Daniel W. Thomas

Clinical Report—Probiotics and Prebiotics in Pediatrics

This clinical report reviews the currently known health benefits of probiotic and prebiotic products, including those added to commercially available infant formula and other food products for use in children. Probiotics are supplements or foods that contain viable microorganisms that cause alterations of the microflora of the host. Use of probiotics has been shown to be modestly effective in randomized clinical trials (RCTs) in (1) treating acute viral gastroenteritis in healthy children; and (2) preventing antibiotic-associated diarrhea in healthy children. There is some evidence that probiotics prevent necrotizing enterocolitis in very low birth weight infants (birth weight between 1000 and 1500 g), but more studies are needed. The results of RCTs in which probiotics were used to treat childhood Helicobacter pylori gastritis, irritable bowel syndrome, chronic ulcerative colitis, and infantile colic, as well as in preventing childhood atopy, although encouraging, are preliminary and require further confirmation. Probiotics have not been proven to be beneficial in treating or preventing human cancers or in treating children with Crohn disease. There are also safety concerns with the use of probiotics in infants and children who are immunocompromised, chronically debilitated, or seriously ill with indwelling medical devices. Prebiotics are supplements or foods that contain a nondigestible food ingredient that selectively stimulates the favorable growth and/or activity of indigenous probiotic bacteria. Human milk contains substantial quantities of prebiotics. There is a paucity of RCTs examining prebiotics in children, although there may be some long-term benefit of prebiotics for the prevention of atopic eczema and common infections in healthy infants. Confirmatory well-designed clinical research studies are necessary.

Sports Drinks and Energy Drinks for Children and Adolescents: Are They Appropriate?

Sports and energy drinks are being marketed to children and adolescents for a wide variety of inappropriate uses. Sports drinks and energy drinks are significantly different products, and the terms should not be used interchangeably. The primary objectives of this clinical report are to define the ingredients of sports and energy drinks, categorize the similarities and differences between the products, and discuss misuses and abuses. Secondary objectives are to encourage screening during annual physical examinations for sports and energy drink use, to understand the reasons why youth consumption is widespread, and to improve education aimed at decreasing or eliminating the inappropriate use of these beverages by children and adolescents. Rigorous review and analysis of the literature reveal that caffeine and other stimulant substances contained in energy drinks have no place in the diet of children and adolescents. Furthermore, frequent or excessive intake of caloric sports drinks can substantially increase the risk for overweight or obesity in children and adolescents. Discussion regarding the appropriate use of sports drinks in the youth athlete who participates regularly in endurance or high-intensity sports and vigorous physical activity is beyond the scope of this report.

The prevalence of gastrointestinal problems in children across the United States with autism spectrum disorders from families with multiple affected members

Objective: To perform a large registry-based study to determine the relative prevalence of gastrointestinal (GI) problems in children with an autism spectrum disorder (ASD) from families with multiple affected members compared with their unaffected sibling(s). Methods: In-home structured retrospective medical history interviews by parent recall were conducted by a pediatric neurologist. Our analysis sample included information about GI health of 589 subjects with idiopathic, familial ASD and 163 of their unaffected sibling controls registered with Autism Genetic Resource Exchange. Individuals with ASD were subgrouped into 3 autism severity groups (Full Autism, Almost Autism, and Spectrum) based on their Autism Diagnostic Interview—Revised and Autism Diagnostic Observation Scale scores. Results: Parents reported significantly more GI problems in children with ASD (249/589; 42%) compared with their unaffected siblings (20/163; 12%) (p < .001). The 2 most common Gl problems in children with ASD were constipation (116/589; 20%) and chronic diarrhea (111/589; 19%). Conditional logistic regression analysis showed that having Full Autism (adjusted odds ratio [AOR] = 14.28, 95% confidence interval [CI]: 6.22–32.77) or Almost Autism (AOR = 5.16, 95% CI 2.02–13.21) was most highly associated with experiencing GI problems. Increased autism symptom severity was associated with higher odds of GI problems (AOR for trend = 2.63, 95% CI: 1.56–4.45). Conclusions: Parents report significantly more GI problems in children with familial ASD, especially those with Full Autism, than in their unaffected children. Increased autism symptom severity is associated with increased odds of having GI problems.

NUTRITIONAL ISSUES IN PEDIATRIC INFLAMMATORY BOWEL DISEASE

Malnutrition, characterized by weight loss, growth failure and micronutrient depletion, are prominent features of inflammatory bowel disease (IBD) in the pediatric age group. Accurate evaluation of the patients nutritional status and appropriate nutritional support, whether enteral or parenteral, constitute integral parts of the management of the growing child with IBD. Over the past two decades, a number of studies have supported the potential use of nutritional therapy to induce remission and to control disease activity in symptomatic Crohns disease. More recently, preliminary studies on the use of dietary supplements of marine-oil-derived omega-3 fatty acids have also indicated a beneficial effect in IBD patients. In parallel with these clinical trials, scientific research has recently focused on the concept that specific dietary alterations can modulate the immune response. Components of the diet that may have particular relevance to mucosal immunity and the pathogenesis of IBD include polyunsaturated fatty acids, nucleotides, and amino acids such as glutamine and arginine. Future research in the interactions between specific nutrients and the immune system will likely increase our understanding of the causes of IBD, as well as enhance the development of novel nutritional therapies for IBD patients.

Brief Report: Treatment of Chronic Inflammatory Bowel Disease in Glycogen Storage Disease Type Ib with Colony-Stimulating Factors

GLYCOGEN storage disease Type Ib is a rare hereditary metabolic disorder characterized by growth failure, hepatomegaly, hypoglycemia, lactic acidosis, and neutrophil deficiency.1 , 2 Except for the...

Effects of cisapride on QT interval in children

Abstract Recent reports of torsade de pointes and heart block associated with prolonged QT interval in children receiving cisapride raise questions about its safety. We prospectively examined the effects of cisapride on the QT interval in children. Electrocardiography was performed on 30 children before and after cisapride was administered. An additional 71 children underwent electrocardiography only after starting cisapride. The incidence of a corrected QT (QTc) interval >440 msec or a marked abnormality in T wave morphology was determined in all 101 children. Cisapride significantly lengthened the QTc with a mean increase of 15.5 ± 4.6 msec (mean ± SEM, p = 0.002) in the 30 children with baseline electrocardiographs. Twelve of the 101 patients were found to have a QTc >440 msec, and one had a new prominent notched T wave in all leads. In these 13 (13%) patients with repolarization abnormalities, other factors that might contribute to a long QT were noted in 11 (85%) patients. We conclude that cisapride use in children is associated with a modest increase in QT interval. The incidence of QTc >440 msec is low. Most children with long QTc have other factors that could compound the effects of cisapride. (J Pediatr 1998;133:51-6)

Reducing the incidence of necrotizing enterocolitis in neonates with hypoplastic left heart syndrome with the introduction of an enteral feed protocol.

Objective: Neonates with hypoplastic left heart syndrome are prone to gastrointestinal complications, including necrotizing enterocolitis, during initiation or advancement of enteral feeds. A feeding protocol was developed to standardize practice across a multidisciplinary team. The purpose of this study was to examine the impact of a standardized feeding protocol on the incidence of necrotizing enterocolitis and overall postoperative gastrointestinal morbidity. Design: Retrospective case–control study. Setting: Cardiothoracic intensive care unit of a tertiary care children’s hospital. Patients: Ninety-eight neonates with hypoplastic left heart syndrome admitted to the cardiothoracic intensive care unit after first-stage palliation. Intervention: A retrospective chart review was performed. Two groups were analyzed: the preprotocol group (n = 52) was examined from January 2000 through December 31, 2001, and the postprotocol group (n = 46) from February 2002 through December 31, 2003. Measurements and Main Results: The incidence of suspected or diagnosed necrotizing enterocolitis as defined by the modified Bell staging criteria was recorded. Data were also collected regarding postoperative day of enteral feed initiation, postoperative day full feeds attained, and postoperative hospital length of stay. Necrotizing enterocolitis was detected in 14 preprotocol (27%) and three postprotocol (6.5%) patients (p < .01). Enteral feeds were initiated later in the postprotocol group (7.5 vs. 5.5 days, p < .001), and number of days to full feeds was also later in the postprotocol group (7 vs. 4 days, p = .02). Hospital length of stay tended to be shorter in the postprotocol group (21.5 vs. 28 days, p = .25). Conclusion: Measures directed at reducing the incidence of necrotizing enterocolitis may reduce morbidity in neonates with hypoplastic left heart syndrome and reduce cost by decreasing hospital length of stay. A standardized feeding protocol instituted to address these problems likely contributed to reducing the incidence of necrotizing enterocolitis in this high-risk population.

Detection of acetaminophen protein adducts in children with acute liver failure of indeterminate cause

OBJECTIVE. Acetaminophen cysteine protein adducts are a widely recognized correlate of acetaminophen-mediated hepatic injury in laboratory animals. The objective of this study was to use a new assay for the detection of acetaminophen cysteine protein adducts in children with acute liver failure to determine the role of acetaminophen toxicity in acute liver failure of unknown cause. METHODS. Serum samples from children with acute liver failure were measured for acetaminophen cysteine protein adducts using high-performance liquid chromatography with electrochemical detection. For comparison, samples from children with well-characterized acetaminophen toxicity and children with known other causes of acute liver failure also were measured for acetaminophen cysteine protein adducts. The analytical laboratory was blinded to patient diagnoses. RESULTS. Acetaminophen cysteine protein adduct was detected in 90% of samples from children with acute liver failure that was attributed to acetaminophen toxicity, 12.5% of samples from children with acute liver failure of indeterminate cause, and 9.6% of samples from children with acute liver failure that was attributed to other causes. Adduct-positive patients from the indeterminate cause subgroup had higher levels of serum aspartate aminotransferase and alanine aminotransferase and lower levels of bilirubin. Adduct-positive patients also had lower rates of transplantation and higher rates of spontaneous remission. CONCLUSIONS. A small but significant percentage of children with acute liver failure of indeterminate cause tested positive for acetaminophen cysteine protein adducts, strongly suggesting acetaminophen toxicity as the cause of acute liver failure. An assay for the detection of acetaminophen cysteine protein adducts can aid the diagnosis of acetaminophen-related liver injury in children.

Inflammatory bowel disease in glycogen storage disease type Ib

We have observed the development of chronic inflammatory bowel disease, indistinguishable from Crohn disease, in two boys with glycogen storage disease type Ib (GSD-Ib). A chance association of these diseases in two patients is unlikely. Studies of their neutrophils showed severe chronic neutropenia (mean absolute granulocyte counts of less than 500 cells/microliter) and markedly deficient chemotactic response (less than 5% of reference values) in the patients with GSD-Ib and normal neutrophil values in four patients with glycogen storage disease type Ia (GSD-Ia). Monocyte counts and responses to chemotactic stimulation were normal in both GSD-Ia and GSD-Ib. Chronic inflammatory bowel disease appears to be associated with GSD-Ib, and neutrophil abnormalities may be involved in the pathogenesis of the bowel inflammation.

The gastric cardia: to be or not to be?

The origin and biologic significance of cardiac gastric mucosa are controversial. Traditionally, it has been considered native mucosa and part of normal foregut development. It has been recently suggested that cardiac mucosa is present only as a metaplastic response to gastroesophageal reflux disease and therefore always abnormal. We evaluated the esophagogastric junction in 100 pediatric autopsy samples to determine the existence, characteristics, and length of pure cardiac mucosa at different ages. No patient had a history of gastroesophageal reflux disease. Cardiac mucosa immediately distal and contiguous to the esophageal squamous mucosa was identified in all 100 samples, varying in length from 0.1 to 3 mm; the mean length was 1 mm. There was an inverse correlation between patient age and length of cardiac mucosa; gender had no influence on measured length. Three patients had mild to moderate histologic esophagitis; two had gastritis. No metaplastic features or Helicobacter pylori were identified. These findings support the concept that there is a normal, variably narrow developmental zone at the esophagogastric junction covered by cardiac mucosa and is present at birth. When cardiac type mucosa is found in biopsy material, it does not necessarily represent evidence of a mucosal metaplastic response to gastroesophageal reflux disease.