Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2025 Dec 11;12(12):CD000512.
doi: 10.1002/14651858.CD000512.pub3.

Low versus high haemoglobin concentration threshold for blood transfusion for preventing morbidity and mortality in very low birthweight infants

Chad Andersen  1   2 , Michael J Stark  1   2 , Tara Crawford  1 , Robin K Whyte  3 , Axel R Franz  4 , Roger F Soll  5 , Haresh Kirpalani  6   7
Affiliations
Meta-Analysis

Low versus high haemoglobin concentration threshold for blood transfusion for preventing morbidity and mortality in very low birthweight infants

Chad Andersen et al. Cochrane Database Syst Rev. .

Abstract

Background: Infants of very low birthweight frequently receive red blood cell transfusions during their primary hospital stay. Generally, this is guided by predetermined haemoglobin or haematocrit thresholds according to a protocol or as prompted by clinical situations, including critical illness or surgery. Recommendations advocate maintaining higher thresholds in the early weeks when the risk of major morbidity is highest, while permitting lower thresholds after this time. In truth, clinicians worry about the potential effect of chronic anaemia on neurodevelopmental outcomes, as well as the risk of transfusion-related complications in the immature host. Clinical trials have reflected this practice by comparing haemoglobin levels adjusted for critical illness, comparing transfusion algorithms that use fixed differences between haemoglobin thresholds, with both thresholds progressively lowered across postnatal age. This is an update of a review first published in 2011.

Objectives: To evaluate the effect of lower (restrictive) compared with higher (liberal) haemoglobin thresholds for transfusion, with or without adjustment for age and critical illness with either fixed or variable transfusion volume, on mortality or later neurodevelopmental outcomes assessed in later infancy at approximately two years postmenstrual age, or the number of transfusions in very low birthweight infants.

Search methods: Searches were conducted in January 2024 in CENTRAL, MEDLINE, Embase, CINAHL, Epistemonikos, and trial registries. We searched the reference lists of related systematic reviews and trials.

Selection criteria: We selected randomised controlled trials (RCTs) of lower or restrictive haemoglobin/haematocrit thresholds compared with liberal or higher haemoglobin/haematocrit thresholds for transfusion in low birthweight infants within three days of birth.

Data collection and analysis: We used standard Cochrane methods. Our main outcomes were a combined outcome of death or neurodevelopmental impairment, all-cause mortality, and the number of transfusions per infant. We expressed our results using mean difference (MD), standardised mean difference (SMD), risk ratio (RR), and risk difference (RD) with 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence.

Main results: Six trials, enrolling 3451 infants, compared transfusion strategies utilising a lower (restrictive) haemoglobin threshold compared to a higher (liberal) haemoglobin threshold. The transfusion thresholds used in these trials reflected prevailing clinical practice at the time of study design. For comparative purposes, they have been labelled as 'restrictive' and 'liberal'. The trials were similar in design, although each used slightly different transfusion algorithms and intervention thresholds. The three larger trials also conducted later neurosensory assessments. The number of infants included in outcome calculations varies across in-hospital versus post-discharge outcomes, assessment methods, and exclusion criteria, and our analysis uses the denominators reported in the original publications. Overall, utilising a lower compared to a higher haemoglobin transfusion threshold results in little or no difference in the combined outcome of death or neurodevelopmental impairment at 18 to 26 months postmenstrual age (RR 1.02, 95% CI 0.95 to 1.09; I2 = 55%; RD 0.01, 95% CI -0.03 to 0.04; 3 studies, 3041 infants; high-certainty evidence). Mortality at 18 to 26 months was also not different (RR 0.99, 95% CI 0.83 to 1.17; I2 = 0%; RD -0.00, 95% CI -0.03 to 0.02; I2 = 0%; 3 studies, 3186 infants; high-certainty evidence). Infants allocated to the restrictive threshold may receive fewer transfusions during the primary hospital stay (mean difference in transfusion number per infant -1.05, 95% CI -1.26 to -0.84; I2 = 84%; 6 studies, 3451 infants; low-certainty evidence).

Authors' conclusions: The trials comparing lower or restrictive versus higher or liberal haemoglobin thresholds for transfusion show little to no difference in important outcomes at hospital discharge and at the time of later neurodevelopmental follow-up. The use of restrictive, as compared to liberal, haemoglobin or haematocrit transfusion thresholds in these trials in infants of very low birthweight results in modest reductions in transfusion exposure and haemoglobin levels. The safety of haemoglobin levels below these lower limits has not been evaluated and should only be considered in the context of randomised controlled trials.

PubMed Disclaimer

Conflict of interest statement

Chad Andersen is the author of an included study (Kirpalani (PINT) 2006). This study was funded by the Canadian Institutes of Health Research (CIHR). He has published opinions relevant to the interventions in the work.

Michael J Stark is the chief investigator (CIA) on National Health and Medical Research Council (NHMRC) Clinical Trials and Cohorts Grant GNT1183561 2020 to 2026 AUD 2070000, which led to the publication of an RCT (Stark 2023). The funds were not paid to him personally. He is a contributing author and member of the clinical reference group for the National Blood Authority (NBA) 2016 Patient Blood Management Guidelines: Module 6 ‐ Neonatal and Paediatrics. NBA, Canberra, Australia.

Tara Crawford does not have any interests to disclose at this time. Whilst she is not an author of the included studies, she has made significant contributions to the field (Crawford 2020).

Robin Whyte is an author of the following three included studies: Connelly 1999, funded by Izaak Walton Killam (IWK) Research Fund, Kirpalani (PINT) 2006, funded by CIHR (Canada) and Kirpalani (TOP) 2020, funded by the National Institute of Child Health and Development (NICHD) and the National Heart, Lung and Blood Institute (NHLBI). He has published opinions relevant to the interventions in the work.

Axel Franz is the co‐ordinating investigator of an included study (Franz (ETTNO) 2020). The ETTNO study was funded by the German Research Foundation (DFG).

Roger Soll is a Co‐ordinating Editor with Cochrane Neonatal but did not take part in this review's editorial assessment or acceptance. He received a grant from the Gerber Foundation to update reviews on interventions for pain and discomfort.

Haresh Kirpalani is the author of two included studies (Kirpalani (PINT) 2006; Kirpalani (TOP) 2020). Kirpalani (PINT) 2006 was funded by CIHR (Canada) and Kirpalani (TOP) 2020 was funded by NHLBI grants U01 HL112776 and U01 HL112748, and NICHD grants UG1 HD068244, UG1 HD053109 and U24 HD095254. Haresh Kirpalani is an Associate Editor with Cochrane Neonatal but did not take part in this review's editorial assessment or acceptance.

The authors of included studies were not involved in the assessment of the risk of bias for their own study, nor involved in any GRADE assessment that used outcome data from their own study.

Update of

References

References to studies included in this review

Bell 2005 {published data only}
    1. 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. [DOI: 10.1542/peds.2004-1884] [PMID: ] - DOI - PMC - PubMed
    1. McCoy TE, Conrad AL, Richman LC, Lindgren SD, Nopoulus PC, Bell EF. Neurocognitive profiles of preterm infants randomly assigned to lower or higher hematocrit thresholds for transfusion. Child Neuropsychology 2011;17(4):347-67. [DOI: 10.1080/09297049.2010.544647] [PMID: ] - DOI - PMC - PubMed
    1. Nopoulos PC, Conrad AL, Bell EF, Strauss RG, Widness JA, Magnotta VA, et al. Long-term outcome of brain structure in premature infants: effects of liberal vs restricted red blood cell transfusions. Archives of Pediatrics & Adolescent Medicine 2011;165(5):443-50. [DOI: 10.1001/archpediatrics.2010.269] [PMID: ] - DOI - PMC - PubMed
Chen 2009 {published data only}
    1. 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. Pediatrics and Neonatology 2009;50(3):110-6. [DOI: 10.1016/S1875-9572(09)60045-0] [PMID: ] - DOI - PubMed
Connelly 1999 {unpublished data only}
    1. Connelly RJ, Stone SH, Whyte RK. Early vs. late red cell transfusion in low birth weight infants. Pediatric Research 1998;43(4):170A.
Franz (ETTNO) 2020 {published data only}
    1. Franz AR, Engel C, Bassler D, Rüdiger M, Thome UH, Maier RF, et al, ETTNO Investigators. 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;326(6):560-70 [Erratum in: JAMA. 2022 Jul 12;328(2):217]. [DOI: 10.1001/jama.2020.10690] [PMID: ] - DOI - PMC - PubMed
Kirpalani (PINT) 2006 {published data only}
    1. Kirpalani H, Whyte RK, Andersen C, Asztalos EV, Heddle N, Blajchman MA, 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. Journal of Pediatrics 2006;149(3):301-7. [DOI: 10.1016/j.jpeds.2006.05.011] [PMID: ] - DOI - PubMed
    1. Whyte RK, Kirpalani H, Asztalos EV, Andersen C, Blajchman M, Heddle N, et al, PINTOS Study Group. Neurodevelopmental outcome of extremely low birth weight infants randomly assigned to restrictive or liberal hemoglobin thresholds for blood transfusion. Pediatrics 2009;123(1):207-13. [DOI: 10.1542/peds.2008-0338] [PMID: ] - DOI - PubMed
Kirpalani (TOP) 2020 {published data only}
    1. Kirpalani H, Bell EF, Hintz SR, Tan S, Schmidt B, Chaudhary AS, et al, Eunice Kennedy Shriver NICHD Neonatal Research. Higher or lower hemoglobin transfusion thresholds for preterm infants. New England Journal of Medicine 2020;383(27):2639-51. [DOI: 10.1056/NEJMoa2020248] [PMID: ] - DOI - PMC - PubMed

References to studies excluded from this review

Blank 1984 {published data only}
    1. Blank JP, Sheagren TG, Vajaria J, Mangurten HH, Benawra RS, Puppala BL. The role of RBC transfusion in the premature infant. American Journal of Diseases of Children 1984;138(9):831‐3. [PMID: ] - PubMed
Meyer 1993 {published data only}
    1. Meyer J, Sive A, Jacobs P. Empiric red cell transfusion in asymptomatic preterm infants. Acta Paediatrica 1993;82(1):30-4. [DOI: 10.1111/j.1651-2227.1993.tb12510.x] [PMID: ] - DOI - PubMed
Mukhopadhyay 2004 {published data only}
    1. Mukhopadhyay K, Ghosh PS, Narang A, Dogra MR. Cut off level for RBC transfusion in sick preterm neonates. Pediatric Research 2004;55:289A.
Ransome 1989 {published data only}
    1. Ransome OJ, Moosa EA, Mothebe FM, Spector I. Are regular 'top-up' transfusions necessary in otherwise well, growing premature infants? South African Medical Journal 1989;75(4):165-6. [PMID: ] - PubMed
Ross 1989 {published data only}
    1. Ross MP, Christensen RD, Rothstein G, Koenig JM, Simmons MD, Noble NA, et al. A randomized trial to develop criteria for administering erythrocyte transfusions to anemic preterm infants 1 to 3 months of age. Journal of Perinatology 1989;9(3):246-53. [PMID: ] - PubMed
Wardle 2002 {published data only}
    1. Wardle SP, Garr R, Yoxall CW, Weindling AM. A pilot randomised controlled trial of peripheral fractional oxygen extraction to guide blood transfusions in preterm infants. Archives of Disease in Childhood. Fetal and Neonatal Edition 2002;86(1):F22-7. [DOI: 10.1136/fn.86.1.f22] [PMID: ] - DOI - PMC - PubMed

Additional references

Aher 2020a
    1. Aher SM, Ohlsson A. Late erythropoiesis-stimulating agents to prevent red blood cell transfusion in preterm or low birth weight infants. Cochrane Database of Systematic Reviews 2020, Issue 1. Art. No: CD004868. [DOI: 10.1002/14651858.CD004868.pub6] - DOI
Aher 2020b
    1. Aher SM, Ohlsson A. Early versus late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants. Cochrane Database of Systematic Reviews 2020, Issue 2. Art. No: CD004865. [DOI: 10.1002/14651858.CD004865.pub4] - DOI
Alkalay 2003
    1. Alkalay AL, Galvis S, Ferry DA, Simmons CF, Krueger RC Jr. Hemodynamic changes in anemic premature infants: are we allowing the hematocrits to fall too low? Pediatrics 2003;112(4):838-45. [DOI: 10.1542/peds.112.4.838] [PMID: ] - DOI - PubMed
Allen 2006
    1. Allen BW, Piantadosi CA. How do red blood cells cause hypoxic vasodilation? The SNO-hemoglobin paradigm. American Journal of Physiology. Heart and Circulatory Physiology 2006;291(4):H1507-12. [DOI: 10.1152/ajpheart.00310.2006] [PMID: ] - DOI - PubMed
Andersen 2006
    1. Andersen CC, Collins CL. Poor circulation, early brain injury, and the potential role of red cell transfusion in premature newborns. Pediatrics 2006;117(4):1464-6. [DOI: 10.1542/peds.2005-3197] [PMID: ] - DOI - PubMed
Bancalari 2012
    1. Bancalari EH, Jobe AH. The respiratory course of extrememly preterm infants: a dilemma for diagnosis and terminology. Journal of Pediatrics 2012;161(4):485-8. [DOI: 10.1016/j.jpeds.2012.05.054] [PMID: ] - DOI - PubMed
Bard 1997
    1. Bard H, Widness JA. The life span of erythrocytes transfused to preterm infants. Pediatric Research 1997;42(1):9-11. [DOI: 10.1203/00006450-199707000-00002] [PMID: ] - DOI - PubMed
Barkemeyer 2000
    1. Barkemeyer BM, Hempe JM. Effect of transfusion on hemoglobin variants in preterm infants. Journal of Perinatology 2000;20(6):355-8. [DOI: 10.1038/sj.jp.7200392] [PMID: ] - DOI - PubMed
Bayley II
    1. Bayley N. Bayley Scales of Infant Development Manual. 2rd edition. San Antonio, Texas: The Psychological Corporation, 1993.
Bayley III
    1. Bayley N. Bayley Scales of Infant Development Manual. 3rd edition. San Antonio, Texas: The Psychological Corporation, 2006.
Bednarek 1998
    1. Bednarek FJ, Weisberger S, Richardson DK, Frantz ID 3rd, Shah B, Rubin LP. Variations in blood transfusions among newborn intensive care units. SNAP II Study Group. Journal of Pediatrics 1998;133(5):601-7. [DOI: 10.1016/s0022-3476(98)70097-6] [PMID: ] - DOI - PubMed
Beeram 2001
    1. Beeram MR, Krauss DR, Riggs MW. Red blood cell transfusion practices in very low birth weight infants in 1990s postsurfactant era. Journal of the National Medical Association 2001;93(10):405-9. [PMID: ] - PMC - PubMed
Bell 1978
    1. Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Annals of Surgery 1978;187(1):1-7. [DOI: 10.1097/00000658-197801000-00001] [PMID: ] - DOI - PMC - PubMed
Bennett‐Guerrero 2007
    1. Bennett-Guerrero E, Veldman TH, Doctor A, Telen MJ, Ortel TL, Reid TS, et al. Evolution of adverse changes in stored RBCs. Proceedings of the National Academy of Sciences of the United States of America 2007;104(43):17063-8. [DOI: 10.1073/pnas.0708160104] [PMID: ] - DOI - PMC - PubMed
Blajchman 2006
    1. Blajchman MA, Vamvakas EC. The continuing risk of transfusion-transmitted infections. New England Journal of Medicine 2006;355(13):1303-5. [DOI: 10.1056/NEJMp068178] [PMID: ] - DOI - PubMed
Blanchette 1984
    1. Blanchette VS, Zipursky A. Assessment of anemia in newborn infants. Clinics in Perinatology 1984;11(2):489-510. [PMID: ] - PubMed
Blank 1984
    1. Blank JP, Sheagren TG, Vajaria J, Mangurten HH, Benawra RS, Puppala BL. The role of RBC transfusion in the premature infant. American Journal of Diseases of Children 1984;138(9):831-3. [DOI: 10.1001/archpedi.1984.02140470031010] [PMID: ] - DOI - PubMed
Cambonie 2007
    1. Cambonie G, Matecki S, Milesi C, Voisin M, Guillaumont S, Picaud JC. Myocardial adaptation to anemia and red blood cell transfusion in premature infants requiring ventilation support in the 1st postnatal week. Neonatology 2007;92(3):174-81. [DOI: 10.1159/000101568] [PMID: ] - DOI - PubMed
Christensen 2008
    1. Christensen RD, Jopling J, Henry E, Wiedmeier SE. The erythrocyte indices of neonates, defined using data from over 12,000 patients in a multihospital health care system. Journal of Perinatology 2008;28(1):24-8. [DOI: 10.1038/sj.jp.7211852] [PMID: ] - DOI - PubMed
Christine 2007
    1. Christine C, Dolk H, Platt MJ, Colver A, Prasauskiene A, Krägeloh-Mann I, SCPE Collaborative Group. Recommendations from the SCPE collaborative group for defining and classifying cerebral palsy. Developmental Medicine and Child Neurology. Supplement 2007;109:35-8. [DOI: 10.1111/j.1469-8749.2007.tb12626.x] [PMID: ] - DOI - PubMed
Crawford 2020
    1. Crawford T, Andersen CC, Stark MJ. Effect of repeat transfusion exposure on plasma cytokine and markers of endothelial activation in the extremely preterm neonate. Transfusion 2020;60(10):2217-24. [DOI: 10.1111/trf.15952] [PMID: ] - DOI - PubMed
Dani 2004
    1. Dani C, Martelli E, Bertini G, Pezzati M, Rossetti M, Buonocore G, et al. Effect of blood transfusions on oxidative stress in preterm infants. Archives of Disease in Childhood. Fetal and Neonatal Edition 2004;89(5):F408-11. [DOI: 10.1136/adc.2003.037085] [PMID: ] - DOI - PMC - PubMed
Deeks 2023
    1. Deeks JJ, Higgins JP, Altman DG (editors). Chapter 10: Analysing data and undertaking meta-analyses. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 6.4 (updated August 2023). Cochrane, 2023. Available from https://www.cochrane.org/handbook.
Delivoria‐Papadopoulos 1971
    1. Delivoria-Papadopoulos M, Morrow G 3rd, Oski FA. Exchange transfusion in the newborn infant with fresh and "old" blood: the role of storage on 2,3-diphosphoglycerate, hemoglobin-oxygen affinity, and oxygen release. Journal of Pediatrics 1971;79(6):898-903. [DOI: 10.1016/s0022-3476(71)80181-6] [PMID: ] - DOI - PubMed
Drew 2017
    1. Drew VJ, Barro L, Seghatchian J, Burnouf T. Towards pathogen inactivation of red blood cells and whole blood targeting viral DNA/RNA: design, technologies, and future prospects for developing countries. Blood Transfusion 2017;15(6):512-21. [DOI: 10.2450/2017.0344-16] [PMID: ] - DOI - PMC - PubMed
Egger 1997
    1. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ (Clinical Research Ed.) 1997;315(7109):629-34. [DOI: 10.1136/bmj.315.7109.629] [PMID: ] - DOI - PMC - PubMed
Fergusson 2012
    1. 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. [DOI: 10.1001/2012.jama.11953] [PMID: ] - DOI - PubMed
Fetus and Newborn 1992
    1. Fetus and Newborn Committee, Canadian Paediatric Society. Guidelines for transfusion of erythrocytes to neonates and premature infants. Canadian Medical Association Journal 1992;147(12):1781-92. [PMID: ] - PMC - PubMed
Fetus and Newborn 2002
    1. Fetus and Newborn Committee, Canadian Paediatric Society. Red blood cell transfusions in newborn infants: revised guidelines. Paediatrics & Child Health 2002;7(8):553-66. [DOI: 10.1093/pch/7.8.553] [PMID: ] - DOI - PMC - PubMed
Franz 2001
    1. Franz AR, Pohlandt F. Red blood cell transfusions in very and extremely low birthweight infants under restrictive transfusion guidelines: is exogenous erythropoietin necessary? Archives of Disease in Childhood. Fetal and Neonatal Edition 2001;84(2):F96-100. [DOI: 10.1136/fn.84.2.f96] [PMID: ] - DOI - PMC - PubMed
Fredrickson 2011
    1. Fredrickson LK, Bell EF, Cress GA, Johnson KJ, Zimmerman MB, Mahoney LT, et al. Acute physiological effects of packed red blood cell transfusion in preterm infants with different degrees of anaemia. Archives of Disease in Childhood. Fetal and Neonatal Edition 2011;96(4):F249-53. [DOI: 10.1136/adc.2010.191023] [PMID: ] - DOI - PMC - PubMed
Frey 2001
    1. Frey B, Losa M. The value of capillary whole blood lactate for blood transfusion requirements in anaemia of prematurity. Intensive Care Medicine 2001;27(1):222-7. [DOI: 10.1007/s001340000712] [PMID: ] - DOI - PubMed
GRADEpro GDT [Computer program]
    1. GRADEpro GDT. Version accessed 23 June 2023. Hamilton (ON): McMaster University (developed by Evidence Prime), 2023. Available at gradepro.org.
Guillén 2012
    1. Guillén Ú, Cummings JJ, Bell EF, Hosono S, Frantz AR, Maier RF, et al. International survey of transfusion practices for extremely premature infants. Seminars in Perinatology 2012;36(4):244-7. [DOI: 10.1053/j.semperi.2012.04.004] - DOI
Hay 2017
    1. Hay S, Zupancic JA, Flannery DD, Kirpalani H, Dukhovny D. Should we believe in transfusion-associated enterocolitis? Applying a GRADE to the literature. Seminars in Perinatology 217;41(1):80-91. [DOI: 10.1053/j.semperi.2016.09.021] [PMID: ] - DOI - PubMed
Higgins 2011
    1. Higgins JP, Altman DG, Sterne JA, editor(s). Chapter 8: Assessing risk of bias in included studies. In: Higgins JP, Churchill R, Chandler J, Cumpston MS, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). Cochrane, 2011. Available from https://www.cochrane.org/authors/handbooks-and-manuals/handbook/archive/....
Hirano 2001
    1. Hirano K, Morinobu T, Kim H, Hiroi M, Ban R, Ogawa S, et al. Blood transfusion increases radical promoting non-transferrin bound iron in preterm infants. Archives of Disease in Childhood. Fetal and Neonatal Edition 2001;84(3):F188-93. [DOI: 10.1136/fn.84.3.f188] [PMID: ] - DOI - PMC - PubMed
Holman 1995
    1. Holman P, Blajchman MA, Heddle N. Noninfectious adverse effects of blood transfusion in the neonate. Transfusion Medicine Reviews 1995;9(3):277-87. [PMID: ] - PubMed
Hosono 2008
    1. Hosono S, Mugishima H, Fujita H, Hosono A, Minato M, Okada T, et al. Umbilical cord milking reduces the need for red cell transfusions and improves neonatal adaptation in infants born at less than 29 weeks' gestation: a randomised controlled trial. Archives of Disease in Childhood. Fetal and Neonatal Edition 2008;93(1):F14-9. [DOI: 10.1136/adc.2006.108902] [PMID: ] - DOI - PubMed
Hume 1997
    1. Hume H. Red blood cell transfusions for preterm infants: the role of evidence-based medicine. Seminars in Perinatology 1997;21(1):8-19. [DOI: 10.1016/s0146-0005(97)80015-8] [PMID: ] - DOI - PubMed
Hébert 1999
    1. Hébert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, et al. A multicentre, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. New England Journal of Medicine 1999;340(6):409-17. [DOI: 10.1056/NEJM199902113400601] [PMID: ] - DOI - PubMed
ICCRP 2005
    1. International Committee for the Classification of Retinopathy of Prematurity (ICCRP). The international classification of retinopathy of prematurity revisited. Archives of Ophthalmology 2005;123(7):991-9. [DOI: 10.1001/archopht.123.7.991] [PMID: ] - DOI - PubMed
Juul  2020
    1. Juul SE, Vu PT, Comstock BA, Wadhawan R, Mayock DE, Courtney SE, et al, Preterm Erythropoietin Neuroprotection Trial Consortium. Effect of high-dose erythropoietin on blood transfusions in extremely low gestational age neonates: post hoc analysis of a randomized clinical trial. JAMA Pediatrics 2020;174(10):933-43. [DOI: 10.1001/jamapediatrics.2020.2271] [PMID: ] - DOI - PMC - PubMed
Keir 2015
    1. Keir AK, Yang J, Harrison A, Pelausa E, Shah PS, Canadian Neonatal Network. Temporal changes in blood product usage in preterm neonates born at less than 30 weeks' gestation in Canada. Transfusion 2015;55(6):1340-6. [DOI: 10.1111/trf.12998] [PMID: ] - DOI - PubMed
Keyes 1989
    1. Keyes WG, Donohue PK, Spivak JL, Jones MD Jr, Oski FA. Assessing the need for transfusion of premature infants and role of hematocrit, clinical signs, and erythropoietin level. Pediatrics 1989;84(3):412-7. [PMID: ] - PubMed
Kirpalani 2022
    1. Kirpalani HM, Prokopchuk-Gauk O, Heddle NM. Use of irradiated red blood cell transfusions in newborns to improve intracerebral saturation. JAMA Pediatrics 2022;176(5):e220149. [DOI: 10.1001/jamapediatrics.2022.0149] - DOI
Kirpalani 2012
    1. Kirpalani H, Zupancic JA. Do transfusions cause necrotizing enterocolitis? The complementary role of randomized trials and observational studies. Seminars in Perinatology 2012;36(4):269-76. [DOI: 10.1053/j.semperi.2012.04.007] [PMID: ] - DOI - PubMed
Kulandavelu 2015
    1. Kulandavelu S, Balkan W, Hare JM. Regulation of oxygen delivery to the body via hypoxic vasodilation. Proceedings of the National Academy of Sciences of the United States of America 2015;112(2):6254-5. [DOI: 10.1073/pnas.1506523112] [PMID: ] - DOI - PMC - PubMed
Lachance 1994
    1. Lachance C, Chessex P, Fouron JC, Widness JA, Bard H. Myocardial, erythropoietic, and metabolic adaptations to anemia of prematurity. Journal of Pediatrics 1994;125(2):278-82. [DOI: 10.1016/s0022-3476(94)70211-x] [PMID: ] - DOI - PubMed
Lacroix 2007
    1. Lacroix J, Hébert PC, Hutchison JS, Hume HA, Tucci M, Ducruet T, et al, TRIPICU Investigators, Canadian Critical Care Trials Group, Pediatric Acute Lung Injury and Sepsis Investigators Network. Transfusion strategies for patients in pediatric intensive care units. New England Journal of Medicine 2007;356(16):1609-19. [DOI: 10.1056/NEJMoa066240] [PMID: ] - DOI - PubMed
Madan 2005
    1. Madan A, Kumar R, Adams MM, Benitz WE, Geaghan SM, Widness JA. Reduction in red blood cell transfusions using a bedside analyzer in extremely low birth weight infants. Journal of Perinatology 2005;25(1):21-5. [DOI: 10.1038/sj.jp.7211201] [PMID: ] - DOI - PubMed
Mally 2006
    1. Mally P, Golombek SG, Mishra R, Nigam S, Mohandas K, Depalhma H, et al. Association of necrotizing enterocolitis with elective packed red blood cell transfusions in stable, growing, premature neonates. American Journal of Perinatology 2006;23(8):451-8. [DOI: 10.1055/s-2006-951300] [PMID: ] - DOI - PubMed
McFaul 2009
    1. McFaul SJ, Corley JB, Mester CW, Nath J. Packed blood cells stored in AS-5 become proinflammatory during storage. Transfusion 2009;49(7):1451-60. [DOI: 10.1111/j.1537-2995.2009.02158.x] [PMID: ] - DOI - PubMed
Meldon 1985
    1. Meldon JH. Blood gas transport and 2,3-DPG. Advances in Experimental Medicine and Biology 1985;191:63-73. [DOI: 10.1007/978-1-4684-3291-6_5] [PMID: ] - DOI - PubMed
Mimica 2008
    1. Mimica AF, Dos Santos AM, Da Cunha DH, Guinsburg R, Bordin JO, Chiba A, et al. A very strict guideline reduces the number of erythrocyte transfusions in preterm infants. Vox Sanguinis 2008;95(2):106-11. [DOI: 10.1111/j.1423-0410.2008.01072.x] [PMID: ] - DOI - PubMed
Moroff 1999
    1. Moroff G, Holme S, AuBuchon JP, Heaton WA, Sweeney JD, Friedman LI. Viability and in vitro properties of AS-1 red cells after gamma irradiation. Transfusion 1999;39(2):128-34. [DOI: 10.1046/j.1537-2995.1999.39299154725.x] [PMID: ] - DOI - PubMed
Ohls 2001
    1. Ohls RK, Ehrenkranz RA, Wright LL, Lemons JA, Korones SB, Stoll BJ, et al. Effects of early erythropoietin therapy on the transfusion requirements of preterm infants below 1250 grams birth weight: a multicenter, randomized, controlled trial. Pediatrics 2001;108(4):934-42. [DOI: 10.1542/peds.108.4.934] [PMID: ] - DOI - PubMed
Ohlsson 2020
    1. Ohlsson A, Aher SM. Early erythropoiesis-stimulating agents in preterm or low birth weight infants. Cochrane Database of Systematic Reviews 2020, Issue 2. Art. No: CD004863. [DOI: 10.1002/14651858.CD004863.pub6] - DOI
Page 2021
    1. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. [DOI: 10.1136/bmj.n71] - DOI
Page 2021a
    1. Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ 2021;372:n160. [DOI: ]
Palisano 1997
    1. Palisano R, Rosenbaum P, Walter S, Russell D, Wood E, Galuppi B. Development and reliability of a system to classify gross motor function in children with cerebral palsy. Developmental Medicine and Child Neurology 1997;39(4):214-23. [DOI: 10.1111/j.1469-8749.1997.tb07414.x] [PMID: ] - DOI - PubMed
Papile 1983
    1. Papile LA, Munsick-Bruno G, Schaefer A. Relationship of cerebral intraventricular hemorrhage and early childhood neurologic handicaps. Journal of Pediatrics 1983;103(2):273-7. [DOI: 10.1016/s0022-3476(83)80366-7] [PMID: ] - DOI - PubMed
Pinto‐Martin 1995
    1. Pinto-Martin JA, Riolo S, Cnaan A, Holzman C, Susser MW, Paneth N. Cranial ultrasound prediction of disabling and nondisabling cerebral palsy at age two in a low birth weight population. Pediatrics 1995;95(2):249-54. [PMID: ] - PubMed
Rabe 2019
    1. Rabe H, Gyte GM, Díaz‐Rossello JL, Duley L. Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and infant outcomes. Cochrane Database of Systematic Reviews 2019, Issue 9. Art. No: CD003248. [DOI: 10.1002/14651858.CD003248.pub4] - DOI
RevMan 2024 [Computer program]
    1. Review Manager (RevMan). Version 7.2.0. The Cochrane Collaboration, 2022. Available at revman.cochrane.org.
Ringer 1998
    1. Ringer SA, Richardson DK, Sacher RA, Keszler M, Churchill WH. Variations in transfusion practice in neonatal intensive care. Pediatrics 1998;101(2):194-200. [DOI: 10.1542/peds.101.2.194] [PMID: ] - DOI - PubMed
Sacks 1984
    1. Sacks LM, Delivoria-Papadopoulos M. Hemoglobin-oxygen interactions. Seminars in Perinatology 1984;8(3):168-83. [PMID: ] - PubMed
Saito‐Benz 2018
    1. Saito‐Benz M, Murphy WG, Tzeng YC, Atkinson G, Berry MJ. Storage after gamma irradiation affects in vivo oxygen delivery capacity of transfused red blood cells in preterm infants. Transfusion 2018;58:2108-12.
Schünemann 2013
    1. Schünemann H, Brożek J, Guyatt G, Oxman A, editor(s). Handbook for grading the quality of evidence and the strength of recommendations using the GRADE approach (updated October 2013). GRADE Working Group, 2013. Available from gdt.guidelinedevelopment.org/app/handbook/handbook.html.
SCPE 2000
    1. Surveillance of Cerebral Palsy in Europe (SCPE). Surveillance of cerebral palsy in Europe: a collaboration of cerebral palsy surveys and registers. Developmental Medicine and Child Neurology 2000;42(12):816-24. [DOI: 10.1017/s0012162200001511] [PMID: ] - DOI - PubMed
Shannon 1995
    1. Shannon KM, Keith JF 3rd, Mentzer WC, Ehrenkranz RA, Brown MS, Widness JA, et al. Recombinant human erythropoietin stimulates erythropoiesis and reduces erythrocyte transfusions in very low birth weight preterm infants. Pediatrics 1995;95(1):1-8. [PMID: ] - PubMed
Shennan 1988
    1. Shennan AT, Dunn MS, Ohlsson A, Lennox K, Hoskins EM. Abnormal pulmonary outcomes in premature infants: prediction from oxygen requirement in the neonatal period. Pediatrics 1988;82(4):527-32. [PMID: ] - PubMed
Siggaard‐Andersen 1990
    1. Siggaard-Andersen O, Gothgen IH, Wimberley PD, Fogh-Andersen N. The oxygen status of the arterial blood revised: relevant oxygen parameters for monitoring the arterial oxygen availability. Scandinavian Journal of Clinical and Laboratory Investigation. Supplementum 1990;203:17-28. [DOI: 10.3109/00365519009087488] [PMID: ] - DOI - PubMed
Silvers 1998
    1. Silvers KM, Gibson AT, Russell JM, Powers HJ. Antioxidant activity, packed cell transfusions, and outcome in premature infants. Archives of Disease in Childhood. Fetal and Neonatal Edition 1998;78(3):F214-9. [DOI: 10.1136/fn.78.3.f214] [PMID: ] - DOI - PMC - PubMed
Simak 2006
    1. Simak J, Gelderman MP. Cell membrane microparticles in blood and blood products: potentially pathogenic agents and diagnostic markers. Transfusion Medicine Reviews 2006;20(1):1-26. [DOI: 10.1016/j.tmrv.2005.08.001] [PMID: ] - DOI - PubMed
Stark 2013
    1. Stark MJ, Keir AK, Andersen CC. Does non-transferrin bound iron contribute to transfusion related immune-modulation in preterms? Archives of Disease in Childhood. Fetal and Neonatal Edition 2013;98(5):F424-9. [DOI: 10.1136/archdischild-2012-303353] [PMID: ] - DOI - PubMed
Stark 2023
    1. Stark MJ, Collins CT, Andersen CC, Crawford TM, Sullivan TR, Bednarz J, et al. Study protocol of the WashT Trial: transfusion with washed versus unwashed red blood cells to reduce morbidity and mortality in infants born less than 28 weeks' gestation - a multicentre, blinded, parallel group, randomised controlled trial. BMJ Open 2023;13(7):e070272. [DOI: 10.1136/bmjopen-2022-070272] [PMID: ] - DOI - PMC - PubMed
Stockman 1984
    1. Stockman JA 3rd, Graeber JE, Clark DA, McClellan K, Garcia JF, Kavey RE. Anemia of prematurity: determinants of the erythropoietin response. Journal of Pediatrics 1984;105(5):786-92. [DOI: 10.1016/s0022-3476(84)80308-x] [PMID: ] - DOI - PubMed
Stockman 1984a
    1. Stockman JA 3rd, Clark DA. Weight gain: a response to transfusion in selected preterm infants. American Journal of Diseases of Children 1984;138(9):828-30. [DOI: 10.1001/archpedi.1984.02140470028009] [PMID: ] - DOI - PubMed
Stockman 1986
    1. Stockman JA 3rd. Anemia of prematurity. Current concepts in the issue of when to transfuse. Pediatric Clinics of North America 1986;33(1):111-28. [DOI: 10.1016/s0031-3955(16)34972-0] [PMID: ] - DOI - PubMed
Stramer 2009
    1. Stramer SL, Hollinger FB, Katz LM, Kleinman S, Metzel PS, Gregory KR, et al. Emerging infectious disease agents and their potential threat to transfusion safety. Transfusion 2009;49(Suppl 2):1S-29S. [DOI: 10.1111/j.1537-2995.2009.02279.x] [PMID: ] - DOI - PubMed
Strauss 2004
    1. Strauss RG, Mock DM, Widness JA, Johnson K, Cress G, Schmidt RL. Post-transfusion 24-hour recovery and subsequent survival of allogeneic red blood cells in the bloodstream of newborn infants. Transfusion 2004;44(6):871-6. [DOI: 10.1111/j.1537-2995.2004.03393.x] [PMID: ] - DOI - PMC - PubMed
Tarnow‐Mordi 2017
    1. Tarnow-Mordi W, Morris J, Kirby A, Robledo K, Askie L, Brown R, et al, Australian Placental Transfusion Study Collaborative Group. Delayed versus immediate cord clamping in preterm infants. New England Journal of Medicine 2017;377(25):2445-5. [DOI: 10.1056/NEJMoa1711281] [PMID: ] - DOI - PubMed
Treleaven 2010
    1. Treleaven J, Gennery A, Marsh J, Norfolk D, Page L, Parker A, et al. Guidelines on the use of irradiated blood components prepared by the British Committee for Standards in Haematology blood transfusion task force. British Journal of Haematology 2010;152(1):35-51. [DOI: 10.1111/j.1365-2141.2021.08444.x] [PMID: ] - DOI - PubMed
Tschirch 2009
    1. Tschirch E, Weber B, Koehne P, Guthmann F, Gise A, Wauer RR, et al. Vascular endothelial growth factor as marker for tissue hypoxia and transfusion need in anemic infants: a prospective clinical study. Pediatrics 2009;123(2):784-90. [DOI: 10.1542/peds.2007-2304] [PMID: ] - DOI - PubMed
Vamvakas 2007
    1. Vamvakas EC, Blajchman MA. Transfusion-related immunomodulation (TRIM): an update. Blood Reviews 2007;21(6):327-48. [DOI: 10.1016/j.blre.2007.07.003] [PMID: ] - DOI - PubMed
van Hoften 2010
    1. Hoften JC, Verhagen EA, Keating P, Ter Horst HJ, Bos AF. Cerebral tissue oxygen saturation and extraction in preterm infants before and after blood transfusion. Archives of Disease in Childhood. Fetal and Neonatal Edition 2010;95(5):F352-8. [DOI: 0.1136/adc.2009.163592 Abstract] [PMID: ] - PubMed
Venancio 2007
    1. Venancio JP, Santos AM, Guinsburg R, Peres Cde A, Shinzato AR, Lora MI. Strict guideline reduces the need for RBC transfusions in premature infants. Journal of Tropical Pediatrics 2007;53(2):78-82. [DOI: 10.1093/tropej/fml062] [PMID: ] - DOI - PubMed
Wardle 2001
    1. Wardle SP, Weindling AM. Peripheral fractional oxygen extraction and other measures of tissue oxygenation to guide blood transfusions in preterm infants. Seminars in Perinatology 2001;25(2):60-4. [DOI: 10.1053/sper.2001.23200] [PMID: ] - DOI - PubMed
Wardrop 1978
    1. Wardrop CA, Holland BM, Veale KE, Jones JG, Gray OP. Nonphysiological anaemia of prematurity. Archives of Disease in Childhood 1978;53(11):855-60. [DOI: 10.1136/adc.53.11.855] [PMID: ] - DOI - PMC - PubMed
Whitehead 2018
    1. Whitehead HV, Vesoulis ZA, Maheshwari A, Rao R, Mathur AM. Anemia of prematurity and cerebral near-infrared spectroscopy: should transfusion thresholds in preterm infants be revised? Journal of Perinatology 2018;38(8):1022-9. [DOI: 10.1038/s41372-018-0120-0] [PMID: ] - DOI - PMC - PubMed
Widness 1996
    1. Widness JA, Seward VJ, Kromer IJ, Burmeister LF, Bell EF, Strauss RG. Changing patterns of red blood cell transfusion in very low birth weight infants. Journal of Pediatrics 1996;129(5):680-7. [DOI: 10.1016/s0022-3476(96)70150-6] [PMID: ] - DOI - PubMed
Zimrin 2009
    1. Zimrin AB, Hess JR. Current issues relating to the transfusion of stored red blood cells. Vox Sanguinis 2009;96(2):93-103. [DOI: 10.1111/j.1423-0410.2008.01117.x] [PMID: ] - DOI - PubMed

References to other published versions of this review

Whyte 1997
    1. Whyte R, Bifano EM. Early erythrocyte transfusion in very-low-birth-weight infants. Cochrane Database of Systematic Reviews 1997, Issue 4. Art. No: CD000512. [DOI: 10.1002/14651858.CD000512] - DOI
Whyte 2011
    1. 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 of Systematic Reviews 2011, Issue 11. Art. No: CD000512. [DOI: 10.1002/14651858.CD000512.pub2] - DOI

LinkOut - more resources