Mechanisms Affecting the Gut of Preterm Infants in Enteral feeding trials (MAGPIE)

Premature birth is increasing, associated with high rates of death, and worse physical & mental outcomes in survivors Basic research in babies is difficult especially where blood samples are needed, and raises important ethical concerns Over the last 20 years, respiratory support has improved meaning more babies now survive Now, the most common causes of death after the first week are due to gut complications or infections Necrotising enterocolitis (NEC) is a serious gut disease occurring in premature babies NEC affects 1 in 10 babies born more than 8 weeks early; 1 in 3 of them require major surgery or die Infections affect 1 in 5 premature babies, may cause death, and doubles the risk of long term problems such as cerebral palsy Our group is already undertaking two NIHR funded studies (SIFT & ELFIN) to examine whether the way we feed premature babies (how quickly, and with what food supplements) affects rates of infection, NEC and brain outcomes: 1) SIFT - Speed of Increasing milk Feeds Trial 2) ELFIN - Enteral Lactoferrin in Neonates Premature babies often take several days to tolerate milk feeds: SIFT compares a slightly faster to a slower rate of increases in the amount of milk, and will see if this affects rates of infections/NEC or brain outcome at 2 years age Lactoferrin, a protein found in human & other animal milk, has anti-infective properties and is present in high levels in breast milk Premature babies do not get much lactoferrin as they only get small amounts of milk, but we can add extra lactoferrin into the baby's milk feeds The ELFIN study will see whether extra lactoferrin given with milk feeds reduces the number of babies who develop infections or NEC The SIFT/ELFIN studies are the largest feeding studies ever, & will recruit >4500 premature babies from 30 hospitals They will tell us whether these interventions affect NEC or sepsis, but not how they are working, nor will they help us understand what to do next if SIFT/ELFIN do not show clear effects The interventions studied may improve outcomes by affecting gut bacteria or other effects on the baby's metabolism The proposed MAGPIE study (Mechanisms Affecting the Gut of Preterm Infants in Enteral feeding trials) will explore how interventions work in the gut The studies divide babies up (to receive specific treatments) in a random manner so that the treatments they receive will be evenly spread between the different study groups MAGPIE will improve understanding of how the study interventions work in the gut, and the mechanisms that lead to gut disease or sepsis Babies who are part of ELFIN can join MAGPIE We will collect stool & urine samples, and analyse the patterns of germs & chemicals This will tell us how the germs & chemicals relate to each other, how they are affected by the study (milk feeds or lactoferrin) or other interventions (eg antibiotics) If babies require an operation and have some gut removed we will examine any 'left over' gut tissue to see how their gut cells were affected Because we are only using left-over samples there is no risk or discomfort to the babies Some babies who were in the SIFT studied have already had stool and urine samples collected The MAGPIE study is a unique opportunity to gain vital scientific knowledge about two important diseases in premature infants with high rates of death & serious morbidity Our findings may help make the diagnosis earlier, and suggest what future treatments may optimise gut health or prevent serious disease in vulnerable infants