Newborn

Register      Login

SEARCH WITHIN CONTENT

FIND ARTICLE

Volume / Issue

Online First

Archive
Volume  3 (2024)
Volume  2 (2023)
Volume  1 (2022)
Related articles

VOLUME 1 , ISSUE 3 ( July-September, 2022 ) > List of Articles

REVIEW ARTICLE

Neonatal Anemia

Neha Chaudhary, Romal Jassar, Rachana Singh

Keywords : Erythropoiesis, Hemoglobin, Hematocrit, Packed red blood cell transfusion

Citation Information : Chaudhary N, Jassar R, Singh R. Neonatal Anemia. 2022; 1 (3):263-270.

DOI: 10.5005/jp-journals-11002-0027

License: CC BY-NC 4.0

Published Online: 07-10-2022

Copyright Statement:  Copyright © 2022; The Author(s).


Abstract

Neonatal anemia is a public health problem of global concern and has significant associations with many short- and long-term morbidities. Many etiological factors ranging from perinatal physiologic transition, hematological maturation, illnesses, and iatrogenic reasons such as the phlebotomies necessary for laboratory evaluation may be involved, and there is a need for careful clinical decisions. In premature infants, the management of anemia also has to factor in the unique hematological transition seen during development, co-morbidities associated with preterm birth, the severity of illness severity, and all the iatrogenic factors. Untreated severe anemia is known to negatively impact long-term growth and neurodevelopment outcomes, making early diagnosis and treatment imperative. Additionally, there is a lack of consensus about the threshold and timing of packed red blood cell transfusions, and we need further consideration in view of various associated complications. Therefore, clinicians need to focus on preventable causes of anemia such as nutritional deficiencies, chronic illness, and excessive phlebotomy losses. In this article, we attempt to summarize the pathophysiology, etiologies, clinical management, and the opportunities in research in the field of neonatal anemia.

PDF Share
  1. Osungbade KO, Oladunjoye AO. Anaemia in Developing Countries: Burden and Prospects of Prevention and Control Anemia. London, UK: IntechOpen 2012:116–129. http://www.intechopen.com/books/anemia/anaemia-in-developing-countries-burden-and-%20prospects-of-prevention-and-control.
  2. Ewusie JE, Ahiadeke C, Beyene J, et al. Prevalence of anemia among under-5 children in the Ghanaian population: estimates from the Ghana demographic and health survey. BMC Public Health 2014;14(1):626. DOI: 10.1186/1471-2458-14-626.
  3. Kassebaum NJ, Jasrasaria R, Naghavi M, et al. A systematic analysis of global anemia burden from 1990 to 2010. Blood 2014;123(5):615–624. DOI: 10.1182/blood-2013-06-508325.
  4. World Health Organization. Global Nutrition Targets 2025: Anaemia Policy Brief. World Health Organization 2014. https://apps.who.int/iris/handle/10665/148556.
  5. Colombatti R, Sainati L, Trevisanuti D. Anemia and transfusion in the neonate. Semin Fetal Neonatal Med 2016;21(1):2–9. DOI: 10.1016/j.siny.2015.12.001.
  6. Widness JA. Pathophysiology of anemia during the neonatal period, including anemia of prematurity. Neoreviews 2008;9(11):e520. DOI: 10.1542/neo.9-11-e520.
  7. Brabin BJ, Kalanda BF, Verhoeff FH, et al. Risk factors for fetal anaemia in a malarious area of Malawi. Ann Trop Paediatr 2004;24(4):311–321. DOI: 10.1179/027249304225019136.
  8. Hirata M, Kusakawa I, Ohde S, et al. Risk factors of infant anemia in the perinatal period. Pediatr Int 2017;59(4):447–451. DOI: 10.1111/ped.13174.
  9. Ghirardello S, Dusi E, Cortinovis I, et al. Effects of red blood cell transfusions on the risk of developing complications or death: an observational study of a cohort of very low birth weight infants. Am J Perinatol 2017;34(1):88–95. DOI: 10.1055/s-0036-1584300.
  10. Howarth C, Banerjee J, Aladangady N. Red blood cell transfusion in preterm infants: current evidence and controversies. Neonatology 2018;114(1):7–16. DOI: 10.1159/000486584.
  11. 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. Transfusion 2015;55(6):1340–1346. DOI: 10.1111/trf.12998.
  12. 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. JAMA 2020;324:560–570. DOI: 10.1001/jama.2020.10690.
  13. Kirpalani H, Bell EF, Hintz SR, et al. Higher or lower hemoglobin transfusion thresholds for preterm infants. N Engl J Med 2020; 383(27):2639–2651. DOI: 10.1056/NEJMoa2020248.
  14. Singh R, Shah BL, Frantz ID 3rd, Necrotizing enterocolitis and the role of anemia of prematurity. Semin Perinatol 2012;36(4):277–282. DOI: 10.1053/j.semperi.2012.04.008.
  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. JAMA 2016;315(9):889–897. DOI: 10.1001/jama.2016.1204.
  16. Le VT, Klebanoff MA, Talavera MM, et al. Transient effects of transfusion and feeding advances (volumetric and caloric) on necrotizing enterocolitis development: a case-crossover study. PLoS One 2017;12(6):e0179724. DOI: 10.1371/journal.pone.0179724.
  17. Xiong X, Buekens P, Alexander S, et al. Anemia during pregnancy and birth outcome: a meta-analysis. Am J Perinatol 2000;17:137–146. DOI: 10.1055/s-2000-9508.
  18. Rahman MM, Abe SK, Rahman MS, et al. Maternal anemia and risk of adverse birth and health outcomes in low- and middle-income countries: systematic review and meta-analysis. Am J Clin Nutr 2016;103(2):495–504. DOI: 10.3945/ajcn.115.107896.
  19. Lee S, Guillet R, Cooper EM, et al. Prevalence of anemia and associations between neonatal iron status, hepcidin, and maternal iron status among neonates born to pregnant adolescents. Pediatr Res 2016;79(1–1):42–48. DOI: 10.1038/pr.2015.183.
  20. Kalteren WS, Verhagen EA, Mintzer JP, et al. Anemia and red blood cell transfusions, cerebral oxygenation, brain injury and development, and neurodevelopmental outcome in preterm infants: a systematic review. Front Pediatr 2021;9:644462. DOI: 10.3389/fped.2021.644462.
  21. Raffaeli G, Manzoni F, Cortesi V, et al. Iron homeostasis disruption and oxidative stress in preterm newborns. Nutrients 2020;12(6):1554. DOI: 10.3390/nu12061554.
  22. Lozoff B, Georgieff MK. Iron deficiency and brain development. Semin Pediatr Neurol 2006;13(3):158–165. DOI: 10.1016/j.spen.2006.08.004.
  23. Chaparro CM. Timing of umbilical cord clamping: effect on iron endowment of the newborn and later iron status. Nutr Rev 2011;69(1):S30–S36. DOI: 10.1111/j.1753-4887.2011.00430.x.
  24. Haider BA, Olofin I, Wang M, et al. Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta-analysis. BMJ 2013;346:f3443. DOI: 10.1136/bmj.f3443.
  25. Parks S, Hoffman MK, Goudar SS, et al. Maternal anemia and maternal, fetal, and neonatal outcomes in a prospective cohort study in India and Pakistan. BJOG 2019;126(6):737–743. DOI: 10.1111/1471-0528.15585.
  26. Porter HJ, Khong TY, Evans MF, et al. Parvovirus as a cause of hydrops fetalis: detection by in-situ hybridization. J Clin Pathol 1988;41(4): 381–383. DOI: 10.1136/jcp.41.4.381.
  27. Garcia-Prats JA. Anemia of prematurity. In: Abrams SA, Mahoney DH, Kim MS (eds.). UpToDate; 2021. Available from: http://www.uptodate.com/contents/anemia-of-prematurity [Accessed May 5, 2022].
  28. Gallagher PG. The neonatal erythrocyte and its disorders. In: Orkin SH, Fisher DE, Look T, et al. (eds.) Nathan and Oski's Hematology and Oncology of Infancy and Childhood, 8th ed. WB Saunders: Philadelphia; 2015. p. 52.
  29. Aher SM, Ohlsson A. Early versus late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants. Cochrane Database Syst Rev 2020;2(2):CD004865.
  30. Powers JM, Sandoval C. Approach to the child with anemia. In: Mahoney DH, Lorin MI, Armsby C (eds.). UptoDate. Available from: http://www.uptodate.com/contents/approach-to-the-child-with-anemia [Accessed May 4, 2022].
  31. Stockman JA 3rd, Oski FA. Physiological anaemia of infancy and the anaemia of prematurity. Clin Hematol 1978;7(1):3–18. PMID: 657601.
  32. Alzaree F, Elbohoty A, Abdellatif M. Early versus delayed umbilical cord clamping on physiologic anemia of the newborn Infant. Open Access Maced J Med Sci 2018;6(8):1399–1404. DOI: 10.3889/oamjms.2018.286.
  33. Hasanbegovic E, Cengic N, Hasanbegovic S, et al. Evaluation and treatment of anemia in premature infants. Med Arch 2016;70(6): 408–412. DOI: 10.5455/medarh.2016.70.408-412.
  34. Vali P, Underwood M, Lakshminrusimha S. Hemoglobin oxygen saturation targets in the neonatal intensive care unit: is there a light at the end of the tunnel? Can J Physiol Pharmacol 2019;97(3):174–182. DOI: 10.1139/cjpp-2018-0376.
  35. Kirpalani H, Whyte RK, Andersen C, et al. The Premature Infants in Need of Transfusion (PINT) study: a randomized, controlled trial of a restrictive (low) versus liberal (high) transfusion threshold for extremely low birth weight infants. J Pediatr 2006;149(3):301–307. DOI: 10.1016/j.jpeds.2006.05.011.
  36. Kleinman S, Caulfield T, Chan P, et al. Toward an understanding of transfusion related acute lung injury: statement of a consensus panel. Transfusion 2004;44(12):1774–1789. DOI: 10.1111/j.0041-1132.2004.04347.x.
  37. Whyte R, Kirpalani H. Low versus high haemoglobin concentration threshold for blood transfusion for preventing morbidity and mortality in very low birth weight infants. Cochrane Database Syst Rev 2011;(11):CD000512. DOI: 10.1002/14651858.CD000512.pub2.
  38. 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 Perinatol 2011;31(3):176–182. DOI: 10.1038/jp.2010.145.
  39. Hunter CJ, De Plaen IG. Inflammatory signaling in NEC: role of NF-kappaB, cytokines and other inflammatory mediators. Pathophysiology 2014;21(1):55–65. DOI: 10.1016/j.pathophys. 2013.11.010.
  40. Maheshwari A, Schelonka RL, Dimmitt RA, et al. Cytokines associated with necrotizing enterocolitis in extremely-low-birth-weight infants. Pediatr Res 2014;76(1):100–108. DOI: 10.1038/pr.2014.48.
  41. Saroha V, Josephson CD, Patel RM. Epidemiology of NEC regarding the influence of red blood cell transfusions and anemia. Clin Perinatol 2019;46(1):101–117. DOI: 10.1016/j.clp.2018.09.006.
  42. La Gamma EF, Blau J. Transfusion-related acute gut injury: feeding, flora, flow, and barrier defense. Semin Perinatol 2012;36(4):294–305. DOI: 10.1053/j.semperi.2012.04.011.
  43. Serenius F, Ewald U, Farooqi A, et al. Neurodevelopmental outcomes among extremely preterm infants 6.5 years after active perinatal care in Sweden. JAMA Pediatr 2016;170(10):954–963. DOI: 10.1001/jamapediatrics.2016.1210.
  44. van Hoften JCR, Verhagen EA, Keating P, et al. Cerebral tissue oxygen saturation and extraction in preterm infants before and after blood transfusion. Arch Dis Child Fetal Neonatal Ed 2010;95(5):F352–F358. DOI: 10.1136/adc.2009.163592.
  45. Balegar KK, Stark MJ, Briggs N, et al. Early cerebral oxygen extraction and the risk of death or sonographic brain injury in very preterm infants. J Pediatr 2014;164(3):475–480.e1. DOI: 10.1016/j.jpeds.2013.10.041.
  46. Whitehead HV, Vesoulis ZA, Maheshwari A, et al. Progressive anemia of prematurity is associated with a critical increase in cerebral oxygen extraction. Early Hum Dev 2019;140:104891. DOI: 10.1016/j.earlhumdev.2019.104891.
  47. Banerjee J, Leung TS, Aladangady N. Cerebral blood flow and oximetry response to blood transfusion in relation to chronological age in preterm infants. Early Hum Dev 2016;97:1–8. DOI: 10.1016/j.earlhumdev.2015.10.017.
  48. El-Dib M, Aly S, Govindan R, et al. Brain maturity and variation of oxygen extraction in premature infants. Am J Perinatol 2016;33(8):814–820. DOI: 10.1055/s-0036-1572542.
  49. Whyte RK, Kirpalani H, Asztalos EV, et al. Neurodevelopmental outcome of extremely low birth weight infants randomly assigned to restrictive or liberal hemoglobin thresholds for blood transfusion. Pediatrics 2009;123(1):207–213. DOI: 10.1542/peds.2008-0338.
  50. Lombardi YL, Ridel C, Touzot M. Anemia and acute kidney injury: the tip of the iceberg? Clin Kidney J 2021;14(2):471–473. DOI: 10.1093/ckj/sfaa202.
  51. Nada A, Askenazi D, Boohaker LJ, et al. Low hemoglobin levels are independently associated with neonatal acute kidney injury: a report from the AWAKEN Study Group. Pediatr Res 2021;89(4):922–931. DOI: 10.1038/s41390-020-0963-x.
  52. Nashimoto M, Murashima M, Kokubu M, et al. Anemia following acute kidney injury after non-cardiac surgery and long-term outcomes: the NARA-AKI cohort study. Clin Kid J 2021;14(2):673–680. DOI: 10.1093/ckj/sfaa184.
  53. Ree IM, Lopriore E. Updates in neonatal hematology: causes, risk factors, and management of anemia and thrombocytopenia. Hematol Oncol Clin North Am 2019;33(3):521–532. DOI: 10.1016/j.hoc.2019.01.013.
  54. Ohls R, Garcia-Prats JA, Kim MS. Red blood cell transfusions in the newborn. UpToDate 2021. http://www.uptodate.com/contents/red-blood-cell-transfusions-in-the-newborn [Accessed April 12, 2022].
  55. Maier RF, Sonntag J, Walka MM, et al. Changing practices of red blood cell transfusions in infants with birth weights less than 1000 g. J Pediatr 2000;136(2):220–224. DOI: 10.1016/s0022-3476(00)70105-3.
  56. Robinson RJ, Rossiter MA. Massive subaponeurotic haemorrhage in babies of African origin. Arch Dis Child 1968;43(232):684–687. DOI: 10.1136/adc.43.232.684.
  57. Teruya J, Tobian A, Armsby C. Red blood cell transfusion in infants and children: Selection of blood products. UpToDate 2022. https://www.uptodate.com/contents/red-blood-cell-transfusion-in-infants-and-children-selection-of-blood-products [Accessed April 12, 2022].
  58. Kim DH. Transfusion practice in neonates. Korean J Pediatr 2018;61(9):265–270. DOI: 10.3345/kjp.2018.06849.
  59. Silliman CC. The two-event model of transfusion-related acute lung injury. Crit Care Med 2006;34(5 Suppl):S124–S131. DOI: 10.1097/01.CCM.0000214292.62276.8E.
  60. Krimmel GA, Baker R, Yanowitz TD. Blood transfusion alters the superior mesenteric artery blood flow velocity response to feeding in premature infants. Am J Perinatol 2009;26(2):99–105. DOI: 10.1055/s-0028-1090595.
  61. Nair J, Gugino SF, Nielsen LC, et al. Packed red cell transfusions alter mesenteric arterial reactivity and nitric oxide pathway in preterm lambs. Pediatr Res 2013;74(6):652–657. DOI: 10.1038/pr.2013.153.
  62. Baron DM, Yu B, Lei C, et al. Pulmonary hypertension in lambs transfused with stored blood is prevented by breathing nitric oxide. Anesthesiology 2012;116(3):637–647. DOI: 10.1097/ALN.0b013e318246ef77.
  63. El-Dib M, Narang S, Lee E, et al. Red blood cell transfusion, feeding and necrotizing enterocolitis in preterm infants. J Perinatol 2011;31(3): 183–187. DOI: 10.1038/jp.2010.157.
  64. Gale C, Modi N, Jawad S, et al. The WHEAT Pilot trial–with holding enteral feeds around packed red cell transfusion to prevent necrotizing enterocolitis in preterm neonates: a multicenter, electronic patient record (EPR), randomized controlled point-of-care pilot trial. BMJ Open 2019;9(9):e033543. DOI: 10.1136/bmjopen-2019-033543.
  65. Lust C, Vesoulis Z, Jackups R Jr, et al. Early red cell transfusion is associated with development of severe retinopathy of prematurity. J Perinatol 2019;39(3):393–400. DOI: 10.1038/s41372-018-0274-9.
  66. Ohlsson A, Aher SM. Early erythropoiesis-stimulating agents in preterm or low birth weight infants. Cochrane Database Syst Rev 2017(11):CD004863. DOI: 10.1002/14651858.CD004863.pub5.
  67. Aher SM, Ohlsson A. Late erythropoiesis-stimulating agents to prevent red blood cell transfusion in preterm or low birth weight infants. Cochrane Database Syst Rev 2019;2(2):CD004868. DOI: 10.1002/14651858.CD004868.pub5.
  68. Mercer JS, Erickson-Owens DA, Deoni SC, et al. The effects of delayed cord clamping on 12-month brain myelin content and neurodevelopment: a randomized controlled trial. Am J Perinatol 2022;39(1):37–44. DOI: 10.1055/s-0040-1714258.
  69. Brown BE, Shah PS, Afifi JK, et al. Delayed cord clamping in small for gestational age preterm infants. Am J Obstet Gynecol 2022;226(2):247.e1–247.e10. DOI: 10.1016/j.ajog.2021.08.003.
  70. Pablo HBD, Galleti MF, Carrascal MP, et al. Impact of the volume of blood collected by phlebotomy on transfusion requirements in preterm infants with birth weight of less than 1500 g. A quasi-experimental study. Arch Argent Pediatr 2020;118(2):109–116. DOI: 10.5546/aap.2020.eng.109.
  71. Mintzer JP, Moore JE. Regional tissue oxygenation monitoring in the neonatal intensive care unit: evidence for clinical strategies and future directions. Pediatr Res 2019;86(3):296–304. DOI: 10.1038/s41390-019-0466-9.
  72. Garvey AA, Kooi EMW, Smith A, et al. Interpretation of cerebral oxygenation changes in the preterm infant. Children (Basel) 2018;5(7):94. DOI: 10.3390/children5070094.
  73. Van Bel F, Mintzer JP. Monitoring cerebral oxygenation of the immature brain: a neuroprotective strategy? Pediatr Res 2018;84(2):159–164. DOI: 10.1038/s41390-018-0026-8.
  74. Banerjee J, Aladangady N. Biomarkers to decide red blood cell transfusion in newborn infants. Transfusion 2014;54(10):2574–2582. DOI: 10.1111/trf.12670.
  75. Alkalay AL, Galvis S, Ferry DA, et al. Hemodynamic changes in anemic premature infants: are we allowing the hematocrits to fall too low? Pediatrics 2003;112(4):838–845. DOI: 10.1542/peds.112.4.838.
  76. Bard H, Fouron JC, Chessex P, et al. Myocardial, erythropoetic and metabolic adaptations to anemia of prematurity in infants with bronchopulmonary dysplasia. J Pediatr 1998;132(4):630–634. DOI: 10.1016/s0022-3476(98)70351-8.
  77. Izraeli S, Ben-Sira L, Harell D, et al. Lactic acid a s a predictor for erythrocyte transfusion in healthy preterm infants with anemia of prematurity. J Pediatr 1993;122(4):629–631. DOI: 10.1016/s0022-3476(05)83551-6.
  78. Tschirch E, Weber B, Koehne P, et al. Vascular endothelial growth dactor as marker for tissue hypoxia and transfusion need in anemic infants: a prospective clinical study. Pediatrics 2009;123(3):784–790. DOI: 10.1542/peds.2007-2304.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.