Effect of Transfusion on the Extension of IVH in Preterm Neonates

Document Type: Original Article


1 Kamali Clinical Research and Developmental Unit, Alborz University of Medical Sciences, Karaj, Iran

2 Faculty of Nursing, Alborz University of Medical Sciences, Karaj, Iran



Background: Today, preterm birth is well known as the major risk factor for intraventricular hemorrhage (IVH). In the first week of life, some preterm infants may have grade 1 IVH extending to severe (grade 3 or 4) IVH by transfusion one or more units. Several previous studies have found that blood and blood product transfusions lead to adverse clinical outcomes in neonates. Therefore, this study aimed to explore the relationship between Red blood cell (RBC) transfusion and extension of IVH in preterm infants.
Methods: For the purposes of the study, an observational retrospective case-control design was utilized. Moreover, all the neonates with grade 1 IVH in our referral hospital were identified in the past 5 years. Afterward, the subjects with extended IVH were compared with those who had resolved IVH.
Results: In total, 1050, 36, and 24 neonates were diagnosed with grade 1, grade 3, and grade 4 IVH, respectively. The mean values of the birth weight of extended IVH and resolved IVH groups were 1285±615 g and 1361±348 g, respectively (P=0.05). Moreover, extended IVH and resolved IVH groups were 29±3 weeks and 30±2 weeks premature, respectively (P=0.36). The low 5-minute Apgar scores of the extended IVH and resolved IVH groups were 5±2 and 7±2, respectively (P=0.000). In addition, the low cord pH of the extended IVH and resolved IVH groups were 7.29±0.1 and 7.37±0.1, respectively (P=0.005). Administration of packed RBC transfusion before and on the day of the diagnosis of grade 1 IVH had the most significant relationship with the extension of IVH (IR, 10.602; 95% CI, 2.81-39.92). The obtained results confirmed that criteria to order the transfusions were similar in both groups, based on which they did not have any proportion of the transfusions of compliance with the guidelines.
Conclusion: Based on the results, there was a great association between restrictive RBC transfusion and extension of a low-grade IVH into a higher grade (3 or 4) IVH. However, the statistical explanation is unclear and more studies are needed to discover the causality of this relationship.


1. Mazouri A, Massahi M, Khalesi N, Kashaki M. Investigation of the relationship between umbilical cord pH and intraventricular hemorrhage of infants delivered preterm. Rev Assoc Med Bras. 2019; 65(5):647-56.
2. Ballabh P. Intraventricular hemorrhage in premature infants: mechanism of disease. Pediatr Res. 2010;
3. Ballabh P, Braun A, Nedergaard M. Anatomic analysis of blood vessels in germinal matrix, cerebral cortex, and white matter in developing infants. Pediatr Res. 2004; 56(1):117-24.
4. Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr. 1978; 92(4):529-34.
5. Van Bel F, Vaes J, Groenendaal F. Prevention, reduction and repair of brain injury of the preterm infant. Front Physiol. 2019; 10:181.
6. Luu TM, Ment LR, Schneider KC, Katz KH, Allan WC, Vohr BR. Lasting effects of preterm birth and neonatal brain hemorrhage at 12 years of age. Pediatrics. 2009; 123(3):1037-44.
7. Romantsik O, Calevo MG, Bruschettini M. Head midline position for preventing the occurrence or extension of germinal matrix‐intraventricular hemorrhage in preterm infants. Cochrane Database Syst Rev. 2017; 7:CD012362.
8. Huang J, Meng J, Choonara I, Xiong T, Wang Y, Wang H, et al. Antenatal infection and intraventricular 

hemorrhage in preterm infants: a meta-analysis. Medicine. 2019; 98(31):e16665.
9. Christensen RD. Associations between “early” red blood cell transfusion and severe intraventricular hemorrhage, and between “late” red blood cell transfusion and necrotizing enterocolitis. Semin Perinatol. 2012; 36(4):283-9.
10. Lee JY, Kim HS, Jung E, Kim ES, Shim GH, Lee HJ, et al. Risk factors for periventricular-intraventricular hemorrhage in premature infants. J Korean Med Sci. 2010; 25(3):418-24.
11. Vela-Huerta M, Amador-Licona M, Medina-Ovando N, Aldana-Valenzuela C. Factors associated with early severe intraventricular haemorrhage in very low birth weight infants. Neuropediatrics. 2009; 40(5):224-7.
12. O'Leary H, Gregas MC, Limperopoulos C, Zaretskaya I, Bassan H, Soul JS, et al. Elevated cerebral pressure passivity is associated with prematurity-related intracranial hemorrhage. Pediatrics. 2009; 124(1): 302-9.
13. Neary E, Ainle FV, El‐Khuffash A, Cotter M, Kirkham C, McCallion N. Plasma transfusion to prevent intraventricular haemorrhage in very preterm infants. Cochrane Database Syst Rev. 2016; 2016(9):CD012341.
14. Aladangady N, Asamoah F, Banerjee J. Blood transfusion and short term outcomes in premature infants. E-PAS. 2014; 2014:41132522014.
15. New HV, Berryman J, Bolton‐Maggs PH, Cantwell C, Chalmers EA, Davies T, et al. Guidelines on transfusion for fetuses, neonates and older children. Br J Haematol. 2016; 175(5):784-828.
16. Wang YC, Chan OW, Chiang MC, Yang PH, Chu SM, Hsu JF, et al. Red blood cell transfusion and clinical outcomes in extremely low birth weight preterm infants. Pediatr Neonatol. 2017; 58(3):216-22.
17. Mohamed A, Shah PS. Transfusion associated necrotizing enterocolitis: a meta-analysis of observational data. Pediatrics. 2012; 129(3):529-40.
18. Collard KJ. Transfusion related morbidity in premature babies: Possible mechanisms and implications for practice. World J Clin Pediatr. 2014; 3(3):19-29.
19. Bassan H. Intracranial hemorrhage in the preterm infant: understanding it, preventing it. Clin Perinatol. 2009; 36(4):737-62.
20. Bednarek FJ, Weisberger S, Richardson DK, Frantz ID 3rd, Shah B, Rubin LP, et al. Variations in blood transfusions among newborn intensive care units. J Pediatr. 1998; 133(5):601-7.
21. Baer VL, Lambert DK, Henry E, Snow GL, Butler A, Christensen RD. Among very‐low‐birth‐weight neonates is red blood cell transfusion an independent risk factor for subsequently developing a severe intraventricular hemorrhage? Transfusion. 2011; 51(6):1170-8.
22. Cote CJ, Lerman J, Todres ID. A practice of anesthesia for infants and children. New York: Elsevier Health Sciences; 2012.
23. Dos Santos A, Guinsburg R, Procianoy RS, Sadeck
Ldos S, Netto AA, Rugolo LM, et al. Variability on red blood cell transfusion practices among Brazilian neonatal intensive care units. Transfusion. 2010; 50(1):150-9.
24. Christensen RD, Henry E, Ilstrup S, Baer VL. A high rate of compliance with neonatal intensive care unit transfusion guidelines persists even after a program to improve transfusion guideline compliance ended. Transfusion. 2011; 51(11):2519-20.
25. von Lindern JS, van den Bruele T, Lopriore E, Walther FJ. Thrombocytopenia in neonates and the risk of intraventricular hemorrhage: a retrospective cohort study. BMC Pediatr. 2011; 11:16. 26. Sparger K, Deschmann E, Sola-Visner M. Platelet transfusions in the neonatal intensive care unit. Clin Perinatol. 2015; 42(3):613-23.
27. Benson JE, Bishop MR, Cohen HL. Intracranial neonatal neurosonography: an update. Ultrasound Q. 2002; 18(2):89-114.
28. Strauss RG. How I transfuse red blood cells and platelets to infants with the anemia and thrombocytopenia of prematurity. Transfusion. 2008; 48(2):209-17.
29. dos Santos AM, Guinsburg R, de Almeida MF, Procianoy RS, Marba ST, Ferri WA, et al. Factors associated with red blood cell transfusions in very-low-birth-weight preterm infants in Brazilian neonatal units. BMC Pediatr. 2015; 15:113.
30. Keir A, Pal S, Trivella M, Lieberman L, Callum J, Shehata N, et al. Adverse effects of small-volume red blood cell transfusions in the neonatal population. Syst Rev. 2014; 3:92.
31. Christensen RD, Baer VL, Lambert DK, Ilstrup SJ, Eggert LD, Henry E. Association, among very‐low‐birthweight neonates, between red blood cell transfusions in the week after birth and severe intraventricular hemorrhage. Transfusion. 2014; 54(1):104-8.
32. Christensen RD, Baer VL, Del Vecchio A, Henry E. Unique risks of red blood cell transfusions in very-low-birth-weight neonates: associations between early transfusion and intraventricular hemorrhage and between late transfusion and necrotizing enterocolitis. J Matern Fetal Neonatal Med. 2013; 26(Suppl 2):60-3.
33. Portugal CA, de Paiva AP, Freire ES, Chaoubah A, Duarte MC, Hallack Neto AE. Transfusion practices in a neonatal intensive care unit in a city in Brazil. Rev Bras Hematol Hemoter. 2014; 36(4):245-9.
34. Bell EF, Strauss RG, Widness JA, Mahoney LT, Mock DM, Seward VJ, et al. Randomized trial of liberal versus restrictive guidelines for red blood cell transfusion in preterm infants. Pediatrics. 2005; 115(6):1685-91.
35. Chirico G. Red blood cell transfusion in preterm neonates: current perspectives. Int J Clin Transfusion Med. 2014; 2:21-8.
36. Mercer JS, Vohr BR, McGrath MM, Padbury JF, Wallach M, Oh W. Delayed cord clamping in very preterm infants reduces the incidence of intraventricular hemorrhage and late-onset sepsis: a 

randomized, controlled trial. Pediatrics. 2006; 117(4):1235-42.
37. Goodarzi R, Molavi MA, Moayedi AR, Sooroo AK, Nazemi A. Evaluation of incidence of intraventricular hemorrhage after blood transfusion in preterm neonates. Life Sci J. 2013; 10(1S):237-41.
38. Hosono S, Mugishima H, Kitamura T, Inami I, Fujita H, Hosono A, et al. Effect of hemoglobin on transfusion and neonatal adaptation in extremely low‐birthweight infants. Pediatr Int. 2008; 50(3): 306-11.
39. Banerjee J, Asamoah FK, Singhvi D, Kwan AW, Morris JK, Aladangady N. Haemoglobin level at birth is associated with short term outcomes and mortality in preterm infants. BMC Med. 2015; 13(1):16.
40. Pegoli M, Mandrekar J, Rabinstein AA, Lanzino G. Predictors of excellent functional outcome in aneurysmal subarachnoid hemorrhage. J Neurosurg. 2015; 122(2):414-8.
41. Chen HL, Tseng HI, Lu CC, Yang SN, Fan HC, Yang RC. Effect of blood transfusions on the outcome of very low body weight preterm infants under two different transfusion criteria. Pediatr Neonatol.
2009; 50(3):110-6.
42. Mukhopadhyay K, Sekhar Ghosh P, Narang A, Dogra M. Cut off level for RBC transfusion in sick preterm neonates. Pediatric Research. Baltimore: International Pediatric Research Foundation Inc; 2004.
43. Valieva OA, Strandjord TP, Mayock DE, Juul SE. Effects of transfusions in extremely low birth weight infants: a retrospective study. J Pediatr. 2009; 155(3):331-7.e1.
44. Rabe H, Diaz-Rossello JL, Duley L, Dowswell T. Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and infant outcomes. Cochrane Database Syst Rev. 2012; 8:CD003248.
45. Fergusson DA, Hébert P, Hogan DL, LeBel L, Rouvinez-Bouali N, Smyth JA, et al. Effect of fresh red blood cell transfusions on clinical outcomes in premature, very low-birth-weight infants: the ARIPI randomized trial. JAMA. 2012; 308(14): 1443-51.
46. Ward RA, Brier ME. Retrospective analyses of large medical databases what do they tell us? J Am Soc Nephrol. 1999; 10(2):429-32.