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不同喂养方式对极早产儿静脉营养相关性胆汁淤积影响的临床研究
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Abstract:
目的：探讨早产儿生后30天内，不同喂养方式对早产儿肠外营养性胆汁淤积(parenteral nutrition- associated cholestasis, PNAC)的影响。方法：选取2017年5月~2023年5月青岛大学附属医院新生儿监护室收治的胎龄 < 32周且体重 < 1500 g的早产儿586例，根据出生后30天内的喂养模式将早产儿分为三组，分别为母乳喂养组，母乳 + 强化剂喂养组，配方奶喂养组，以PNAC发病率为主要观察对象，以谷丙转氨酶异常，住院时间为次要观察对象。结果：分析了来自430名胎龄 < 32周早产儿的数据。三组间胆汁淤积发病率(P = 0.005)，有统计学意义，谷丙转氨酶异常发病率(P = 1)，无统计学意义。将不同组间有统计意义或可能对胆汁淤积产生影响的观察数据纳入二元logistic回归分析显示，与配方奶相比，母乳可看成减少胆汁淤积发生的独立的保护性因素(P < 0.001)，肠外营养时间、晚发败血症为胆汁淤积发生的独立危险因素(P < 0.001)。Cox回归分析显示，母乳喂养组与配方奶喂养组对早产儿出院时间的影响没有差异，胆汁淤积未增加早产儿住院时间延长的风险，早产儿常见并发症发病风险之间无差异。结论：极早产儿生后30天内，与配方奶喂养相比，母乳喂养和母乳 + 强化剂喂养胆汁淤积发病率较低，且母乳喂养可视为减低胆汁淤积发病风险的独立影响因素，不同喂养模式下，早产儿谷丙转氨酶异常发病率及其他常见并发症发病风险无差异，住院时间无差异。
Objective: To investigate the effects of different feeding patterns on parenteral nutrition-associated cholestasis (PNAC) in preterm infants within 30 days after birth. Methods: 586 preterm infants with gestational age < 32 weeks and weight < 1500 g were selected from the neonatal care unit of Affili-ated Hospital of Qingdao University from May 2017 to May 2023. According to the feeding patterns within 30 days after birth, the preterm infants were divided into three groups: breast feeding group, breast milk + fortifier feeding group, and formula feeding group. The incidence of PNAC was the main observation object, and the abnormal alanine aminotransferase and length of hospital stay were the secondary observation objects. Results: Data from 430 preterm infants <32 weeks of ges-tational age were analyzed. The incidence of cholestasis among the three groups (P = 0.005) was statistically significant, while the incidence of abnormal alanine aminotransferase (P = 1) was not statistically significant. Binary logistic regression analysis showed that breast milk was an inde-pendent protective factor for reducing cholestasis compared with formula milk (P < 0.001), and parenteral nutrition time and late sepsis were independent risk factors for cholestasis (P < 0.001). Cox regression analysis showed that there was no difference between the breastfeeding group and the formula feeding group on the discharge time of preterm infants, cholestasis did not increase the risk of prolonged hospital stay of preterm infants, and there was no difference in the risk of common complications of preterm infants. Conclusion: The incidence of cholestasis in very preterm infants within 30 days after birth is lower than that of formula feeding, breastfeeding or breast milk plus fortifier feeding, and breastfeeding can be regarded as an independent factor to reduce the risk of cholestasis. There is no difference in
| [1] | Nakamura, K., Matsumoto, N., Nakamura, M., Takeuchi, A., Kageyama, M. and Yorifuji, T. (2020) Exclusively Breast-feeding Modifies the Adverse Association of Late Preterm Birth and Gastrointestinal Infection: A Nationwide Birth Co-hort Study. Breastfeeding Medicine, 15, 509-515. https://doi.org/10.1089/bfm.2020.0064 |
| [2] | Ni？o, D.F., Sodhi, C.P. and Hackam, D.J. (2016) Necrotizing Enterocolitis: New Insights into Pathogenesis and Mechanisms. Nature Re-views Gastroenterology & Hepatology, 13, 590-600. https://doi.org/10.1038/nrgastro.2016.119 |
| [3] | Gialeli, G., Panagopoulou, O., Liosis, G. and Siahanidou, T. (2023) Potential Epigenetic Effects of Human Milk on Infants’ Neuro-development. Nutrients, 15, Article No. 3614. https://doi.org/10.3390/nu15163614 |
| [4] | Kim, S.Y. and Yi, D.Y. (2020) Components of Human Breast Milk: From Macronutrient to Microbiome and MicroRNA. Clinical and Experi-mental Pediatrics, 63, 301-309. https://doi.org/10.3345/cep.2020.00059 |
| [5] | Embleton, N.D., Jennifer Moltu, S., Lapillonne, A., Van Den Akker, C.H.P., Carnielli, V., Fusch, C., Gerasimidis, K., Van Goudoever, J.B., Haiden, N., Iacobelli, S., Johnson, M.J., Meyer, S., Mihatsch, W., De Pipaon, M.S., Rigo, J., Zachariassen, G., Bronsky, J., Indrio, F., K？glmeier, J., De Koning, B., Norsa, L., Verduci, E. and Domell？f, M. (2023) Enteral Nutrition in Preterm Infants (2022): A Position Paper from the ESPGHAN Committee on Nutrition and Invited Experts. Journal of Pediatric Gas-troenterology and Nutrition, 76, 248-268.
https://doi.org/10.1097/MPG.0000000000003642 |
| [6] | Pandita, A., Gupta, V. and Gupta, G. (2018) Neonatal Cholestasis: A Pandora’s Box. Clinical Medicine Insights: Pediatrics, 12. https://doi.org/10.1177/1179556518805412 |
| [7] | 中华医学会儿科学分会新生儿学组, 中国医师协会新生儿科医师分会感染专业委员会. 新生儿败血症诊断及治疗专家共识(2019年版) [J]. 中华儿科杂志, 2019, 57(4): 252-257. |
| [8] | 邵肖梅, 叶鸿瑁, 丘小汕. 实用新生儿学[M]. 第5版. 北京: 人民卫生出版社, 2019: 632-639. |
| [9] | 中华医学会儿科学分会眼科学组. 早产儿视网膜病变治疗规范专家共识[J]. 中华眼底病杂志, 2022, 38(1): 10-13. |
| [10] | 何洋, 李文星, 唐军, 等. 早产儿喂养不耐受临床诊疗指南(2020) [J]. 中国当代儿科杂志, 2020, 22(10): 1047-1055. |
| [11] | 蔡威, 汤庆娅, 王莹, 等. 中国新生儿营养支持临床应用指南[J]. 临床儿科杂志, 2013, 31(12): 1177-1182. |
| [12] | Denton, C., Price, A., Friend, J., Manithody, C., Blomenkamp, K., Westrich, M., Kakarla, V., Phillips, W., Krebs, J., Abraham Munoz, S., Osei, H. and Jain, A.K. (2018) Role of the Gut-Liver Axis in Driving Par-enteral Nutrition-Asso- ciated Injury. Children (Basel), 5, Article No. 136. https://doi.org/10.3390/children5100136 |
| [13] | Madnawat, H., Welu, A.L., Gilbert, E.J., Taylor, D.B., Jain, S., Manithody, C., Blomenkamp, K. and Jain, A.K. (2020) Mechanisms of Parenteral Nutrition-Associated Liver and Gut Injury. Nutrition in Clinical Practice, 35, 63-71.
https://doi.org/10.1002/ncp.10461 |
| [14] | Lacaille, F., Gupte, G., Colomb, V., D’antiga, L., Hartman, C., Hojsak, I., Kolacek, S., Puntis, J., Shamir, R. and ESPGHAN Working Group of Intestinal Failure and Intestinal Transplantation (2015) Intestinal Failure-Associated Liver Disease: A Position Paper of the ESPGHAN Working Group of Intestinal Failure and Intestinal Transplantation. Journal of Pediatric Gastroenterology and Nutrition, 60, 272-283. https://doi.org/10.1097/MPG.0000000000000586 |
| [15] | Belkaid, Y. and Harrison, O.J. (2017) Homeostatic Immun-ity and the Microbiota. Immunity, 46, 562-576.
https://doi.org/10.1016/j.immuni.2017.04.008 |
| [16] | Carter, B.A. and Shulman, R.J. (2007) Mechanisms of Disease: Update on the Molecular Etiology and Fundamentals of Parenteral Nutrition Associated Cholestasis. Nature Clinical Practice. Gastroenterology and Hepatology, 4, 277- 287. https://doi.org/10.1038/ncpgasthep0796 |
| [17] | Lester, R., St Pyrek, J., Little, J.M. and Adcock, E.W. (1983) Diversity of Bile Acids in the Fetus and Newborn Infant. Journal of Pediatric Gastroenterology and Nutrition, 2, 355-364. https://doi.org/10.1002/j.1536-4801.1983.tb08510.x |
| [18] | Al-Alaiyan, S., Elsaidawi, W., Alanazi, A.M., Qeretli, R.A., Abdulaziz, N.A. and Alfattani, A. (2022) Ursodeoxycholic Acid and SMOFlipid for Treating Parenteral Nutrition Associated Cholestasis in Infants. Cureus, 14, e22060.
https://doi.org/10.7759/cureus.22060 |
| [19] | El Kasmi, K.C., Ghosh, S., Anderson, A.L., Devereaux, M.W., Bal-asubramaniyan, N., D’Alessandro, A., Orlicky, D.J., Suchy, F.J., Shearn, C.T. and Sokol, R.J. (2022) Pharmacologic Activation of Hepatic Farnesoid X Receptor Prevents Parenteral Nutrition-Associated Cholestasis in Mice. Hepatology, 75, 252-265. https://doi.org/10.1002/hep.32101 |
| [20] | 陈蓓, 苏萍, 韩进天, 等. 极早早产儿早期持续鼻饲输注喂养预防胃肠外营养相关性胆汁淤积[J]. 广东医学, 2012, 33(15): 2298-2300. https://doi.org/10.3969/J.Issn.1001-9448.2012.15.043 |
| [21] | Feldman, A.G. and Sokol, R.J. (2021) Neonatal Cho-lestasis: Updates on Diagnostics, Therapeutics, and Prevention. Neoreviews, 22, E819-E836. https://doi.org/10.1542/neo.22-12-e819 |
| [22] | Jackson, R.L., White, P.Z. and Zalla, J. (2021) SMOFlipid vs In-tralipid 20%: Effect of Mixed-Oil vs Soybean-Oil Emulsion on Parenteral Nutrition-Associated Cholestasis in the Neo-natal Population. JPEN Journal of Parenteral and Enteral Nutrition, 45, 339-346. https://doi.org/10.1002/jpen.1843 |
| [23] | Chappell, L.C., Bell, J.L., Smith, A., Linsell, L., Juszczak, E., Dixon, P.H., Chambers, J., Hunter, R., Dorling, J., Williamson, C., Thornton, J.G. and PITCHES Study Group (2019) Ursodeoxy-cholic Acid versus Placebo in Women with Intrahepatic Cholestasis of Pregnancy (PITCHES): A Randomised Controlled Trial. The Lancet, 394, 849-860.
https://doi.org/10.1016/S0140-6736(19)31270-X |
| [24] | Feldman, A.G. and Sokol, R.J. (2019) Neonatal Cholestasis: Emerging Molecular Diagnostics and Potential Novel Therapeutics. Nature Reviews Gastroenterology & Hepatology, 16, 346-360.
https://doi.org/10.1038/s41575-019-0132-z |
| [25] | Brink, L.R. and L？nnerdal, B. (2020) Milk Fat Globule Membrane: The Role of Its Various Components in Infant Health and Development. The Journal of Nutritional Biochemistry, 85, Article ID: 108465.
https://doi.org/10.1016/j.jnutbio.2020.108465 |
| [26] | Agostoni, C., Marangoni, F., Bernardo, L., Lammardo, A.M., Galli, C. and Riva, E. (1999) Long-Chain Polyunsaturated Fatty Acids in Human Milk. Acta Paediatrica Supplement, 88, 68-71.
https://doi.org/10.1111/j.1651-2227.1999.tb01303.x |
| [27] | Carr, L.E., Virmani, M.D., Rosa, F., Munblit, D., Ma-tazel, K.S., Elolimy, A.A. and Yeruva, L. (2021) Role of Human Milk Bioactives on Infants’ Gut and Immune Health. Frontiers in Immunology, 12, Article ID: 604080.
https://doi.org/10.3389/fimmu.2021.604080 |
| [28] | Andreas, N.J., Kampmann, B. and Mehring Le-Doare, K. (2015) Human Breast Milk: A Review on Its Composition and Bioactivity. Early Human Development, 91, 629-635. https://doi.org/10.1016/j.earlhumdev.2015.08.013 |
| [29] | Zhou, S., et al. (2019) Association of Serum Bilirubin in Newborns Affected by Jaundice with Gut Microbiota Dysbiosis. The Journal of Nutritional Biochemistry, 63, 54-61. https://doi.org/10.1016/j.jnutbio.2018.09.016 |
| [30] | Li, M., Liu, S., Wang, M., Hu, H., Yin, J., Liu, C. and Huang, Y. (2020) Gut Microbiota Dysbiosis Associated with Bile Acid Metabolism in Neonatal Cholestasis Disease. Scientific Re-ports, 10, Article No. 7686.
https://doi.org/10.1038/s41598-020-64728-4 |
| [31] | Lin, Q.X., Huang, W.W., Shen, W., Deng, X.S., Tang, Z.Y., Chen, Z.H., Zhao, W. and Fan, H.Y. (2022) Intrahepatic Cholestasis of Pregnancy Increases Inflammatory Susceptibility in Neonatal Offspring by Modulating Gut Microbiota. Frontiers in Immunology, 13, Article ID: 889646. https://doi.org/10.3389/fimmu.2022.889646 |
| [32] | Kimura, S., Yokoyama, S., Pilon, A.L. and Kurotani, R. (2022) Emerging Role of an Immunomodulatory Protein Secretoglobin 3A2 in Human Diseases. Pharmacology & Therapeutics, 236, Article ID: 108112.
https://doi.org/10.1016/j.pharmthera.2022.108112 |
| [33] | Lapidaire, W., Lucas, A., Clayden, J.D., Clark, C. and Fewtrell, M.S. (2022) Human Milk Feeding and Cognitive Outcome in Preterm Infants: The Role of Infection and NEC Reduction. Pediatric Research, 91, 1207-1214.
https://doi.org/10.1038/s41390-021-01367-z |
