GASTROINTESTINAL DISEASE AND NUTRITION
From Clinical Pediatrics, presented February 14-17, 2008, by the American Academy of Pediatrics, California Chapter 2
Robert A. Cannon, MD, Clinical Professor of Pediatrics, Gastroenterolgy, and Nutrition, University of California, Davis, School of Medicine, Sacramento
Gastroesophageal Reflux Disease (GERD)
| Terms: often used interchangeably; gastroesophageal reflux—describes material coming up from stomach into esophagus; GERD—more associated with adults; term used when symptoms or complications occur; other terms include regurgitation and vomiting (more forceful than regurgitation) |
| Diagnosis: no gold standard; if infants spit up, called reflux; barium swallow has low sensitivity and specificity; decision to work up or refer patient depends on individual case (eg, whether patient doing well or has problems); other issues length of treatment, agents used, and action to take after treatment |
| Manifestations: changes in reflux disease as children age (eg, vomiting in infants, adult symptoms in adolescents); mimicry of reflux seen with dysphagia (eg, eosinophilic esophagitis [EE]); heartburn in infants may present as irritability; spectrum of symptoms of reflux, depending on age; big peak in reflux in first few months after birth; ≈60% of children with reflux in first few months of life improve by 1 yr of age (90% by 18 mo of age); 40 to 60 million adults have significant reflux; spectrum seen in older children with reflux (some patients have nonspecific abdominal pain, depending on their age); most children <8 yr of age have difficulty vocalizing abdominal pain; most adolescents less apt to vomit (compared to, eg, infants); few children have chest pain; appropriate to use conservative therapy (ie, lifestyle changes and acid suppression) to manage suspected reflux; if patient at high risk and does not do well with empiric therapy, evaluation necessary; high-risk patients — those who have had tracheoesophageal fistula repair (always have some esophageal dysmotility, causing problems with acid clearing); patients with cystic fibrosis may have significant reflux; patients with central nervous system impairment with cerebral palsy or those with multiple allergic disorders (if concerned about EE), require evaluation; no effective prokinetic agent available (metoclopramide ineffective); in older patients, management must continue for longer period (improvement not always seen by 6 wk); in older children, dental erosions consistent sign of reflux; tests—upper gastrointestinal (GI) series not good test for reflux (good test if concerned about anatomic issues, eg, malrotation); esophageal pH monitoring excellent tool but not necessary in all patients; biopsy and endoscopy—not necessary in infants |
| Conservative treatment options: in infants—includes positioning and increasing viscosity and core density of feedings; adding rice cereal to milk increases core density and decreases volume; also decreases emesis; for thickened formula, 1 tbsp of cereal for every 1 to 2 mL of formula (has 30 to 34 cal/mL); hypoallergenic formula worth trying; if infant formula-fed, casein hydrolysate or amino acid-based formula acceptable, but not for extended period; small frequent feedings better; positioning—when person supine, esophagus at bottom of stomach (when swallowing saliva or when lower esophageal sphincter [LES] transiently relaxed, contents likely to come up); supine position protects against sudden infant death syndrome (SIDS); prone positioning less likely to cause reflux; car seats and infant seats make condition worse; rice cereal works as well as adding rice starch, depending on pH of stomach; in adolescents—counsel patients that reflux possible lifelong problem; those with problems (eg, GERD, reflux esophagitis, recurrent aspiration, asthma) need more aggressive therapy (ie, lifestyle changes alone not enough); lifestyle changes—avoiding soda and coffee; sleeping with head of bed elevated few inches; losing weight; avoiding or quitting smoking |
| Pharmacotherapy: antacids—infrequently used, except in cases of indigestion after meal; effect not long-lasting; histamine type 2-receptor antagonists (H2 RAs) and proton pump inhibitors (PPIs) used more often; no good prokinetic agents; surface agents (eg, sucralfate) not practical, due to frequency of dosing needed; approaches to acid-reducing therapy—“step down” (start treatment with PPI and attempt to discontinue) or “step up” (start with H2 RA and switch to PPI; method preferred by speaker); highly effective in some patients; expensive; necessary to give adequate dose of H2 RAs; dosage recommendations in many textbooks too low for reflux; recommended dose—cimetidine 40 mg/kg per day (adult dose 800 mg bid); ranitidine 5 to 10 mg/kg per day; few side effects |
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PPIs: effective; only 2 studied extensively in children (omeprazole and lansoprazole [Prevacid]); other PPIs used off-label (no pediatric studies to support efficacy); no randomized controlled trials comparing PPIs; multiple case series of children refractory to H2 RA that document efficacy of PPIs; not approved for use in infants; pediatric labeling (Food and Drug Administration approval) only for lansoprazole (approved for children 1-11 yr of age) and omeprazole (approved for children 2-16 yr of age); both indicated for erosive esophagitis; dose issue in younger children (1-2 yr of age) because typical dose of 1 mg/kg per day equivalent to adult dose; in first 2 yr of life, most patients require 0.1 to 3.0 mg/kg per day; for single dose of PPI, optimal time 30 min before breakfast (PPIs active only when acid pump active); with bid dosing, second dose given before evening meal; unlike adults, children with significant reflux have less reflux at night; single dose adequate for most patients; study of long-term PPI therapy (up to 11 yr) demonstrates safety with no significant side effects; concern in adults about hip fractures and bone loss not yet seen in children; metoclopramide—not particularly effective; insufficient evidence to support or oppose use; study—effect of baclofen on esophagogastric motility and reflux disease; randomized controlled trial; showed that baclofen helpful in reducing transient LES relaxation (major mechanism for reflux in adults and children); caveat— not recommended therapy |
| Management guidelines: questionable whether “irritable” infants with gastroesophageal reflux need PPI therapy; study of 125 participants thought to have reflux, referred to tertiary center, and treated with PPIs; only 13% had significant problem (eg, abnormal pH, esophagitis); in those treated, no difference in irritability; data suggest that most infants with reflux do not have esophagitis; aggressive acid suppression resulted in no difference in outcome (probably coexisting problem); in long-term follow-up of children with reflux, significant number of children continue to have symptoms (eg, heartburn), still require therapy, or better off with surgery |
| Physician education: Web site www.cdhnf.org (Children’s Digestive Health and Nutrition Foundation) |
| Eosinophilic esophagitis: symptoms mimic reflux but histologic features different; type of inflammation (esophagus loaded with eosinophils); in typical presentation, child unable to swallow; considered allergic phenomenon; responds to PPI therapy |
| Summary: except for incidence in infancy, GERD lifelong disease in most patients; acid suppression heals mucosal disease but may not change symptoms; treatment in childhood may improve quality of life and lead to better outcomes; many gaps in knowledge remain (eg, complications, long-term risks of acid suppression) |
| PROBIOTICS FROM A GASTROENTEROLOGIST’S PERSPECTIVE |
| Case: girl, 7 yr of age, developed Clostridium difficile colitis with toxic megacolon after one course of amoxicillin and clavulanate (Augmentin); 7 admissions to pediatric intensive care unit in 1 yr with recurrent toxic megacolon; improved after treated with one course of Lactobacillus rhamnosus GG (LGG) |
| Prebiotics vs probiotics: probiotics “good” bacteria; prebiotics food for good bacteria; prebiotics encourage growth of good microbes; probiotics have microbial action, modulate immune system, and enhance mucosal function; not all prebiotics and probiotics same |
| Prebiotics: available in different forms (eg, fructo-oligosaccharides, sugar alcohols); energy sources for microbes; encourage growth of population of beneficial organisms (enzymes inducible by prebiotics) |
| Mechanisms of action of probiotics: direct antimicrobial actions—secrete antimicrobial substances (eg, hydrogen peroxide, acids, bacteriocidins); occupy space; consume substrate; modulation of immune system—alter cytokines (increase anti-inflammatory cytokines, eg, interleukin [IL]-10, transforming growth factor [TGF]- β decrease proinflammatory cytokines, eg, tumor necrosis factor [TNF], IL-8); dependent on dose and strain; augment innate immunity by increasing natural killer (NK) cell activity; increase local IgA secretion in GI tract; also increase mucin secretion, decrease apoptosis, and improve mucosal immunity; not all probiotics have these properties |
| Probiotics in clinical disease: numerous studies, often with conflicting results; necessary to look at meta-analyses and large trials; difference between European and American products; Europe more advanced in testing and research of probiotics; issue of adult data vs pediatric data; some data from studies of adults not transferable to pediatric cases, especially very young children; various products not equal; effects and duration often time-limited |
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Acute diarrhea: reviews looked at >50 papers; concluded that early intervention more helpful; no benefit found in severe viral disease and in bloody diarrhea; effect of probiotics not significantly beneficial (reduce duration of diarrhea by ≈1 day; ≈1 to 2 fewer stools per day); minimum number of organisms necessary per day ≈10 billion; probiotics in commercial yogurts—study looked at commercial yogurts for content of live bacteria (Lactobacillus casei and Bifidobacterium); all commercial yogurts meet National Yogurt Association standard of 108 colony-forming units (CFUs) per gram; number of bacteria in average yogurt serving does not meet therapeutic level needed for children with acute diarrhea; goal 10 billion CFUs per day, and average yogurt has 5 x 108 CFUs (6-7 oz required) |
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Prevention of diarrhea: 9 trials, mostly in children; effective (prevention of diarrhea or significant decrease in clinical symptoms) in ≈33% of patients; in antibiotic-associated diarrhea (AAD)—trials suggest clinical outcomes improved by ≈50% by using probiotics with antibiotics (or after course of antibiotic if patient has symptoms of AAD); 6 randomized controlled trials in children showed risk of developing AAD decreased from ≈30% to 12%, with significant differences among strains; Cochrane Review reported no significant effect |
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Irritable bowel syndrome (IBS): adult studies only; pain and bloating most amenable; 30% to 40% response rate; many unanswered questions, eg, markers of relief, length of benefit |
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Breast milk-induced or cow’s milk-induced colitis: study of LGG (Culturelle) given to infants with rectal bleeding secondary to cow’s milk in mother’s breast milk; both LGG group and placebo group had maternal cow’s milk restriction; conclusion no improvement in cow’s milk protein colitis |
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Colic: study of Lactobacillus reuteri vs simethicone in treatment of colic; breastfed infants treated for ≈1 wk with placebo or simethicone and L reuteri; both groups had maternal cow’s milk restriction; colicky symptoms improved within 1 wk of treatment; episodes of crying also decreased significantly; strain now available in United States |
| Efficacy data for probiotics in GI disorders: technical review by North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition; in inflammatory bowel disease—2 conditions difficult to treat (pouchitis); VSL#3 (European preparation), now available in United States, effective; no data to show that LGG effective in Crohn’s disease; in ulcerative colitis—suggestion that VSL helpful; in irritable bowel syndrome—some data in adults that certain strains of probiotics useful; in AAD—evidence that LGG and Saccharomyces boulardii helpful (data not impressive but may have significant economic impact); in C difficile diarrhea—good evidence that LGG and S boulardii useful; in acute diarrhea—day improvement with Lactobacillus species; in allergy— good evidence for prevention of atopic dermatitis with LGG; for Helicobacter pylori eradication—no evidence that probiotics helpful; LGG—on market for ≈10 yr; useful in AAD and C difficile diarrhea; speaker gives at end of course of treatment; humanized strain; S boulardii (Florastor)—same indications and efficacy as Culturelle; yeast (not bacteria); helpful in C difficile diarrhea; all probiotics have miniscule amounts of milk or soy protein; VSL#3—used in pouchitis and ulcerative colitis and IBS in adults; expensive; Bifidobacterium infantis (Align)—recently released; primarily indicated for IBS in adults; Lactinex—no data to support efficacy; only 1 million CFUs per dose |
| Summary: not all probiotic strains equal; dose and timing important (earlier better; ≥10 billion CFUs/day in children and adults to obtain minimum benefit); yogurt appealing to patients (tastes good) but need enough (6-7 oz) to obtain benefit; length of intervention varies with disease; length of benefit varies; unregulated industry |
Suggested Reading
Bisset GS 3rd et al: Misconceptions concerning gastroesophageal reflux in children. Pediatrics 116:513; author reply 513, 2005; Boyle RJ et al: Probiotic use in clinical practice: what are the risks? Am J Clin Nutr 83:1256, 2006; Cabana MD et al: Probiotics in primary care pediatrics. Clin Pediatr (Phila) 45:405, 2006; Corvaglia L et al: Starch thickening of human milk is ineffective in reducing the gastroesophageal reflux in preterm infants: a crossover study using intraluminal impedance. J Pediatr 148:265, 2006; Galpin L et al: Effect of Lactobacillus GG on intestinal integrity in Malawian children at risk of tropical enteropathy. Am J Clin Nutr 82:1040, 2005; Gionchetti P et al: Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology 124:1202, 2003; Hassall E et al: Characteristics of children receiving proton pump inhibitors continuously for up to 11 years duration. J Pediatr 150:262, 2007; Hassall E: Decisions in diagnosing and managing chronic gastroesophageal reflux disease in children. J Pediatr 146:S3, 2005; Hibbs AM et al: Metoclopramide for the treatment of gastroesophageal reflux disease in infants: a systematic review. Pediatrics 118:746, 2006; Khoshoo V et al: Are we overprescribing antireflux medications for infants with regurgitation? Pediatrics 120:946, 2007; Kripke C: Treating GER in children younger than two years. Am Fam Physician 71:2091, 2005; Lasser MS et al: National trends in the use of antireflux procedures for children. Pediatrics 118:1828, 2006; Martin RJ et al: Gastroesophageal reflux in preterm infants: is positioning the answer? J Pediatr 151:560, 2007; Mattioli G et al: Esophageal impedance/pH monitoring in pediatric patients: preliminary experience with 50 cases. Dig Dis Sci 51:2341, 2006; Ng DK et al: Possible confounding factors in an oral probiotics trial: breast milk. Pediatrics 115:1442, 2005; Omari TI et al: Effect of baclofen on esophagogastric motility and gastroesophageal reflux in children with gastroesophageal reflux disease: a randomized controlled trial. J Pediatr 149:468, 2006; Vanderhoof JA et al: Efficacy of a pre-thickened infant formula: a multicenter, double-blind, randomized, placebo-controlled parallel group trial in 104 infants with symptomatic gastroesophageal reflux. Clin Pediatr (Phila) 42:483, 2003.
Educational Objectives
| The goal of this program is to improve the management of gastroesophageal reflux disease (GERD) and explain the appropriate use of probiotics in the treatment of gastrointestinal (GI) diseases in children. After hearing and assimilating this program, the clinician will be better able to: |
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Describe conservative treatment options for GERD in infants and older children. |
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Choose the appropriate pharmacotherapy for children with GERD. |
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Distinguish eosinophilic esophagitis from GERD. |
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Describe the mechanisms of action of probiotics. |
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Utilize the efficacy data on probiotics for GI disorders. |
Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and planning committee reported nothing to disclose.
Acknowledgements
Dr. Cannon was recorded at Clinical Pediatrics, held February 14-17, 2008, in Palm Springs, CA, and sponsored by the American Academy of Pediatrics, California Chapter 2. The Audio-Digest Foundation thanks Dr. Cannon and the sponsor for their cooperation in the production of this program.
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