Red Blood Cell Transfusion and Clinical Outcomes in Extremely Low Birth Weight Preterm Infants

Yu-Cheng Wang, Oi-Wa Chan, Ming-Chou Chiang, Peng-Hong Yang, Shih-Ming Chu, Jen-Fu Hsu, Ren-Huei Fu, Reyin Lien

​

Paediaric and Neonatology (2016)

Dr Wan Noor Falah Wan Yahaya

Mmed Transfusion

About This Study

• Done by group of researcher Department of Paediatric,Tan Yen General Hospital and Division of Neonatology, Department of Paediatrics, Chang-Gun Memorial Hospital

​

• From Jan 1,2009 until Dec,2010

​

About This Study

Outline

INTRODUCTION

INTRODUCTION

Born Too Soon: The Global Action Report On Preterm Birth published by the World Health Organisation and partners in 2015 reports that 15 million babies (1 in 10) are born premature every year and more than one million babies die annually from preterm birth complications.

“Annually, an average of 12.3 per cent of the 500,000 births recorded in Malaysia are premature, premature birth is one of the main causes of infant mortality in the world,”says the health ministry’s director of medical development division, Datuk Dr Azman Abu Bakar ( Malay mail, 2014)

“Premature babies require specialised care compared to their full-term peers,” says Dr See Kwee Ching, president of the Perinatal Society of Malaysia.

(NST, 2012)��

INTRODUCTION

(Report of the Malaysian National Neonatal Registry 2010)

Introduction

INTRODUCTION

Introduction

​

Major complications of preterm birth

Death

RDS

NEC

ROP

Infection

Jaundice

Hypoglycaemia

Hypothermia

BPD

IVH

• Studies had been done to demonstrate each complications and its associated factors in order to improve the survival of preterm babies.
• ??? association of red blood cell transfusions with morbidities and mortality in preterm infants.

Guideline for red blood cell transfusion in neonatal is very controversial and vary widely amongst practitioner and institutions

The majority of extremely preterm neonates (less than 28 weeks gestation) receive at least one red cell transfusion (Guidelines on transfusion for fetuses, neonates and older children, 2016)

Challenge in neonatal and infant transfusion

• Immature haematopoeitic system
• Limited ability tolerate thermal / metabolic alteration from transfusion

However, in the past two decades, there have been increasing concerns of possible deleterious effects from RBC transfusion in patients under critical care (Hebert et al., 1999).

Studies on neonatal populations have suggested associations between RBC transfusion and increased risk of specific complications such as chronic lung disease (CLD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), and extension of intraventricular hemorrhage (IVH) ( Wang Y-C et al.,2016).

In neonatal intensive care units (NICUs) most transfusions are given to preterm neonates mostly less than 32 weeks gestational age , some of them will require transfusion beyond 28 days of life (National Comparative Audit, 2010)

Objective

​

To examine association between RBC transfusion and in hospital mortality, short term morbidities and late neurodevelopmental outcome in ELBW preterm infant

Methodology

Study Design

​

• Retrospective cohort study by medical record

Study Location

​

• NICU of Chang Gung Memorial Hospital in Lin Kou, Taiwan

​

Study Duration

​

• January 2009 to December 2010

Study criteria

INCLUSION

​

• Birth weight < 1000 g (ELBW)

​

• Admission between 24 hours of life

​

EXCLUSION

​

• Chromosomal anomalies or major congenital structural abnormalities
• Died within 7 days of life

Tranfusion guideline

• Asymptomatic with HCT < 21% and no compensatory reticulocytosis

​

• Symptomatic with oxygen dependency, ventilator dependency, poor weight gain despite adequate nutritional provision, and a HCT< 31%

​

• HCT < 36% but oxygen requirement is > 35% or needs ventilator/ assisted breathing

​

• Phlebotomy blood loss reaches 15% of patient’s total blood volume in the 1st week of life.

​

Transfusion

• Type specific , Rh compatible, leucocyte poor RBC
• 10-15ml/kg of BW over 2-3 hours

​

Number of PC transfusion within 7 days, 30 days and 60 days recorded

Outcomes

PRIMARY

• In hospital mortality
• NEC
• ROP
• BPD
• Late onset sepsis

SECONDARY

• Severe neurodevelopmental impairment at 24 months CA assessed by Bayley Scales of Infant Development, 2^nd Edition

Study definition

ROP

• Performed by ophtalmologists
• classified according to the International Classification of Retinopathy of Prematurity

IVH

• presence of intracranial bleeding in any region of the brain.
• Its stages will be assessed by Papile Classification

NEC

• diagnosis based on systemic and radiographic signs
• severity will be assessed by Bell’s Criteria

BPD

• based on NICHD/ NHLBI/ ORD BPD workshop summary
• Need oxygen and PPV at 36weeks postmenstrual age

Late-onset sepsis

• Culture-proven sepsis occuring 7 days after birth

Statistical Analysis

Results

Results

BPD : 71 % (70/98)

ROP : 34 % (33/90)

NEC : 3 % (3/98)

Sepsis : 45 % (44/98)

​

4 Respi failure

2 NEC

3 sepsis

2 IVH

1 renal failure

​

Results

• Demographic data and RBC transfusion in survivor infant

​

• Association of RBC transfusion during specific period and neonatal death/morbidities

​

• Adjusted linear regression coefficients for frequency RBC transfusion and Bayley scores at 18-24months CA

1

2

3

Result

Result

Result

DISCUSSION

Strength

• It was performed at a single institution with one set of policies and physicians running the blood transfusion service.

​

.

Discussion

• RBC transfusion in ELBW infants associated with increased risk of neonatal death and risk of ROP.
• However, it has favorable effect on the late cognitive development assessed by MDI score assesssed at 18-24 months of CA.

Discussion - Mortality

• Same as study by dos Santos et. al showing that VLBW infants who received transfusion within 28 days OL had 50 % risk of in-hospital mortality compared to those who did not.

Discussion - ROP

• Correlation between frequency of RBC transfusion within 30 days OL and development of ROP.
• Agreement with Dani et. al
• Possible mechanism is due to increased oxidative injury.

Discussion - NEC

• Mally et al described subset of premature infants who developed NEC after 48 hours following transfusion.
• Wallestein et. al refuted the correlation.
• In this study, it did not reach the statistically significant.

Discussion - IVH

• There is correlation however unable to delineate whether transfusion was the result or effect of severe IVH because majority of IVH occur during the first 7 days OL.

Discussion - BPD

• Chen et al reported 29 times higher risk of developing CLD in VLBW infants who received RBC transfusion >30 ml over the first month OL.
• In this study, infants who develop BPD received more RBC transfusion than no/mild BPD, however did not reach statistically significance.

Discussion – Cognitive

• Association between 7 days postnatal age with higher MDI score, indicating favorable cognitive outcome at 18 months and 24 months of CA.
• Same as PINTOS study.
• Postulate that it could be due to neuronal salvage through avoidance of CNS hypoxia.
• However, some study show no effect or favors the restrictive group.

​

Limitation

• Most of the studies show detrimental effect of RBC transfusion however unable to provide any cellular or molecular evidence of causality due to it is a retrospective study.
• Factors associated with the need of RBC transfusion could overlap the contributing factors towards mortality and morbidities.
• Lack of a well validated scoring system for disease severity to be applied.

​

​

​

Conclusion

• Anemia holds a significant threat to ELBW infants.
• Detrimental impacts could be due to RBC transfusion.
• Decision to transfused should be made in tremendous caution.

​

Red Blood Cell Transfusion And Clinical Outcomes in Extremely Premature Infant In HUSM

Duration : 1 June 2015- 30 May 2017

n = 97

GUIDELINES

Guidelines

(Howarth et al., 2018)

Guidelines

Guidelines on transfusion for fetuses, neonates and older

Children, 2016

Guidelines

(Howarth et al., 2018)

Conclusion

​

• Lots of controversy in neonatal transfusion
• More studies are needed
• Evidence needs assessment
• Expert based opinion

​