Exploring Gastro-oesophageal Reflux in Infants and Children.

Abstract

Background: Gastro-oesophageal reflux in babies, young children and teenagers is a frequent cause of symptoms, parental concern and paediatric referrals. Sequelae can include failure to thrive, haematemesis, and recurrent aspiration. Current conservative management includes reassurance, feeding assessment and parental education, whilst more interventionist options include medications and surgery. Prior to 2008, clinical practice was often individualised, with a paucity of evidence for treatments in infants and children (or treatment decisions were extrapolated from evidence in adults), and no robust synthesis of the evidence was available to provide evidence-based guidance so clinicians could understand best how to treat their patients. Aims and Objectives: This PhD research aimed to identify the current issues in infants and children with either gastro-oesophageal reflux (GOR) or gastro-oesophageal reflux disease (GORD) and investigate the evidence-base for current management strategies. I highlight the current gaps, and aim to improve current management of GORD, including expanding the evidence-base. To understand the current evidence-base, I initially undertook a systematic review of all original trials of pharmacological treatments for GOR/GORD (Article I). I evaluated the role of pH studies as a key objective outcome for infants and children with GORD (Article II). This technique has now evolved to include impedance, and based on this evidence, I set up a pH/impedance monitoring service in Poole for paediatric patients. I then appraised the evidence-base using Cochrane methodology given the improved robustness of evidence given by well-designed randomised controlled trials (Article III). As part of this research series, I was then invited to be one of the two general paediatric expert advisors in developing National Institute of Health and Care Excellence (NICE) guidelines (NG1) and supportive information including patient information, an audit tool and costing template, including developing the ten important clinical questions, leading this through stakeholder feedback, robustly interpreting the evidence base to make national guidance and research recommendations (Article IV). I pilot-tested the audit tool locally to ensure that the paediatric department at Poole hospital appropriately recognises ‘Red Flag’ symptoms for gastro- oesophageal reflux (Article V) and helped develop NICE Quality Standards: a series of evidence- based statements against which clinicians caring for children with reflux could audit their practice. I then led the updating of the Cochrane evidence-base between 2016-2022 using new methodology, having independently extracted the data (Article VI). The NICE reflux guidance (NG1) research recommendations and Articles III and VI recommendations included better assessments and treatment for GORD in children with neurodisability, such as cerebral palsy. I then undertook a service evaluation of children with neurodisability to understand how many of them had received treatment for GORD (Article VII), and learned there was a lack of an appropriate symptom tool to evaluate symptoms of GORD in children with neurodisability, given their affected gastrointestinal motility, alternative feeding strategies (e.g. tube feeding), multiple interacting medications, and issues with communication. I have developed a symptom tool based on modification of the PGSQ (Paediatric Gastro-oesophageal Reflux Symptom Questionnaire) and have tested this in the patient population (Article VIII). Methods: This mixed-methods thesis incorporates secondary data in the form of literature reviews through Oxford Centre for Evidence-Based Research (CEBM), then the Cochrane reviews following standard methodologies (including Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach and primary data collection. Summary of Results: The studies in this thesis added to the body of knowledge through providing unique evidence for the following: • There is now a detailed evaluation of the existing literature using Cochrane and NICE methodology to help clinicians best decide how to treat children with GORD. • The appropriate utility of investigations such as pH/impedance monitoring (effective in linking symptoms with episodes of GOR), endoscopy and barium swallows (do not use to assess GORD) is characterised. • H2 antagonists and proton pump inhibitors are effective treatments for reflux oesophagitis in children (in terms of symptom relief, improvements of pH/impedance metrics, and oesophageal healing on endoscopy. • There is evidence of an absence of effect for Domperidone, which has associated risks in adults in terms of QT prolongation, and the prescribing of domperidone has been restricted to specialist use only. • The NICE audit tool is effective at assessing services’ ability to identify children with other causes for symptoms of GORD. • Children with neurodisability and GORD have a tailored symptom tool for evaluation of their reflux symptoms Conclusion: The evidence-base contained in this thesis provides a robust foundation for caring for infants and children with GORD and identifies the issues with the current evidence-base for assessing and treating children with neurodisability; who often have more severe GORD, combined with an inability to adequately communicate the degree of discomfort, and are more at risk of severe complications (vomiting blood/oesophagitis/aspiration pneumonia). This thesis makes further suggestions for future studies, having developed a symptom severity assessment tool in children with neurodisability.