Mechanisms Affecting Gut of Preterm Infants receiving blood transfusion with different feed interventions - MAGPIE 2 study

• Research question In very preterm babies (<30+0 weeks of gestational age) receiving blood transfusion in neonatal units (Population), does pausing or withholding of feeds from 4 hours before, during and 4 hours after blood transfusion (Intervention) compared to continuation of feeds (Comparator) improve blood flow and gut tissue oxygenation (Outcomes). • Background Around 7000 UK babies are born very preterm annually and need specialist care. Many die or have serious long-term health problems; preterm birth is the biggest cause of childhood death in the UK. Necrotising enterocolitis (NEC) is a serious gut condition affecting 1 in 10 of babies born before 28 weeks of gestation. Babies with NEC often require surgery; a third of them die. NEC is an increasing cause of death or disability and a top three research priority for preterm babies. NEC risk factors include prematurity, fetal growth restriction, formula feeding, sepsis, anaemia and blood transfusion. Research suggests that changes in blood flow to the gut, reducing gut tissue oxygen, weakening defence mechanisms, and making the gut wall more vulnerable to injury all play a role. Two routine interventions that affect gut blood flow and tissue oxygenation are milk feeding and blood transfusion and there is a well described link between blood transfusion and NEC. The WithHolding Enteral feeds Around Transfusion (WHEAT) Trial is an ongoing randomised trial in very preterm babies. It is comparing pausing feeds during blood transfusion with continuing feeds. Feeding during blood transfusion may lead to reduced blood flow and relative ischaemia of the gut tissue resulting in NEC, but this mechanism remains unproven. While the WHEAT trial will tell us if withholding feeds around transfusion prevents NEC, it will not tell us how NEC is caused, or how pausing or continuing milk feeds around transfusion affects gut tissue oxygen levels. The MAGPIE-2 study aims to examine these putative mechanisms within the WHEAT trial. • Aims and objectives Our primary aim is to determine if pausing or withholding of feeds from 4 hours before, during, to 4 hours after blood transfusion, compared to continuing feeds results in improved gut tissue oxygenation. Additionally, we aim to determine if pausing feeds during blood transfusion improves superior mesenteric artery (SMA) blood flow to the gut; and whether preceding grades of anaemia (affect the degree of tissue oxygenation and blood flow changes in the gut between these two groups. • Methods Multicentre, observational study nested within the ongoing WHEAT randomised controlled trial (RCT). WHEAT is an effectiveness study but will not evaluate mechanisms leading to NEC. WHEAT will recruit 2167 babies in the UK with detailed clinical and NEC data, offering a unique opportunity to embed mechanistic research into the pathogenesis of NEC and its prevention. We will non-invasively measure gut tissue oxygenation, by near infra-red spectroscopy (NIRS), and Doppler ultrasound SMA blood flow, in a subset of the WHEAT trial. • Anticipated impact and dissemination If MAGPIE-2 shows that gut tissue oxygenation changes following blood transfusion when feeds are paused, compared to when feeds are continued, this will inform international neonatal blood transfusion practice. MAGPIE-2 was co-developed with the WHEAT trial Patient/Parents Advisory group (PAG) and other PPI partners and will work with them to publicly disseminate the results.