The safety and efficacy of red cell transfusions in neonates: a systematic review of randomized controlled trials

Abstract

SummaryPremature neonates commonly receive red blood cell (RBC) transfusions. This study systematically identified and appraised randomized controlled trials (RCTs) where the intervention was 'transfusion of red blood cells' from searches of multiple databases. Primary review outcomes were mortality, neurodevelopmental and respiratory endpoints. Two reviewers extracted data and assigned overall quality. Twenty-seven RCTs were identified and grouped into four predefined categories: trials comparing RBC transfusion versus no transfusion/placebo (n = 3); different thresholds for transfusion (n = 6); differing doses or administration schedule (n = 4), or different types or products of RBC (n = 14). In the threshold group of trials, enrolling 679 neonates, no significant differences in mortality (relative risk 1·22, 95% confidence interval 0·84-1·75) or chronic lung disease were found. Only two trials assessed neurodevelopment outcomes, both within the threshold group, but with differing results. The largest subgroup of RCTs by number evaluated different media for storage of red cells (n = 7), enrolling 221 neonates. The methodological quality of many RCTs was poor. The design of future RCTs can be informed by the lessons from this review. Many trials failed to report on outcomes that would be considered of primary importance to clinicians. Consistent reporting of adverse events is required, and endpoints need to include neurodevelopmental outcomes.

Adverse effects of small-volume red blood cell transfusions in the neonatal population

“…The limited reporting of adverse effects in neonatal transfusion trials, the quality of the studies identified as well as the risk of bias inherent in studies in this area are likely to be significant limitations to our review [9]. However, the identification and collation of all current known adverse effects due to, or associated with, RBC transfusion in neonates are key steps in improving the reporting of these important events.…”

“…There are several recognised potential adverse associations related to RBC transfusions unique to neonates [9]. Associations between receipt of RBC transfusions and development of necrotising enterocolitis [10], intraventricular haemorrhage [11,12] retinopathy of prematurity [13], chronic lung disease [14] as well as mortality [15,16] have all been described.…”

How we decide when a neonate needs a transfusion

“…RCTs comparing red cell transfusion with no transfusion (or a placebo) would therefore be expected to provide the highest levels of evidence for the absolute need and benefit of red cell transfusion in any sub‐group of neonates. In a recent systematic review, only three RCTs were identified that compared outcomes between neonates who received a red cell transfusion and those who did not, or those who received 5% albumin (Venkatesh et al , ). All three trials were single centre RCTs with a small sample size and while they reported a significant decrease in the number of transfusions, they did not report on clinically relevant neonatal outcomes (Blank et al , ; Bifano, ; Meyer et al , ).…”

“…See text for details of sources informing these thresholds, including BCSH guidelines (Gibson et al , ; Treleaven et al , ), Handbook of Transfusion Medicine (McClelland, ), and systematic reviews (Whyte & Kirpalani, ; Venkatesh et al , )…”

Anaemia in the Premature Infant and Red Blood Cell Transfusion: New Approaches to an Age-Old Problem

“…Several uniquely neonatal adverse associations have been demonstrated in epidemiological studies [29]. These include death [30], necrotising enterocolitis (NEC) [26,31], intraventricular haemorrhage (IVH) [32,33], retinopathy of prematurity (ROP) [34] and chronic lung disease (CLD) [35].…”