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The safety and efficacy of red blood cell transfusions in neonates: A systematic review

Presented at the Neonatal Society 2012 Summer Meeting (programme).

Venkatesh V, Khan R, Hopewell S, Doree C, Curley A, Stanworth S

Cambridge University Hospital NHS Foundation Trust, Cambridge, UK

Background: Red Blood Cell (RBC) transfusions are an expensive, scarce and risk associated resource. Premature and very low birth weight infants account for nearly three quarters of neonatal RBC transfusions. There is increasing concern that RBC transfusions may severely affect clinical outcomes (1). The Serious Hazards of Transfusion (SHOT) UK Haemovigilance Scheme reports that infants account for a greater number proportionately of all adverse events following transfusion compared with adults (2). We undertook a systematic review of the randomised controlled trial (RCT) to analyse the evidence for the safety and efficacy of red cell transfusion in neonates from an original wider systematic review that evaluated the clinical effects of red blood cell transfusions at all ages (3).

Methods: We identified RCTs where the intervention was ‘transfusion of red blood cells’ from searches of multiple databases including the Cochrane Central register of controlled trials, Medline (1950-2010), NBS SRI, IEMR, IMSEAR, UKCRN, ICTRP, ReFeR and mRCT. Two reviewers independently assessed each study against predetermined inclusion/ exclusion criteria and independently extracted data regarding participant and intervention characteristics and assessment techniques, outcomes and assigned overall quality and strength of evidence ratings based on predetermined criteria. The primary review outcomes were mortality, chronic lung disease and neurodevelopment endpoints.

Results: We identified 27 RCTs; three studies compared RBC transfusion versus no transfusion/ placebo; four compared RBC transfusions of differing doses or administration schedule; 14 compared differing types or products of transfusion and 6 RCTs were identified comparing different threshold triggers of transfusion. In the threshold trials no significant differences in mortality and or chronic lung disease were observed although a trend favouring the liberal arm was noted. Only one RCT assessed neurodevelopment and found no significant difference. In the storage trials only one of five trials evaluated the clinically relevant outcomes of mortality and NEC while all trials reported a significant reduction in the number of donor exposures. Overall the methodological quality of the RCTs was poor.

Figure 1: Forest plot of mortality in neonates who received RBC transfusions of differing thresholds.

Conclusion: There are a large number of reported trials of red cell transfusion in this population. Despite this areas of concern included the nature of the intervention, outcomes measures, sample size and the quality of the trials. Many trials failed to report on clinical outcomes including mortality, chronic lung disease or other major neonatal co-morbidities which are considered clinically relevant.

Corresponding author:

1. Karam O, Tucci M, Bateman ST et al. Association between length of storage of red blood cell units and outcome of critically ill children: A prospective observational study. Crit Care. 2010;14:R57
2.Transfusion SHOT. Serious hazards of transfusion annual report 2008. uploads/2010/2003/Summary-2008.pdf
3. Wilkinson KL, Brunskill SJ, Dorée C et al. The clinical effects of red blood cell transfusions: an overview of the randomized controlled trials evidence base. Transfus Med Rev. 2011 Apr;25(2):145-155.e2.

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