Phenotypical profiling of gut health in very preterm infants developing necrotising enterocolitis using a multi-modal approach

In the UK around 100,000 babies are cared for in neonatal units yearly; many are preterm and have a high risk of death and long-term disability. Necrotising enterocolitis (NEC) a dreaded condition affecting the gut, can affect up to 7% of those who are born very preterm (VPT: earlier than 32 weeks of pregnancy). NEC typically affects babies 4-6 weeks after birth, leads to death of the gut wall, often requires surgery and is a leading cause of neonatal death.

Amongst those who require surgery one-third will die and a third will have significant long-term disability or complications related to gut. NEC also affects the brain: almost half NEC survivors have long-term problems like cerebral palsy or learning difficulties. NEC is one of the top three research priorities for premature babies, identified by parents, patients, doctors, nurses, and researchers.

We know that being born more preterm, small or after slow growth in pregnancy, receiving antibiotics on several occasions or formula milk feeds increase the risk of NEC, but the disease sets in very abruptly and usually unexpectedly. Therefore, recognising signs or predicting NEC a day or two earlier could be critical in reducing the adverse consequences and better outcomes.

In the neonatal units we routinely monitor heart and lung health using heart rate, blood pressure and oxygen levels in the blood continuously; this enables us to detect important condition like infection earlier. But there are no established methods to continuously monitor gut health in the neonatal units. From our previous research, we have established normative measurements of oxygen levels in the tissues of the brain and gut.

From laboratory-based studies we also know that certain bacterial and chemical changes occur in the stools (poo) of the VPT babies days before the NEC becomes apparent. We want to use these to predict NEC.

We will recruit 425 VPT babies over 3-years from two tertiary care hospitals in London. We will record detailed maternal and baby data and observations such as heart rate, oxygen levels in blood, and blood pressure every second during a baby's neonatal stay. We will also measure oxygen level in the brain and the gut and collect daily stool samples from the nappies of the babies to measure bacterial and chemical changes in the stool.

We will then combine all these complex data to identify changes that occur before a baby develops NEC. We believe that we will be able to identify changes in these measures before a baby becomes sick with NEC.

If we are able to predict NEC in advance, this will open up the possibility of treating to prevent NEC - for example with medications that prevent inflammation or antibiotics - to stop or modify NEC and save lives and improve lifelong outcomes.

We are consulting parent focus groups and the UK Bliss baby charity as we design the study. The findings of the study will be shared through healthcare and academic research websites and social media; presented in conferences and published in peer-reviewed scientific journals. We believe that this study will have dramatic short- and long-term health benefits for vulnerable babies and drive better care at national and international levels.