Mechanisms Affecting the Gut of Preterm Infants Receiving Blood Transfusion With Different Enteral Feed Interventions
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 270
- 试验地点
- 1
- 主要终点
- Change in Splanchnic-Cerebral Oxygenation Ratio (SCOR) post-transfusion
研究概览
简要总结
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.
详细描述
MAGPIE-2 is a mechanistic observational study nested within the WHEAT International randomised controlled trial, which compares two standard neonatal care practices: withholding versus continuing enteral feeds during red blood cell transfusion in very preterm infants. While WHEAT evaluates clinical outcomes such as necrotising enterocolitis (NEC), MAGPIE-2 is designed to explore the physiological mechanisms that may underlie the development of NEC in this context.
NEC is a leading cause of morbidity and mortality in extremely preterm infants, with onset often temporally associated with blood transfusion. The pathophysiology is thought to involve gut ischaemia, inflammation, and impaired perfusion, but the precise mechanisms remain unclear. MAGPIE-2 addresses this gap by applying non-invasive monitoring techniques to assess gut and brain oxygenation and perfusion in infants undergoing transfusion.
The study will recruit 270 infants (135 per arm) already enrolled in the WHEAT trial. These infants will undergo weekly and peri-transfusion assessments using near-infrared spectroscopy (NIRS) and Doppler ultrasound. NIRS will measure cerebral and splanchnic (gut) tissue oxygenation, allowing calculation of the Splanchnic-Cerebral Oxygenation Ratio (SCOR), a validated marker of gut perfusion. Doppler ultrasound will assess blood flow in the superior mesenteric artery (SMA), which supplies the gut regions most vulnerable to NEC.
Measurements will be taken:
Weekly (2-hour NIRS and SMA Doppler) until 34 weeks corrected gestational age or discharge Peri-transfusion: continuous NIRS from 4 hours before to 4 hours after transfusion (12-hour window), and 2-hour recordings at approximately 24 and 48 hours post-transfusion The primary outcome is the relative change in SCOR post-transfusion between the two feeding strategies. Secondary outcomes include changes in cerebral and splanchnic oxygenation, SMA peak systolic and diastolic velocities, and the relationship between pre-transfusion haemoglobin levels and perfusion metrics. The study also includes an assessment of inter-operator variability in Doppler measurements and a mediation analysis to explore causal pathways.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 23 Weeks 至 30 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Very preterm babies (born between 23 to <30 weeks of gestational age ) in the WHEAT International trial
- •Written informed consent from parents
排除标准
- •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
结局指标
主要结局
Change in Splanchnic-Cerebral Oxygenation Ratio (SCOR) post-transfusion
时间窗: Continuous from 4 hours pre-transfusion to 4 hours post-transfusion (12-hour window) for each transfusion received with WHEAT Trial intervention; plus additional weekly 2-hour recordings until 34 weeks corrected age or neonatal discharge.
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.
次要结局
- Change in Cerebral Oxygenation (crSO2) Post-Transfusion(Continuous from 4 hours pre-transfusion to 4 hours post-transfusion (12-hour window) for each transfusion received with WHEAT Trial intervention; plus additional weekly 2-hour recordings until 34 weeks corrected age or neonatal discharge.)
- Change in Splanchnic Oxygenation (srSO2) Post-Transfusion(Continuous from 4 hours pre-transfusion to 4 hours post-transfusion (12-hour window) for each transfusion received with WHEAT Trial intervention; plus additional weekly 2-hour recordings until 34 weeks corrected age or neonatal discharge.)
- Change in SMA Peak Systolic Velocity Post-Transfusion(Weekly Doppler ultrasound assessments until 34 weeks corrected age or neonatal discharge.)
- Change in SMA Diastolic Velocity Post-Transfusion(Weekly Doppler ultrasound assessments until 34 weeks corrected age or neonatal discharge.)
- Relationship Between Pre-Transfusion Haemoglobin and SCOR, crSO2, srSO2(Continuous from 4 hours pre-transfusion to 4 hours post-transfusion (12-hour window) for each transfusion received with WHEAT Trial intervention; plus additional NIRS weekly 2-hour recordings until 34 weeks corrected age or neonatal discharge.)
- Relationship Between Haemoglobin and SMA Doppler Parameters(Weekly Doppler ultrasound assessments until 34 weeks corrected age or neonatal discharge.)
- Inter-Operator Variability in SMA Doppler Measurements(One-time assessment during weekly Doppler ultrasound in a subset of 35 infants across 7 centres.)