Probiotics and prebiotics in infants and children.

Probiotics and prebiotics have a major influence on gastrointestinal flora composition. This review analyses the relationship between this change in flora composition and health benefits in children. Literature databases were searched for relevant articles. Despite exhaustive research on the subject in different indications, such as prevention and treatment of acute gastroenteritis, antibiotic associated diarrhea (AAD), traveler's diarrhea, inflammatory bowel disease, irritable bowel syndrome, Helicobacter pylori, necrotizing enterocolitis, constipation, allergy and atopic dermatitis, colic and extraintestinal infections, reports of clear benefits for the use of prebiotics and probiotics in pediatric disorders remain scarce. The best evidence has been provided for the use of probiotics in acute gastroenteritis and in prevention of AAD. However, AAD in children is in general mild, and only seldom necessitates additional interventions. Overall, the duration of acute infectious diarrhea is reduced by approximately 24 hours. Evidence for clinically relevant benefit in all other indications (inflammatory bowel disease, irritable bowel syndrome, constipation, allergy) is weak to nonexistent. Selected probiotic strains given during late pregnancy and early infancy decrease atopic dermatitis. Adverse effects have very seldom been reported. Since the risk seems minimal to nonexistent, prebiotics and probiotics may be helpful in the prevention and treatment of some disorders in children, although the evidence for benefit is limited. The best evidence has been accumulated for some lactobacilli strains and for Saccharomyces boulardii in the reduction of the duration of acute diarrhea due to gastroenteritis and prevention of AAD.

Probiotics and prebiotics in pediatric diarrheal disorders.

INTRODUCTION: In pediatrics, prebiotics and/or probiotics are added to infant formula, mainly to prevent diseases such as diarrheal disorders. Probiotic food supplements and medication are frequently used in the treatment of diarrheal disorders. This paper reviews the recent published evidence on these topics. AREAS COVERED: Relevant literature published using PubMed and CINAHL was collected and reviewed. Recent review papers were give special attention. EXPERT OPINION: The addition of pre- and/or probiotics to infant formula seems not harmful, but the evidence for benefit is limited. Most probiotics are commercialized as food supplements, and therefore do not qualify for medication legislation. Worldwide, Saccharomyces boulardii is the only strain which is registered as "medication" in the majority of countries. Efficacy data can only be considered if performed with the commercialized product. Some products reduce the risk for antibiotic-associated diarrhea and reduced the duration of acute infectious diarrhea with about 24 h. Overall, data in the other indications (inflammatory bowel disease, irritable bowel syndrome) are disappointing, although there are some recent promising results. The use of food supplements as medication opens the discussion to create a category of "medical food."

Rapid test for fecal calprotectin levels in children with Crohn disease.

Assessment of fecal calprotectin, a surrogate marker of mucosal inflammation, is a promising means to monitor therapeutic response in pediatric inflammatory bowel disease, especially if the result is readily available. We tested the performance of a novel calprotectin rapid test, Quantum Blue, versus the conventional enzyme-linked immunosorbent assay in 134 stool samples from 56 pediatric patients with Crohn disease. The intraclass correlation coefficient analysis reflected good agreement (intraclass correlation coefficient 0.97 [95% confidence interval 0.95-0.98]) but agreement was better in lower values, where dilutions were not required. Using a cutoff of 100 µg/g for normal values, the percentage agreement between the 2 tests was 87%. The optimal cutoff values to guide clinical decisions in the therapy of inflammatory bowel disease have yet to be determined.

Physiological and bifidogenic effects of prebiotic supplements in infant formulae.

OBJECTIVES: This randomized controlled trial involving 110 healthy neonates studied physiological and bifidogenic effects of galactooligosaccharides (GOS), oligofructose, and long-chain inulin (fructooligosaccharides, FOS) in formula. METHODS: Subjects were randomized to Orafti Synergy1 (50 oligofructose:50 FOS) 0.4 g/dL or 0.8 g/dL, GOS:FOS (90:10) 0.8 g/dL, or a standard formula according to Good Clinical Practice guidelines. A breast-fed group was included for comparison. Outcome parameters were weight, length, intake, stool characteristics, crying, regurgitation, vomiting, adverse events, and fecal bacterial population counts. Statistical analyses used nonparametric tests. RESULTS: During the first month of life, weight, length, intake, and crying increased significantly in all of the groups. Regurgitation and vomiting scores were low and similar. Stool frequency decreased significantly and similarly in all of the formula groups but was lower than in the breast-fed group. All of the prebiotic groups maintained soft stools, only slightly harder than those of breast-fed infants. The standard group had significantly harder stools at weeks 2 and 4 compared with 1 (P < 0.001 and P = 0.0279). The total number of fecal bacteria increased in all of the prebiotic groups (9.82, 9.73, and 9.91 to 10.34, 10.38, and 10.37, respectively, log10 cells/g feces, P = 0.2298) and more closely resembled the breast-fed pattern. Numbers of lactic acid bacteria, bacteroides, and clostridia were comparable. In the SYN1 0.8 g/dL and GOS:FOS groups, Bifidobacterium counts were significantly higher at D14 and 28 compared with D3 and were comparable with the breast-fed group. Tolerance and growth were normal. CONCLUSIONS: Stool consistency and bacterial composition of infants taking SYN1 0.8 g/dL or GOS:FOS-supplemented formula were closer to the breast-fed pattern. There was no risk of dehydration.

The Influence of Neocate in Paediatric Short Bowel Syndrome on PN Weaning.

Clinical management of short bowel syndrome remains a multistage process. Although PN is crucial, early introduction of enteral feeding is mandatory. We describe retrospectively 4 patients with an ultrashort bowel who could be weaned off PN on very short terms after introduction of an amino-acid-based formula (Neocate). Patient 1 had congenital short bowel with 50 cm small bowel and 30 cm colon. He had persistent diarrhoea on a semielementary formula. When Neocate was introduced he could be weaned from PN within 6 months. Patient 2 needed multiple surgical interventions because of NEC at D 27. He maintained 40 cm small bowel and an intact colon and remained PN dependent on semielemental formula. After introducing Neocate, PN could be weaned within 3 months. In the next 2 patients, Neocate was introduced as initial enteral feeding after bowel resection following antenatal midgut volvulus. Patient 3 had 20 cm small bowel and an intact colon. PN was weaned after 2 months. Patient 4 had 9 cm small bowel and an intact colon. PN was weaned after 13 months. In all patients Ileocaecal valve (ICV) was preserved. No consensus is reached on the type of formula to use for short bowel syndrome. Compared to recent data in the literature, the weaning period in these 4 patients was significantly shortened on an aminoacid based formula. The reason for this may lie in the antiallergic properties of this formula. We recommend the use of an amino-acid-based formula to induce earlier weaning of PN.

A two-year old boy with recurrent bouts of acute abdominal pain.

In a small number of patients with pancreas divisum (with stenotic minor papilla) a relative obstruction to pancreatic exocrine secretory flow results in pancreatitis. We report a 2-year-old boy presenting with recurrent bouts of abdominal pain. The diagnosis of acute pancreatitis was made based on blood biochemistry results. Ultrasound, computed tomography and magnetic resonance imaging showed several abdominal pseudocysts, peritoneal exsudate and confirmed pancreatitis but initially failed to reveal the aetiology. Ascites and cysts contained pancreatic enzymes. After weeks of combined conservative and surgical treatment, a magnetic resonance cholangiopancreaticography with secretin, showed a pancreas divisum with a cyst between the ducts of Santorini and Wirsung. Based on these findings, two endoscopic papillotomies (minor and major papilla) were performed. Three years follow-up was uneventful. In a child with recurrent pancreatitis or pancreatitis with chronic recurrent abdominal pain it is crucial to search aggressively for congenital abnormalities, including pancreas divisum. Secretin-enhanced magnetic resonance cholangiopancreaticography or diffusion-weighted magnetic resonance imaging is a valuable diagnostic tool for visualizing pancreatic duct anatomy.

Pulmonary embolism due to injection of Histoacryl and Lipiodol during endoscopic sclerotherapy of fundic varices.

UNLABELLED: Pulmonary N-butyl-2-cyanoacrylate embolism is one of the potential risks associated with endoscopic obliteration of fundic gastric varices. Due to its uncommon nature, especially in children, no consensus has been proposed on its optimal management. CASE REPORT: An 11-year-old boy with a longstanding history of lung- and liver fibrosis with portal hypertension causing haematemesis underwent endoscopic therapy for fundic varices. Shortly after injection of 0.5 ml of a N-butyl-2-cyanoacrylate (Histoacryl) and lipid soluble ethiodized oil (Lipiodol) mixture, he desaturated with secondary hypotension and bradycardia. Pulmonary embolism was confirmed on chest X-ray. The boy was successfully treated conservatively. Clinical symptoms subsided and he was discharged after three days. Pulmonary infiltrations persisted for two weeks. CONCLUSION: Patients including children undergoing obliteration of gastric varices with Histoacryl and Lipiodol should be subjected to a close follow-up. Coexisting lung conditions may enhance the risk of pulmonary embolism and can also influence the outcome.

Videomanometry reveals clinically relevant parameters of swallowing in children.

OBJECTIVE: The aim of this pilot study is to demonstrate the technical and clinical feasibility of videomanometry to assess swallowing in infants and young children presenting with dysphagia. METHODS: We performed videomanometry using a combined solid state catheter and a perfused manometric sleeve assembly in eight patients (2-28 months) presenting at a tertiary care institution with symptoms of dysphagia. Solid state sensors were positioned at the inferior margin of the valleculae and the laryngeal entrance and the upper esophageal sphincter sleeve assembly was positioned across the upper esophageal sphincter. Manometric and radiological data were digitally recorded simultaneously using a manofluoromixer. Liquid bolus swallows were recorded in each patient and different geometric parameters of deglutition were measured. RESULTS: Placement and fixation of the catheter was well tolerated and no adverse effects occurred. The children easily swallowed test boluses as selected during clinical examination. Results indicate that pharyngeal contractility can be evaluated as well as relaxation of the upper esophageal sphincter during swallowing of wet boluses. CONCLUSIONS: Videomanometry in young children is feasible with the limited discomfort of the placement of the catheter. It is a promising technique that will allow more accurate assessment of pediatric oropharyngeal dysphagia.

Development of the orohypopharyngeal cavity in normal infants and young children.

OBJECTIVE: To study the growth of the oropharynx and hypopharynx in infants and young children by measuring the lengths of the segments between nasopharyngeal valve and tongue base, tongue base and arytenoids, and arytenoids and upper esophageal sphincter. These measurements will be used as references for developing manofluoroscopy to study deglutition in infants and young children. PATIENTS AND METHODS: Twenty-three children (14 boys, 9 girls) between birth and 4 years of age were prospectively studied. All children had near normal growth parameters and were free of medical illnesses or other major medical conditions that are known to influence the pharyngeal cavity. Lateral videofluoroscopy was used to assess the pharyngeal structures during breathing. All images were digitally recorded and analyzed using a computer program designed specifically for this study. RESULTS AND CONCLUSIONS: Statistically significant correlations were found between the age or height of the patient and the distance from velopharyngeal valve to tongue base and the distance from tongue base to arytenoids, showing a linear increase of the length of the oro- and hypopharynx with age and patient height. There was no significant difference in the pharyngeal distances between boys and girls. On the basis of these results, a linear regression comparison could be established to define the length of each pharyngeal segment for any age until 4 years and for the 50th percentile of height.

Functional foods in pediatrics.

The philosophy that food can be health promoting beyond its nutritional value is gaining acceptance. Known disease preventive aspects of nutrition have led to a new science, the 'functional food science'. Functional foods, first introduced in Japan, have no universally accepted definition but can be described as foods or food ingredients that may provide health benefits and prevent diseases. Currently, there is a growing interest in these products. However, not all regulatory issues have been settled yet. Five categories of foods can be classified as functional foods: dietary fibers, vitamins and minerals, bioactive substances, fatty acids and pro-, pre- and symbiotics. The latter are currently the main focus of research. Functional foods can be applied in pediatrics: during pregnancy, nutrition is 'functional' since it has prenatal influences on the intra-uterine development of the baby, after birth, 'functional' human milk supports adequate growth of infants and pro- and prebiotics can modulate the flora composition and as such confer certain health advantages. Functional foods have also been studied in pediatric diseases. The severity of necrotising enterocolitis (NEC), diarrhea, irritable bowel syndrome, intestinal allergy and lactose intolerance may be reduced by using functional foods. Functional foods have proven to be valuable contributors to the improvement of health and the prevention of diseases in pediatric populations.

13C mixed triglyceride breath test: a noninvasive method to assess lipase activity in children.

BACKGROUND: Results from the 13C mixed triglyceride (MTG) breath test correlate with duodenal lipase activity in adults. This noninvasive test is a potential screening and diagnostic tool for children with fat malabsorption. The aim of this study was to adapt the methodology of the MTG breath test to study test meals and sampling methods and to define normal values for healthy children of all age groups; premature and full-term infants have similar pancreatic lipase deficiencies. METHODS: After parental consent was obtained, 12 premature infants (< 37 weeks gestation and with body weights > 2 kg), 12 full-term infants (1-6 months old), 20 children (3-10 years old), and 20 teenagers (11-17 years old) were tested. All children were thriving well, had no gastrointestinal or respiratory problems, and had not received any medication that contained natural 13C. For the premature and full-term infants, a formula was prepared that had a low and stable natural 13C content mixed with 100 mg 13C-labeled MTG (1,3-distearyl, 2-[13C-carboxyl] octanoyl glycerol) and 1 g polyethylene-glycol 3350. The best accepted test meal for children over 3 years old was a slice of white bread with 5 g butter and 15 g chocolate paste, mixed with 250 mg 13C-labeled MTG, and a glass of 100 mL whole-fat milk. Children over 3 years old were able to blow through a straw in a vacutainer for collecting the breath samples. In children under 3 years old, expired air was collected by aspirating breath via a nasal prong. Carbon dioxide production was calculated according to weight, age, and sex. RESULTS: For healthy pediatric control participants, the mean values for cumulative excretion of 13CO2 as a percentage of the administered dose after 6 hours were 23.9 +/- 5.2% in premature infants, 31.9 +/- 7.7% in full-term infants, 32.5 +/- 5.3% in children, and 28.0 +/- 5.4% in teenagers. The mean value for healthy adults is 35.6% with a lower reference limit of 22.8%. CONCLUSIONS: Age-specific test meals and breath-sampling techniques for the MTG breath test were defined. The mean values for different age groups may serve as guidelines for normal values in the pediatric population. The cumulative values for expired 13CO2 were above the lower limit for adults, which suggests that preduodenal lipases compensates for pancreatic lipase deficiency in premature and full-term infants.

Lactose-[13C]ureide breath test: a new, noninvasive technique to determine orocecal transit time in children.

BACKGROUND: The lactose-[13C]ureide breath test (LUBT) is a novel, noninvasive test to determine orocecal transit time. Lactose ureide resists the action of brush border enzymes and is metabolized by colonic bacteria. The purpose of the present study was to adapt this breath test for children of various age groups and to determine whether it can be applied in infants, newborns, and preterms to study the development of small intestinal motility. METHODS: In a group of 20 children (3-17 years) in vitro stool analysis and in vivo LUBT results were compared. From each subject a blank stool sample and a sample produced after induction with unlabeled lactose ureide were incubated with 10 mg lactose-[13C]ureide in small, closed bottles. Ten-milliliter CO2 samples were aspirated from the bottles using a needle and a syringe every 30 minutes for 24 hours. All children performed the breath test after induction of 500 mg unlabeled lactose ureide three times the prior day. A liquid test meal (chocolate milk) with 250 mg lactose-[13C]ureide was ingested. Breath samples were collected every 15 minutes for 10 hours. In a second group of 32 children (age range, 0-3 years) consisting of 6 children between 1 and 3 years of age, 6 infants between 6 and 12 months, 13 infants between 0 and 6 months, and 7 preterm infants, only the in vitro stool analysis was performed. Stools were collected for stool incubation, as described. RESULTS: The mean orocecal transit time in the group of 20 children aged 3 to 17 years was 255 minutes (range, 165-390 minutes). Stool incubations demonstrated a clear 13CO2 peak in all infants aged more than 8 months, indicating that their colonic bacterial enzymic activity hydrolyses lactose ureide. However, in all infants aged less than 6 months and in preterm infants, the 13CO2 signal was absent, indicating that those subjects were unable to hydrolyze lactose ureide. CONCLUSION: Infants aged less than 6 months do not host the appropriate bacterial enzymic activity for splitting lactose ureide. The authors conclude that the LUBT can be applied in infants aged more than 8 months, after weaning to solid foods, to determine orocecal transit time.

Gastric emptying in formula-fed and breast-fed infants measured with the 13C-octanoic acid breath test.

BACKGROUND: The 13C-octanoic acid breath test, a noninvasive method for measuring gastric emptying, was used to compare the gastric-emptying rate of formula-fed and breast-fed infants. Octanoic acid, a medium-chain fatty acid marked with the stable isotope 13C is immediately absorbed in the duodenum. Because gastric emptying is the rate-limiting step for the absorption of medium-chain fatty acids, the fraction of 13C expired in the breath indicates the rate of gastric emptying. METHODS: Twenty-nine newborn infants (16 boys, 13 girls) were investigated, with parental consent. The infants had a mean gestational age at birth of 34.5 weeks (range, 27-41 weeks) and a birth weight of 2148 g (range, 960-4100 g). Their mean weight on the day of the test was 2496 g (range, 1998-4140 g), and their mean age was 23 days (range, 7-74 days). Each infant received a test meal after a maximum fasting period of 3 hours. Fourteen infants were fed formula milk (Nutrilon Premium, NV Nutricia, Zoetermeer, The Netherlands) with 13C-octanoic acid and 15 infants received expressed mother's milk mixed with 13C-octanoic acid. After obtaining two basal breath samples and the feeding, breath samples were collected using a nasal prong, every 5 minutes during the first half hour and every 15 minutes during the next 3.5 hours. Analysis of the expired 13C fraction in the breath samples was performed using isotope-ratio mass spectrometry, and the gastric emptying curve and gastric emptying parameters were determined. RESULTS: The mean half-emptying time determined by the 13C-octanoic acid breath test was 65 minutes (range, 27-98 minutes) for the formula fed infants and 47 minutes (range, 16-86 minutes) for the breast-fed infants. The difference between the half-emptying times is significant (t-test, p < 0.05). CONCLUSIONS: The results of the 13C-octanoic acid breath test indicated faster gastric emptying of human milk than formula. Our findings are in accordance with those in earlier studies, using the invasive-dilution technique; noninvasive and detailed ultrasonography, which is not easily used because it is operator dependent and the observation time is short; or cineesophago-gastroscintigraphy, which is less suitable for infants (because of the radiation involved). The 13C-octanoic acid breath test is a safe and noninvasive method for measuring gastric emptying in small infants and allows comparison of various feeding methods.

Lipid digestion in cystic fibrosis: comparison of conventional and high-lipase enzyme therapy using the mixed-triglyceride breath test.

BACKGROUND: Fat maldigestion occurs in most patients with cystic fibrosis. Conventional pancreatic enzyme replacement therapy partially corrects this defect. In this study, the mixed-triglyceride breath test was used to evaluate whether high-lipase enzymes are equivalent to conventional enzymes in improving fat maldigestion in children with cystic fibrosis. METHODS: Fat digestion was studied in 11 patients with a mean age of 10.5 years. The mean intake of conventional enzyme capsules a day was 19. Four 13C mixed-triglyceride tests were performed on separate days and in random order. One test was taken without enzyme substitution, one with three capsules of 8,000 FIP units Creon (pancreatinum, Kali-chemie Pharma, Hannover, Germany) and one with one capsule of 25,000 FIP units. The fourth test was made with 13C octanoic acid to study gastric emptying time. RESULTS: Without enzyme intake, the mean cumulative percentage of 13C dose exhaled after 6 hours was 7.2+/-3.7%. This increased to 14.4+/-4% with intake of conventional pancreatinum and to 14.3+/-5.1% with intake of high-lipase pancreatinum (p = 0.0008 for both; paired t-test). There was no difference between both treatments. Also, the time course of 13C exhalation measured by percentage of 13CO2 exhaled per hour did not differ between enzyme treatments. CONCLUSIONS: The 13C mixed-triglyceride test is noninvasive and documents improved lipid digestion with pancreatic enzyme replacement therapy. If the lipase dose is kept constant, results obtained with high-lipase preparations are equivalent to those obtained with conventional preparations.

Bedside placement of pH-guided transpyloric small bowel feeding tubes in critically ill infants and small children.

BACKGROUND AND METHODS: The small bowel of critically ill infants and small children was cannulated using a soft feeding tube with a pH sensor at the distal tip. By monitoring pH, the tubes were guided through the stomach into the small bowel. RESULTS: Successful placements were performed in 36 of 37 (97%) attempts in 29 critically ill patients whose age was 7.9 +/- 6.3 months and weight was 5.9 +/- 2.6 kg. Continuous jejunal feedings were administered for 3.7 +/- 3.1 weeks without difficulties or complications in all but one patient. CONCLUSION: pH-guided jejunal tube placement provides a safe, easy bedside alternative to fluoroscopic, endoscopic or surgical placement in critically ill infants and small children.

A model for calculating the hospital costs for pediatric endoscopy.

BACKGROUND: Hospitals increasingly need, besides effectiveness data, accurate and reliable cost data to allocate their resources as efficiently as possible. In this article, a framework to calculate the hospital costs of setting up a new activity is presented and applied to pediatric endoscopy. METHODS: The cost calculations were based on a detailed registration of labor time, materials, space, and equipment needed to perform endoscopy in pediatric patients in a tertiary care hospital, the University Hospital in Leuven, Belgium. RESULTS: The initial investment expenses amount to 70,000 ECU ($91,000 in U.S. money), assuming that the facilities of the adult endoscopy unit can be shared. The additional variable cost for each procedure, including labor time and materials, varies between 100 and about 170 ECU ($130 and $221 U.S.), depending on the type of endoscopy (upper or lower, diagnostic or therapeutic). These basic data can be used to calculate the total costs for pediatric endoscopy under alternative scenarios (e.g., varying total number of procedures). CONCLUSIONS: The costing exercise has given the hospital better insights into the working procedures (and hence costs) of pediatric endoscopy. Other organizations will be able to apply this framework in their setting, since all included cost components, as well as volumes and unit prices, are reported separately.