Award Title: Improving understanding of indications for and timing of surgery in infants with Necrotising Enterocolitis
Funder: Department of Health and Social Care

Abstract: What influences surgical decision-making in Necrotising Enterocolitis (NEC) and can routinely available data be used to accurately identify surgical NEC? Background Necrotising enterocolitis (NEC) causes severe bowel inflammation and critical illness in predominantly preterm infants with 1000 cases yearly in the UK.2 Despite intensive care treatment, 25% fail to improve requiring surgery to remove ischaemic bowel. Early identification of infants that would benefit from surgery is challenging but important since delay in surgery may contribute to poor outcomes. About 20% of NEC infants die before surgery.3 Mortality rate following surgery is 35% and, in survivors, 9% remain on parenteral nutrition at 1 year with 59% experiencing neurodevelopmental problems.4 Work I have undertaken demonstrates that a delay to undertaking surgery in NEC is associated with poor outcome.1 I hypothesise that early, accurate identification of neonates with surgical NEC will allow earlier surgical intervention and ultimately improve outcomes. Objectives WS1-Identify previously developed methods for the identification of surgical NEC WS2-Evaluate accuracy of previously reported methods for identification of surgical NEC in a multi-centre dataset WS3-Understand current surgical decision-making in NEC Methods WS1) Systematic review +/- meta-analyses -Months 1-9 Systematic review of methods that identify surgical NEC (preliminary search: 3019 results [PubMed-28/7/21]). Primary outcome will be effectiveness of a method to correctly identify surgical NEC in derivation / validation cohorts. Meta-analysis of effectiveness estimates will be undertaken if appropriate. Results will be incorporated into WS2. WS2) Diagnostic test accuracy study of methods which identify surgical NEC -Months 7-18 Methods identified in WS1 will be evaluated on our existing dataset of routinely collected data extracted from 4 neonatal units (680 infants) (including clinical, laboratory [WCC, CRP, platelets, blood gases] and vital signs [HR, BP]). Reference test is diagnosis of surgical NEC, or death before surgery with confirmed NEC. WS3) Mixed methods study of current practice -h;Months 19-33 i)Survey of all (~250) UK consultant paediatric surgeons with focussed interviews of 25 surgeons to understand current practice around surgical decision-making-h; purposive sampling of survey responses will identify a maximum diversity sub-set of surgeons for interview. Thematic analysis of transcripts will identify relevant themes related to rationale for surgical practice. ii)Prospective observational study of relationship between surgical decision-making and outcomes - to record actual practice a 9-month cohort study (50-75 infants with confirmed NEC in 10 high-volume units) will be undertaken. Semi-structured interviews will be conducted with surgeons about surgical decision-making soon after decisions were made, including babies who did and didn't have surgery. Clinical and outcome data will be obtained with linkage to the National Neonatal Research Database allowing exploration of variations in surgical decision-making and outcomes. Impact and dissemination This research will identify an optimal method to identify surgical NEC, describe current surgical decision-making and enhance our understanding of its association with outcome. Existing data suggest that accurate identification and earlier surgery has genuine potential to improve important life-long outcomes. Results will be co-produced with PPI partners and disseminated across traditional scientific and new media channels aimed at key stakeholders.

Lay Abstract: Aims of the research Necrotising enterocolitis (NEC) is a devastating disease of the bowel that causes babies to require intensive care treatment with some needing major surgery. Babies who survive NEC have a high incidence of significant long term health problems. I want to understand how surgeons currently decide which babies get surgery and to investigate whether better methods than are currently used can help surgeons identify which babies need surgery and when. Ultimately I aim to use this information to improve outcomes for these babies. Background Necrotising enterocolitis causes severe bowel inflammation resulting in babies becoming critically unwell. It mainly affects premature babies (who can be born as early as 22 weeks) in the first few weeks of life. Around 1000 babies per year in the UK develop NEC. A quarter of babies don't respond to intensive care treatment and require surgery to remove bowel which has died to prevent them from getting sicker. Sadly, about a third of the most unwell babies don't survive. Those that do are often left with significant long-term health problems. These include neurological disability and being left with inadequate bowel to feed normally meaning they require long-term feeding into the vein. NEC is a significant burden to families as well as health resources. Deciding which babies will benefit from surgery is challenging. Surgeons must weigh up the risks and benefits of performing major surgery on a tiny baby in the knowledge that surgery itself may cause harm. This uncertainty causes delays in performing surgery which may contribute to poor outcomes. Work I have undertaken demonstrates a link between later surgery and worse outcomes prompting my aim to explore whether performing surgery earlier may improve outcomes. To do this I need to be able to identify babies who need surgery accurately and earlier than we do at present and understand more about how surgeons determine timing of surgery currently. Design and method To investigate the best way to identify babies who need surgery for NEC and relate those to outcome I will:	Identify previously reported methods of identifying babies who need surgery for NEC. This will be done through a detailed review of the existing research in this field. 	I will then use an existing large database of babies with NEC from 4 neonatal units (680 babies) to test the how good these methods are.I will also undertake work with surgeons to understand how they currently make decisions about surgery in babies with NEC and explore the impact of how decisions were made on clinical outcomes. Understanding how surgeons make decisions and the impact on outcomes is important for implementation of the findings of my research. Patient and public involvementNECUK (the UK family support charity for NEC), along with a parent group, have been fully involved in the conception, development and design of my proposal and strongly agree on its importance. I will meet with them regularly throughout the study to ensure that my work is acceptable and relevant to parents and patients. Representatives from BLISS, the preterm baby charity, will also attend these meetings. Dissemination Results will be disseminated at multidisciplinary meetings, peer-reviewed publication and via charity partners including on the NECUK and BLISS websites. I will give presentations at charity partner meetings alongside traditional scientific presentation and peer-reviewed journal publication, specifically targeting surgeons and neonatologists. Ultimately my findings are likely to inform future research exploring the role of better surgical decision-making in improving outcomes.

Research Activity Codes: 6.4 SURGERY;7.3 MANAGEMENT AND DECISION MAKING
Health Categories: ORAL AND GASTROINTESTINAL;REPRODUCTIVE HEALTH AND CHILDBIRTH