Coeliac Disease in Children-A Clinical Review Including Novel Treatment Agents.

Coeliac disease (CD) affects almost of 1% of the population, yet remains undiagnosed in the majority. Though the demonstration of enteropathy in duodenal biopsy was traditionally the essential criterion for the diagnosis of coeliac disease, the guidelines published by the European Society of Paediatric Gastroenterology and Nutrition (ESPGHAN) in 2012, and revised in 2020, paved the way to a no-biopsy approach to diagnosis. In a select group of children meeting certain criteria, a definitive diagnosis of CD can now be made without the need for duodenal biopsies. This is being increasingly applied in clinical practice. It is well established that untreated coeliac disease is associated with several chronic adverse health conditions. At present, a strict gluten-free diet remains the only effective treatment for CD. The advances in our understanding of the pathogenesis of CD have led to a search for alternative treatment agents. Several investigational agents are in various phases of clinical trials at present. In this review, we outline the clinical aspects of coeliac disease and summarise various investigational treatment agents.

A Co-Designed Online Education Resource on Gastrostomy Feeding for Parents and Caregivers to Support Clinical Care.

OBJECTIVE: Children with complex needs and severe disability may undergo gastrostomy insertion to support feeding difficulties. Parent education programs are critical components of clinical care pathways but there is little information on parent-reported educational needs. This study describes the collaborative process that yielded a resource to assist parents considering gastrostomy tube placement for their children, and the evaluation of the resource. METHODS: A qualitative descriptive study was conducted to identify parent needs for gastrostomy education. Based on these data and codesigning with parents with a child with gastrostomy tube, an online resource comprising video and written materials was developed. Twenty parents then evaluated its suitability for parent learning. RESULTS: Data describing parent needs were coded into categories which represented the gastrostomy "journey"-Decision Making, Hospital Stay and Living with Gastrostomy. Called Nourish , the gastrostomy training resource comprised 19 videos and 18 accompanying worksheets. Twenty parent caregivers rated it highly for its support for learning, confidence building, and planning. CONCLUSION: The process that created Nourish generated a useful resource for parents considering or managing gastrostomy tube feedings for their child. Positive feedback suggests that this approach could be a valuable adjunct to clinical care.

Coeliac disease in childhood: An overview.

Coeliac disease (CD) is an autoimmune condition, characterised by an immunological response to ingestion of gluten in genetically susceptible individuals, affecting about 1% of the population in many regions of the world. Increased knowledge regarding the pathogenesis, improved diagnostic techniques and increased awareness over the years have transformed our understanding of CD such that it is no longer a rare enteropathy, but rather a common multisystem disorder which affects individuals of all ages and results in wide-ranging clinical manifestations. Only a minority of children now present with the classical clinical picture of profound diarrhoea and malnutrition. An increasing number of children with CD present with either mild, non-specific gastrointestinal symptoms or extra-intestinal manifestations or even be asymptomatic, as in many screening-detected children. Knowledge about these diverse manifestations and a high index of suspicion is essential so that appropriate investigations can be undertaken, diagnosis established and treatment initiated. Although traditionally small bowel biopsy is considered essential for the diagnosis, recent guidelines from various professional bodies have paved the way to a biopsy-free diagnosis in a subset of symptomatic children. Life long, strict gluten-free diet still remains the only effective treatment at present, although several novel therapeutic agents are in various phases of clinical trials.

Assessment of European Society of Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines in an Australian paediatric population.

Coeliac disease (CD) diagnosis is based on clinical assessment, detection of specific autoantibodies and histological examination of small intestinal biopsies. The European Society of Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines have recently been updated and recommend CD may be diagnosed without a biopsy or HLA typing in symptomatic patients with high titre IgA tissue transglutaminase antibodies (aTTG) and positive endomysial antibodies (EMA). However, the need for EMA in patients with high level aTTG has been questioned. We aimed to determine the diagnostic benefit of HLA typing, EMA and IgG antibodies to deamidated gliadin (DGP) in children with high level aTTG. We prospectively evaluated children presenting for assessment of possible CD. All patients underwent small bowel biopsy, serological testing and HLA typing. Results were analysed and correlated with histopathological diagnosis. A total of 209 children were assessed; 61.5% were found to have CD and 29% could have avoided biopsy as per 2020 ESPGHAN guidelines. Titres of aTTG ≥60 U/mL or DGP ≥28 U/mL gave 100% specificity and 100% positive predictive value (PPV) for CD. HLA typing and EMA did not improve the PPV of patients with aTTG ≥60 U/mL, but addition of DGP ≥28 U/mL improved diagnostic sensitivity whilst retaining 100% specificity. Addition of HLA and EMA testing in patients with high titre aTTG antibodies does not improve diagnostic performance and may possibly be omitted from the serological workup in these patients. Our data support combining aTTG and DGP testing and optimising cut-offs to maximise specificity as an alternative biopsy-free diagnostic approach.

Gastrostomy and quality of life in children with intellectual disability: a qualitative study.

OBJECTIVE: Children with intellectual disability and marked feeding difficulties may undergo gastrostomy insertion to assist with their nutritional and medication needs. Use has increased recently for younger children, and it is intended to provide long-term support. This study explored the perceived value of gastrostomy for the quality of life (QOL) of children with intellectual disabilities and their families. METHODS: Twenty-one primary caregivers of children with intellectual disability aged 2-18 years participated in semistructured telephone interviews. Data were analysed using directed content analysis, and data were coded to existing QOL domains relevant to children with intellectual disability and their families. RESULTS: Benefits in each of the child and family QOL domains were represented in the interview data. For children, the impacts of gastrostomy for the physical health domain were predominant, supplemented by experiences of value for emotional well-being, social interactions, leisure activities and independence. For families, gastrostomy was integrated into multiple aspects of QOL relating to family interactions, parenting, resources and supports, health and safety, and advocacy support for disability. Shortcomings related to difficulties with equipment and complications. CONCLUSIONS: Our comprehensive overview of the value of gastrostomy for children with intellectual disability and their families was classified within a QOL framework. Gastrostomy was mainly supportive over long time periods across many QOL domains. Findings will be of use to patient counselling and education and the development of family support resources.

Risk of Hospitalizations Following Gastrostomy in Children with Intellectual Disability.

OBJECTIVE: To examine the frequency of hospital admissions before and after gastrostomy insertion in children with severe intellectual disability. STUDY DESIGN: We conducted a retrospective cohort study using linked health administrative and disability data from Western Australia (WA) and New South Wales (NSW). Children born between 1983 and 2009 in WA and 2002 and 2010 in NSW who had a gastrostomy insertion performed (n = 673 [WA, n = 325; NSW, n = 348]) by the end of 2014 (WA) and 2015 (NSW) were included. Conditional Poisson regression models were used to evaluate the age-adjusted effect of gastrostomy insertion on acute hospitalizations for all-cause, acute lower respiratory tract infections (LRTI), and epilepsy admissions. RESULTS: The incidence of all-cause hospitalizations declined at 5 years after procedure (WA cohort 1983-2009: incidence rate ratio, 0.70 [95% CI, 0.60-0.80]; WA and NSW cohort 2002-2010: incidence rate ratio, 0.63 [95% CI, 0.45-0.86]). Admissions for acute LRTI increased in the WA cohort and remained similar in the combined cohort. Admissions for epilepsy decreased 4 years after gastrostomy in the WA cohort and were generally lower in the combined cohort. Fundoplication seemed to decrease the relative incidence of acute LRTI admissions in the combined cohort. CONCLUSIONS: Gastrostomy was associated with health benefits including reduced all-cause and epilepsy hospitalizations, but was not protective against acute LRTI. These decreases in hospitalizations may reflect improved delivery of nutrition and medications.

Epidemiology of gastrostomy insertion for children and adolescents with intellectual disability.

The largest group of recipients of pediatric gastrostomy have neurological impairment with intellectual disability (ID). This study investigated trends in first gastrostomy insertion according to markers of disadvantage and ID etiology. Linked administrative and health data collected over a 32-year study period (1983-2014) for children with ID born between 1983 and 2009 in Western Australia were examined. The annual incidence rate change over calendar year was calculated for all children and according to socioeconomic status, geographical remoteness, and Aboriginality. The most likely causes of ID were identified using available diagnosis codes in the linked data set. Of 11,729 children with ID, 325 (2.8%) received a first gastrostomy within the study period. The incidence rate was highest in the 0-2 age group and there was an increasing incidence trend with calendar time for each age group under 6 years of age. This rate change was greatest in children from the lowest socioeconomic status quintile, who lived in regional/remote areas or who were Aboriginal. The two largest identified groups of ID were genetically caused syndromes (15.1%) and neonatal encephalopathy (14.8%).Conclusion: Gastrostomy is increasingly used in multiple neurological conditions associated with ID, with no apparent accessibility barriers in terms of socioeconomic status, remoteness, or Aboriginality. What is Known: • The use of gastrostomy insertion in pediatrics is increasing and the most common recipients during childhood have neurological impairment, most of whom also have intellectual disability (ID). What is New: • Nearly 3% of children with ID had gastrostomy insertion performed, with the highest incidence in children under 3 years of age. • Gastrostomy use across different social groups was equitable in the Australian setting.

Impact of Gastrostomy Placement on Nutritional Status, Physical Health, and Parental Well-Being of Females with Rett Syndrome: A Longitudinal Study of an Australian Population.

OBJECTIVES: To evaluate how age-related trends in nutritional status, physical health, and parental well-being in females with Rett syndrome may be related to gastrostomy placement and to examine the impact of the procedure on mortality. STUDY DESIGN: We included 323 females from the Australian Rett Syndrome Study and analyzed their demographic, genetic, and child and parental health data collected from over 6 waves of follow-up questionnaire between 2000 and 2011. We used mixed-effects models to estimate the association between repeated measures of outcomes and age, gastrostomy placement and their interaction and Cox proportional hazards regression models to estimate relative risks of mortality for individuals with gastrostomy. RESULTS: Nearly one-third (30.3%) of the cases underwent gastrostomy placement. Nutritional status based on weight, height, and body mass index (BMI) improved over time, and BMI was greater in individuals with gastrostomy placement than in those without (adjusted ß = 0.87, 95% CI 0.02-1.73). There was no association between gastrostomy placement and individual's physical health outcomes or parental physical and mental health, nor did the age trend of these outcomes vary by gastrostomy insertion status. Nevertheless, among those at risk of suboptimal weight, the all-cause mortality rate was greater in those who had gastrostomy placement compared with those who had not (hazard ratio 4.07, 95% CI 1.96-8.45). CONCLUSION: Gastrostomy placement was associated with improvement in BMI in females with Rett syndrome, but its long-term impact on individuals and their families is unclear.

Evolving Trends of Gastrostomy Insertion Within a Pediatric Population.

OBJECTIVE: Gastrostomy insertion in pediatrics is usually used in children with complex needs and severe disability. The accessibility and acceptance of the procedure is increasing but population-based occurrence data are lacking and there is limited understanding of its use in clinical subgroups. METHODS: This birth cohort study investigated the trends in first gastrostomy insertion among a pediatric population born between 1983 and 2009 in Western Australia using linked administrative and health data collected over a 32-year period (1983-2014). Indications were identified using diagnosis codes from linked hospitalization data and grouped according to a refined classification system. Age and birth cohort patterns of first gastrostomy use, over calendar year and age respectively, were described. RESULTS: Of the 690,688 children born between 1983 and 2009, 466 underwent a gastrostomy insertion. Overall, the prevalence was approximately 7 cases per 10,000 births. New gastrostomy insertions were increasingly performed in children during the preschool years over calendar years and in successive birth cohorts. Children with a neurological disorder constituted the largest group receiving gastrostomy (n = 372; 79.8) including 325 (87.4%) with comorbid intellectual disability. CONCLUSIONS: New gastrostomy insertion among children who require long-term enteral feeding support increased over the study period. The procedure is most often performed in the context of severe neurological disability, including intellectual disability, and offers families potential for long-term home-based management of feeding difficulties.

Transition to adult care for pediatric liver transplant recipients: the Western Australian experience.

Transition to adult care is a vulnerable period for pediatric transplant recipients and is associated with reduced medication compliance, graft loss, and increased mortality. Psychosocial outcomes in young adults differ between pediatric transplant recipients and their healthy peers. We conducted a single-center, retrospective cohort study of all pediatric liver transplant recipients who were transitioned through our center. This study aimed to assess the outcomes of transitioned pediatric liver transplant recipients at an Australian center, including mortality, adherence, and psychosocial morbidity. The 1- and 5-year survival rates following transition were 100% and 92%, respectively. There were no episodes of late rejection. In total, 66.7% of patients were compliant with immunosuppression and 61.1% of patients were compliant with clinic attendance. There was a significant relationship between medication compliance and clinic attendance, as well as presence of psychological issues with clinic non-attendance. Psychosocial outcomes were in keeping with age-matched data from the general population. All patients were employed or studying following transition. This is the first study of its kind in the Australian population, and outcomes were superior to published international data. Despite the demonstrated good outcomes, transition programs may improve healthcare engagement in this cohort.

Experience of gastrostomy using a quality care framework: the example of rett syndrome.

Rett syndrome is one of many severe neurodevelopmental disorders with feeding difficulties. In this study, associations between feeding difficulties, age, MECP2 genotype, and utilization of gastrostomy were investigated. Weight change and family satisfaction following gastrostomy were explored. Data from the longitudinal Australian Rett Syndrome Database whose parents provided data in the 2011 family questionnaire (n=229) were interrogated. We used logistic regression to model relationships between feeding difficulties, age group, and genotype. Content analysis was used to analyze data on satisfaction following gastrostomy. In those who had never had gastrostomy and who fed orally (n=166/229), parents of girls<7 years were more concerned about food intake compared with their adult peers (odds ratio [OR] 4.26; 95% confidence interval [CI] 1.29, 14.10). Those with a p.Arg168 mutation were often perceived as eating poorly with nearly a 6-fold increased odds of choking compared to the p.Arg133Cys mutation (OR 5.88; 95% CI 1.27, 27.24). Coughing, choking, or gagging during meals was associated with increased likelihood of later gastrostomy. Sixty-six females (28.8%) had a gastrostomy, and in those, large MECP2 deletions and p.Arg168 mutations were common. Weight-for-age z-scores increased by 0.86 (95% CI 0.41, 1.31) approximately 2 years after surgery. Families were satisfied with gastrostomy and felt less anxious about the care of their child. Mutation type provided some explanation for feeding difficulties. Gastrostomy assisted the management of feeding difficulties and poor weight gain, and was acceptable to families. Our findings are likely applicable to the broader community of children with severe disability.

The long term physical consequences of gastroschisis.

PURPOSE: To determine the progress, physical and metabolic outcomes of gastroschisis survivors. METHODS: Fifty children born with gastroschisis were assessed with a health questionnaire, physical assessment, bone density and nutritional blood parameters at a median age of 9years (range 5-17). RESULTS: After initial abdominal closure, 27/50 (54%) required additional surgical interventions. Ten (20%) children had complex gastroschisis (CG). Abdominal pain was common: weekly in 41%; and requiring hospitalization in 30%. The weight, length and head circumference z-scores improved by a median 0.88 (p=0.001), 0.56 (p=0.006) and 0.74 (p=0.018) of a standard deviation (SD) respectively from birth; 24% were overweight or obese at follow up. However, those with CG had significantly lower median weight z-scores (-0.43 v 0.49, p=0.0004) and body mass index (BMI) (-0.48 v 0.42, p=0.001) at follow up compared to children with simple gastroschisis. Cholesterol levels were elevated in 24% of children. Bone mineral density was reassuring. There were 15 instances of low blood vitamin and mineral levels. CONCLUSIONS: Although gastroschisis survival levels are high, many children have significant ongoing morbidity. Children with simple gastroschisis showed significant catch up growth and a quarter had become overweight.

Prevalence, clinical investigation, and management of gallbladder disease in Rett syndrome.

AIM: This study determined the prevalence of cholelithiasis and/or cholecystectomy in Rett syndrome, described gallbladder function in a clinical cohort, and identified recommendations for assessment and management of gallbladder disease. METHOD: The incidence of cholelithiasis/cholecystectomy was estimated from data describing 270 and 681 individuals with a pathogenic MECP2 mutation in the Australian Rett Syndrome Database and the International Rett Syndrome Phenotype Database respectively. Gallbladder function in 25 females (mean age 16y 5mo, SD 20y 7mo, range 3y 5mo-47y 10mo) with Rett syndrome (RTT) was evaluated with clinical assessment and ultrasound of the gallbladder. The Delphi technique was used to develop assessment and treatment recommendations. RESULTS: The incidence rate for cholelithiasis and/or cholecystectomy was 2.3 (95% confidence interval [CI] 1.1-4.2) and 1.8 (95% CI 1.0-3.0) per 1000 person-years in the Australian and International Databases respectively. The mean contractility index of the gallbladder for the clinical sample was 46.5% (SD 38.3%), smaller than for healthy individuals but similar to children with Down syndrome, despite no clinical symptoms. After excluding gastroesophageal reflux, gallbladder disease should be considered as a cause of abdominal pain in RTT and cholecystectomy recommended if symptomatic. INTERPRETATION: Gallbladder disease is relatively common in RTT and should be considered in the differential diagnosis of abdominal pain in RTT.

Gastrointestinal dysmotility in Rett syndrome.

OBJECTIVES: Through evidence review and the consensus of an expert panel, we developed recommendations for the clinical management of gastroesophageal reflux disease, constipation, and abdominal bloating in Rett syndrome. METHODS: Based on review of the literature and family concerns expressed on RettNet, initial draft recommendations were created. Wherein the literature was lacking, 25 open-ended questions were included. Input from an international, multidisciplinary panel of clinicians was sought using a 2-stage modified Delphi process to reach consensus agreement. Items related to the clinical assessment and management of gastroesophageal reflux disease, constipation, and abdominal bloating. RESULTS: Consensus was achieved on 78 of 85 statements. A comprehensive approach to the assessment of gastroesophageal reflux and reflux disease, constipation, and abdominal bloating was recommended, taking into account impairment of communication skills in Rett syndrome. A stepwise approach to the management was identified with initial use of conservative strategies, escalating to pharmacological measures and surgery, if necessary. CONCLUSIONS: Gastrointestinal dysmotility occurs commonly in Rett syndrome. These evidence- and consensus-based recommendations have the potential to improve care of dysmotility issues in a rare condition and stimulate research to improve the present limited evidence base.

Assessment and management of nutrition and growth in Rett syndrome.

OBJECTIVES: We developed recommendations for the clinical management of poor growth and weight gain in Rett syndrome through evidence review and the consensus of an expert panel of clinicians. METHODS: Initial draft recommendations were created based upon literature review and 34 open-ended questions in which the literature was lacking. Statements and questions were made available to an international, multidisciplinary panel of clinicians in an online format and a Microsoft Word-formatted version of the draft via e-mail. Input was sought using a 2-stage modified Delphi process to reach consensus. Items included clinical assessment of growth, anthropometry, feeding difficulties and management to increase energy intake, decrease feeding difficulties, and consideration of gastrostomy. RESULTS: Agreement was achieved on 101 of 112 statements. A comprehensive approach to the management of poor growth in Rett syndrome is recommended that takes into account factors such as feeding difficulties and nutritional needs. A body mass index of approximately the 25th centile can be considered as a reasonable target in clinical practice. Gastrostomy is indicated for extremely poor growth, if there is risk of aspiration and if feeding times are prolonged. CONCLUSIONS: These evidence- and consensus-based recommendations have the potential to improve care of nutrition and growth in a rare condition and stimulate research to improve the present limited evidence base.

Gastroesophageal reflux in the 21st century.

PURPOSE OF REVIEW: Gastroesophageal reflux (GER) remains a common, challenging problem for clinicians, with differentiation of normal development from disease a particular issue. This review updates clinicians on advances in diagnosis of GER, relationship to other problems, and current practice in management. RECENT FINDINGS: Development and understanding of multichannel intraluminal impedance-pH monitoring has given insights into the relationship of GER to symptoms. Medical treatment has changed little. Avoidance of overmedicalizing normal development is the major issue for clinicians. Laparoscopic fundoplication is established as equivalent to open fundoplication. Newer endoscopic techniques have only limited use in children to date. SUMMARY: Major changes in pediatric GER relate to understanding of physiology and relationship of GER to symptoms. The major challenge for clinicians involve differentiation of normal from abnormal GER, and applying the most relevant management.

Duodenal bulb biopsy in children for the diagnosis of coeliac disease: experience from Perth, Australia.

AIM: The study aims to assess the usefulness of duodenal bulb biopsy in the diagnosis of coeliac disease (CD) in a paediatric population. METHODS: Since February 2009, in our institution, we have routinely included duodenal bulb biopsy in addition to distal duodenal biopsies in children undergoing diagnostic upper gastrointestinal endoscopy. All children diagnosed with CD between February 2009 and May 2011 were identified, and those children who had biopsy finding of CD limited to duodenal bulb were reviewed with regard to clinical, serological and histopathological parameters. Duodenal bulb biopsy reports of those children who did not have CD were also reviewed as control group. RESULTS: A total of 101 children were diagnosed with CD during the study period. The mean age was 8.21 years (±3.63), 33 males and 68 females. There were 8 out of 101 (7.92%) who had histological changes consistent with CD exclusively in the duodenal bulb, with normal histology in the distal duodenum. None of duodenal bulb biopsy was abnormal in the control group. CONCLUSIONS: In some children, diagnostic CD changes may be limited to the duodenal bulb only and hence we recommend that duodenal bulb biopsies be included routinely in children suspected with CD to improve the diagnostic yield.

Food refusal in 1-year-old child.

This is a case report of a 1-year-old, otherwise healthy, girl who presented with the history of refusal of solid foods and vomiting of 1-month duration. She underwent upper gastrointestinal endoscopy, which revealed an eye-catching endoscopic finding and the cause of her symptoms.