MAGPIE-2 is a prospective observational study designed to investigate the physiological mechanisms linking blood transfusion and enteral feeding practices to gut perfusion and oxygenation in very preterm infants. The study is nested within the WHEAT International randomised controlled trial, which compares two standard care approaches: withholding versus continuing milk feeds during red blood cell transfusion. While WHEAT evaluates clinical outcomes such as necrotising enterocolitis (NEC), MAGPIE-2 focuses on the underlying physiological changes that may contribute to NEC development.
NEC is a serious gastrointestinal condition affecting approximately 10% of extremely preterm infants and is associated with high mortality and long-term neurodevelopmental impairment. Previous observational studies have suggested a temporal link between blood transfusion and NEC onset, particularly when feeds are continued during transfusion. However, the mechanisms remain poorly understood.
MAGPIE-2 will use non-invasive monitoring tools-near-infrared spectroscopy (NIRS) and Doppler ultrasound-to measure cerebral and splanchnic (gut) tissue oxygenation and superior mesenteric artery (SMA) blood flow. These measurements will be used to calculate the Splanchnic-Cerebral Oxygenation Ratio (SCOR), a validated marker of gut tissue perfusion and ischaemia. A reduction in SCOR may indicate compromised gut oxygenation, potentially contributing to NEC.
The study will recruit 270 infants (135 per arm) already enrolled in the WHEAT trial. Weekly measurements will be taken until 34 weeks corrected gestational age or discharge. Peri-transfusion monitoring includes continuous NIRS from 4 hours before to 4 hours after transfusion, and additional 2-hour recordings at approximately 24 and 48 hours post-transfusion. SMA Doppler assessments will be performed weekly.
Primary outcomes include changes in SCOR post-transfusion between the two feeding strategies. Secondary outcomes include changes in cerebral and splanchnic oxygenation, SMA blood flow velocities, and the impact of severe anaemia (pre-transfusion haemoglobin ≤80 g/L) on these parameters. The study also includes an assessment of inter-operator variability in Doppler measurements.
MAGPIE-2 aims to provide mechanistic insights that could inform safer transfusion and feeding practices in neonatal care, potentially reducing the incidence of NEC in this vulnerable population.
Very preterm babies (born between 23 to <30 weeks of gestational age ) in the WHEAT International trial
Written informed consent from parents
Babies who are deemed too unstable to perform the non-invasive monitoring and the ultrasound scan measurements by the attending clinical team
Babies who have already developed Bells stage 2 NEC, had bowel surgery or congenital abdominal conditions such as congenital diaphragmatic hernia, gastroschisis and exomphalos
This study will recruit 270 very preterm infants born between 23 and 30 weeks gestational age who are already enrolled in the WHEAT International trial. These infants are receiving care in neonatal units across the UK participating in WHEAT. MAGPIE-2 will include 135 infants in each arm of the WHEAT trial (feeds withheld vs continued during transfusion). All participants must have informed parental consent for additional non-invasive monitoring. The study population represents a high-risk group for necrotising enterocolitis (NEC), and the inclusion criteria align with the WHEAT trial to ensure consistency in clinical context and intervention exposure. Exclusion criteria include infants with pre-existing NEC, congenital abdominal anomalies, or those deemed clinically unstable for monitoring.
Cohort
Prospective
Not listed
Change in Splanchnic-Cerebral Oxygenation Ratio (SCOR) post-transfusion
SCOR is calculated as the ratio of splanchnic (gut) to cerebral tissue oxygenation, measured using near-infrared spectroscopy (NIRS). A reduction in SCOR may indicate gut hypoperfusion or ischaemia. This outcome assesses the relative change in SCOR following blood transfusion in infants whose feeds were withheld versus continued.
Change in Cerebral Oxygenation (crSO2) Post-Transfusion
Measures cerebral tissue oxygenation using NIRS to assess impact of transfusion and feeding strategy.
Change in Splanchnic Oxygenation (srSO2) Post-Transfusion
Measures gut tissue oxygenation using NIRS to evaluate perfusion changes post-transfusion.
Change in SMA Peak Systolic Velocity Post-Transfusion
Assesses SMA blood flow velocity using Doppler ultrasound to evaluate gut perfusion.
Change in SMA Diastolic Velocity Post-Transfusion
Measures SMA end-diastolic velocity to assess vascular resistance and perfusion.
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Imperial College Healthcare NHS Trust
Lead sponsor
University of Leeds
Collaborator
Imperial College London
Collaborator
Nottingham University Hospitals NHS Trust
Collaborator
