Title: Medium-chain triglyceride supplementation and the impact on growth, clinical outcomes and fat absorption in children with biliary atresia
Funder: Health Education England

Abstract: BackgroundBiliary atresia (BA) is a devastating disease requiring intensive nutrition support, however the evidence for dietetic management is limited. Infants with BA have congenital biliary obstruction and require kasai portoenterostomy surgery to restore bile flow. Despite this, BA progresses to liver transplant in 50% by age two. Impaired fat absorption and therefore severe growth failure are common features, necessitating dietetic input. Dietetic management involves supplementation with medium-chain triglyceride (MCT) fat, however there is no consensus on how much to give. MCTs are given as they do not require bile for their digestion, unlike regular fat (long-chain triglycerides, LCT). The theory follows that MCT supplementation increases fat absorption to improve growth, nutritional status and overall outcome, although limited research has investigated this. MCT supplementation involves providing anywhere from 30% to 75% of the total fat as MCT, however, there is no evidenced-based consensus on the ideal concentration.Research questionHow does MCT concentration impact on growth, clinical outcomes and fat absorption in children with BA?The research question will be addressed through three work packages (WP): a scoping review, retrospective medical notes review and feasibility randomised controlled trial (RCT). The overall project will inform the development of a future phase-III RCT to test how different concentrations of MCT supplementation impact on growth in infants with BA.Aims To undertake a scoping review on how MCT concentration impacts on fat absorption, growth, nutritional status and clinical outcomes in children with cholestatic liver disease. (WP1) To undertake a retrospective medical records review to investigate the association between MCT concentration with growth and clinical outcomes in BA. (WP2) To carry out a feasibility RCT to determine the characteristics of an acceptable and achievable study protocol for a future RCT investigating the impact of different concentrations of MCT on growth in infants with BA. (WP3)MethodsThe scoping review (WP1) will critically evaluate the evidence and knowledge gaps regarding how MCT supplementation and its concentration (none, low, medium, high) impacts on factors including fat absorption, growth, nutritional status and clinical outcomes (morbidity, mortality, transplant). The retrospective review (WP2) will examine the association between MCT concentration with growth and clinical outcomes in 200 children in the two years post kasai portoenterostomy. The feasibility RCT (WP3) will include 30 infants given low or high MCT feeds for six weeks. Feasibility parameters will include recruitment, retention, fidelity, study procedures and acceptability to participants (questionnaire, interview) and health care professionals (focus group). Growth, feed intake and feed tolerance will be recorded. TimelinesThe protocol and ethical review for WP2 and WP3 will be prepared and submitted whilst WP1 is being undertaken. WP2 and WP3 will then be performed concurrently.Impact and disseminationResearch on MCT supplementation is urgently required and has the potential to benefit children and their caregivers but also society given the high costs of morbidity to the National Health Service. The findings will be published in peer-reviewed scientific journals, presented at conference and shared with help from the Children's Liver Disease Foundation.

Lay abstract: Biliary atresia (BA) in infants is a rare liver disease requiring nutrition support but the evidence for how this is best done is lacking. In BA, bile ducts develop abnormally or become blocked, so bile does not flow to the intestines. The blockage damages the liver such that half of patients may require a liver transplant by age two. Another consequence of BA is poor growth due to fats not being absorbed properly. Nutrition management involves supplementation with a fat called medium-chain triglycerides (MCT). Unlike regular fat, MCTs are absorbed without the need for bile. MCTs are incorporated into specialist feeds or can be added using MCT oil (made from coconut oil). The aim of MCT supplementation is to absorb more fat resulting in improved growth, improved nutritional status and improved overall outcome.What is the problem? MCTs are used widely in the NHS but there is no consensus on how much to give. Infants are given anywhere from 30% to 75% of their total fat intake as MCT with the remainder being regular fat. Has research been done?Limited research has focused on how different MCT concentrations (low, medium, high, none) affect growth and fat absorption.What is the research question?How do different MCT concentrations impact on growth, clinical outcomes and fat absorption in infants with BA? What is our aim? Our aim is to carry out a future randomised controlled trial (RCT) comparing growth in infants receiving different concentrations of MCT. To prepare for this RCT we first need to carry out three studies. They will help to answer the research question and test whether such a trial would be feasible and acceptable. The three studies consist of:1. Scoping reviewWe will summarise what is known and make clear what is not known about how MCT concentration affects fat absorption, growth and clinical outcomes.2. Retrospective reviewWe will review the medical records of 200 children with BA. The aim will be to see whether the MCT concentration given predicts growth and clinical outcomes in the first two years after diagnosis.3. Feasibility RCTThirty infants with BA will be given low (30%) or high (70%) MCT feeds for six weeks. Safflower oil (regular fat) or refined coconut oil (MCTs) will be added to the usual MCT feed to make up the right amounts. The low MCT group will have 30% of the fat as MCT and the high MCT group will have 70% of the fat as MCT. Information on weight, feed intake and tolerance will be recorded. Caregivers will continue to be supported with any growth or feeding issues by their usual dietitian. Caregivers will be asked about their experiences of being in the study through a short questionnaire and interview. Health care professionals will be asked about the study's acceptability in a focus group. How will patients benefit?Infants with BA are receiving nutrition care based on limited, outdated evidence. A better understanding of MCT supplementation could improve growth and nutritional status of infants with BA. It could also help children avoid later medical complications.What about public and patient involvement (PPI)? Seventeen caregivers of children with BA advised on the research question, methods and dissemination plan. Caregivers of children with BA will be invited to form a panel for the future project.How will findings be disseminated? We will disseminate our findings through scientific journals and conferences. On the advice of PPI members, we will collaborate with the Children's Liver Disease Foundation to share findings with caregivers.

Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: ORAL AND GASTROINTESTINAL