Evaluation_and_Treatment_of_Functional.24 (1).pdf

CLINICAL GUIDELINE Evaluation and Treatment of Functional Constipation in Infants and Children: Evidence-Based Recommendations From ESPGHAN and NASPGHAN M.M. Tabbers, C. DiLorenzo, M.Y. Berger, C. Fau...

CLINICAL GUIDELINE Evaluation and Treatment of Functional Constipation in Infants and Children: Evidence-Based Recommendations From ESPGHAN and NASPGHAN M.M. Tabbers, C. DiLorenzo, M.Y. Berger, C. Faure, M.W. Langendam, S. Nurko, A. Staiano, Y. Vandenplas, and M.A. Benninga ABSTRACT Results: This evidence-based guideline provides recommendations for the Background: Constipation is a pediatric problem commonly encountered by evaluation and treatment of children with functional constipation to many health care workers in primary, secondary, and tertiary care. To assist standardize and improve their quality of care. In addition, 2 algorithms medical care providers in the evaluation and management of children with were developed, one for the infants 75% of the working group mem- therapeutic interventions (questions 5, 6, and 9) was graded as bers voted 6, 7, 8, or 9. The consensus was reached for all of follows (10): the questions. A decision was made to present 2 algorithms (Figs. 1 and 2).
High: Further research is unlikely to change our confidence in In contrast to the earlier guidelines, one pertains to the infant from the estimate of effect. birth to 6 months (instead of 1 year) and the other to the older child
Moderate: Further research is likely to have an important (7,8). This decision was based on the fact that defecation problems impact on our confidence in the estimate of effect and may in infants 2 Action weeks old 5 4 Re-assessment Treatment No Adherence? No effective? Re-education 11 12 Evaluation after Functional Yes 2-4 weeks constipation 6 7 Treatment Maintenance Treatment Yes Yes effective? therapy effective? Treatment: 9 14 13 Education Diet: verify proper formula preparation Diary Yes 8 No Relapse? 15 Wean Relapse? Yes Refer Observe 16 17 18 Yes Has previous Improve treatment No treatment been sufficient? 20 19 Yes Treatment Alarm signs/ No Continue therapy effective? symptoms? 22 21 26 Yes Yes Consider hypo- Tailor testing for Reconsider No Response? allergic formula No differential organic diseases for 2-4 weeks diagnosis 27 25 24 23 FIGURE 1. Algorithm for the evaluation and treatment of infants 4 years need to fulfill 2 of the criteria for at least frequent associated symptom, but its presence is not considered a 2 months, and to be included in the latter group children need to have a criterion for functional constipation. The role that constipation plays developmental age of at least 4 years and have insufficient criteria to in children with predominant abdominal pain is not clear. TABLE 2. Rome III diagnostic criteria for functional constipation In the absence of organic pathology, 2 of the following must occur  For a child with a developmental age 6 months, with at least all age groups. 10 minutes of straining and crying before successful passage of Voting: 9, 9, 9, 9, 9, 9, 9, 9 soft stools, in the absence of other health problems. Parents (2) Based on expert opinion, the diagnosis of functional describe infants with dyschezia as straining for many minutes, constipation is based on history and physical examination. screaming, crying, and turning red or purple in the face with Voting: 9, 9, 9, 9, 9, 9, 9, 9 effort. The symptoms persist for 10 to 20 minutes, until soft or liquid stools are passed. Stools are usually evacuated daily. The symptoms begin in the first months of life and resolve spon- taneously after a few weeks. In the absence of any scientific Question 2: What Are the Alarm Signs and literature evaluating this condition, infant dyschezia is not dis- Symptoms That Suggest the Presence of an cussed in this document. Underlying Disease Causing the Constipation? Not all of the children with defecation problems fulfill the Rome criteria, and other definitions have been proposed Although diagnosis of constipation is based on the history that are less stringent and have only included ‘‘difficulty with and physical examination, subjective symptom description is unre- defecation for at least 2 weeks, which causes significant distress liable in infants and many children 60 hours) and nonconstipated chil-  Imperforate anus dren (CTT  60 hours) was evaluated and reported a best AUC of  Anal stenosis 0.84 (95% CI 0.79–0.89; scored by a consultant). The discriminative Pelvic mass (sacral teratoma) power was dependent on the level of experience of the radiologist  Spinal cord anomalies, trauma, tethered cord (Barr scores of the junior physician and the student were poorer, with Abnormal abdominal musculature (prune belly, gastroschisis, Down AUCs of 0.76 and 0.61 (95% CI 0.69–0.82 and 0.53–0.69).  syndrome) In conclusion, evidence supports not using an abdominal Pseudoobstruction (visceral neuropathies, myopathies, radiography to diagnose functional constipation. mesenchymopathies) Multiple endocrine neoplasia type 2By 3.3 CTT (Fig. 2, Box 25) HD ¼ Hirschsprung disease.  More likely in the younger child. Four studies were included evaluating the value of CTT in y More likely in the older child. diagnosing clinically defined childhood constipation. Gutiérrez et al www.jpgn.org 263 Copyright 2014 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.  Tabbers et al JPGN
Volume 58, Number 2, February 2014 TABLE 4. Key points of history and physical examination to guide in the evaluation of constipation in infants/toddlers and children/adolescents Infant/toddler Child/adolescent Functional constipation Functional constipation History History Starts after a few weeks to months of life (not at birth) Starts after a few weeks to months of life (not at birth) Obvious precipitating factors coinciding with the start of symptoms: Sometimes precipitating factors coinciding with the start of fissure, change of diet, timing of toilet training, infections, symptoms: fissure, change of diet, infections, changing house, changing house, starting nursery starting school, fears and phobias, major change in family, Normal passage of meconium new medicines, travel Examination Normal passage of meconium Generally well, weight and height within normal limits Examination Normal growth Generally well, weight and height within normal limits, fit and active Normal appearance of anus and surrounding area Normal growth Soft abdomen Normal appearance of anus and surrounding area Normal appearance of the skin and anatomical structures of Soft abdomen (palpable fecal mass possible) lumbosacral/gluteal regions Normal appearance of the skin and anatomical structures of Normal gait, tone strength, and reflexes of lower limbs lumbosacral/gluteal regions Toilet phobia Normal gait, tone strength, and reflexes of lower limbs Cystic fibrosis Sexual abuse Respiratory problems Social history Failure to thrive Extreme fear during anal inspection/rectal examination, anal scars, Celiac disease, hypothyroidism fissures, hematomas Family history Depression Growth delay, developmental delay Personal and family history Dietary protein allergy Anorexia Personal and family history (allergy) Cystic fibrosis Eczema Respiratory problems HD Difficulty gaining weight Onset of symptoms 48 h Family history Bloody diarrhea, bilious vomiting Growth delay Failure to thrive HD Abdominal distension Reported from birth or first few weeks of life Tight empty rectum in presence of palpable abdominal fecal mass Passage of meconium >48 h Explosive stool and air from rectum upon withdrawal of examining finger Growth delay, abdominal distension, bilious vomiting Anatomic malformations Massive abdominal distension Anal stenosis: ribbons stools, tight anal canal on rectal examination Tight empty rectum in presence of palpable abdominal fecal mass Abnormal anal position Explosive stool and air from rectum upon withdrawal of examining finger Sacral teratoma Sacral teratoma Sacral agenesis Sacral agenesis Spinal cord anomalies Spinal cord anomalies, trauma Weakness in legs, locomotor delay Weakness in legs, abnormal motility Pilonidal dimple covered by a tuft of hair Pilonidal dimple covered by a tuft of hair Gluteal cleft deviation Gluteal cleft deviation Absent anal and cremasteric reflex Absent anal and cremasteric reflex Decreased lower extremity tone and/or strength Decreased lower extremity tone and/or strength Abnormal deep tendon reflexes of lower extremity Abnormal deep tendon reflexes of lower extremity Prune belly, gastroschisis, Down syndrome Prune belly, gastroschisis, Down syndrome Abnormal abdominal musculature Abnormal abdominal musculature Pseudoobstruction Pseudoobstruction, MEN type 2B Reported from birth or first few weeks of life Family history Failure to thrive Reported from birth or first few weeks of life Abdominal distension and bilious vomiting Failure to thrive Urinary bladder distension Abdominal distension and bilious vomiting Urinary bladder distension HD ¼ Hirschsprung disease; MEN ¼ multiple endocrine neoplasia. (33) found that in constipated children the mean CTT was signifi- CTT was significantly different from the mean in the control group cantly prolonged compared with the control group (mean  (mean  SD 58.25  17.46 compared with 30.18  13.15). de standard deviation [SD] 49.57  25.38 versus 29.08  8.3); CTT Lorijn et al (29) presented an AUC of 0.90 (range 0.83–0.96), was inversely related to the number of defecations per week. indicating that CTT is a good discriminator between children with Zaslavsky et al (34) found that in constipated children the mean and without clinical constipation who were referred to a pediatric 264 www.jpgn.org Copyright 2014 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.  JPGN
Volume 58, Number 2, February 2014 Evaluation and Treatment of Functional Constipation in Children TABLE 5. Alarm signs and symptoms in constipation decreased significantly (from [mean  SD] 42.1  15.4 to 26.9  5.6 mm). Klijn et al (38) found a statistically significant Constipation starting extremely early in life (48 h (4.9 cm) and the control group (2.1 cm). The cutoff value was Family history of HD 3.3 cm, where >3.3 cm indicated constipation. The study by Singh Ribbon stools et al (36) reported an AUC of 0.85 (0.79–0.90), indicating that Blood in the stools in the absence of anal fissures measuring rectal diameter on ultrasound examination is a moderate- Failure to thrive to-good discriminator between children with and without con- Fever stipation. Bilious vomiting In conclusion, evidence does not support the routine use Abnormal thyroid gland of rectal ultrasound to diagnose functional constipation. Severe abdominal distension Perianal fistula Abnormal position of anus (4) Based on expert opinion, if only 1 of the Rome III Absent anal or cremasteric reflex criteria is present and the diagnosis of functional Decreased lower extremity strength/tone/reflex constipation is uncertain, a digital examination of the Tuft of hair on spine anorectum is recommended. Sacral dimple Voting: 7, 8, 8, 8, 9, 9, 9, 9 Gluteal cleft deviation (5) Based on expert opinion, in the presence of alarm signs Extreme fear during anal inspection or symptoms or in patients with intractable constipation, Anal scars a digital examination of the anorectum is recommended to exclude underlying medical conditions. HD ¼ Hirschsprung disease. Voting: 7, 8, 8, 8, 8, 9, 9, 9 (6) The routine use of an abdominal radiograph to diagnose gastroenterology department. In the study by Benninga et al (27), a functional constipation is not indicated. CTT of 62 hours had a sensitivity of 52% (43–61) and a Voting: 8, 8, 9, 9, 9, 9, 9, 9 specificity of 91% (85–97), indicating that a CTT 600 mOsm/L) supple- The search identified 263 studies. None fulfilled our mental fluid, and normal fluid intake. This study has a high risk of inclusion criteria. No studies have assessed the diagnostic value bias: no information was provided about randomization, blinding, of scintigraphy in children with functional constipation. or the rate of loss-to-follow-up monitoring. No statistical assess- ment was conducted. The RCT found similar stool frequency at 3 weeks for the 3 groups. Because of the missing data such as means (17) Based on expert opinion, colonic manometry may be with SD, a GRADE evidence profile could not be performed. indicated in patients with intractable constipation In conclusion, evidence does not support the use of extra before considering surgical intervention. Voting: 7, 7, 8, 9, 9, 9, 9, 9 fluid intake in the treatment of functional constipation. (18) The routine use of MRI of the spine is not recommended in patients with intractable consti- 6.3 Physical Activity (Fig. 2, Box 9 ‘‘Education’’) pation without other neurologic abnormalities. Voting: 7, 7, 9, 9, 9, 9, 9, 9 There are no randomized studies that evaluate the effect of (19) Based on expert opinion, we do not recommend increased physical activity in childhood constipation. obtaining full-thickness colonic biopsies to diagnose colonic neuromuscular disorders in children with 6.4 Prebiotics intractable constipation. Voting: 7, 8, 8, 8, 8, 9, 9, 9 (20) Based on expert opinion we do not recommend 6.5 Probiotics routine use of colonic scintigraphy studies in children The present search identified 153 studies, including 4 sys- with intractable constipation. tematic reviews (9,56,57,64). Tabbers et al (9) performed a GRADE Voting: 9, 9, 9, 9, 9, 9, 9, 9 assessment for most of the interventions. In the latter assessment, different inclusion criteria and outcome measures were used com- pared with the present review. No evidence was found supporting Question 6: What Is the Additional Effect of the the use of prebiotics and probiotics (9). The other reviews included the same 2 RCTs concerning probiotics (56,57,64). Two systematic Following Nonpharmacologic Treatments in reviews included the same study concerning prebiotics but did not Children With Functional Constipation? perform a GRADE evaluation (56,57). After these reviews, 3 more RCTs, fulfilling our inclusion criteria, evaluating the effect of For the role of CMP-free diet: see question 4.1 (Fig. 1, Box probiotics, were published (65–67). It was, however, only possible 24; Fig. 2, Box 21). to perform a GRADE evidence profile of 1 study owing to missing data in the other 2 studies (67). Therefore, we discuss these 2 studies. 6.1 Fiber (Fig. 1, Box 8; Fig. 2, Box 9 ‘‘Education’’) Guerra et al (65) carried out a crossover double-blind trial in 59 Brazilian children with functional constipation according to The search identified 111 studies including 3 systematic Rome III criteria. This study has a low risk of bias. The patients reviews (9,56,57). Tabbers et al (9) performed a Clinical Evidence were randomized in 2 groups to receive either a goat yogurt GRADE evaluation for most of the interventions. They, however, supplemented with 109 colony-forming unit/mL Bifidobacterium used different inclusion criteria and outcome measures compared longum daily or only the yogurt for a period of 5 weeks. The with the present review. They found limited evidence that results were only graphically presented without reporting absolute additional fiber improves constipation compared with placebo numbers. and that increased fiber intake is not as effective as lactulose. Coccorullo et al (66) performed a double-blind randomized Pijpers et al (56) included 2 studies concerning fiber and concluded placebo-controlled study in 44 formula-fed infants with a diagnosis that the pooled weighted standardized mean difference was 0.35 of functional chronic constipation according to Rome III criteria. bowel movements per week in favor of fiber (95% CI 0.04 to This study has a low risk of bias. One group received supplement- 0.74), which is neither statistically significant nor clinically ation with the probiotic Lactobacillus reuteri (DSM 17938) and the relevant. The third and most recent systematic review concluded other group received a placebo. L reuteri was administered at a dose that studies were highly diverse with regard to the participants, of 108 colony-forming units in 5 drops of oil suspension once per interventions, and outcome measures; therefore, a meta-analysis day for 8 weeks. Infants treated with L reuteri had a significantly could not be performed (57). Based on these 3 reviews, 3 studies higher defecation frequency than placebo after 2, 4, and 8 weeks of www.jpgn.org 267 Copyright 2014 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.  Tabbers et al JPGN
Volume 58, Number 2, February 2014 treatment. The results were graphically presented without reporting Quality of evidence: very low. absolute numbers with means and SDs, and there was no mean difference for outcome measures between the 2 groups. In summary, 1 study reporting the effect of prebiotics and (24) The routine use of prebiotics is not recommended in 5 studies reporting the effect of probiotics fulfilled our inclusion the treatment of childhood constipation. criteria. It was possible to perform a GRADE evidence profile Voting:9,9,9,9,9,9,9,9 concerning the prebiotic study and 3 concerning probiotic studies. In conclusion, evidence does not support the use of pre- or Quality of evidence: low. probiotics in the treatment of childhood constipation. (25) The routine use of probiotics is not recommended in 6.6 Behavioral Therapy (Fig. 2, Boxes 11, 27, and the treatment of childhood constipation. 35) and 6.7 Biofeedback (Fig. 2, Box 35) Voting: 7, 8, 8, 9, 9, 9, 9, 9 The search identified 194 studies including 3 systematic reviews (9,57,68). All of the reviews concluded that behavioral Quality of evidence: low. therapy in addition to laxatives is not more effective than laxatives alone. Only 1 study (69) fulfilled our inclusion criteria: see (26) The routine use of an intensive behavioral protocolized Appendix, question 6, http://links.lww.com/MPG/A295. Concern- therapy program in addition to conventional treatment ing biofeedback therapy, 2 systematic reviews included the same is not recommended in childhood constipation. studies with the same outcome measures (57,68). See GRADE Voting: 9, 9, 9, 9, 9, 9, 9, 9 evidence profiles in Appendix, question 7, http://links.lww.com/ (27) Based on expert opinion, we recommend demysti- MPG/A295. fication, explanation, and guidance for toilet training In conclusion, evidence does not support the use of (in children with a developmental age of at least behavioral therapy or biofeedback in the treatment of child- 4 years) in the treatment of childhood constipation. hood constipation. Voting: 7, 8, 8, 8, 8, 9, 9, 9 Comment: There may be benefit to refer children with constipation and behavioral abnormalities to a mental health pro- vider (Fig. 2, boxes 11, 27, and 35). Quality of evidence: low. 6.8 Multidisciplinary Treatment (Pediatrician or Pediatric Gastroenterologist, Dietician, (28) The use of biofeedback as additional treatment is not recommended in childhood constipation. Psychologist, and Physical Therapist) Voting: 7,8,8,9,9,9,9,9 No RCTs were found. Quality of evidence: low. 6.9 Alternative Medicine (Including Acupuncture, Homeopathy, Mind-Body Therapy, Musculoskeletal Manipulations Such As Osteopathic and (29) Based on expert opinion, we do not recommend the Chiropractic and Yoga) routine use of multidisciplinary treatment in childhood constipation. No RCTs were found. Voting: 9,9,9,9,9,9,9,9 Quality of evidence: very low. Quality of evidence: low. (21) A normal fiber intake is recommended in children (30) Based on expert opinion, we do not recommend with constipation. the use of alternative treatments in childhood con- Voting: 6, 8, 9, 9, 9, 9, 9, 9 stipation. Voting: 9, 9, 9, 9, 9, 9, 9, 9 Quality of evidence: low. (22) Based on expert opinion, we recommend a normal Question 7: What Is the Most Effective and fluid intake in children with constipation. Safest Pharmacologic Treatment in Children Voting: 9, 9, 9, 9, 9, 9, 9, 9 With Functional Constipation? The search identified 252 studies including 5 systematic Quality of evidence: low. reviews (9,56,70–72). Among the 5 systematic reviews, the review of Price et al (70) did not include any drug trial. Lee-Robichaud et al (23) Based on expert opinion, we recommend a normal (71) performed a review to determine whether lactulose or poly- physical activity in children with constipation. ethylene glycol (PEG) was more effective in treating chronic Voting: 9, 9, 9, 9, 9, 9, 9, 9 constipation and fecal impaction in adults and children. We included the 5 pediatric studies from that review in this guideline: 268 www.jpgn.org Copyright 2014 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.  JPGN
Volume 58, Number 2, February 2014 Evaluation and Treatment of Functional Constipation in Children see GRADE evidence profiles for pooled outcome measures in 7.2 Which Pharmacologic Treatment Should Be Appendix, question 7, http://links.lww.com/MPG/A295 (73–77). Given for Maintenance Therapy? (Fig. 1, Boxes 10 Tabbers et al (9) investigated the effectiveness of most of the pharmacologic interventions but used different inclusion criteria and 14; Fig. 2, Box 13) and outcome measures compared with our guidelines. In separate In conclusion, evidence shows that PEG is more effective reviews, both Candy et al (72) and Pijpers et al (56) concluded that compared with lactulose, milk of magnesia, mineral oil, or because of the heterogeneity of the included studies with regard to placebo. More studies have been performed evaluating the effec- participants, interventions, and outcome measures, statistical pool- tiveness of lactulose than studies evaluating the effect of milk of ing of the results was not possible for most of the interventions. magnesia and mineral oil in children with constipation. More Nine studies fulfilled our inclusion criteria and were not already important, lactulose is considered to be safe for all ages. For these included by Lee-Robichaud et al (see GRADE evidence profiles in reasons, lactulose is recommended in case PEG is not available. Appendix, question 7, http://links.lww.com/MPG/A295) (78–86). Furthermore, evidence does not support the addition of enemas to No RCTs were found about the optimal dosages of the different the chronic use of PEG in children with constipation. medications (see Table 6 for recommended dosages of most fre- quently used oral and rectal laxatives). 7.3 How Long Should Children Receive Medical Therapy? (Fig. 1, Box 14; Fig. 2, Box 13) 7.1 Which Pharmacologic Treatment Should Be No RCTs have investigated the optimal duration of medical Given for Disimpaction? (Fig. 2, Boxes 6 and 11) treatment in children with functional constipation. No placebo-controlled studies have evaluated the effect of Quality of evidence: very low. oral laxatives or enemas on disimpaction. One study compared the effect of PEG to enemas but could not detect a difference in effect (31) The use of PEG with or without electrolytes orally 1 to (85). 1.5 g  kg1  day1 for 3 to 6 days is recommended as In conclusion, evidence shows that PEG and enemas are the first-line treatment for children presenting with equally effective for fecal disimpaction. fecal impaction. Comment: High-dose PEG given orally is associated with a Voting: 6, 7, 7, 8, 8, 9, 9, 9 higher frequency of fecal incontinence during treatment of the fecal (32) An enema once per day for 3 to 6 days is recommended impaction compared with enema use; however, based on the for children with fecal impaction, if PEG is not argument that PEG can be administered orally, the working group available. decided to prefer PEG. TABLE 6. Dosages of most frequently used oral and rectal laxatives Oral laxatives Dosages Osmotic laxatives Lactulose 1–2 g/kg, once or twice/day PEG 3350 Maintenance: 0.2–0.8 g  kg1  day1 PEG 4000 Fecal disimpaction: 1–1.5 g  kg1  day1 (with a maximum of 6 consecutive days) Milk of magnesia (magnesium hydroxide) 2–5 y: 0.4–1.2 g/day, once or divided 6–11 y: 1.2–2.4 g/day, once or divided 12–18 y: 2.4–4.8 g/day, once or divided Fecal softeners Mineral oil 1–18 y: 1–3 mL  kg1  day1, once or divided, max 90 mL/day Stimulant laxatives Bisacodyl 3–10 y: 5 mg/day >10 y: 5–10 mg/day Senna 2–6 y: 2.5–5 mg once or twice/day 6–12 y: 7.5–10 mg/day >12 y: 15–20 mg /day Sodium picosulfate 1 mo–4 y: 2.5–10 mg once/day 4–18 y: 2.5–20 mg once/day Rectal laxatives/enemas Bisacodyl 2–10 y: 5 mg once /day >10 y: 5–10 mg once /day Sodium docusate 6 y: 120 mL Sodium phosphate 1–18 y: 2.5 mL/kg, max 133 mL/dose NaCl Neonate 1 kg: 10 mL >1 y: 6 mL/kg once or twice/day Mineral oil 2–11 y: 30–60 mL once/day >11 y: 60–150 mL once/day PEG ¼ polyethylene glycol. www.jpgn.org 269 Copyright 2014 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.  Tabbers et al JPGN
Volume 58, Number 2, February 2014 Quality of evidence: very low. comparing different types of surgical procedures for the adminis- tration of antegrade enemas have been published. (33) The use of PEG with or without electrolytes is recommended as the first-line maintenance treatment. 8.3 Transcutaneous Nerve Stimulation (TNS) A starting dose of 0.4 g  kg1  day1 is (Fig. 2, Boxes 34 and 35) recommended and the dose should be adjusted according to the clinical response. Transcutaneous electrical stimulation is a noninvasive and Voting: 7, 7, 8, 8, 9, 9. Two members (who had painless form of interferential therapy in which 4 surface electro- disclosed a COI with industry manufacturing des are applied to the skin (2 abdominal, just below the costal PEG) did not participate in the discussion and did margin; 2 paraspinal, over muscles between T9 and L2 spinal not vote. segments), which produce 2 sinusoidal currents that cross within (34) The addition of enemas to the chronic use of PEG is the body (93). not recommended in children with constipation. See the GRADE evidence profile of 1 study in Appendix, Voting: 7, 8, 8, 8, 8, 9, 9, 9 question 8, http://links.lww.com/MPG/A295 (94). In this RCT, (35) The use of lactulose as the first-line maintenance investigators report a significant improvement of quality of life treatment is recommended, if PEG is not available. in children treated with TNS; however, the basal scores of quality of Voting: 7, 7, 8, 8, 8, 9, 9, 9 life in the 2 groups were not similar, thus precluding any valuable (36) Based on expert opinion, the use of milk of magnesia, conclusion. In addition, in another report, TNS decreased transit mineral oil, and stimulant laxatives may be con- time in treated patients but no data on stool pattern and frequency sidered as an additional or second-line treatment. were reported (95). Voting: 7, 7, 7, 7, 9, 9, 9, 9 In conclusion, evidence does not support the use of TNS in children with intractable constipation. Quality of evidence: low. Quality of evidence: low. (37) Based on expert opinion, maintenance treatment (39) Based on expert opinion, we do not recommend the should continue for at least 2 months. All symptoms routine use of lubiprostone, linaclotide, and pruca- of constipation symptoms should be resolved for at lopride in children with intractable constipation. least 1 month before discontinuation of treatment. Voting: 9, 9, 9, 9, 9, 9, 9, 9 Treatment should be decreased gradually. Voting: 7,7,8,8,8,8,9,9 (38) Based on expert opinion, in the developmental stage Quality of evidence: low. of toilet training, medication should only be stopped once toilet training is achieved. (40) Based on expert opinion, we recommend antegrade Voting: 7,7,7,8,8,9,9,9 enemas in the treatment of selected children with intractable constipation. Voting: 7, 7, 8, 8, 8, 9, 9 (General practitioner did Question 8: What Is the Efficacy and Safety of not vote because of lack of experience.) Novel Therapies for Children With Intractable Constipation? Quality of evidence: very low. 8.1 Lubiprostone, Linaclotide, and Prucalopride (41) The routine use of TNS in children with intractable Lubiprostone, linaclotide, and prucalopride are drugs that constipation is not recommended. have been found to be effective in constipated adults. To date, no Voting: 9, 9, 9, 9, 9, 9, 9, 9 randomized studies have been published in children. Question 9: What Is the Prognosis and What 8.2 Surgery (Fig. 2, Boxes 34 and 35) Are Prognostic Factors in Children With The use of ACE has been reported as a successful therapeutic Functional Constipation? option for patients with long-lasting constipation when maximal conventional therapy is not successful. The antegrade delivery of One systematic review was included (96). In addition to the cleansing solutions enables the patient to evacuate the colon at systematic review, 2 studies were added (97,98). In total, 15 pro- regular intervals, avoiding impaction of feces and reducing fecal spective studies were included, of which 7 were performed in tertiary incontinence. care hospitals, 6 in general pediatric practices, and 1 in primary care; No randomized studies were found. in 1 study the location was not specified (97–111). Borowitz et al (98) Comment: Six open retrospective studies are available in reported that primary care physicians tend to undertreat childhood children suggesting that ACE may be an option in children with constipation. This is in line with the results of Bongers et al (97) that intractable constipation (87–92). Potential complications (devel- delay in treatment, defined as time between age at onset and first opment of granulation tissue, leakage around the tube, tube dis- presentation at the department of pediatric gastroenterology, is lodgment, skin infection, and stoma stenosis) should be thoroughly negatively related to recovery (OR 0.81, 95% CI 0.71–0.91). More- considered and discussed with parents and children. No data over, it also agrees with the results of van den Berg et al (109), who 270 www.jpgn.org Copyright 2014 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.  JPGN
Volume 58, Number 2, February 2014 Evaluation and Treatment of Functional Constipation in Children found that duration of symptoms 3 months from symptom onset correlates constipation in the absence of alarm symptoms. with longer duration of symptoms. (12) Based on expert opinion, a 2- to 4-week trial of avoidance of CMP may be indicated in the child with intractable constipation. 9.2 What Are Prognostic Factors in Children With (13) Routine laboratory testing to screen for hypothyroid- Functional Constipation? ism, celiac disease, and hypercalcemia is not recommended in children with constipation in the See Table 7. absence of alarm symptoms. (14) Based on expert opinion, the main indication to perform ARM in the evaluation of intractable TABLE 7. Summary of evidence for any of the following factors being constipation is to assess the presence of the RAIR. related to the prognosis of functional constipation (see Appendix for (15) Rectal biopsy is the gold standard for diagnosing HD. more details, http://links.lww.com/MPG/A295) We do not recommend performing barium enema as (16) There is limited /insufficient evidence relative to the prognostic value an initial diagnostic tool for the evaluation of children of functional constipation of the following factors with constipation. Demographics/history: age at presentation, age at onset, duration (17) Colonic manometry may be indicated in patients with of symptoms