SIGNEC2018_2 | Special Interest Group in Necrotizing Enterocolitis

Meeting of the Special Interest Group in Necrotizing Enterocolitis, London 2018

Day Two – Clinical research and improvements in practice

Dr Gopi Menon

Joanne Ferguson

Dr Chris Stewart

Prof Andy Ewer

Our NEC journey

Marie Spruce

Mother, Nurse & Expert by experience

NEC UK Charity

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Marie Spruce is a paediatric critical care nurse and team member of NEC UK, which is a charity dedicated to supporting families affected by NEC, improving family centred care and supporting innovative research. She presented on her journey with her son Freddie who developed severe NEC resulting in short bowel syndrome, intestinal failure and home PN. Freddie spent 8 months in hospital and had multiple surgeries before being discharged home on PN. He is now 2 and a half years old with developmental delay and his future is uncertain. She discussed the difficulties she faced whilst in hospital and how professionals could better support families with long term admissions. She highlighted the need for donor milk and research, particularly how professionals could help increase participation in both, and looked at quality of life discussions and the importance of revisiting these conversations when NEC is a condition which has so many short and long term implications. She looked at working with families and involving them in care, particularly acknowledging parental concerns, and how early discharge planning benefits everyone practically, financially and emotionally.

Marie gave an insight into life with a child on home PN to help raise awareness of the difficulties faced by survivors and their families. Finally, she looked at her involvement in NEC UK – what the charity has achieved in the last year, its on-going commitments and future plans. For more information, please visit their website.

Our NEC journey

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Intestinal Rehabilitation & Intestinal Transplantation

Dr.Girish Gupte

Consultant Paediatric Hepatologist

Birmingham Children’s Hospital NHS Foundation Trust

Contact information

Loss of small intestine in NEC can lead to short bowel syndrome and chronic intestinal failure. Intestinal rehabilitation aims to wean a child off PN, which can take years to achieve and sometimes requires intestinal transplantation. Dr Girish Gupte described the roles of intestinal rehabilitation and transplantation in the treatment of NEC and their implementation in practice. He presented data on national and international outcomes in this area. He highlighted the importance of early referral to the transplant team; children with intestinal failure benefit more from early intervention and management.

Dr Gupte enlightened the audience with a description of local regional practice in Birmingham and the Midlands and once again encouraged clinicians to have earlier discussions with the transplant team. Earlier referral and innovative surgical strategies have resulted in improved long-term survival of children referred for intestinal transplantation.

Improving the long term cognitive function of babies with NEC: from animal models to potential therapies

David J. Hackam, MD, PhD, FACS

Garrett Professor & Chief of Pediatric Surgery

Professor of Surgery, Pediatrics and Cell Biology

Johns Hopkins University School of Medicine

Pediatric Surgeon-in-Chief and Co-Director

Johns Hopkins Children’s Center

The Charlotte R. Bloomberg Children’s Center

The Hackam Lab

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Dr David Hackam reminded the audience that one of the most important long-term complications observed in children who survive NEC early in life is the development of severe neurological impairment. Remarkably, the pathways leading to NEC-associated neurological impairment remain unknown, thus limiting the development of prevention strategies. The Hackam laboratory has shown in prior studies that NEC development requires the expression of the lipopolysaccharide receptor toll-like receptor 4 (TLR4) on the intestinal epithelium, activation of which by bacteria in the newborn gut leads to mucosal inflammation. In seeking to understand the development of NEC-associated neurological impairment, Dr Hackam’s team has shown that TLR4 signalling in the intestine leads to a dramatic release of the ‘danger molecule’ HMGB1, leading to the activation of microglial cells in the brain, reduced myelination and cognitive impairment. They have also identified a gut-brain signalling axis in the premature host in which intestinal TLR4 signalling in NEC leads to intestinal epithelial HMGB1 release, leading to activation of microglia and neurological dysfunction. Strikingly, Dr Hackam further demonstrated that an orally administered dendrimer-based nanotherapeutic approach to target activated microglia can prevent NEC-associated neurological dysfunction in neonatal mice. These findings reveal the molecular pathways leading to the development of NEC-associated brain injury, and also provide a justification for early removal of diseased intestine in NEC in order to prevent ongoing brain injury. Dr Hackam provided a rationale for the further development of targeted therapies that protect the developing brain, which may offer new hope for those who develop NEC in early childhood.

Quality Improvement to reduce NEC

Dr. Gopi Menon MD FRCPCH

Consultant Neonatologist

Royal Infirmary of Edinburgh

Honorary Senior Lecturer

University of Edinburgh

President

British Association of Perinatal Medicine

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Dr Gopi Menon described how NEC is one of the most important unsolved neonatal morbidities. There is considerable variation in incidence and associated mortality. Quality improvement is generally not amenable to off-the-shelf solutions and needs to be tailored to suit local circumstances; Dr Menon illustrated this with examples of what has been done in his unit in Edinburgh. Quality improvement is best progressed by:

benchmarking with similar units
identifying potentially better practices from the literature and from colleagues
developing a driver diagram identifying the systems and processes involved and forces influencing these
forming a multi-professional quality improvement group including parent representation
giving attention to focusing effort where it is most needed
working on wide staff engagement
understanding that it is best done as an iterative process using small tests of change, but that it is never complete.

Quality Improvement to reduce NEC

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Novel treatment approaches to necrotizing enterocolitis: hope on the horizon!

Misty Good, MD

Assistant Professor of Pediatrics

Washington University School of Medicine

Department of Pediatrics

Division of Newborn Medicine

St. Louis Children’s Hospital, Missouri

The Good Lab
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Dr Misty Good’s laboratory focuses on the signalling pathways involved in the mucosal immune response during NEC and how these responses can be modified or prevented through dietary modifications or targeted intestinal epithelial therapies. Utilising a humanised neonatal mouse model of intestinal injury, Dr Good’s team has discovered an immunomodulatory approach to preventing experimental NEC and is determining the mechanisms involved in this protection. Dr Good is currently working with the USA Food and Drug Administration agency on a future clinical trial with this therapeutic strategy for NEC in premature infants. Furthermore, she reviewed several key research techniques performed in her laboratory including human and mouse intestinal epithelial and stem cell culture, as well as the development of the first ‘NEC-on-a-chip’ microfluidic model system. Taken together, these novel approaches to new experimental model systems of NEC along with a promising drug discovery, offer families and clinicians hope on the horizon for the prevention and treatment of this devastating disease.

NEC Day, 17th May

Joanne Ferguson

Parent Representative & Website Editor, SIGNEC

Adviser, The NEC Society

Follow @jgillferguson

Joanne Ferguson described how SIGNEC worked with partners at the NEC Society, the PGG Institute in Brazil and NEC UK to make 17 May 2018 the first day ever dedicated to this devastating disease. Parents and professionals around the world joined together to raise awareness of NEC, and as it was agreed that there should be more emphasis on clinicians and researchers in future, delegates were asked to contribute ideas at a unit and global level to mark the occasion in 2019. These included ways to build on relationships with milk banks as World Breastmilk Donation Day takes place on 19 May.

NEC Day, 17th May

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Role of Ultrasound in the diagnosis of NEC

Caron Parsons, MB ChB PhD FRCR

Consultant Radiologist & Clinical Lecturer

Warwick Medical School, Health Sciences

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Necrotising enterocolitis (NEC) is the most common and serious acquired gastrointestinal disorder of the premature infant. Currently standard imaging for diagnosis and follow-up of NEC is the abdominal x-ray but early signs of NEC are neither sensitive nor specific. Ultrasound (US) should be considered as an adjunct to the abdominal x-ray, and has the advantage of allowing real time direct visualization, has the potential to appropriately stage NEC, involves no radiation, is a bedside study and provides prognostic information. Real time direct visualisation of neonatal bowel allows evaluation of bowel wall thickening/ thinning, echogenicity[2], perfusion and peristalsis. Identifying free fluid and focal collections has a significant impact on diagnostic certainty. US is more sensitive for the detection of pneumatosis, portal venous gas, free gas, fluid and the quality of fluid. Distinguishing NEC from other acquired neonatal intestinal diseases (ANIDs) such as spontaneous intestinal perforation and septic ileus is often difficult, as there can be an overlap of signs, however particular attention should aim to identify decreased Doppler signal in mesenteric vessels and bowel wall, echogenic free fluid and bowel wall thinning. Consistent US settings and technique should be maintained to allow recognition of both normal and pathological neonatal bowel. US is widely available and easy to perform following training, and needs to be encouraged in the context of a multi-disciplinary approach.

Role of Ultrasound in the diagnosis of NEC

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Infant microbiome in health and disease: current understanding and future direction

Dr Christopher J Stewart, PhD

Faculty Fellow

Institute of Cellular Medicine

Newcastle University

Contact & Research information Follow @CJStewart7

Dr Stewart provided an overview of how the gut microbiome develops in term and preterm infants. In the first part of his talk, Dr Stewart talked about his recent work on the TEDDY cohort; a study of over 12,000 stool samples from nearly 1000 infants that underwent microbiome sequencing. The results showed that diet (receipt of breast milk or not) is the major factor associated with the bacterial community in infants in early life. Specifically, breastfeeding increased the relative abundance of Bifidobacterium in the gut. In the second part of his talk, Dr Stewart summarized his published and ongoing research on the preterm gut microbiome in NEC and sepsis. In comparison to health controls, preterm infants who go on to develop NEC or sepsis have reduced bacterial diversity, lower relative abundance of Bifidobacterium, and a less stable development of the microbiome over the initial weeks of life. Dr Stewart’s Lab is now building on this work to investigate the underlying disease mechanisms and determine if microbial therapy (e.g., probiotics) represent a tangible option for reducing the incidence of NEC and sepsis in preterm infants.