Michiel P. van Wijk

Childhood constipation: longitudinal follow-up beyond puberty

BACKGROUND & AIMS Sparse data exist about the prognosis of childhood constipation and its possible persistence into adulthood. METHODS A total of 418 constipated patients older than 5 years at intake (279 boys; median age, 8.0 yr) participated in studies evaluating therapeutic modalities for constipation. All children subsequently were enrolled in this follow-up study with prospective data collection after an initial 6-week intensive treatment protocol, at 6 months, and thereafter annually, using a standardized questionnaire. RESULTS Follow-up was obtained in more than 95% of the children. The median duration of the follow-up period was 5 years (range, 1-8 yr). The cumulative percentage of children who were treated successfully during follow-up was 60% at 1 year, increasing to 80% at 8 years. Successful treatment was more frequent in children without encopresis and in children with an age of onset of defecation difficulty older than 4 years. In the group of children treated successfully, 50% experienced at least one period of relapse. Relapses occurred more frequently in boys than in girls (relative risk 1.73; 95% confidence interval, 1.15-2.62). In the subset of children aged 16 years and older, constipation still was present in 30%. CONCLUSIONS After intensive initial medical and behavioral treatment, 60% of all children referred to a tertiary medical center for chronic constipation were treated successfully at 1 year of follow-up. One third of the children followed-up beyond puberty continued to have severe complaints of constipation. This finding contradicts the general belief that childhood constipation gradually disappears before or during puberty.

Efficacy of proton-pump inhibitors in children with gastroesophageal reflux disease: A systematic review

INTRODUCTION: Use of proton-pump inhibitors (PPIs) for the treatment of gastroesophageal reflux disease (GERD) in children has increased enormously. However, effectiveness and safety of PPIs for pediatric GERD are under debate. OBJECTIVES: We performed a systematic review to determine effectiveness and safety of PPIs in children with GERD. METHODS: We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for randomized controlled trials and crossover studies investigating efficacy and safety of PPIs in children aged 0 to 18 years with GERD for reduction in GERD symptoms, gastric pH, histologic aberrations, and reported adverse events. RESULTS: Twelve studies were included with data from children aged 0–17 years. For infants, PPIs were more effective in 1 study (compared with hydrolyzed formula), not effective in 2 studies, and equally effective in 2 studies (compared with placebo) for the reduction of GERD symptoms. For children and adolescents, PPIs were equally effective (compared with alginates, ranitidine, or a different PPI dosage). For gastric acidity, in infants and children PPIs were more effective (compared with placebo, alginates, or ranitidine) in 4 studies. For reducing histologic aberrations, PPIs showed no difference (compared with ranitidine or alginates) in 3 studies. Six studies reported no differences in treatment-related adverse events (compared with placebo or a different PPI dosage). CONCLUSIONS: PPIs are not effective in reducing GERD symptoms in infants. Placebo-controlled trials in older children are lacking. Although PPIs seem to be well tolerated during short-term use, evidence supporting the safety of PPIs is lacking.

Long-Term Prognosis for Childhood Constipation: Clinical Outcomes in Adulthood

OBJECTIVES: This study examines long-term prognoses for children with constipation in adulthood and identifies prognostic factors associated with clinical outcomes. METHODS: In a Dutch tertiary hospital, children (5–18 years of age) who were diagnosed as having functional constipation were eligible for inclusion. After a 6-week treatment protocol, prospective follow-up evaluations were conducted at 6 and 12 months and annually thereafter. Good clinical outcomes were defined as ≥3 bowel movements per week for ≥4 weeks, with ≤2 fecal incontinence episodes per month, irrespective of laxative use. RESULTS: A total of 401 children (260 boys; median age: 8 years [interquartile range: 6–9 years]) were included, with a median follow-up period of 11 years (interquartile range: 9–13 years). The dropout rate during follow-up was 15%. Good clinical outcomes were achieved by 80% of patients at 16 years of age. Thereafter, this proportion remained constant at 75%. Poor clinical outcomes at adult age were associated with: older age at onset (odds ratio [OR]: 1.15 [95% confidence interval [CI]: 1.02–1.30]; P = .04), longer delay between onset and first visit to our outpatient clinic (OR: 1.24 [95% CI: 1.10–1.40]; P = .001), and lower defecation frequency at study entry (OR: 0.92 [95% CI: 0.84–1.00]; P = .03). CONCLUSIONS: One-fourth of children with functional constipation continued to experience symptoms at adult age. Certain risk factors for poor clinical outcomes in adulthood were identified. Referral to a specialized clinic should be considered at an early stage for children who are unresponsive to first-line treatment.

Rectal Fecal Impaction Treatment in Childhood Constipation: Enemas Versus High Doses Oral PEG

OBJECTIVE: We hypothesized that enemas and polyethylene glycol (PEG) would be equally effective in treating rectal fecal impaction (RFI) but enemas would be less well tolerated and colonic transit time (CTT) would improve during disimpaction. METHODS: Children (4–16 years) with functional constipation and RFI participated. One week before disimpaction, a rectal examination was performed, symptoms of constipation were recorded, and the first CTT measurement was started. If RFI was determined, then patients were assigned randomly to receive enemas once daily or PEG (1.5 g/kg per day) for 6 consecutive days. During this period, the second CTT measurement was started and a childs behavior questionnaire was administered. Successful rectal disimpaction, defecation and fecal incontinence frequencies, occurrence of abdominal pain and watery stools, CTTs (before and after disimpaction), and behavior scores were assessed. RESULTS: Ninety-five patients were eligible, of whom 90 participated (male, n = 60; mean age: 7.5 ± 2.8 years). Forty-six patients received enemas and 44 PEG, with 5 dropouts in each group. Successful disimpaction was achieved with enemas (80%) and PEG (68%; P = .28). Fecal incontinence and watery stools were reported more frequently with PEG (P < .01), but defecation frequency (P = .64), abdominal pain (P = .33), and behavior scores were comparable between groups. CTT normalized equally (P = .85) in the 2 groups. CONCLUSION: Enemas and PEG were equally effective in treating RFI in children. Compared with enemas, PEG caused more fecal incontinence, with comparable behavior scores. The treatments should be considered equally as first-line therapy for RFI.

Role of the multichannel intraluminal impedance technique in infants and children

Recently, multichannel intraluminal impedance (MII) was added to the repertoire of tests available to study esophageal (patho)physiology in children. MII has since been used in 2 major areas. First, it has been used as a diagnostic test for gastroesophageal reflux disease (GERD). The main advantage over traditional pH monitoring is its ability to detect both acid and nonacid gastroesophageal reflux (GER) and to discern between liquid and gas GER. Although feasible with multiple pH sensors, the MII technique routinely detects the proximal extent of a GER episode. When a pH sensor is added to the MII-catheter, important information about the acidity of a GER event can be gathered. The second area in which the role of MII has been investigated is that of esophageal function testing. Manometry classically reveals information about esophageal pressure patterns and sphincter function, but does not inform us about bolus flow. MII not only detects the presence of esophageal flow but also adds information on the direction of flow, duration of bolus presence, completeness of bolus clearance, and composition of a bolus. The combination of MII with manometry enables determination of the relationship between esophageal pressures and flow and, therefore, enhances evaluation of esophageal function in terms of assessment of mechanisms of esophageal volume clearance. In addition, this technique will improve our understanding of (patho)physiological mechanisms in pediatric GERD and other esophageal motility disorders.

Measurement of mucosal conductivity by MII is a potential marker of mucosal integrity restored in infants on acid-suppression therapy.

Esophageal multichannel intraluminal impedance (MII) allows measurement of the conductivity of adjacent contents. During esophageal rest, raw impedance levels may represent mucosal integrity. We assessed the influence of proton pump inhibitors (PPIs) on presumed mucosal integrity by reanalyzing raw MII levels of 21 pH-MII tracings from infants with gastroesophageal reflux (GER) disease before and after esomeprazole treatment. Median (interquartile range) esophageal MII increased during treatment, 938 (652–1304) versus 1885 (1360–2183) Ohm, P < 0.0001. Patients with lower MII levels demonstrated a larger increase on therapy: Spearman r2 = 0.28, P = 0.014. No correlation with standard GER parameters was observed. In conclusion, PPI therapy increases MII levels in infants with symptomatic GER disease.

Small Volumes of Feed Can Trigger Transient Lower Esophageal Sphincter Relaxation and Gastroesophageal Reflux in the Right Lateral Position in Infants

OBJECTIVE To investigate the threshold amount of constantly infused feed needed to trigger lower esophageal sphincter relaxation (TLESR) in the right lateral position (RLP) and left lateral position (LLP). STUDY DESIGN Eight healthy infants (3 male; gestational age: 32.9 +/- 2.4 weeks; corrected age: 36.1 +/- 1.3 weeks) were studied using an esophageal impedance-manometry catheter incorporating an intragastric infusion port. After tube placement, infants were randomly positioned in RLP or LLP. They were then tube-fed their normal feed (62.5 [40 to 75] mL) at an infusion rate of 160 mL/h. Recordings were made during the feed and 15 minutes thereafter. The study was repeated with the infant in the opposite position. RESULTS More TLESRs were triggered in the RLP compared with LLP (4.0 [3.0 to 6.0] vs 2.5 [1.0 to 3.0], P = .027). First TLESR occurred at a significantly lower infused volume in RLP compared with LLP (10.6 +/- 9.4 vs 21.0 +/- 4.9 mL, P = .006). The percentage of feed infused at time of first TLESR was significantly lower in RLP compared with LLP (17.6% +/- 15.5% vs 35.4% +/- 8.02%, P = .005). CONCLUSIONS In the RLP, TLESRs and gastroesophageal reflux are triggered at volumes unlikely to induce gastric distension.

Efficacy and Safety of Histamine-2 Receptor Antagonists

IMPORTANCE Histamine-2 receptor antagonists (H2RAs) are frequently used in the treatment of gastroesophageal reflux disease (GERD) in children; however, their efficacy and safety is questionable. OBJECTIVE To systematically review the literature to assess the efficacy and safety of H2RAs in pediatric GERD. EVIDENCE REVIEW PubMed, EMBASE, and the Cochrane database were searched for randomized clinical trials investigating the efficacy and safety of H2RAs in pediatric GERD. Two reviewers independently extracted data from the included articles. The quality of the evidence was assessed using the Grades of Recommendations, Assessment, Development, and Evaluation approach. When possible, infants and children were analyzed separately. FINDINGS Eight studies with a total of 276 children (0-15 years of age) were included. Compared with the placebo, H2RAs were more effective in the reduction of symptoms in terms of histologic healing and increasing gastric pH and had a larger overall treatment effect. In infants, H2RAs were only more effective in terms of histologic healing. Comparing H2RAs with antacids, H2RAs were more effective in symptom reduction in only 1 study. H2RAs compared with proton pump inhibitors were not significantly different in any of the outcome measures. For safety analysis, data were not reported in a quantitative manner and for all outcomes, the quality of evidence was very low. CONCLUSIONS AND RELEVANCE Evidence to support the efficacy and safety of H2RAs in infants and children is limited and of poor quality. Well-designed placebo-controlled trials are needed before thorough conclusions can be drawn.

Body positioning and medical therapy for infantile gastroesophageal reflux symptoms.

Objective:Proton-pump inhibitors (PPIs) reduce acid gastroesophageal reflux (GER) and esophageal acid exposure in infants; however, they do not reduce total GER or symptoms attributed to GER. Reflux is reduced in the left lateral position (LLP). We hypothesize that the effect of LLP in combination with acid suppression is most effective in reducing GER symptoms in infants. Methods:In this prospective sham-controlled trial, infants (0–6 months) with symptoms suggestive of gastroesophageal reflux disease were studied using 8-hour pH-impedance, cardiorespiratory and video monitoring, direct nurse observation, and a validated questionnaire. Infants demonstrating a positive GER symptom association were randomized to 1 of 4 groups; PPI + LLP, PPI + head of cot elevation (HE), antacid (AA) + LLP, or AA + HE. HE and AA were considered “sham” therapies. After 2 weeks the 8-hour studies were repeated on-therapy. Results:Fifty-one patients were included (aged 13.6 [2–26] weeks). PPI + LLP was most effective in reducing GER episodes (69 [13] to 46 [10], P < 0.001) and esophageal acid exposure (median [interquartile range] 8.9% [3.1%–18.1%] to 1.1% [0%–4.4%], P = 0.02). No treatment group showed improvement in crying/irritability, although vomiting was reduced in AA + LLP (from 7 [2] to 2 [0] episodes P = 0.042). LLP compared with HE produced greater reduction in total GER (−21 [4] vs −10 [4], P = 0.056), regardless of acid-suppressive therapy. Acid exposure was reduced on PPI compared with AA (−6.8 [2.1] vs −0.9 [1.4]%, pH < 4, P = 0.043) regardless of positional intervention. A post-hoc analysis using automated analysis software revealed a significant reduction in crying symptoms in the PPI + LLP group (99 [65–103] to 62 [32–96] episodes, P = 0.018). Conclusions:“Symptomatic gastroesophageal reflux disease” implies disease causation for distressing infant symptoms. In infants with symptoms attributed to GER, LLP produced a significant reduction in total GER, but did not result in a significant improvement in symptoms other than vomiting; however, automated analysis appeared to identify infants with GER-associated crying symptoms who responded to positioning therapy. This is an important new insight for future research.

Evaluation of gastroesophageal function and mechanisms underlying gastroesophageal reflux in infants and adults born with esophageal atresia

PURPOSE To evaluate the mechanisms underlying gastroesophageal reflux (GER) following esophageal atresia (EA) repair and gastroesophageal function in infants and adults born with EA. METHODS Ten consecutive infants born with EA as well as 10 randomly selected adult EA patients were studied during their first postoperative follow-up visit and a purposely planned visit, respectively. A (13)C-octanoate breath test and esophageal pH-impedance-manometry study were performed. Mechanisms underlying GER and esophageal function were evaluated. RESULTS Transient lower esophageal sphincter relaxation (TLESR) was the most common mechanism underlying GER in infants and adults (66% and 62%, respectively). In 66% of all GER episodes, no clearing mechanism was initiated. On EFT, normal motility patterns were seen in six patients (four infants, two adults). One of these adults had normal motility overall (>80% of swallows). Most swallows (78.8%) were accompanied by abnormal motility patterns. Despite this observation, impedance showed normal bolus transit in 40.9% of swallows. Gastric emptying was delayed in 57.1% of infants and 22.2% of adults. CONCLUSIONS TLESR is the main mechanism underlying GER events in patients with EA. Most infants and adults have impaired motility, delayed bolus clearance, and delayed gastric emptying. However, normal motility patterns were seen in a minority of patients.