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State-of-the-Art Pediatrics

November 2019

What's New: Management of Functional Constipation in Children 

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Author: John M. Rosen, MD | Pediatric Gastroenterology | Associate Professor of Pediatrics, UMKC School of Medicine  
    
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Column editor: Amita R. Amonker, MD | Pediatric Hospitalist | Assistant Professor of Pediatrics, UMKC School of Medicine 
 
Constipation is an extremely common presenting symptom in children, both at the primary care and gastroenterology specialty clinics. Constipation can be generally defined by difficulty passing a bowel movement. This can be due to bowel movements that are too hard or too large, or even relatively soft, but infrequent or incompletely evacuated. There is a wide variety of stooling frequency that can be normal, and daily (or even more frequent!) bowel movements do not prove that a child is not constipated. If these daily bowel movements are small, hard or painful, then constipation remains as a possible diagnosis.

Constipation can result in significant anxiety for the patient or caregiver due to potential symptom experience of abdominal pain, decreased appetite, painful bowel movements and fecal incontinence.  Parents see the discomfort of their toddler, are nervous about fecal continence as kindergarten approaches, or don’t know how to guide their teenager, who won’t poop outside the home.  Additionally, there is frequently worry about what might be the underlying cause. Despite this being a common, frustrating, and sometimes difficult-to-manage problem, children and their families can be reluctant to discuss with peers or seek help related to social stigma, and expected normative behavior related to stooling. 

Diagnosis

Most (~95%) children do not have an underlying identifiable cause for their difficulty stooling.  Instead, they have functional constipation. Functional constipation is defined by Rome IV criteria (consensus, expert, clinical definition based on symptoms only) and having at least 2 of the following for at least one month:

Infants to 4 years of age

  1. Two or fewer defecations per week
  2. History of excessive stool retention
  3. History of painful or hard bowel movements
  4. History of large diameter stools
  5. Presence of a large fecal mass in the rectum

And in toilet trained children

  1. Soiling at least once a week with small or large amount of poop in underwear
  2. History of large diameter stools which clog the toilet

> 4 years of age

  1. Two or fewer defecations per week in a child of developmental age at least 4 years
  2. At least one episode of fecal incontinence per week
  3. History of retentive posturing or excessive volitional stool retention
  4. History of painful or hard bowel movements
  5. Presence of a large fecal mass in the rectum
  6. History of large diameter stools which can obstruct the toilet

Symptoms cannot be explained by another condition

Certain disorders can be associated with constipation including celiac disease, hypothyroidism, Hirschsprung disease, spinal/neuromuscular abnormalities, hypocalcemia and anorectal malformations.  However, in the absence of clinical features indicative of a specific disorder, or alarm symptoms (blood in stools, failure to thrive, sacral dimple, etc.), testing is not recommended or required to make the diagnosis of functional constipation.

Frequently, abdominal X-ray is used to “diagnose” constipation. This is an inadequate test for many reasons and should be considered sparingly. The X-ray reflects a single 2-dimensional moment of colonic stool burden. It does not assess symptom experience, stool density or volume, and commonly shows stool in the colon (where it is supposed to be) in patients who are NOT constipated. Research in the emergency room setting has described how reliance on X-ray for constipation can result in false support for the diagnosis, and delay identification of other disorders. Even when experienced radiologists are using validated scoring systems, their agreement on abdominal X-ray stool burden is poor. When possible, diagnosis of constipation should be based on clinical history and physical exam.

Treatment

General treatment of constipation will not be reviewed in detail, and guidance can be found in many sources including our own publication (Colombo, Peds in Review, 2015). The basic outline of management remains the same:

  1. Identification of constipation as the diagnosis
  2. Education of the patient and family about the diagnosis   
    a. Expectations for treatment (often protracted, requires a routine)
    b. Goals for treatment (soft bowel movements that are easy to get out, achieve continence)
  3. Cleanout if large stool burden present
  4. Maintenance medical and behavioral management plan to prevent exacerbation

Frequently used maintenance medical management includes dietary modification or use of osmotic laxatives. Although sometimes effective, dietary modification for pediatric functional constipation has poor evidence to support its use. High-fiber diets can also be difficult to administer and result in excessive gas production, worsening constipation-related abdominal distension or discomfort (“beans, beans the magical fruit…”). Osmotic laxatives are familiar (lactulose, magnesium hydroxide/Milk of Magnesia, polyethylene glycol 3350/Miralax) and can be an effective first-line treatment. These medicines don’t always work or are not always tolerated. And although there is no published scientific evidence demonstrating significant harm from these medications (and limited safety evidence does exist), there continues to be intermittently voiced concern in the public and press about potential adverse effects, so knowledge of alternative options is beneficial.

Stimulant Laxatives

Stimulant laxatives, sennosides and bisacodyl, are an alternative option with emerging data in children.  These medications are metabolized (at least in part by Bifidobacteria-produced enzymes), and then metabolites work locally in the colon to cause contractions. Colonic contractions are typically sensed as the urge to stool (sometimes as nausea or discomfort) and propel liquid or solid stool toward the rectum. Children with chronic constipation may have conditioned ignorance of regular contraction signals and benefit from a stronger contraction that is more easily recognized, leading to a behavioral action of stooling for symptom relief. Further, these medicines can result in more complete evacuation of rectal stool, instead of just the train engine passing through, additional cars (maybe even the caboose) will pass. Paradoxically, children with frequent small stools can actually have reduction of stool frequency (with increased volume of stool) while taking stimulant laxatives, and incontinence may be better controlled due to improved emptying of retained stool. 

Questions are often raised about the safety of stimulant laxatives, particularly when used on a daily basis for an extended period of time. There is not a consensus answer to this question of safety. Most doctors and nurses remember learning about the danger of chronic stimulant laxative use during their training. However, evidence does not exist demonstrating these dangers in humans. This common teaching and “general knowledge” may derive from the use of phenolphthalein-derived laxatives in the past. These medications were considered “safe and effective” until 1997 when the FDA reclassified them as “not generally recognized as safe and effective” based on increased risk of cancer in rodents. Data does not support a clear link between phenolphthalein-derived laxative use and human cancer.  Sennosides and bisacodyl are NOT phenolphthalein-derived laxatives and their function and safety has been explored in a murine model (National Toxicology Report CAS 8013-11-4, Toxicology Study of Senna, 2012). A recent review of long-term senna use in children acknowledges reports of perianal rash at higher doses, but found no evidence of other adverse events or tolerance/dependence (Vilanova-Sanchez, J Peds Surg, 2018).

Practically, sennosides and bisacodyl come in a variety of easily administered, generally child-accepted formulations. Senna comes in liquid (8.8mg/5mL), capsule (8.6mg), and chocolate chewable (15mg) most commonly. Bisacodyl is available as a tablet (5mg), suppository (5mg), and pre-filled enema syringe (10mg/37mL). Their different formulations and mechanisms of action can be very attractive to patients and parents who feel osmotic laxative treatment is not effective or not preferred.

Pelvic Floor Therapy

Pelvic floor therapy is aimed at improving recognition and control of pelvic floor muscles. These muscles are integral in the purposeful retention and evacuation of stool (and urine) and can become dysfunctional in the setting of chronic voiding disorders in children. The muscles can also have intrinsic dysfunction or post-injury abnormalities, but this is much less common in pediatrics. Identification of dyssynergic defecation, or incoordination between the voluntary external anal sphincter relaxation and increased intra-abdominal pressure required for evacuating stool can be determined with anorectal manometry, but is not required prior to referral. Pelvic floor therapy can be performed by physical therapists, occupational therapists, nurses, physicians and other practitioners dependent on state regulations. Finding a practitioner comfortable with children can be difficult, as typical pelvic floor PT patients are post-partum women. The initial visit between a pediatric patient and pelvic floor therapist may include only education and rapport-building, as this can be uncomfortable for children and their parents due to unfamiliarity with the process. There are internal and external devices, and the approach in children typically is to use external (i.e., perianal) surface electrodes with biofeedback. This provides real-time feedback, often in a gamified design (e.g., make the bird fly over the mountain) that helps isolate appropriate muscle groups and encourages active and effective participation in therapy. Like many other physical therapy regimens, children may undergo a series of in-person sessions every 1-2 weeks for a limited time, then continue with practice of these exercises at home, sometimes returning for a brush-up/refresher after a few months if needed. Data supporting efficacy of pelvic floor therapy in children with constipation or fecal incontinence is very limited and not all supportive. However, with an accepting patient and skilled therapist, and along with a medical and behavioral bowel management plan, pelvic floor therapy can be an effective adjunct (Zar-Kessler, Dig Dis, 2019).

Novel Medications

New medications with alternative mechanism of action are developed often given the large market for their use in adults with constipation and irritable bowel syndrome-constipation type (IBS-C). These medications are not FDA-approved for use in pediatric constipation. In fact, there are no medicines FDA-approved for long-term use in pediatric constipation despite the clinical need for medicines to be used in this manner. Two main barriers exist for the use of novel medications in children: 1. Efficacy and safety data is very limited or not available and 2. Novel medications can be expensive and are not readily covered by prescription drug insurance plans. These are major barriers, but children who do not respond to “standard” treatments or cannot tolerate them have limited other options.

Lubiprostone/Amitiza is a twice-daily capsule that causes intestinal fluid secretion through the chloride channel-2 (ClC-2) along the intestinal epithelium. This fluid secretion is thought to soften stools and secondarily improve transit due to distension of the bowel. Reduction of intestinal permeability has also been shown in animal models, although the role for this in disease or symptom control is unclear.  Extensive supportive data exists in adults regarding safety and efficacy in functional constipation and IBS-C. For children, a multicenter open-label study was completed demonstrating that lubiprostone was well tolerated and increased spontaneous bowel movement frequency (Hyman, J Pediatr Gastroenterol Hepatol Nutr, 2014). Side effects included nausea (19%), vomiting (12%), and diarrhea (8%) in the study, although side effects are rare anecdotally. 

Linaclotide/Linzess is a guanylate cyclase-C agonist, activating this receptor throughout the upper and lower GI tract and is not thought to have systemic absorption/activity. Activation of these receptors increases intestinal transit and reduces visceral hypersensitivity. As a result, it is indicated for adult functional constipation and IBS-C. Studies in children with functional constipation (NCT02559570) and IBS-C (NCT02559817) were ongoing until this year. Initial analyses published on clinicaltrials.gov do not indicate superiority of linaclotide in any functional constipation outcome measures when compared to placebo. Adverse effects were rare, with diarrhea most commonly reported. The IBS-C study was terminated, and no results are available at this time. 

Neither medication should be used in patients less than 6 years old due to severe dehydration associated with these medications when initially tested in neonatal mice. Both lubiprostone and linaclotide’s capsule forms can be a reprieve for patients who are fatigued from daily osmotic laxatives (i.e., PEG-3350), but whose bowel movements would benefit from softening. 

Conclusion

Functional constipation is a common disorder in children, but many tools are available to aid in management. Determination of the best plan for a specific patient is paramount, as adherence to a medication and behavior management plan is necessary to determine if a treatment is effective for symptom control. Emerging pharmaceuticals and other strategies (constipation action plan, squatty potty, etc.) aimed at bowel management are exciting steps in better treatment for constipated children.

For more information about constipation myths and facts, listen to the NASPGHAN-sponsored “Bowel Sounds: The Pediatric GI Podcast” episode from Oct. 14, 2019 – Pediatric Constipation.

https://podcasts.apple.com/us/podcast/id1479342168

Apple podcast link

https://open.spotify.com/show/47siDPxpfBkC1xjDW5HnBM

Spotify podcast link

http://naspghan.buzzsprout.com

@bowelsounds

Twitter handle for podcast