Diana R. Mager

Prevalence of metabolic bone disease in children with celiac disease is independent of symptoms at diagnosis.

Objectives: Given dietary gluten exposure, growing children with celiac disease may experience malabsorption of nutrients, negatively affecting bone health. The purpose of this study was to determine the prevalence of low bone mass in children with celiac disease, according to the presence of symptoms at diagnosis. Materials and Methods: A retrospective chart review of the Stollery Childrens Hospital Celiac Clinic charts (April 1989–September 2007) was conducted. Bone mineral density (BMD) of the spine was measured using dual energy x-ray absorptiometry. Demographics, symptoms at presentation, and anthropometric and biochemical data relevant to bone health were recorded. Results: Seventy-four children (9.6 ± 3.7 years; range 3.3–16.0 years) were included. Lumbar BMD z scores more than or equal to −1 were observed in 58 cases (65%), z scores below −1 but above −2 were observed in 14 cases (19%) and z scores less than or equal to −2 were observed in 12 cases (16%). There was no significant difference in mean lumbar BMD z scores between symptomatic and asymptomatic children (P = 0.34). When adjusted for bone age and bone surface area, BMD lumbar z score was inversely correlated with age at diagnosis (P < 0.05). Conclusions: An equivalent reduction in spine bone mass was observed in children with celiac disease at diagnosis regardless of the presence of symptoms. Delayed diagnosis of children with celiac disease may increase the risk of adult osteoporosis. Appropriate screening of children at risk of celiac disease for the purpose of early diagnosis, as well as routine evaluation of bone mineral density in such children, are important to prevent long-term complications associated with poor bone health.

Prevalence of vitamin K deficiency in children with mild to moderate chronic liver disease.

Objectives: Children with chronic liver disease are at risk for vitamin K deficiency because of fat malabsorption and inadequate dietary intake. The objective of this study was to determine the prevalence of vitamin K deficiency in children with mild to moderate chronic cholestatic and noncholestatic liver disease. Methods: Vitamin K status was examined in 43 children (0.25-15.9 years) with mild to moderate chronic cholestatic liver disease, 29 children (0.9-16.9 years) with chronic mild to moderate noncholestatic liver disease, and in 44 healthy children (1-18 years). Vitamin K status was assessed by the plasma PIVKA-II (protein induced in vitamin K absence) assay (enzyme-linked immunosorbent assay). Plasma PIVKA-II values greater than 3 ng/mL are indicative of vitamin K deficiency. Results: The mean plasma PIVKA-II (±SD) in cholestatic, noncholestatic, and healthy children was 61.9 ±144, 1.2 ± 3, and 2.1 ± ng/mL, respectively (P < 0.002). Fifty-four percent of the children supplemented with vitamin K had plasma PIVKA-II greater than 3 ng/mL. Plasma conjugated bilirubin, total bile acids, and severity of liver disease were positively correlated with plasma PIVKA-II levels (P < 0.05). Conclusions: Vitamin K deficiency is prevalent in children with mild to moderate chronic cholestatic liver disease, even with vitamin K supplementation. Elevated PIVKA-II levels occurred in children with a normal prothrombin, indicating that more sensitive markers of vitamin K status should be used in children with chronic liver disease. Vitamin K deficiency was related to degree of cholestasis and severity of liver disease in children. Children without cholestasis did not exhibit vitamin K deficiency.

Resting Energy Expenditure in the Parenterally Fed Pediatric Population With Crohn's Disease

BACKGROUND Malnutrition is a common sequela of Crohns disease (CD) and may result in reduced skeletal muscle function and growth retardation. Energy requirements of parenterally fed hospitalized pediatric patients with active CD were measured using indirect calorimetry, to assess whether Food Agriculture Organization (FAO)/World Health Organization (WHO)/United Nations University (UNU) equations provide appropriate estimations of energy requirements in this patient population. METHODS Twenty hospitalized patients with active CD fed exclusively via parenteral nutrition (PN) were investigated. A chart review and patient interviews were conducted to assess disease duration, location, laboratory parameters, and symptomology associated with CD. Disease severity was quantified using the Pediatric Crohns Disease Activity Index. Each subject underwent indirect calorimetry, bioelectrical impedance analysis, and anthropometric assessment once the ordered PN met estimated macronutrient requirements of each patient (predicted resting energy expenditure x1.3). Predicted resting energy expenditure (REE) was determined using the FAO/WHO/UNU equations. RESULTS REE showed a strong correlation with predicted REE (r(2) = .73, p < .01). CONCLUSIONS Measured REE did not significantly differ from predicted resting energy requirements. This indicates that REE for the parenterally fed pediatric patients with CD can be accurately predicted using the FAO/WHO/UNU equations.

Use of N-Acetyl Cysteine for the Treatment of Parenteral Nutrition-induced Liver Disease in Children Receiving Home Parenteral Nutrition

The use of long-term parenteral nutrition (PN) in children with significant gut failure has been associated with progressive cholestatic liver disease (1–4). Progression to liver cirrhosis and end-stage liver disease are well-known consequences of long-term dependence on PN. The etiology of liver disease related to PN administration seems to be multifactorial (1–3). There is evidence linking the macronutrient and micronutrient content of PN solutions to the onset and severity of PN-induced liver cholestasis (4). Recent studies in animal models, in particular, have demonstrated an association between the onset of cholestatic liver disease and intravenous (IV) methionine (MET) intake (4–6). Most commercial PN solutions have relatively higher amounts of MET and little or no cysteine (CYS) because of the instability of CYS in solution (7). Inasmuch as CYS is an important precursor of glutathione (GSH), it was hypothesized that provision of parenteral CYS could potentially counteract the oxidative stress that occurs in liver cholestasis (8). Recently, our group showed that Nacetyl cysteine (NAC) can be used as a source of CYS in PN solutions in piglets (9). We supplemented 2 infants and 1 child with PN-induced liver disease who were receiving PN at home with IV NAC as an adjunctive therapy to minimize further liver damage induced by PN.

Effect of Orthotopic Liver Transplantation (OLT) on Branched-Chain Amino Acid Requirement

Little is known regarding the impact of liver transplantation on amino acid requirements in children. Since plasma levels of the branched-chain amino acids (BCAA) are decreased in the presence of normal levels of the aromatic amino acids after liver transplantation, normalization of hepatic function may not fully correct changes in BCAA metabolism that occur in the pretransplant period. The goal of the present study was to determine total BCAA requirements of children following liver transplantation. The requirement of total BCAA was determined using indicator amino acid oxidation (IAAO) in five clinically stable children (5.7 ± 3.5 y, mean ± SD) 1–8 y post liver transplantation. Children received in random order 6 graded intakes of total BCAA. Individual BCAA in the test diet were provided in the same proportions as present in egg protein to minimize the potential interactive effects of individual BCAA on assessment of requirement. Total BCAA requirement was determined by measuring the oxidation of L-[1-13C] phenylalanine to 13CO2 [F13CO2 in μmol/kg/h], after a primed, continuous infusion of the tracer and using a two-phase linear regression crossover regression analysis. The estimated average requirement and the upper limit of the 95% CI for total BCAA in children who have undergone liver transplantation were 172 and 206 mg/kg/d), respectively. Total BCAA requirement in children who have undergone orthotopic liver transplantation (OLT) remain increased in the post-liver transplant period when compared with healthy school aged children, but is decreased when compared with children with mild-moderate chronic cholestatic (MCC) liver disease.

Role of glucagon-like peptide-2 deficiency in neonatal short-bowel syndrome using neonatal piglets

Background:Short-bowel syndrome (SBS) is the most common cause of neonatal intestinal failure. Recovery requires intestinal adaptation, dependent on enteral nutrition (EN) and growth factors such as glucagon-like peptide–2 (GLP-2), which is secreted from L cells in the ileum. Neonatal SBS often results in loss of ileum; therefore, we hypothesized that without ileum, endogenous GLP-2 production would be inadequate to promote adaptation. We compared endogenous GLP-2 production and adaptation in neonatal animals with SBS, with and without ileum.Methods:Neonatal piglets (4–6 d) were randomized to 75% mid-intestinal resection, 75% distal-intestinal resection, or sham control without resection. Postoperatively, all piglets commenced parenteral nutrition (PN), tapering as EN was increased to maintain specific growth.Results:The resected SBS piglets developed intestinal failure, requiring a longer duration of PN support and experiencing fat malabsorption. The piglets without ileum were not able to wean from PN during the study and did not show adaptation, specifically growth in intestinal length or crypt hyperplasia on histology of the jejunum. Adaptation was observed in the resected SBS piglets with ileum, and these piglets also had an increased plasma GLP-2 level that was not observed in piglets without ileum.Conclusion:SBS piglets with ileum undergo adaptation associated with increased endogenous GLP-2 production. SBS piglets without ileum undergo limited adaptation and severe intestinal failure, requiring prolonged PN support. This appears to be related to a deficiency in endogenous GLP-2 production.

Exploring Anthropometric and Laboratory Differences in Children of Varying Ethnicities with Celiac Disease

BACKGROUND Celiac disease (CD) is a common autoimmune disorder with an increasing prevalence, including in ethnic minorities. OBJECTIVE To report the frequency of CD diagnosis in ethnic minorities presenting to a Canadian pediatric celiac clinic and to determine whether ethnic differences exist at diagnosis or follow-up. METHODS Patients with biopsy-proven CD diagnosed at a multidisciplinary celiac clinic between 2008 and 2011 were identified through the clinic database. Data at referral, and six-month and 12-month follow-ups were collected. These included demographics, self-reported ethnicity, symptoms, anthropometrics and laboratory investigations, including serum immunoglobulin antitissue transglutaminase (aTTG). RESULTS A total of 272 patients were identified; 80% (n = 218) were Caucasian (group 1) and 20% (n = 54) were other ethnicities. South Asians (group 2) comprised 81% (n = 44) of the minority population. No differences in age or sex were found between the two groups. Group 1 patients presented more often with gastrointestinal symptoms (71% versus 43%; P < 0.001), while patients in group 2 presented more often with growth concerns (21% versus 68%; P < 0.001). At diagnosis, serum aTTG level was consistently lower in group 1 compared with group 2 (367 IU⁄mL versus 834 IU⁄mL; P = 0.030). Both groups reported symptom improvement at six months and one year. At the end of one year, aTTG level was more likely to be normal in group 1 compared with group 2 (64% versus 29%; P < 0.001). CONCLUSION Although they represent a minority group, South Asian children comprised a significant proportion of CD patients presenting to a Canadian celiac clinic. South Asian children were more likely to present with growth concerns, which has important implications for timely diagnosis in this population. In addition, the apparent delay in normalization of aTTG levels suggests that careful follow-up and culturally focused education supports should be developed for South Asian children with CD.

Parental perceptions regarding lifestyle interventions for obese children and adolescents with nonalcoholic fatty liver disease.

BACKGROUND Nonalcoholic fatty liver disease (NAFLD) affects 30% of obese children globally. The main treatment for NAFLD is to promote gradual weight loss through lifestyle modification. Very little is known regarding parental perspectives about the barriers and facilitators that influence the ability to promote healthy lifestyle behaviours in children with NAFLD. OBJECTIVES To explore and describe parental perspectives regarding barriers to and facilitators of implementing lifestyle modification in children with NAFLD. METHODS A mixed-methods approach, including qualitative methodology (focus groups) and validated questionnaires (Lifestyle Behaviour Checklist), was used to assess parental perceptions regarding barriers to and facilitators of lifestyle change in parents of children with healthy body weights (control parents) and in parents of children with NAFLD (NAFLD parents). RESULTS NAFLD parents identified more problem behaviours related to food portion size and time spent in nonsedentary physical activity, and lower parental self-efficacy than parents of controls (P<0.05). Major barriers to lifestyle change cited by NAFLD parents were lack of time, self-motivation and role modelling of healthy lifestyle behaviours. In contrast, control parents used a variety of strategies to elicit healthy lifestyle behaviours in their children including positive role modelling, and inclusion of the child in food preparation and meal purchasing decisions, and perceived few barriers to promoting healthy lifestyles. Internet sources were the main form of nutrition information used by parents. CONCLUSIONS Lifestyle modification strategies focused on promoting increased parental self-efficacy and parental motivation to promote healthy lifestyle behaviour are important components in the treatment of obese children with NAFLD.

Vitamin D Status, Cardiometabolic, Liver, and Mental Health Status in Obese Youth Attending a Pediatric Weight Management Center

Background: Vitamin D (VitD) deficiency and obesity are reaching epidemic proportions in North America, particularly in those with comorbid conditions such as diabetes or liver disease. The study objective was to determine the prevalence of suboptimal vitD status and interrelationships with anthropometric, cardiometabolic, liver, mental health, and lifestyle (sleep/screen time) parameters in an ambulatory population of children with obesity. Methods: Children (2–18 years) attending a pediatric weight management clinic (n = 217) were retrospectively reviewed. Variables studied included anthropometric (weight, height, body mass index, waist circumference), vitD (serum 25-hydroxyvitamin D), cardiometabolic (systolic blood pressure, diastolic blood pressure, glucose, insulin, homeostasis model assessment for insulin resistance, triglyceride, high-density lipoprotein, low-density lipoprotein, total cholesterol), liver enzymes (alanine aminotransferase, gamma-glutamyl transferase), and mental health (number, diagnosis) parameters. Results: Suboptimal vitD status (25-hydroxyvitamin D <75 nmol/L was present in 76% of children with obesity (12.0 ± 2.9 years). Blood pressure categorized as prehypertension, stage I hypertension, and stage II hypertension was present in 14%, 25%, and 7% of children, respectively. Mental health diagnoses including anxiety, attention-deficit hyperactivity disorder, mood disorders, and learning disabilities/developmental delays occurred in 18%, 17%, 10%, and 15%, of children, respectively. Waist circumferences >100 cm were associated with lower vitD levels (58 ± 18 vs 65 ± 17 nmol/L; P = 0.01). VitD status ≥50 nmol/L was associated with lower insulin (15.8 [11.7–23.1] mU/L vs 21.1 [14.3–34.2] mU/L; P < 0.01) and homeostasis model assessment for insulin resistance (3.5 [2.5–4.9] vs 4.8 [3.1–6.9]; P < 0.01) values and systolic blood pressure percentiles (73.0 ± 25.8 vs 80.6 ± 17.0; P = 0.04). Conclusions: Children with obesity had a high prevalence of vitD deficiency, particularly those at risk for hypertension, reduced insulin sensitivity, and central obesity.

Managing the pediatric patient with celiac disease: a multidisciplinary approach

Celiac disease (CD) is an autoimmune reaction to gluten, leading to intestinal inflammation, villous atrophy, and malabsorption. It is the most common autoimmune gastrointestinal disorder, with an increasing prevalence. A life-long gluten-free diet (GFD) is an effective treatment to alleviate symptoms, normalize autoantibodies, and heal the intestinal mucosa in patients with CD. Poorly controlled CD poses a significant concern for ongoing malabsorption, growth restriction, and the long-term concern of intestinal lymphoma. Achieving GFD compliance and long-term disease control poses a challenge, with adolescents at particular risk for high rates of noncompliance. Attention has turned toward innovative management strategies to improve adherence and achieve better disease control. One such strategy is the development of multidisciplinary clinic approach, and CD is a complex life-long disease state that would benefit from a multifaceted team approach as recognized by multiple national and international bodies, including the National Institutes of Health. Utilizing the combined efforts of the pediatric gastroenterologist, registered dietitian, registered nurse, and primary care provider (general practitioner or general pediatrician) in a CD multidisciplinary clinic model will be of benefit for patients and families in optimizing diagnosis, provision of GFD teaching, and long-term adherence to a GFD. This paper discusses the benefits and proposed structure for multidisciplinary care in improving management of CD.