Association between 4%-tetrasodium EDTA and sepsis in neonatal piglets: A retrospective cohort study.

BACKGROUND: Central line-associated bloodstream infections are a major concern for children with intestinal failure and in animal research using parenteral nutrition (PN). In neonatal piglets receiving PN, we compared sepsis, line occlusions, line replacements, mortality, and costs with and without the use of a 4%-tetrasodium ethylenediaminetetraacetic acid (T-EDTA) locking solution. METHODS: We performed a retrospective review of piglets with a central venous jugular catheter enrolled in 14-day exclusive PN (TPN) trials or in 7-day short bowel syndrome (SBS) trials, before and after initiation of T-EDTA. Lines were locked with a 1-ml solution for 2 h daily (T-EDTATPN, n = 17; T-EDTASBS, n = 48) and compared with our prior standard of care using 1.5-ml heparin flushes twice daily (CONTPN, n = 34; CONSBS, n = 48). Line patency and signs of sepsis were checked twice daily. Jugular catheters were replaced for occlusions whenever possible. Humane end points were used for sepsis not responding to antibiotic treatment or unresolved catheter occlusions. RESULTS: Compared with CON, sepsis was reduced using T-EDTA, significantly for TPN (P = 0.006) and with a trend for SBS piglets (P = 0.059). Line occlusions necessitating line changes were reduced 15% in TPN studies (P = 0.16), and no line occlusions occurred for T-EDTA SBS piglets. CONCLUSION: In our neonatal piglet research, use of T-EDTA locking solution decreased sepsis and, although not statistically significant, reduced occlusions requiring line replacements. Given the expense of animal research, adding a locking solution must be cost-effective, and we were able to show that T-EDTA significantly reduced total research costs and improved animal welfare.

Small and large bowel anatomy is associated with enteral autonomy in infants with short bowel syndrome: A retrospective cohort study.

BACKGROUND: Achievement of enteral autonomy (EA) is the ultimate treatment goal in pediatric intestinal failure (IF). We aimed to assess predictors of EA in pediatric short bowel syndrome (SBS) and explore the impact of residual small bowel (SB) and large bowel (LB) length on EA. METHODS: A retrospective cohort study was performed on infants aged <12 months (n = 367, six centers) with SBS referred between 2010 and 2015. The cohort was stratified based on the achievement of EA. Statistical testing was completed using t-test, chi-square, Cox proportional hazards regression model, and Kaplan-Meier analysis. RESULTS: EA was achieved in 229 patients. In the multivariable analysis, the percentage of residual LB (hazard ratio [HR] = 1.02; 95% CI = 1.01-1.02) and SB (HR = 1.01; 95% CI = 1.01-1.02) length, presence of the ileocecal valve (HR = 2.02; 95% CI=1.41-2.88), and not coming from a high-volume transplantation center (HR = 2.42; 95% CI = 1.68-3.49) were positively associated with EA, whereas a negative association was seen with the presence of stoma at the time when shortest remnant was documented (HR = 0.72; 95% CI = 0.52-1.00). EA achievement was significantly different between the anatomical subgroups (log-rank test P < 0.001) with an EA rate of 80.4% in infants with ≥50% SB and LB (median time 209 days); 62.5% with ≥50% SB and <50% LB (397 days); 58.3% with <50% SB and ≥50% LB (1192 days), and 25.9% with <50% SB and LB. Necrotizing enterocolitis (NEC) was not associated with a better achievement of EA (NEC vs other etiologies: log-rank test P = 0.33). CONCLUSIONS: Overall, 62% of infants with IF secondary to SBS achieved EA over a mean time of follow-up of 2.3 years. A colon length of >50% can compensate for the loss of small bowel (<50%) and account for similar EA rates as those in children with residual SB > 50%.

Clinical Features of Children With Serology Negative, Biopsy Positive Celiac Disease.

The prevalence of pediatric serological negative celiac disease (SNCD) is poorly described, with few recognized clinical predictors beyond immunoglobulin A (IgA) deficiency or reduced gluten intake. The purpose of this retrospective review was to describe the prevalence of SNCD at the Stollery Children's Hospital and identify clinical features to help in recognition of these cases. Patients with a positive biopsy and negative serology (SNCD) were compared to those with positive biopsy and serology. SNCD diagnosis required clinical correlation and either confirmatory genetics or follow up endoscopy on a gluten-free diet. Of the 424 patients who met celiac disease (CD) criteria, 4.7% (n = 20) fulfilled our criteria for SNCD. There was a significant difference in the rates of IgA deficiency between the 2 groups, but no other clinical features were found that allowed for ready identification of SNCD patients.

In parenteral nutrition-fed piglets, fatty acids vary by lipid emulsion and tissue sampled.

BACKGROUND: Children with intestinal failure without liver disease may be given soy-based lipid emulsion (SLE) or mixed lipid emulsion (MLE; containing soy, medium-chain triglyceride, olive, and/or fish oils). Both differ in essential fatty acid content: MLE has added arachidonic acid (AA) and docosahexaenoic acid (DHA). The aim of this study, in neonatal piglets, was to compare serum and tissue fatty acid composition when the emulsions were given at unrestricted doses. METHODS: We compared SLE (n = 15) and MLE (n = 15) at doses of 10-15 g/kg/day in parenteral nutrition (PN). On day 14 we collected serum and tissues. Using gas-liquid chromatography, percentage fatty acids were measured in serum, brain, and liver phospholipid. Comparisons were made to reference values from litter-matched controls (n = 8). RESULTS: Comparing median values, linoleic acid (LA) was lower for MLE vs SLE in serum (-27%), liver (-45%), and brain (-33%) (P < 0.001). AA was lower for MLE in serum (-25%), liver (-40%), and brain (-10%). DHA was higher for MLE in serum (+50%), liver (+200%), and brain (+10%). AA levels were lower for MLE vs control piglets in serum (-81%), liver (-63%), and brain (-9%). DHA levels were higher in serum (+41%), liver (+38%), and brain (+19%). CONCLUSION: This study in piglets has shown that, at unrestricted doses, MLE treatment is associated with low serum and tissue AA compared with SLE and healthy litter-matched controls. Although not yet proven, low tissue AA levels may have functional consequences, and these data support current practice avoiding MLE dose restriction.

Review and Critical Appraisal of Clinical Practice Guidelines of Modalities Used in the Diagnosis of Celiac Disease.

Background: There is controversy over the recommendations for specific serological strategies implemented and the need for a biopsy to confirm celiac disease (CeD). We reviewed and appraised the current clinical practice guidelines (CPGs) to assess the quality and reliability of recommendations for CeD diagnosis in pediatric and adult populations. Methods: We searched databases, including MEDLINE, EMBASE, Web of Science, and CINAHL, between December 2010 and January 2021 for CPGs. Four independent reviewers extracted data. Appraisal of Guidelines Research and Evaluation (AGREE II) criteria were applied by two reviewers, and a standardized score was calculated for each of the six domains. A cut-off of 60% was used to identify high-quality guidelines. Results: A total of 654 records were identified, 10 of which were eligible for data extraction. Both adult and pediatric CPGs averaged above 70% for the domains of 'scope and purpose' and 'clarity and presentation'. For 'stakeholder involvement', the mean adult and pediatric CPG scores were below the cut-off. Only one adult-focused guideline exceeded the cut-off for the 'rigour of development' domain. 'Applicability' scores were most alarming, with adult CPGs averaging 21% and pediatric CPGs averaging 23%. Conclusion: Our review and appraisal of the CPGs for the diagnosis of CeD highlight significant discrepancies in clinical recommendations and some concerns regarding methodological rigour, particularly in stakeholder engagement, rigour, and applicability. Creating a Canadian guideline of high methodological quality that overcomes these weaknesses is critical to optimize patient care and ensuring accurate diagnoses in CeD.

Intestinal Failure-Associated Liver Disease and Growth Pre- and Post-Transition to a Composite Lipid Emulsion.

OBJECTIVES: Infants with intestinal failure have an increased risk of intestinal failure-associated liver disease (IFALD). Composite intravenous lipid emulsion (ILE) may reduce the risk of cholestasis. The primary outcome was to compare IFALD rates in infants with intestinal failure, between those receiving a composite ILE versus soybean oil ILE. The secondary outcome compared growth between these 2 groups. METHODS: At our 2 tertiary neonatal/pediatric hospitals, we identified all patients (≤1 year old) who received ≥6 weeks parenteral nutrition (PN) from 2010 to 2018. Data included liver and growth parameters. IFALD was defined as serum conjugated bilirubin (CB) >33 µmol/L (≥2 mg/dL). Nonparametric tests were used for all comparisons. RESULTS: Fifty infants (35 composite ILE, 15 soybean oil ILE) were included. Those on composite ILE received PN for longer (10.1 vs 7.6 weeks; P = 0.001) and had higher baseline CB (29 vs 6.5 µmol/L; P = 0.001). No differences were found by 6 weeks (14.5 vs 5 µmol/L; P = 0.54) and by PN cessation (4 vs 4 µmol/L; P = 0.33). The proportion of patients with IFALD decreased from 54% to 20% for composite ILE, while stable given soybean oil ILE (7%). There were no differences in weight, length, or head circumference z scores ( P > 0.05). CONCLUSIONS: In our institutions, over 8 years, chronic intestinal failure was rare. Composite ILE was the predominant lipid choice for infants who needed longer courses of PN or had developed cholestasis. Despite longer PN duration, and higher baseline CB, overall rates of IFALD decreased with composite ILE. Regardless of parenteral lipid used, there were no differences in growth.

Variation in Testing for and Incidence of Celiac Autoimmunity in Canada: A Population-Based Study.

BACKGROUND & AIMS: The incidence of biopsy-confirmed celiac disease has increased. However, few studies have explored the incidence of celiac autoimmunity based on positive serology results. METHODS: A population-based cohort study assessed testing of tissue transglutaminase antibodies (tTG-IgA) in Alberta from 2012 to 2020. After excluding prevalent cases, incident celiac autoimmunity was defined as the first positive tTG-IgA result between 2015 and 2020. Testing and incidence rates for celiac autoimmunity were calculated per 1000 and 100,000 person-years, respectively. Incidence rate ratios (IRRs) were calculated to identify differences by demographic and regional factors. Average annual percent changes (AAPCs) assessed trends over time. RESULTS: The testing rate of tTG-IgA was 20.2 per 1000 person-years and remained stable from 2012 to 2020 (AAPC, 1.2%; 95% confidence interval [CI], -0.5 to 2.9). Testing was higher in female patients (IRR, 1.66; 95% CI, 1.65-1.66), those living in metropolitan areas (IRR, 1.39; 95% CI, 1.38-1.40), and in areas of lower socioeconomic deprivation (lowest compared to highest IRR, 1.24; 95% CI, 1.23-1.25). Incidence of celiac autoimmunity was 33.8 per 100,000 person-years and increased from 2015 to 2020 (AAPC, 6.2%; 95% CI, 3.1-9.5). Among those with tTG-IgA results ≥10 times the upper limit of normal, the incidence was 12.9 per 100,000 person-years. The incidence of celiac autoimmunity was higher in metropolitan settings (IRR, 1.28; 95% CI, 1.21-1.35) and in the least socioeconomically deprived areas compared to the highest (IRR, 1.22; 95% CI, 1.14-1.32). CONCLUSIONS: Incidence of celiac autoimmunity is high and increasing, despite stable testing rates. Variation in testing patterns may lead to underreporting the incidence of celiac autoimmunity in nonmetropolitan areas and more socioeconomically deprived neighborhoods.

The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position on the Role of the Registered Dietitian Nutritionist in the Care of the Pediatric Patient With Chronic Gastrointestinal Diseases.

The optimization of nutrition is essential for the growth and development of all children, including those with gastrointestinal (GI) conditions that can variably affect nutrient intake, absorption, or metabolism. Registered Dietitian Nutritionists (RDNs) are essential partners in delivering high quality care for pediatric GI disorders, but limited evidence is available to support the role of the RDN in the care of these patients. This position paper outlines the evidence supporting the role of the RDN in the management of chronic pediatric GI issues in both inpatient and outpatient settings. Gaps in the literature, opportunities for future research, and barriers to RDN access are discussed.

When is enteral nutrition indicated?

Enteral nutrition (EN) is a vital component of nutrition around the world. EN allows for delivery of nutrients to those who cannot maintain adequate nutrition by oral intake alone. Common questions regarding EN are when to initiate and in what scenarios it is safe. The answers to these questions are often complex and require an evidence-based approach. The Board of Directors of the American Society for Parenteral and Enteral Nutrition (ASPEN) established an Enteral Nutrition Committtee to address the important questions surrounding the indications for EN. Consensus recommendations were established based on eight extremely clinically relevant questions regarding EN indications as deemed by the Enteral Nutrition Committee. These consensus recommendations may act as a guide for clinicians and stakeholders on difficult questions pertaining to indications for EN. This paper was approved by the ASPEN Board of Directors.

Food Environment and Youth Intake May Influence Uptake of Gluten-Free Food Guide Recommendations in Celiac Disease.

A gluten-free (GF) food guide for children and youth (4-18 years) living with celiac disease (CD) has been developed and extensively evaluated by stakeholders, including registered dietitians. A case study analysis was conducted on data from 16 households of youth with CD to examine how factors related to parental food literacy, the home food environment, and food purchasing patterns may influence food guide uptake by Canadian youth with CD and their families. Households were of higher socioeconomic status, parents had good food literacy, and the home food availability of fruits, vegetables and GF grains was diverse. However, households also had a diverse supply of convenience foods and snack options. Youth reported consuming a larger proportion of these foods (>35% dietary intake) and had suboptimal diet quality. Dietary intake of fruits and vegetables were below GF plate model recommendations by over 30%. Despite limited economical barriers, good parental food literacy, and diverse food availability, meeting fruit and vegetable recommendations based on the pediatric GF food guide remains a major challenge. Findings inform that effective strategies and healthy public policies to support the uptake of GF food guide recommendations are needed to improve the health outcomes of youth with CD.

Probiotic treatment vs empiric oral antibiotics for managing dysbiosis in short bowel syndrome: Impact on the mucosal and stool microbiota, short-chain fatty acids, and adaptation.

BACKGROUND: Infants and children with short bowel syndrome (SBS) are presumed to be at risk of gut microbial dysbiosis with potential sequelae of bacterial overgrowth that include sepsis, d-lactic acidosis, mucosal inflammation, and malabsorption. In neonatal piglets with SBS, we compared intestinal microbial composition, short-chain fatty acids (SCFAs), and adaptation given probiotic (PRO) treatment (Lactobacillus and Bifidobacterium spp) vs oral metronidazole (MET). METHODS: Following 75% distal small intestinal resection, piglets were allocated to PRO (500 mg twice a day, n = 7), MET (15 mg/kg twice a day, n = 8), and placebo (PLA) (500 mg twice a day, n = 8). After 10 days of parenteral and enteral nutrition, 16S ribosomal RNA gene amplicon sequencing (colon tissue and stool) was undertaken and SCFA analysis (stool and colon effluent) was performed using gas chromatography. RESULTS: In colon, Shannon diversity was higher for PRO compared with MET and PLA (P = 0.002). PRO and PLA increased abundance of Bacteroidetes species (eg, Bacteroides fragilis) compared with MET (P < 0.001). PRO, compared with PLA, increased abundance of Firmicutes species (eg, Lactobacillus fermentum) (P < 0.001). MET increased abundance of Proteobacteria members, predominately Enterobacteriaceae, compared with PRO (P = 0.004). In stool, microbial findings were similar and SCFA (butyrate) concentrations were highest for PRO (P = 0.003) compared with MET. CONCLUSION: In pediatric SBS, the empiric use of oral antibiotics, such as MET, is common for presumed clinical consequences of microbial dysbiosis. In this study of SBS piglets, that approach was associated with decreased microbial diversity and increased abundance of potentially inflammatory Proteobacteria. In contrast, a PRO treatment using Lactobacillus and Bifidobacterium spp increased both diversity and SCFAs.

The effect of fecal microbial transplant on intestinal microbial composition in short-bowel neonatal piglets.

BACKGROUND: Short-bowel syndrome (SBS) in neonates is associated with microbial dysbiosis due to intestinal surgery, prolonged hospitalization, enteral nutrition, and repeated antibiotic exposure. Sepsis and liver disease, leading causes of morbidity and mortality in SBS, may relate to such intestinal dysbiosis. We investigated the safety and feasibility of fecal microbial transplant (FMT) to alter intestinal microbial composition in SBS piglets. METHODS: Following a 75% distal small-intestinal resection, piglets were fed parenteral nutrition with an elemental diet and randomized to saline (SAL; n = 12) or FMT (n = 12) treatments delivered by gastric tube on day 2 (d2). The FMT donor was a healthy adult pig. Comparisons were also made to healthy sow-fed littermate controls (SOW; n = 6). Stool samples were collected daily, and tissue samples were collected at baseline and termination. Microbial DNA was extracted from stool and analyzed using 16S ribosomal RNA sequencing. RESULTS: All piglets survived to the end point. On d2-d4, FMT piglets had some differences in microbiota composition compared with SAL, SOW, and donor counterparts. Between base and term, there were transitory changes to alpha and beta diversity in FMT and SAL. CONCLUSION: FMT treatment in postsurgical neonatal piglets with SBS appears safe, with no increase in sepsis and no mortality. In SBS piglets, FMT induced transient changes to the intestinal microbiota. However, these changes did not persist long-term.

Mealtime Support: A Pilot Case Series study of an Effective, Cost-saving Outpatient Hunger-Based Feeding Program for Tube Dependency.

Tube feeding is essential for children who cannot meet nutritional requirements orally. Over time, this can lead to tube dependency with negative impacts on the quality of life of children and families. Objective: We aimed to examine the efficacy of a multidisciplinary child-led, hunger-based approach called "Mealtime Support" at the Stollery Children's Hospital in Edmonton. Nutritional outcomes, parental satisfaction, and cost implications were evaluated over 9 months postprogram completion per child. Methods: The ambulatory meal program was delivered 2-3 times a day, for 2 weeks, by an occupational therapist and dietitian, under medical supervision. Hunger was promoted by reducing tube fed calories by 80% before commencement. Caregivers completed 12-question subjective surveys pre- and postintervention. Microcosting methods compared costs between the program and ongoing tube feeding. Results: From 2016 to 2017, 6 children were enrolled and 5 completed the program. At 1-month postintervention, 4/5 of the children were 100% orally fed. Parents reported improvement in mealtime struggles (P = 0.005), reduction in worry about their child's eating (P = 0.005), and improvement in their child's appetite/variety foods eaten (P = 0.004). Over 2 years, the potential cost savings were estimated at $43,471.00. By 6 months, all feeding tubes were removed. Conclusions: Mealtime support was safe and successful in reducing tube dependency and cost-effective compared to no intervention or hospital based programs, which suggests that there is a need to develop and fund Canadian outpatient feeding programs.

Nutritional considerations of a paediatric gluten-free food guide for coeliac disease.

The gluten-free (GF) diet is the only treatment for coeliac disease (CD). While the GF diet can be nutritious, increased reliance on processed and packaged GF foods can result in higher fat/sugar and lower micronutrient intake in children with CD. Currently, there are no evidence-based nutrition guidelines that address the GF diet. The objective of this cross-sectional study was to describe the methodological considerations in forming a GF food guide for Canadian children and youth (4-18 years) with CD. Food guide development occurred in three phases: (1) evaluation of nutrient intake and dietary patterns of children on the GF diet, (2) pre-guide stakeholder consultations with 151 health care professionals and 383 community end users and (3) development of 1260 GF diet simulations that addressed cultural preferences and food traditions, diet patterns and diet quality. Stakeholder feedback identified nutrient intake and food literacy as important topics for guide content. Except for vitamin D, the diet simulations met 100 % macronutrient and micronutrient requirements for age-sex. The paediatric GF plate model recommends intake of >50 % fruits and vegetables (FV), <25 % grains and 25 % protein foods with a stronger emphasis on plant-based sources. Vitamin D-fortified fluid milk/unsweetened plant-based alternatives and other rich sources are important to optimise vitamin D intake. The GF food guide can help children consume a nutritiously adequate GF diet and inform policy makers regarding the need for nutrition guidelines in paediatric CD.

Evaluation of a paediatric gluten-free food guide by children and youth with coeliac disease, their parents and health care professionals.

There are currently no universal evidence-based nutrition guidelines that address the gluten-free (GF) diet for children/youth (4-18 years). A GF food guide was created to help children/youth with coeliac disease (CD) and their families navigate the complexities of following a GF diet. Guide formation was based on pre-guide stakeholder consultations and an evaluation of nutrient intake and dietary patterns. The study objective was to conduct an evaluation on guide content, layout, feasibility and dissemination strategies from end-stakeholder users (children/youth with CD, parents/caregivers and health care professionals). This is a cross-sectional study using a multi-method approach of virtual focus groups and an online survey to conduct stakeholder evaluations. Stakeholders included children/youth (4-18 years), their parents/caregivers in the coeliac community (n 273) and health care professionals (n 80) with both paediatric and CD experience from across Canada. Thematic analysis was performed on focus group responses and open-ended survey questions until thematic saturation was achieved. χ2 and Fisher's exact statistical analyses were performed on demographic and close-ended survey questions. Stakeholders positively perceived the guide for content, layout, feasibility, ethnicity and usability. Stakeholders found the material visually appealing and engaging with belief that it could effectively be used in multi-ethnic community and clinical-based settings. Guide revisions were made in response to stakeholder consultations to improve food selection (e.g. child-friendly foods), language (e.g. clarity) and layout (e.g. organisation). The evaluation by end-stakeholders provided practical and patient-focused feedback on the guide to enable successful uptake in community and clinical-based settings.

Gastro-oesophageal reflux disease in children with neurological impairment: a retrospective cohort study.

OBJECTIVES: To determine the incidence and prevalence of gastro-oesophageal reflux disease (GERD) diagnosis and treatment in children with neurological impairment (NI) along with relationship to key variables. DESIGN: This is a population-based retrospective cohort study. SETTING: This study takes place in Alberta, Canada. PATIENTS: Children with NI were identified by hospital-based International Classification of Diseases (ICD) codes from 2006 to 2018. MAIN OUTCOME MEASURES: Incidence and prevalence of a GERD diagnosis identified by: (1) hospital-based ICD-10 codes; (2) specialist claims; (3) dispensation of acid-suppressing medication (ASM). Age, gender, complex chronic conditions (CCC) and technology assistance were covariates. RESULTS: Among 10 309 children with NI, 2772 (26.9%) met the GERD definition. The unadjusted incidence rate was 52.1 per 1000 person-years (50.2-54.1). Increasing numbers of CCCs were associated with a higher risk of GERD. The HR for GERD associated with a gastrostomy tube was 4.56 (95% CI 4.15 to 5.00). Overall, 2486 (24.1%) of the children were treated with ASMs of which 1535 (61.7%) met no other GERD criteria. The incidence rate was 16.9 dispensations per year (95% CI 16.73 to 17.07). The prevalence of gastrojejunostomy tubes was 1.1% (n=121), surgical jejunostomy tubes was 0.7% (n=79) and fundoplication was 3.4% (n=351). CONCLUSIONS: The incidence of GERD in children with NI greatly exceeds that of the general paediatric population. Similarly, incidence rate of medication dispensations was closer to the rates seen in adults particularly in children with multiple CCCs and gastrostomy tubes. Further research is needed to determine the appropriate use of ASMs balancing the potential for adverse effects in this population.

Importance of public-private partnerships for nutrition support research: An ASPEN Position Paper.

Parenteral and enteral nutrition support are key components of care for various medical and physiological conditions in infants, children, and adults. Nutrition support practices have advanced over time, driven by the goals of safe and sufficient delivery of needed nutrients and improved patient outcomes. These advances have been, and continue to be, dependent on research and development studies. Such studies address aspects of enteral and parenteral nutrition support: formulations, delivery devices, health outcomes, cost-effectiveness, and related metabolism. The studies are supported by public funding from the government and by private funding from foundations and from the nutrition support industry. To build public trust in nutrition support research findings, it is important to underscore ethical research conduct and reporting of results for all studies, including those with industry sponsors. In 2019, American Society for Parenteral and Enteral Nutrition's (ASPEN's) Board of Directors established a task force to ensure integrity in nutrition support research that is done as collaborative partnerships between the public (government and individuals) and private groups (foundations, academia, and industry). In this ASPEN Position Paper, the Task Force presents principles of ethical research to guide administrators, researchers, and funders. The Task Force identifies ways to curtail bias and to minimize actual or perceived conflict of interests, as related to funding sources and research conduct. Notably, this paper includes a Position Statement to describe the Task Force's guidance on Public-Private Partnerships for research and funding. This paper has been approved by the ASPEN Board of Directors.

Association Between Celiac Disease and Autism Spectrum Disorder: A Systematic Review.

OBJECTIVE: The aim of the study was to perform a systematic review assessing the research investigating the association between celiac disease (CD) and autism spectrum disorder (ASD). METHODS: A literature search of MEDLINE and EMBASE was performed without limits placed on year or language. Observational studies reporting on the occurrence of CD among patients with ASD and/or the occurrence of ASD among patients with CD were included. Study design, characteristics, diagnostic criteria for ASD and CD, and the frequency of positive cases in the studied sample were recorded. Study quality was assessed using an adapted Newcastle-Ottawa Quality Assessment Scale. Due to substantial heterogeneity between studies, a meta-analysis was not performed. RESULTS: Of the 298 unique citations identified within our search strategy, 17 articles evaluating the association between CD and ASD were included. Of those articles, 13 observed samples of patients with ASD, and 6 observed samples of patients with CD. Overall, most studies had small sample sizes and reported no evidence for an association between the 2 conditions. However, a limited number of population-based studies of higher quality suggested a potential association between CD and ASD. CONCLUSIONS: Most studies assessing an association between CD and ASD are at risk for systematic and/or random error. A potential link has, however, been shown in a handful of high-quality studies, and, therefore, this comorbidity cannot be ruled out. Future studies should recruit larger sample sizes, include precise definitions of CD and ASD, and exclude patients with ASD on a gluten-free diet.

FODMAP intake in children with coeliac disease influences diet quality and health-related quality of life and has no impact on gastrointestinal symptoms.

Children with coeliac disease (CD) following the gluten-free diet may experience ongoing gastrointestinal symptoms despite strict adherence. The study objective was to evaluate the association between foods high in fermentable oligo/di/monosaccharides, and polyols (FODMAP) and gastrointestinal symptoms, and the potential implications to diet quality and health-related quality of life in CD children. Dietary intake was studied in age-sex matched children 5-18 years (CD, n = 46; non-coeliac mild chronic gastrointestinal complaints [GIC], n = 46; healthy controls [HC], n = 46). CD children consumed fewer foods high in FODMAPs compared to GIC and HC (p < .0001). FODMAP intake was not related to gastrointestinal symptoms in CD children (p > 0.05) but was positively associated with child health-related quality of life (p < 0.05). FODMAP intake from fruits and vegetables was positively associated with diet adequacy and total diet quality in CD children (p < 0.05). FODMAP intake may influence diet quality and health-related quality of life but has no impact on gastrointestinal symptoms in CD children.

Comparing the Intestinotrophic Effects of 2 Glucagon-Like Peptide-2 Analogues in the Treatment of Short-Bowel Syndrome in Neonatal Piglets.

BACKGROUND: In treating short-bowel syndrome (SBS), autonomy from parenteral nutrition (PN) relies upon intestinal adaptation, which can be augmented by glucagon-like peptide-2 (GLP-2) analogues. In neonatal piglets with SBS, we compared intestinal adaptation following treatment with 2 GLP-2 analogues: teduglutide (TED) and apraglutide (APRA) METHODS: Following 75% distal small-intestinal resection, piglets were allocated to 4 treatment groups: saline (CON: n = 8), twice weekly APRA (5 mg/kg/dose; n = 8), and TED once daily (TED, 0.05 mg/kg/dose; n = 8) or twice daily (TEDBID, 0.05 mg/kg/dose; n = 7). Pharmacokinetic (PK) studies were undertaken, and on day 7, small-intestinal length and weight were measured and jejunal tissue collected for histology. RESULTS: PK profiles were different between the 2 analogues. To achieve a comparable exposure to APRA, TED requires twice daily injection (TEDBID). Compared with CON, APRA and TEDBID increased small-bowel length (cm) (CON: 141, APRA: 166, TED: 153, TEDBID: 165; P = .004), whereas APRA increased small-bowel weight (g) (CON: 26, APRA: 33, TED: 28, TEDBID: 31; P = .007) and villus height (mm) (CON: 0.59, APRA: 0.90, TED: 0.58, TEDBID: 0.74; P < .001). CONCLUSION: APRA injected only twice during the 7 consecutive days demonstrated a superior intestinotrophic effect compared with TED injected once daily. Even at more comparable drug exposure, when TED was injected twice a day, APRA showed superior trophic activity at the mucosal level. This is highly relevant for the treatment of pediatric SBS, given the markedly lower dose frequency by subcutaneous injection of APRA.