalized from August 2016 to December 2019 were retrospectively analyzed. Preterm infants were divided into L-carnitine group and non-L-carnitine group according to the prophylactic use of L-carnitine within 72 hours after admission, and the levels of lipids and bilirubin were compared between the two groups. Results A total of 261 EPI (151 boys and 110 girls) were enrolled, and the mean gestational age was (26.5±1.3) weeks and the mean birth weight was (907.3±175.9) g. There were 139 patients in L-carnitine group and 122 in non-L-carnitine group. The 1-minute Apgar score and the proportion of prenatal dexamethasone use in L-carnitine group were higher than those in non-L-carnitine group, and the differences were statistically significant (P<0.05). Compared with non-L-carnitine group, L-carnitine group had lower total bilirubin level at week 1 and 2, higher bile acid level at week 2, lower direct bilirubin level at week 4, higher triglyceride level at week 1, lower blood urea nitrogen and creatinine levels and higher alanine aminotransferase level at week 1 and 2, and the differences were statistically significant (P<0.05). Among 261 patients, 66 had parenteral nutrition associated cholestasis (PNAC), including 33 patients (23.7%) in the L-carnitine group and 33 (27.0%) in the non-L-carnitine group. Binary logistic regression analysis showed that triacylglycerol level at the fourth week of hospitalization was a risk factor for PNAC (P<0.05). There was no significant correlation between prophylactic use of L-carnitine and the occurrence of PNAC (P>0.05). Conclusions Early prophylactic use of L-carnitine in EPI can regulate bilirubin and lipid metabolism, but it will not reduce the incidence of PNAC, nor affect liver and kidney function.

Key words: L-carnitine, metabolism of lipid, metabolism of bilirubin, extremely premature infant

余彦亮, 陈雪雨, 范国清, 陈春, 林冰纯, 赵捷, 黄智峰, 杨传忠. 左旋肉碱在超未成熟儿脂类及胆红素代谢中的作用[J]. 临床儿科杂志, 2022, 40(6): 431-435.

YU Yanliang, CHEN Xueyu, FAN Guoqing, CHEN Chun, LIN Bingchun, ZHAO Jie, HUANG Zhifeng, YANG Chuanzhong. Effect of L-carnitine on lipid and bilirubin metabolism in extremely premature infants[J]. Journal of Clinical Pediatrics, 2022, 40(6): 431-435.

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参考文献 16

[1]	McNelis K, Fu TT, Poindexter B. Nutrition for the extremely preterm infant[J]. Clin Perinatol, 2017, 44(2): 395-406. doi: S0095-5108(17)30015-5 pmid: 28477668
[2]	Harding JE, Cormack BE, Alexander T, et al. Advances in nutrition of the newborn infant[J]. Lancet, 2017, 389(10079): 1660-1668. doi: S0140-6736(17)30552-4 pmid: 28443560
[3]	Lamhonwah AM, Barić I, Lamhonwah J, et al. Attention deficit/hyperactivity disorder as an associated feature in OCTN2 deficiency with novel deletion (p.T440-Y449)[J]. Clin Case Rep, 2018, 6(4): 585-591. doi: 10.1002/ccr3.1316
[4]	Ozturk MA, Kardas Z, Kardas F, et al. Effects of L~carnitine supplementation on respiratory distress syndrome development and prognosis in premature infants: a single blind randomized controlled trial[J]. Exp Ther Med, 2016, 11(3): 1123-1127. doi: 10.3892/etm.2015.2964
[5]	Liu Q, Wu J, Shen W, et al. Analysis of amino acids and acyl carnitine profiles in low birth weight, preterm, and small for gestational age neonates[J]. J Matern Fetal Neonatal Med, 2017, 30(22): 2697-2704. doi: 10.1080/14767058.2016.1261395
[6]	Sánchez-Pintos P, Pérez-Muñuzuri A, Cocho JÁ, et al. Evaluation of carnitine deficit in very low birth weight preterm newborns small for their gestational age[J]. J Matern Fetal Neonatal Med, 2016, 29(6): 933-937. doi: 10.3109/14767058.2015.1024647 pmid: 25777790
[7]	Fohner AE, Garrison NA, Austin MA, et al. Carnitine palmitoyltransferase 1A P479L and infant death: policy implications of emerging data[J]. Genet Med, 2017, 19(8): 851-857. doi: 10.1038/gim.2016.202
[8]	Potter CJ. Cholestasis in the premature infant[J]. Clin Perinatol, 2020, 47(2): 341-354. doi: S0095-5108(20)30021-X pmid: 32439115
[9]	Sanchez SE, Braun LP, Mercer LD, et al. The effect of lipid restriction on the prevention of parenteral nutrition-associated cholestasis in surgical infants[J]. J Pediatr Surg, 2013, 48(3): 573-578. doi: 10.1016/j.jpedsurg.2012.08.016
[10]	Sundekilde UK, Downey E, O'Mahony JA, et al. The effect of gestational and lactational age on the human milk metabolome[J]. Nutrients, 2016, 8(5): 304. doi: 10.3390/nu8050304
[11]	Salguero Olid A, Blanco Sánchez G, Alonso Ojembarrena A. A systematic review about prophylactic L~carnitine administration in parenteral nutrition of extremely preterm infants[J]. Farm Hosp, 2018, 42(4): 168-173.
[12]	Clark MA, Stein REK, Silver EJ, et al. Carnitine deficiency in preterm infants: a national survey of knowledge and practices[J]. J Neonatal Perinatal Med, 2017, 10(4): 381-386. doi: 10.3233/NPM-16146 pmid: 29286927
[13]	Clark RH, Chace DH, Spitzer AR. Impact of L-carnitine supplementation on metabolic profiles in premature infants[J]. J Perinatol, 2017, 37(5): 566-571. doi: 10.1038/jp.2016.253 pmid: 28079870
[14]	Ng K, Stoll B, Chacko S, et al. Vitamin E in new-generation lipid emulsions protects against parenteral nutrition-associated liver disease in parenteral nutrition-fed preterm pigs[J]. JPEN J Parenter Enteral Nutr, 2016, 40(5): 656-671. doi: 10.1177/0148607114567900
[15]	Wang N, Yan W, Hong L, et al. Risk factors of parenteral nutrition-associated cholestasis in very-low-birthweight infants[J]. J Paediatr Child Health, 2020, 56(11): 1785-1790. doi: 10.1111/jpc.14826
[16]	王彩菲. 左卡尼汀在预防早产儿胆汁淤积症的临床对照研究[J]. 中外医学研究, 2019, 17(7): 152-153.

组别	例数	胎龄(x±s)/周	出生体质量(x±s)/g	性别/ 男[n(%)]	Apgar评分[M(P₂₅~P₇₅)]/min		胎膜早破 [n(%)]	产前地塞米松[n(%)]
组别	例数	胎龄(x±s)/周	出生体质量(x±s)/g	性别/ 男[n(%)]	1分钟	5分钟	胎膜早破 [n(%)]	产前地塞米松[n(%)]
左旋肉碱组	139	26.6±1.5	902.9±152.1	82(59.0)	8.0(5.0~10.0)	10.0(9.0~10.0)	39(28.1)	103(74.1)
非左旋肉碱组	122	26.4±1.2	912.3±200.3	69(56.6)	7.0(5.0~9.0)	10.0(9.0~10.0)	40(32.8)	71(58.2)
统计量		t=1.32	t=0.43	χ²=0.16	Z=2.25	Z=0.01	χ²=3.18	χ²=10.22
P		0.189	0.668	0.691	0.025	0.993	0.365	0.017

组别	例数	总胆红素/μmol·L^-1			直接胆红素/μmol·L^-1			胆汁酸/μmol·L^-1
组别	例数	1周	2周	4周	1周	2周	4周	1周	2周	4周
左旋肉碱组	139	99.2 (79.9~140.6)	54.0 (31.5~94.8)	34.4 (18.9~77.9)	6.9 (4.6~8.6)	7.8 (6.0~12.1)	8.1 (6.4~19.7)	18.5 (12.1~24.8)	24.6 (16.6~34.0)	35.9 (23.5~47.8)
非左旋肉碱组	122	120.7 (90.6~145.0)	66.0 (45.5~102.1)	45.0 (26.2~81.0)	6.8 (5.7~8.5)	8.6 (6.7~11.8)	9.9 (7.5~29.5)	18.0 (11.6~23.5)	19.3 (13.6~29.5)	31.7 (22.8~43.3)
Z值		2.07	2.60	1.92	0.97	1.33	2.20	0.48	2.48	1.22
P		0.039	0.009	0.055	0.331	0.183	0.028	0.695	0.013	0.224

组别	例数	胆固醇/mmol·L^-1			三酰甘油/mmol·L^-1
组别	例数	1周	2周	4周	1周	2周	4周
左旋肉碱组	139	3.5(2.9~4.4)	3.2(2.7~3.9)	2.8(2.3~3.6)	1.7(1.1~2.6)	1.3(1.0~2.3)	1.2(0.9~2.0)
非左旋肉碱组	122	3.6(2.5~4.4)	3.3(2.7~3.9)	2.8(2.2~3.3)	1.1(0.7~2.2)	1.3(0.8~2.0)	1.1(0.8~1.7)
Z值		0.23	0.04	0.92	3.48	0.84	0.21
P		0.820	0.971	0.357	0.001	0.400	0.832

组别	例数	ALT/U·L^-1			BUN/mmol·L^-1			CR/μmol·L^-1
组别	例数	1周	2周	4周	1周	2周	4周	1周	2周	4周
左旋肉碱组	139	7.0 (6.0~9.0)	8.0 (7.0~9.8)	9.5 (8.0~13.8)	8.5 (5.9~11.3)	3.3 (2.3~4.7)	1.4 (1.1~2.2)	78.5 (63.8~88.5)	57.0 (48.3~67.8)	44.0 (38.0~51.0)
非左旋肉碱组	122	7.0 (5.0~8.0)	7.0 (6.0~8.0)	9.0 (8.0~12.4)	10.0 (7.4~12.4)	4.5 (2.9~6.3)	1.6 (1.2~2.4)	82.0 (70.3~96.0)	63.0 (53.0~76.0)	46.5 (38.8~55.0)
Z值		2.40	4.93	1.56	2.23	3.65	1.31	2.31	2.34	1.16
P		0.016	<0.001	0.119	0.026	<0.001	0.191	0.021	0.019	0.246

因素	回归系数	标准误	Wald χ²值	OR(95%CI)	P
胎龄	-0.25	0.17	2.07	0.778(0.553~1.095)	0.151
体质量	0.00	0.00	0.34	1.001(0.998~1.003)	0.561
预防性使用左旋肉碱	-0.10	0.38	0.07	0.904(0.433~1.889)	0.789
胆固醇（1周）	-0.16	0.19	0.72	0.852(0.589~1.233)	0.396
胆固醇（2周）	-0.33	0.23	2.06	0.716(0.454~1.130)	0.151
胆固醇（4周）	0.13	0.18	0.49	1.136(0.795~1.625)	0.484
三酰甘油（1周）	0.15	0.11	2.01	1.166(0.943~1.443)	0.157
三酰甘油（2周）三酰甘油（4周）常量	-0.05 0.49 5.17	0.09 0.20 4.23	0.37 6.47 1.50	0.950(0.805~1.122) 1.633(1.119~2.383) 176.23	0.546 0.011 0.222