输血相关性坏死性小肠结肠炎的思考

doi:10.12372/jcp.2022.22e0361

摘要/Abstract

摘要：

新生儿坏死性小肠结肠炎（NEC）是一种新生儿时期严重威胁生命的胃肠道疾病,多以腹胀、呕吐、血便及休克等非特异性症状为主要临床表现,在早产儿中症状更不典型。目前广泛被认可的NEC病因包括早产、感染、缺氧缺血和喂养不当等。近年来,红细胞输注（RBCT）与NEC之间的相关性受到广泛关注。文章通过梳理输血与NEC的相关性、输血相关性坏死性小肠结肠炎（TANEC）的影响因素及发病机制和TANEC的预防等方面的研究进展,认为TANEC是客观存在的,但贫血本身才是TANEC的发病基础,预防贫血、合理输血是减少TANEC的基本策略。

关键词: 坏死性小肠结肠炎, 红细胞输注, 新生儿

Abstract:

Neonatal necrotizing enterocolitis (NEC) is a serious and life-threatening gastrointestinal disease in the neonatal period. The atypical clinical manifestations of NEC, especially in premature infants, are abdominal distension, vomiting, bloody stools and shock. At present, the widely known pathogenesis of NEC includes preterm birth, infection, hypoxia-ischemia and improper feeding, etc. In recent years, the association between red blood cell transfusion (RBCT) and NEC was widely concerned. This article reviewed the relationship between RBCT and NEC, the influence factors, possible pathologic mechanism and the prevention strategies of transfusion-associated necrotizing enterocolitis (TANEC). Based on the available evidences, the author believes that TANEC is a clinical condition. However, anemia is the basis for the onset of TANEC. Prevention of anemia and reasonable blood transfusion are the basic strategies to reduce TANEC.

Key words: necrotizing enterocolitis, red blood cell transfusion, newborn

雷小平, 罗丽娟. 输血相关性坏死性小肠结肠炎的思考[J]. 临床儿科杂志, 2022, 40(9): 647-653.

LEI Xiaoping, LUO Lijuan. Transfusion-associated necrotizing enterocolitis[J]. Journal of Clinical Pediatrics, 2022, 40(9): 647-653.

图/表 2

参考文献 53

[1]	Neu J. Necrotizing enterocolitis: the future[J]. Neonatology, 2020, 117(2): 240-244. doi: 10.1159/000506866
[2]	Meister AL, Doheny KK, Travagli RA. Necrotizing enterocolitis: it's not all in the gut[J]. Exp Biol Med (Maywood), 2020, 245(2): 85-95. doi: 10.1177/1535370219891971 pmid: 31810384
[3]	McGrady GA, Rettig PJ, Istre GR, et al. An outbreak of necrotizing enterocolitis. Association with transfusions of packed red blood cells[J]. Am J Epidemiol, 1987, 126(6): 1165-1172. pmid: 3687923
[4]	El-Dib M, Narang S, Lee E, et al. Red blood cell transfusion, feeding and necrotizing enterocolitis in preterm infants[J]. J Perinatol, 2011, 31: 183-187. doi: 10.1038/jp.2010.157 pmid: 21252964
[5]	Singh R, Visintainer PF, Frantz ID 3rd, et al. Association of necrotizing enterocolitis with anemia and packed red blood cell transfusions in preterm infants[J]. J Perinatol, 2011, 31: 176-182. doi: 10.1038/jp.2010.145 pmid: 21273983
[6]	Wan-Huen P, Bateman D, Shapiro MD, et al. Packed red blood cell transfusion is an independent risk factor for necrotizing enterocolitis in premature infants[J]. J Perinatol, 2013, 33: 786-790. doi: 10.1038/jp.2013.60 pmid: 23702619
[7]	Stritzke AI, Smyth J, Synnes A, et al. Transfusion associated necrotising enterocolitis in neonates[J]. Arch Dis Child Fetal Neonatal Ed, 2013, 98: F10-F14. doi: 10.1136/fetalneonatal-2011-301282
[8]	Ahle M, Drott P, Elfvin A, et al. Maternal, fetal and perinatal factors associated with necrotizing enterocolitis in Sweden. A national case-control study[J]. PLoS One, 2018, 23: 13(3): e0194352.
[9]	Garg P, Pinotti R, Lal CV, et al. Transfusion-associated necrotizing enterocolitis in preterm infants: an updated meta-analysis of observational data[J]. J Perinat Med, 2018, 46(6): 677-685. doi: 10.1515/jpm-2017-0162
[10]	Teišerskas J, Bartašienė R, Tamelienė R. Associations between red blood cell transfusions and necrotizing enterocolitis in very low birth weight infants: ten-year data of a tertiary neonatal unit[J]. Medicina (Kaunas), 2019, 55(1): 16.
[11]	王又平, 郑美玉, 肖晔莹, 等. 早产儿坏死性小肠结肠炎影响因素分析及发病预测模型的构建[J]. 中国当代儿科杂志, 2022, 24(1): 41-48.
[12]	Wallenstein MB, Arain YH, Birnie KL, et al. Red blood cell transfusion is not associated with necrotizing enterocolitis: a review of consecutive transfusions in a tertiary neonatal intensive care unit[J]. J Pediatr, 2014, 165: 678-682. doi: 10.1016/j.jpeds.2014.06.012
[13]	Janjindamai W, Prapruettrong A, Thatrimontrichai A, et al. Risk of necrotizing enterocolitis following packed red blood cell transfusion in very low birth weight infants[J]. Indian J Pediatr, 2019, 86(4): 347-353. doi: 10.1007/s12098-019-02887-7 pmid: 30790187
[14]	Josephson CD, Wesolowski A, Bao G, et al. Do red cell transfusions increase the risk of necrotizing enterocolitis in premature infants?[J]. J Pediatr, 2010, 157: 972-978. doi: 10.1016/j.jpeds.2010.05.054
[15]	Patel RM, Knezevic A, Shenvi N, et al. Association of red blood cell transfusion, anemia, and necrotizing enterocolitis in very low-birth-weight infants[J]. JAMA, 2016, 315: 889-897. doi: 10.1001/jama.2016.1204 pmid: 26934258
[16]	Sharma R, Kraemer DF, Torrazza RM, et al. Packed red blood cell transfusion is not associated with increased risk of necrotizing enterocolitis in premature infants[J]. J Perinatol, 2014, 34: 858-862. doi: 10.1038/jp.2014.59 pmid: 25144159
[17]	Crabtree CS, Pakvasa M, Radmacher PG, et al. Retrospective case-control study of necrotizing enterocolitis and packed red blood cell transfusions in very low birth weight infants[J]. J Neonatal Perinatal Med, 2018, 11(4): 365-370. doi: 10.3233/NPM-1634 pmid: 30149467
[18]	Flannery DD, Foglia EE. The contributions of red blood cell transfusion and severe anemia in necrotizing enterocolitis: causes or confounders?[J]. J Perinatol, 2017, 37(6): 626-628. doi: 10.1038/jp.2017.32 pmid: 28333160
[19]	Sood BG, Rambhatla A, Thomas R, et al. Decreased hazard of necrotizing enterocolitis in preterm neonates receiving red cell transfusions[J]. J Matern Fetal Neonatal Med, 2015, 29(5): 737-744. doi: 10.3109/14767058.2015.1016422
[20]	AlFaleh K, Al-Jebreen A, Baqays A, et al. Association of packed red blood cell transfusion and necrotizing enterocolitis in very low birth weight infants[J]. J Neonatal Perinatal Med, 2014, 7: 193-198. doi: 10.3233/NPM-14814048 pmid: 25318632
[21]	Keir AK, Yang J, Harrison A, et al. Temporal changes in blood product usage in preterm neonates born at less than 30 weeks' gestation in Canada[J]. Transfusion, 2015, 55(6): 1340-1346. doi: 10.1111/trf.12998 pmid: 25652740
[22]	Mohamed A, Shah PS. Transfusion associated necrotizing enterocolitis: a meta-analysis of observational data[J]. Pediatrics, 2012, 129(3): 529-540. doi: 10.1542/peds.2011-2872 pmid: 22351894
[23]	Rai SE, Sidhu AK, Krishnan RJ. Transfusion-associated necrotizing enterocolitis re-evaluated: a systematic review and meta-analysis[J]. J Perinat Med, 2018, 46(6): 665-676. doi: 10.1515/jpm-2017-0048
[24]	Maheshwari A, Patel RM, Christensen RD. Anemia, red blood cell transfusions, and necrotizing enterocolitis[J]. Semin Pediatr Surg, 2018, 27(1): 47-51. doi: S1055-8586(17)30145-2 pmid: 29275817
[25]	Kirpalani H, Bell EF, Hintz SR, et al. Higher or lower hemoglobin transfusion thresholds for preterm infants[J]. N Engl J Med, 2020, 383(27): 2639-2651. doi: 10.1056/NEJMoa2020248
[26]	Franz AR, Engel C, Bassler D, et al. Effects of liberal vs restrictive transfusion thresholds on survival and neurocognitive outcomes in extremely low-birth-weight infants: the ETTNO randomized clinical trial[J]. JAMA, 2020, 324(6): 560-570. doi: 10.1001/jama.2020.10690 pmid: 32780138
[27]	Ozcan B, Aydemir O, Isik DU, et al. Severe anemia is associated with intestinal injury in preterm neonates[J]. Am J Perinatol, 2020, 37(6): 603-606. doi: 10.1055/s-0039-1683982
[28]	Howarth C, Banerjee J, Aladangady N. Red blood cell transfusion in preterm infants: current evidence and controversies[J]. Neonatology, 2018, 114(1): 7-16. doi: 10.1159/000486584 pmid: 29550819
[29]	Hyung N, Campwala I, Boskovic DS, et al. The relationship of red blood cell transfusion to intestinal mucosal injury in premature infants[J]. J Pediatr Surg, 2017, 52(7): 1152-1155. doi: S0022-3468(16)30531-0 pmid: 27887684
[30]	Pammi M, Hollister E, Neu J. Gut injury and the microbiome in neonates[J]. Clin Perinatol, 2020, 47(2): 369-382. doi: 10.1016/j.clp.2020.02.010
[31]	Bowker RM, Yan X, De Plaen IG. Intestinal micro-circulation and necrotizing enterocolitis: the vascular endothelial growth factor system[J]. Semin Fetal Neonatal Med, 2018, 23(6): 411-415. doi: 10.1016/j.siny.2018.08.008
[32]	Arthur CM, Nalbant D, Feldman HA, et al. Anemia induces gut inflammation and injury in an animal model of preterm infants[J]. Transfusion, 2019, 59(4): 1233-1245.
[33]	MohanKumar K, Namachivayam K, Song T, et al. A murine neonatal model of necrotizing enterocolitis caused by anemia and red blood cell transfusions[J]. Nat Commun, 2019, 10(1): 3494. doi: 10.1038/s41467-019-11199-5 pmid: 31375667
[34]	Reynolds JD, Ahearn GS, Angelo M, et al. S-nitrosohemoglobin deficiency: a mechanism for loss of physiological activity in banked blood[J]. Proc Natl Acad Sci U S A, 2007, 104(43): 17058-17062. doi: 10.1073/pnas.0707958104 pmid: 17940022
[35]	Gladwin MT, Kim-Shapiro DB. Storage lesion in banked blood due to hemolysis-dependent disruption of nitric oxide homeostasis[J]. Curr Opin Hematol, 2009, 16(6): 515-523. doi: 10.1097/MOH.0b013e32833157f4 pmid: 19701085
[36]	Rogers S, Doctor A. Red blood cell dysfunction in critical illness[J]. Crit Care Clin, 2020, 36(2): 267-292. doi: 10.1016/j.ccc.2019.12.008
[37]	Blau J, Calo JM, Dozor D, et al. Transfusion-related acute gut injury: necrotizing enterocolitis in very low birth weight neonates after packed red blood cell transfusion[J]. J Pediatr, 2011, 158(3): 403-409. doi: 10.1016/j.jpeds.2010.09.015
[38]	Remy KE, Hall MW, Cholette J, et al. Mechanisms of red blood cell transfusion-related immunomodulation[J]. Transfusion, 2018, 58(3): 804-815. doi: 10.1111/trf.14488
[39]	刘誉, 杨慧霞. 2020年美国妇产科医师协会分娩后延迟脐带结扎的专家共识解读[J]. 中华妇产科杂志, 2021, 56(07): 516-518.
[40]	Wang Y, Song J, Sun H, et al. Erythropoietin prevents necrotizing enterocolitis in very preterm infants: a randomized controlled trial[J]. J Transl Med, 2020, 18(1): 308. doi: 10.1186/s12967-020-02459-w
[41]	Akisu M, Durmaz B, Koroglu OA, et al. The effects of IGF-1 and erythropoietin on apoptosis and telomerase activity in necrotizing enterocolitis model[J]. Pediatr Res, 2021, 90(3): 559-564. doi: 10.1038/s41390-020-01195-7
[42]	New HV, Berryman J, Bolton-Maggs PH, et al. British Committee for Standards in Haematology. Guidelines on transfusion for fetuses, neonates and older children[J]. Br J Haematol, 2016, 175(5): 784-828. doi: 10.1111/bjh.14233
[43]	中华人民共和国国家卫生健康委员会. 儿科输血指南(WS/T 795-202)[M/OL]. http://www.nhc.gov.cn/fzs/s7852d/202202/1484f47dcf824ee8bae3ad7b6809e603/files/d1cfad6849c945b591556494b3de7d2d.pdf.
[44]	Fergusson D, Hébert PC, Lee SK, et al. Clinical outcomes following institution of universal leukoreduction of blood transfusions for premature infants[J]. JAMA, 2003, 289(15): 1950-1966. doi: 10.1001/jama.289.15.1950
[45]	Villeneuve A, Arsenault V, Lacroix J, Tucci M. Neonatal red blood cell transfusion[J]. Vox Sang, 2021, 116(4): 366-378. doi: 10.1111/vox.13036 pmid: 33245826
[46]	梁润哲, 张志涛, 吕远, 等. 脐带血自体回输在产时手术及新生儿外科手术中应用的可行性探讨[J]. 中国实用妇科与产科杂志, 2019, 35(5): 589-592.
[47]	Shende P, Khanolkar B. Human breast milk-based nutritherapy: a blueprint for pediatric healthcare[J]. J Food Drug Anal, 2021, 29(2): 203-213.
[48]	Yeo KT, Kong JY, Sasi A, et al. Stopping enteral feeds for prevention of transfusion-associated necrotising enterocolitis in preterm infants[J]. Cochrane Database Syst Rev, 2019, 2019(10): CD012888.
[49]	Pitzele A, Rahimi M, Armbrecht E, et al. Packed red blood cell transfusion (PRBC) attenuates intestinal blood flow responses to feedings in pre-term neonates with normalization at 24 hours[J]. J Matern Fetal Neonatal Med, 2015, 28(15): 1770-1773. doi: 10.3109/14767058.2014.971746 pmid: 25269406
[50]	Marin T, Josephson CD, Kosmetatos N, et al. Feeding preterm infants during red blood cell transfusion is associated with a decline in postprandial mesenteric oxygenation[J]. J Pediatr, 2014, 165(3): 464-471. doi: 10.1016/j.jpeds.2014.05.009
[51]	Balegar VKK, Jayawardhana M, Martin AJ, et al. Association of bolus feeding with splanchnic and cerebral oxygen utilization efficiency among premature infants with anemia and after blood transfusion[J]. JAMA Netw Open, 2020, 3(2): e200149.
[52]	Jasani B, Rao S, Patole S. Withholding feeds and transfusion-associated necrotizing enterocolitis in preterm infants: a systematic review[J]. Adv Nutr, 2017, 8(5): 764-769. doi: 10.3945/an.117.015818 pmid: 28916576
[53]	王琦凡, 许白叶, 赖素贤, 等. 暂停肠道喂养对新生儿输血相关性坏死性小肠结肠炎的保护作用分析[J]. 中华新生儿科杂志, 2017, 32(3): 176-179.