Management of Childhood Functional Constipation

      Key Words

      • 1
        Explain the criteria for functional constipation diagnosis.
      • 2
        Manage children with functional constipation using the most current evidence-based recommendations.
      • 3
        Discuss first- and second-line medications for fecal disimpaction and maintenance therapy.
      Constipation is a common problem during childhood, and 0.7% to 29.6% of children are constipated worldwide (
      • Mugie S.M.
      • Benninga M.A.
      • Di Lorenzo C.
      Epidemiology of constipation in children and adults: A systematic review.
      ). This condition accounts for 3% to 5% of pediatric primary care visits and up to 25% of gastroenterology consultations (
      • Di Lorenzo C.
      Childhood constipation: Finally some hard data about hard stools!.
      ,
      • Youssef N.
      • Di Lorenzo C.
      Childhood constipation evaluation and treatment.
      ). Children presenting to the emergency department with abdominal pain are most often diagnosed with constipation (
      • Caperell K.
      • Pitetti R.
      • Cross K.P.
      Race and acute abdominal pain in a pediatric emergency department.
      ). Constipated children have more outpatient and emergency department visits, and their overall annual medical cost is approximately twice as much as that of children without constipation (
      • Choung R.S.
      • Shah N.D.
      • Chitkara D.
      • Branda M.E.
      • Van Tilburg M.A.
      • Whitehead W.E.
      • Talley N.J.
      Direct medical costs of constipation from childhood to early adulthood: A population-based birth cohort study.
      ). Nearly all childhood constipation is functional, but 5% to 10% is due to an organic cause (
      • Youssef N.
      • Di Lorenzo C.
      Childhood constipation evaluation and treatment.
      ). In contrast to organic causes, functional constipation is not a result of a structural or biochemical abnormality (
      • Lewis M.L.
      • Palsson O.S.
      • Whitehead W.E.
      • van Tilburg M.A.L.
      Prevalence of functional gastrointestinal disorders in children and adolescents.
      ).
      A joint evidenced-based guideline for the evaluation and treatment of functional constipation was published in 2014 by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (
      • Tabbers M.M.
      • Di Lorenzo C.
      • Berger M.Y.
      • Faure C.
      • Langendam M.W.
      • Nurko S.
      • Benninga M.A.
      Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN.
      ). The guideline recommends the use of the ROME III definitions to diagnose functional constipation when there is no organic pathology (see Box 1). These definitions have evolved over the past 30 years and are used as criteria to identify functional gastrointestinal disorders (
      • Drossman D.
      Functional gastrointestinal disorders: History, pathophysiology, clinical features, and Rome IV.
      ). To fulfill the ROME III definitions, infants and children up to 4 years of age must have two or more of the criteria for at least 1 month. Children with a developmental age of at least 4 years must have a minimum of two criteria at least weekly for a minimum of 2 months, without criteria supporting irritable bowel syndrome (
      • Tabbers M.M.
      • Di Lorenzo C.
      • Berger M.Y.
      • Faure C.
      • Langendam M.W.
      • Nurko S.
      • Benninga M.A.
      Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN.
      ). Since the 2014 guideline publication, ROME IV definitions have been introduced. They are similar to the ROME III definitions except that a 1-month duration of symptoms is needed to define constipation in children of all ages (
      • Benninga M.A.
      • Nurko S.
      • Faure C.
      • Hyman P.E.
      • St James Roberts I.
      • Schechter N.L.
      Childhood functional gastrointestinal disorders: Neonate/toddler.
      ,
      • Hyams J.S.
      • Di Lorenzo C.
      • Saps M.
      • Shulman R.J.
      • Staiano A.
      • van Tilburg M.
      Childhood functional gastrointestinal disorders: Child/adolescent.
      ).
      ROME III: Diagnostic criteria for functional constipation
      Child with developmental age < 4 years:
      • ≤ 2 defecations/week
      • At least one incontinence per week after the acquisition of toileting skills
      • History of excessive stool retention
      • History of painful or hard bowel movements
      • Presence of a large fecal mass in the rectum
      • History of large-diameter stools that may obstruct the toilet
      Additional symptoms may include irritability, decreased appetite, and/or early satiety, which may resolve immediately after defecation of a large stool.
      Child with developmental age ≥ 4 years:
      • ≤ 2 defecations in the toilet per week
      • At least one episode of fecal incontinence per week
      • History of retentive posturing or excessive volitional stool retention
      • History of painful or hard bowel movements
      • Presence of a large fecal mass in the rectum
      • History of large-diameter stools that may obstruct the toilet
      Source:
      • Tabbers M.M.
      • Di Lorenzo C.
      • Berger M.Y.
      • Faure C.
      • Langendam M.W.
      • Nurko S.
      • Benninga M.A.
      Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN.
      .
      Fecal impaction is defined as a hard mass palpated in the lower abdomen, an enlarged rectum filled with a large amount of stool on rectal examination, or the abdominal radiography finding of excessive stool in the distal colon (
      • Tabbers M.M.
      • Di Lorenzo C.
      • Berger M.Y.
      • Faure C.
      • Langendam M.W.
      • Nurko S.
      • Benninga M.A.
      Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN.
      ). An impaction is present in 30% to 75% of constipated children and more than 90% of children with fecal incontinence (
      • Benninga M.A.
      • Voskuijl W.P.
      • Taminiau J.A.J.M.
      Childhood constipation: Is there new light in the tunnel?.
      ,
      • Loening-Baucke V.
      Encopresis.
      ).
      Infant dyschezia is a condition categorized by the ROME IV criteria that occurs in infants younger than 9 months of age and typically resolves spontaneously in 3 to 4 weeks. The infant strains and screams for at least 10 minutes before successfully or unsuccessfully passing soft stool (
      • Benninga M.A.
      • Nurko S.
      • Faure C.
      • Hyman P.E.
      • St James Roberts I.
      • Schechter N.L.
      Childhood functional gastrointestinal disorders: Neonate/toddler.
      ). Bowel movements usually happen daily. It is believed this behavior occurs because of the inability to coordinate increased intra-abdominal pressure with relaxation of the pelvic floor muscle. As muscle coordination improves during infancy, this condition resolves (
      • Tabbers M.M.
      • Di Lorenzo C.
      • Berger M.Y.
      • Faure C.
      • Langendam M.W.
      • Nurko S.
      • Benninga M.A.
      Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN.
      ,
      • Youssef N.
      • Di Lorenzo C.
      Childhood constipation evaluation and treatment.
      ). Evidence supports that infant dyschezia does not lead to infant functional constipation, and there is no role for treatment other than providing reassurance to parents (
      • Kramer E.A.H.
      • den Hertog-Kuijl J.H.
      • van den Broek L.M.C.L.
      • van Leengoed E.
      • Bulk M.W.
      • Kneepkens C.M.F.
      • Benninga M.A.
      Defecation patterns in infants: A prospective cohort study.
      ).

      Functional Causes of Constipation

      Bowel movement frequency and consistency is a function of diet composition and gastrointestinal motility. The stool pattern of exclusively breastfed infants can vary from multiple times a day to soft, infrequent bowel movements. Infants fed standard infant formula produce fewer daily stools than breastfed infants, although by 4 months of age they have similar bowel movement frequency. Breastfed infants produce larger stools than those fed standard infant formula until food introduction. This is because breast milk contains nonnutritive proteins and oligosaccharides that are not digested or absorbed (
      • Weaver L.T.
      • Ewing G.
      • Taylor L.C.
      The bowel habit of milk-fed infants.
      ). Standard infant formulas contain higher levels of lipids and minerals, particularly calcium fat acid soaps, which contribute to stool hardness (
      • Nowacki J.
      • Lee H.
      • Lien R.
      • Cheng S.
      • Li S.
      • Yao M.
      • Mutungi G.
      Stool fatty acid soaps, stool consistency and gastrointestinal tolerance in term infants fed infant formulas containing high sn-2 palmitate with or without oligofructose: A double-blind, randomized clinical trial.
      ,
      • Quinlan P.T.
      • Lockton S.
      • Irwin J.
      • Lucas A.L.
      The relationship between stool hardness and stool composition in breast- and formula-fed infants.
      ). When standard infant formula is introduced to breastfed infants, fewer and firmer stools are produced (
      • Lloyd B.L.
      • Halter R.J.
      • Kuchan M.J.
      • Baggs G.E.
      • Ryan A.S.
      • Masor M.L.
      Formula tolerance in postbreastfed and exclusively formula-fed infants.
      ). Soy formula–fed infants have harder stools because soy formula contains a small amount of fiber, whereas other formulas do not (
      • Hyams J.S.
      • Treem W.R.
      • Etienne N.L.
      • Weinerman H.
      • MacGilpin D.
      • Hine P.
      • Burke G.
      Effect of infant formula on stool characteristics of young infants.
      ).
      Bowel movement frequency decreases with age. Stool production occurs more often in the first month of life and may be attributed to immaturity of the gastrointestinal tract. Research supports a decrease in mean bowel movement frequency between 1 and 4 years of age. After 4 years of age, bowel movement frequency remains unchanged (
      • Baker S.
      • Liptak G.
      • Colletti R.
      • Croffie J.
      • Di Lorenzo C.
      • Ector W.
      • Nurko S.
      Evaluation and treatment of constipation in infants and children: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
      ). There is a positive correlation between infrequency of bowel movements and hardness of stool. This is due to increasing whole gut transit time with age (
      • Weaver L.T.
      • Steiner H.
      The bowel habit of young children.
      ).

      Development of Constipation

      Parents may misinterpret withholding as straining or an attempt to defecate.
      The passage of hard stool can be perceived as painful and is the most frequently reported event resulting in constipation (
      • Borowitz S.M.
      • Cox D.J.
      • Sutphen J.L.
      • Kovatchev B.
      Treatment of childhood encopresis: A randomized trial comparing three treatment protocols.
      ). Pain leads to stool withholding because the child becomes afraid to defecate. In turn, the withholding creates a cycle of more pain when defecating. Withholding behavior during infancy includes arching the back and stiffening the legs, whereas older children tightly cross their legs or exhibit other unusual postures (
      • Loening-Baucke V.
      Prevalence, symptoms and outcome of constipation in infants and toddlers.
      ). Parents may misinterpret withholding as straining or an attempt to defecate.
      The withholding behavior causes contraction of the external anal sphincter and gluteal and pelvic floor muscles. The fecal mass then moves out of the rectal ampulla and back into the rectosigmoid colon, where the stool becomes harder and larger. Bowel movement frequency is decreased because the rectum accommodates the stool, and the urge to defecate goes away. Fecal incontinence, or leakage of liquid feces around the retained fecal mass, may happen and can be perceived by parents as diarrhea. In children older than developmental age 4 years, fecal incontinence is referred to as encopresis (
      • Benninga M.A.
      • Voskuijl W.P.
      • Taminiau J.A.J.M.
      Childhood constipation: Is there new light in the tunnel?.
      ).
      Toilet training is the second most often reported event leading to functional constipation (
      • Borowitz S.M.
      • Cox D.J.
      • Sutphen J.L.
      • Kovatchev B.
      Treatment of childhood encopresis: A randomized trial comparing three treatment protocols.
      ). It can be a challenge for some parents to toilet train their children. Research supports that stool toileting refusal occurs in 1 of every 5 children. This leads to stool withholding behavior and incontinence. Many parents of these children do not see this as a problem. Their immediate goal is for their child to wear underwear and not have stool incontinence rather than use the toilet to defecate (
      • Taubman B.
      Toilet training and toiling refusal for stool only: A prospective study.
      ). Children who are constipated before starting toilet training are also more difficult to train (
      • Schonwald A.
      • Sherritt L.
      • Stadtler A.
      • Bridgemohan C.
      Factors associated with difficult toilet training.
      ). Most children without developmental delay who do not toilet train by age four years are stool toileting refusers (
      • Taubman B.
      Toilet training and toiling refusal for stool only: A prospective study.
      ).
      Functional constipation is associated with some behavioral conditions, such as autism and attention deficit hyperactivity disorder (ADHD). It is the most common gastrointestinal problem in children with autism spectrum disorder. Younger autistic children, those with increased social impairment, or those with lack of expressive language are more likely to be constipated (
      • Gorrindo P.
      • Williams K.C.
      • Evon B.L.
      • Walker L.S.
      • McGrew S.G.
      • Levitt P.
      Gastrointestinal dysfunction in autism: Parental report, clinical evaluation, and associated factors.
      ). Children with ADHD are more apt to have constipation and fecal incontinence than children without ADHD (
      • McKeown C.
      • Hisle-Gorman E.
      • Eide M.
      • Gorman G.H.
      • Nylund C.M.
      Association of constipation and fecal incontinence with attention-deficit/hyperactivity disorder.
      ). Contributors to constipation in these children include ignoring the urge to defecate and being too focused on their environment. Constipation is also a known adverse effect of ADHD medications such as methylphenidate, atomoxetine, and dexamphetamine (
      • Peeters B.
      • Noens I.
      • Philips E.M.
      • Kuppens S.
      • Benninga M.A.
      Autism spectrum disorders in children with functional defecation disorders.
      ). However, the literature indicates that the rate of constipation does not differ significantly between children taking prescribed ADHD medications and those children with ADHD not taking medication (
      • McKeown C.
      • Hisle-Gorman E.
      • Eide M.
      • Gorman G.H.
      • Nylund C.M.
      Association of constipation and fecal incontinence with attention-deficit/hyperactivity disorder.
      ).
      Children with bladder dysfunction are more likely to have bowel dysfunction. Fecal retention contributes to vesicoureteral reflux and urinary tract infections to the same degree, or more so, than dysfunctional voiding. Increased stool in the rectum can cause abnormal bladder pressure and function (
      • Koff S.A.
      • Wagner T.T.
      • Jayanthi V.R.
      The relationship among dysfunctional elimination syndromes, primary vesicoureteral reflux and urinary tract infections in children.
      ). Urinary tract infections and enuresis occur in 30% of constipated children (
      • Benninga M.A.
      • Voskuijl W.P.
      • Taminiau J.A.J.M.
      Childhood constipation: Is there new light in the tunnel?.
      ).
      Other causes of functional constipation include stress, diet changes such as the introduction of solids or cow's milk, illness, and change in routine. Many children refuse to defecate at school or in public toilets. It can be difficult for children to stop playing to use the toilet. Particularly, using a computer or other electronic devices and playing outside contribute to withholding or waiting to defecate. Children can also be in a hurry when defecating and, therefore, do not spend enough time completely emptying the rectum of stool.

      Evaluation of Constipation

      Constipated children may not present with a reported change in stool frequency or consistency. Instead, health care advice is sought for abdominal pain, decreased appetite, urinary dysfunction, or vomiting (
      • Carr B.C.
      • Cheng J.
      The evaluation and management of constipation in the pediatric emergency department.
      ). Parents are often unaware of their child's bowel pattern, and subjective description is unreliable in most children younger than 8 years (
      • Tabbers M.M.
      • Di Lorenzo C.
      • Berger M.Y.
      • Faure C.
      • Langendam M.W.
      • Nurko S.
      • Benninga M.A.
      Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN.
      ). The Bristol Stool Scale, an evidence-based tool, is helpful to use with children and their parents to accurately determine the consistency of the child's stool. A modified version of this scale (with Type 3 and Type 5 eliminated) is reliable when used with children 8 years of age and older. The modified scale descriptors should be read to children 6 to 8 years of age so that their responses are correct (
      • Lane M.M.
      • Czyzewski D.I.
      • Chumpitazi M.D.
      • Shulman R.J.
      Reliability and validity of a modified Bristol stool form scale for children.
      ).
      A thorough history and physical examination are sufficient to diagnose functional constipation. If an alarm sign that could indicate an underlying condition for the constipation is present (see Box 2), further work-up is necessary. When a child is being evaluated functional constipation, the current evidence-based recommendations do not support (a) digital examination of the anorectum, unless there is one ROME III criterion and functional constipation is uncertain, alarm signs are present, or there is intractable constipation; (b) abdominal radiograph, unless fecal impaction is suspected and physical examination is unreliable or not possible; (c) routine laboratory tests for hypothyroid, celiac disease, or hypercalcemia, unless alarm symptoms are present; and (d) cow's milk allergy testing, unless there are alarm signs (
      • Tabbers M.M.
      • Di Lorenzo C.
      • Berger M.Y.
      • Faure C.
      • Langendam M.W.
      • Nurko S.
      • Benninga M.A.
      Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN.
      ).
      Alarm signs and symptoms in constipation
      Tabled 1
      Constipation starting extremely early in life (< 1 month)Perianal fistula
      Passage of meconium > 48 hoursAbnormal position of anus
      Family history of Hirschsprung diseaseAbsent anal or cremasteric reflex
      Ribbon stoolsTuft of hair on spine
      Blood in the stools in the absence of anal fissuresSacral dimple
      Failure to thriveGluteal cleft deviation
      FeverExtreme fear during anal inspection
      Bilious vomitingAnal scars
      Abnormal thyroid gland
      Severe abdominal distension
      Decreased lower extremity strength/tone/reflex
      (
      • Tabbers M.M.
      • Di Lorenzo C.
      • Berger M.Y.
      • Faure C.
      • Langendam M.W.
      • Nurko S.
      • Benninga M.A.
      Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN.
      )

      Treatment of Constipation

      Nonpharmacologic Therapy

      Traditional nonpharmacologic therapies include diet changes, specifically increasing fiber in the diet. There is weak evidence that diet has a major role in childhood constipation treatment (
      • Walia R.
      • Mulheran N.
      • Khan R.
      • Cuffari C.
      Chronic constipation in children: An overview.
      ). Furthermore, there is no evidence that diet reduces constipation when there is stool withholding and retention (
      • Loening-Baucke V.
      Encopresis.
      ). Fiber is often considered a remedy for constipation but may instead worsen symptoms if the child is severely constipated (
      • Muller-Lissner S.A.
      • Kamm M.A.
      • Scarpignato C.
      • Wald A.
      Myths and misconceptions about chronic constipation.
      ). A well-balanced diet that includes whole grains, fruits, and vegetables is recommended for children with constipation (
      • Baker S.
      • Liptak G.
      • Colletti R.
      • Croffie J.
      • Di Lorenzo C.
      • Ector W.
      • Nurko S.
      Evaluation and treatment of constipation in infants and children: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
      ). The 2014 functional constipation guidelines do not support the following therapies for the treatment of childhood functional constipation: fiber supplements, extra fluid intake, routine use of pre- or probiotics, or alternative treatments such as acupuncture or chiropractic therapy (
      • Tabbers M.M.
      • Di Lorenzo C.
      • Berger M.Y.
      • Faure C.
      • Langendam M.W.
      • Nurko S.
      • Benninga M.A.
      Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN.
      ).

      Pharmacologic Therapy

      Medications used in the treatment of functional constipation include those for treating impaction and drugs for ongoing maintenance therapy.

      Medications for disimpaction

      If a disimpaction is not done before starting maintenance therapy, the child is more likely to have fecal incontinence, abdominal pain, and bloating (
      • Benninga M.A.
      • Voskuijl W.P.
      • Taminiau J.A.J.M.
      Childhood constipation: Is there new light in the tunnel?.
      ). Evidence shows that oral polyethylene glycol (PEG) and enemas are equally effective for fecal disimpaction (
      • Tabbers M.M.
      • Di Lorenzo C.
      • Berger M.Y.
      • Faure C.
      • Langendam M.W.
      • Nurko S.
      • Benninga M.A.
      Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN.
      ). PEG can take 2 to 3 days to result in complete disimpaction and is better tolerated by children than enemas. Enemas are rectally administered fluid containing chemical agents that can influence gut motility, cause an osmotic effect, or both. Common adverse effects of enemas are abdominal pain and anorectal discomfort (
      • Koppen I.J.N.
      • Lammers L.A.
      • Benninga M.A.
      • Tabbers M.M.
      Management of functional constipation in children: Therapy in practice.
      ). Although enemas result in faster disimpaction because their effect occurs within minutes, they are invasive and limited to distal colon disimpaction (
      • Alper A.
      • Pashankar D.S.
      Polyethylene glycol: A game changer laxative for children.
      ). Current recommendations for fecal disimpaction are found in Box 3.
      Medication recommendations for fecal disimpaction
      Tabled 1
      First line treatment: oral PEG, with or without electrolytes, 1.5 g/kg/day for 3 to 6 days; maximum dose 100 g/day
      If PEG is not available, one enema per rectum daily for 3 to 6 days:
      Bisacodyl2-10 years: 5 mg once a day
      >10 years: 5-10 mg once a day
      Sodium docusate< 6 years: 60 ml
      >6 years: 120 ml
      Sodium phosphate1-18 years: 2.5 ml/kg, maximum = 133 ml/dose
      Mineral oil2-11 years: 30-60 ml once a day
      >11 years: 60-150 ml once a day
      Note. PEG, polyethylene glycol.
      Sources:
      • Tabbers M.M.
      • Di Lorenzo C.
      • Berger M.Y.
      • Faure C.
      • Langendam M.W.
      • Nurko S.
      • Benninga M.A.
      Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN.
      ,
      • Taketomo C.K.
      • Hodding J.H.
      • Kraus D.M.
      Pediatric & neonatal dosage handbook.
      .

      Maintenance therapy

      Medication is required to ensure that daily soft bowel movements are painless and completely emptied from the rectosigmoid colon (
      • Loening-Baucke V.
      Encopresis and soiling.
      ). Over time, the rectal caliber returns to its normal size, and the child resumes a regular defecation pattern (
      • Bulloch B.
      • Tenenbein M.
      Constipation: Diagnosis and management in the pediatric emergency department.
      ). Maintenance medications commonly used for treating constipation in children include osmotic laxatives, lubricants, and stimulants (Box 4).
      Maintenance medication recommendations for constipation
      Tabled 1
      Oral medications:
      First line: PEG, with or without electrolytes, at a starting dose of 0.4 g/kg/day and adjusted to achieve desired effect
      If PEG is not available, lactulose 1-2 g/kg, once or twice a day, or 1.5-3 ml/kg/day
      Second line or additional treatment:
      Milk of magnesia2-5 years: 0.4-1.2 g/day, once or divided
      6-11 years: 1.2-2.4 g/day, once or divided
      12-18 years: 2.4-4.8 g/day, once or divided
      Mineral oil1-18 years: 1-3 ml/kg/day, once or divided, maximum 90 ml/day
      Bisacodyl3-10 years: 5 mg/day, > 10 years: 5-10 mg/day
      Senna2-6 years: 4.4-6.6 mg at bedtime, maximum dose 6.6 mg twice a day
      6-12 years: 8.8-13.2 mg at bedtime, maximum dose 13.2 mg twice a day
      >12 years: 17.6-26.4 mg at bedtime, maximum dose 26.4 mg twice a day
      Note. PEG, polyethylene glycol.
      Sources:
      • Tabbers M.M.
      • Di Lorenzo C.
      • Berger M.Y.
      • Faure C.
      • Langendam M.W.
      • Nurko S.
      • Benninga M.A.
      Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN.
      ;
      • Taketomo C.K.
      • Hodding J.H.
      • Kraus D.M.
      Pediatric & neonatal dosage handbook.
      .
      Osmotic laxatives increase the water content of stool. PEG 3350 (Miralax, Bayer Corporation, Whippany, NJ) is the most frequently used form of PEG and has excellent efficacy and safety. Its molecular structure keeps water molecules in the intestine by means of hydrogen connections (
      • Koppen I.J.N.
      • Lammers L.A.
      • Benninga M.A.
      • Tabbers M.M.
      Management of functional constipation in children: Therapy in practice.
      ). Miralax is minimally absorbed in the intestine, and most of it is excreted in the feces. The effect of Miralax usually takes 1 to 2 days, and electrolyte absorption is not affected even at large doses (
      • Hammer H.F.
      • Santa Ana C.A.
      • Schiller L.R.
      • Fordtran J.S.
      Studies of osmotic diarrhea induced in normal subjects by ingestion of polyethylene glycol and lactulose.
      ,
      • Horn J.R.
      • Mantione M.
      • Johanson J.F.
      OTC polyethylene glycol 3350 and pharmacists' role in managing constipation.
      ). Miralax can be added to any hot or cold beverage, and 17 g should be mixed with 4 to 8 fluid ounces. Despite being tasteless, some children complain of a texture change, so it should be mixed well. To be effective, Miralax needs to be given daily, and tips to help with compliance can be helpful for parents (see Box 5). The most common reported adverse effects are bloating, cramping, and gas.
      Parent tips for Miralax compliance
      • Set alarm on your phone to remember to give it.
      • Stir it until fully dissolved.
      • Switch it up—mix in a variety of beverages.
      • Give it when your child is thirsty and has time to drink it—for example, after school.
      • Observe your child drinking the entire dose.
      The U.S. Food and Drug Administration (FDA) investigated reports of neuropsychiatric events in children who use PEG 3350 (Miralax) and concluded that there was no supported evidence (
      • U.S. Food and Drug Administration
      Potential signals of serious risks/hew safety information identified by the adverse event reporting system (AERS) between October = December 2011.
      ). Again, neurologic or psychological adverse effects of prolonged use of PEG 3350 have recently become a concern reported by some parents. Ethylene glycol can be a neurotoxin and may be found in PEG 3350 products. An FDA-commissioned study is currently being conducted at the Children's Hospital of Philadelphia to better understand the absorption of low-molecular-weight ingredients, like ethylene glycol, in the pediatric population (
      • U.S. Department of Health and Human Services
      The use of polyethylene glycol in the pediatric population (R01).
      ).
      The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition's position regarding PEG 3350 usage for constipation is that there is no evidence to support serious adverse effects. It is recommended that parents who have concerns with the safety of Miralax discuss this with their child's health care provider before discontinuing it (). According to the 2014 functional constipation guidelines, evidence shows that PEG is more effective than lactulose, magnesium hydroxide (milk of magnesia), mineral oil, and placebo and is the first drug of choice (
      • Tabbers M.M.
      • Di Lorenzo C.
      • Berger M.Y.
      • Faure C.
      • Langendam M.W.
      • Nurko S.
      • Benninga M.A.
      Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN.
      ).
      Lactulose is a nonabsorbable carbohydrate osmotic laxative that consists of galactose and lactose. In the colon, it is fermented by intraluminal bacteria into hyperosmolar molecular weight acids. This causes intraluminal water retention and a decrease in intraluminal pH, resulting in an increase in colonic peristalsis. The bacterial fermentation of lactulose also creates gas formation, which further causes intestinal distension and increased peristalsis (
      • Koppen I.J.N.
      • Lammers L.A.
      • Benninga M.A.
      • Tabbers M.M.
      Management of functional constipation in children: Therapy in practice.
      ). It is not absorbed in the intestine and is safe for children of all ages. The onset of action is 8 to 12 hours, with stool produced in 1 to 2 days. Adverse effects include gas, bloating, and cramping. The current guidelines recommend lactulose if PEG is not available. It is a safe medication and there are more studies supporting its effectiveness compared with second-line medications (
      • Tabbers M.M.
      • Di Lorenzo C.
      • Berger M.Y.
      • Faure C.
      • Langendam M.W.
      • Nurko S.
      • Benninga M.A.
      Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN.
      ).
      The osmotic laxative effect of milk of magnesia occurs because it contains hyperosmolar agents that are poorly absorbed, creating an osmotic gradient. This causes the colon to distend, and peristalsis increases. Its onset of action is 2 to 8 hours, and adverse effects include diarrhea, hypotension, weakness, and lethargy. It is eliminated in the kidneys, with unabsorbed drug excreted in the stool (
      • Taketomo C.K.
      • Hodding J.H.
      • Kraus D.M.
      Pediatric & neonatal dosage handbook.
      ). It should not be given to children with severe renal impairment, because accumulation of magnesium can lead to magnesium intoxication (
      • Koppen I.J.N.
      • Lammers L.A.
      • Benninga M.A.
      • Tabbers M.M.
      Management of functional constipation in children: Therapy in practice.
      ).
      Mineral oil, or liquid paraffin, is an emollient and acts primarily as a stool lubricant. It is a derivative of petroleum and is not absorbed by the intestines. When given orally, its laxative effect usually takes 1 to 2 days. Mineral oil does not interfere with fat-soluble vitamin tissue storage (
      • Sharif F.
      • Curshell E.
      • O'Driscoll K.
      • Bourke B.
      Liquid paraffin: A reappraisal of its role in the treatment of constipation.
      ). It should not be used in children younger than 1 year or in those who have difficulty swallowing, because there is the risk of lipoid pneumonia if aspiration occurs. It can leak from the rectum, and the oil discharge is orange in color. Oil leakage usually happens when there is retained stool or an excess of mineral oil (
      • Taketomo C.K.
      • Hodding J.H.
      • Kraus D.M.
      Pediatric & neonatal dosage handbook.
      ).
      Stimulants, such as bisacodyl and senna, are considered a second-line treatment for constipation. These medications, when metabolized in the colon, act directly on the intestinal mucosa, increasing intestinal motility and/or increasing water and electrolyte secretion. The laxative effect occurs in 6 to 8 hours, and although abdominal cramping is a common adverse effect, stimulants are usually well tolerated (
      • Koppen I.J.N.
      • Lammers L.A.
      • Benninga M.A.
      • Tabbers M.M.
      Management of functional constipation in children: Therapy in practice.
      ). There is concern of disturbed colonic motility with long-term stimulant therapy. Research supports that 6 months of senna therapy does not induce chronic changes in colonic motility in rats (
      • Fioramonti J.
      • Dupuy C.
      • Bueno M.
      In vivo motility of rat colon chronically pretreated with sennosides.
      ). The development of melanosis coli, a brown discoloration of the colon, with stimulant usage has no functional significance (
      • Muller-Lissner S.A.
      • Kamm M.A.
      • Scarpignato C.
      • Wald A.
      Myths and misconceptions about chronic constipation.
      ).

      Length of treatment

      Maintenance therapy should continue for at least 2 months, and all constipation symptoms should be resolved for a minimum of 1 month before changing the medication regimen. Medications should then be decreased slowly. Stopping medication therapy too soon can lead to relapse of constipation. More research is needed to determine the most optimal duration and tapering of medication therapy to prevent relapse or worsening of constipation (
      • Tabbers M.M.
      • Di Lorenzo C.
      • Berger M.Y.
      • Faure C.
      • Langendam M.W.
      • Nurko S.
      • Benninga M.A.
      Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN.
      ).

      Medications Under Investigation

      Three medications used successfully for the treatment of adult constipation may have a future role in the management of childhood constipation. Linactolide (Linzess, Ironwood Pharmaceuticals, Cambridge, MA), an oligopeptide agonist of guanylate cyclase, acts locally in the intestine to increase fluid secretion and motility; lubiprostone (Amitiza, Takeda Pharmaceuticals, Deerfield, IL), a chloride channel activator, increases intestinal fluid secretion and facilitates intestinal transit and passage of stool; and prucalopride (Resolor, Shire Pharmaceuticals, Cambridge, MA), a highly selective serotonin 5-HT4 receptor agonist, influences peristalsis and stimulates secretions (
      • Keating G.M.
      Prucalopride: A review of its use in the management of chronic constipation.
      ,
      • Wald A.
      Management of chronic constipation in adults.
      ). These medications are presently not recommended for use in children because of a lack of studies (
      • Tabbers M.M.
      • Di Lorenzo C.
      • Berger M.Y.
      • Faure C.
      • Langendam M.W.
      • Nurko S.
      • Benninga M.A.
      Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN.
      ).

      Treatment of Infant Functional Constipation

      When an infant is constipated, there is no evidence for recommending one brand of standard infant formula over another, because they contain similar ingredients and nutritional composition (
      • Marks K.
      Infant and toddler nutrition.
      ). Formula should not be diluted with more water, because this decreases its caloric density and can contribute to electrolyte abnormalities. Juice is often suggested to help constipation. Sorbitol, an undigestible, osmotically active carbohydrate that attracts water, is naturally contained in some infant juices such as prune, pear, and apple. Although sorbitol-containing juices increase the frequency and water content of stools, they should not replace formula intake (
      • Sood M.R.
      Prevention and treatment of acute constipation in infants and children.
      ). Alternatively, replacing water with infant juice when mixing formula does not interfere with the amount of formula consumed. For example, substituting ½ ounce water with ½ ounce infant juice 1 to 3 times a day for young infants, and 1 ounce water with 1 ounce infant juice 1 to 3 times a day for infants 3 to 4 months of age or older, can be beneficial. For infants who are eating solid foods, sorbitol-containing fruit purees can be given.
      A glycerin suppository, which is a rectal osmotic laxative, can be given occasionally to infants for immediate constipation relief. Suppositories are not recommended routinely, because this may lead to bowel dependency and can also be irritating to the anus or rectal mucosa (
      • Sood M.R.
      Prevention and treatment of acute constipation in infants and children.
      ). Lactulose is safe to give to infants younger than 6 months, and Miralax can be used in infants 6 months and older (
      • Vandenplas Y.
      • Benninga M.
      • Broekaert J.F.
      • Falconer J.
      • Gottrand F.
      • Guarino A.
      • Wilschanski M.
      Functional gastro-intestinal disorder algorithms focus on early recognition, parental reassurance and nutritional strategies.
      ).

      Education of Parents

      To be compliant with the treatment plan, the parents need to understand causes of functional constipation.
      To be compliant with the treatment plan, the parents need to understand causes of functional constipation. To provide thorough education, the initial visit should be at least 30 minutes, especially when the constipated child presents with fecal incontinence (
      • Di Lorenzo C.
      Childhood constipation: Finally some hard data about hard stools!.
      ). Only 50% of parents know that their child is constipated, and few understand that fecal incontinence is a result of constipation (
      • Loening-Baucke V.
      Encopresis and soiling.
      ). When there is little improvement in their child's condition, parents need regular reassurance that there is no organic cause for the constipation.
      Parents should understand the importance of medication therapy. They should know the purpose of medications and when to decrease or discontinue them. Some parents are reluctant to give daily medication for constipation, especially if it is needed long term. It is not uncommon for parents to stop medication once their child is passing soft stools or there is no longer fecal incontinence. The most frequent cause of constipation relapse is stopping medication treatment too soon (
      • Loening-Baucke V.
      Encopresis.
      ). Therefore, regular medical visits are essential to evaluate the child's progress and to ensure that the treatment plan is being followed.

      Behavior Therapy

      Withholding behavior due to painful stools should stop when the child is passing soft daily stools and is no longer afraid to defecate. It is helpful for parents to understand that it is difficult to withhold when doing such activities as running, walking, taking warm baths or showers, swimming, and sleeping. It can be frustrating for parents of children who withhold when playing, choose to no longer use the toilet independently to defecate, or are resistant when instructed to use it. Earning privileges can be a motivator for the child to follow the treatment plan. For example, to encourage the child who withholds when using electronics, electronic time could be allowed only if it is earned by defecating independently, cooperating when instructed to use the toilet, and taking daily medication. Assigning a specific amount of electronic time for each of these behaviors, with more time being earned for the most desired behavior, should increase the child's willingness to improve. An intensive behavior therapy program in combination with laxatives is not recommended. However, children who have behavior issues in addition to constipation may benefit from mental health therapy (
      • Tabbers M.M.
      • Di Lorenzo C.
      • Berger M.Y.
      • Faure C.
      • Langendam M.W.
      • Nurko S.
      • Benninga M.A.
      Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN.
      ).
      During toilet training, the child who is afraid to pass a bowel movement is unlikely to defecate in the toilet. It is not uncommon for parents to place their child on the toilet when they observe withholding behavior. Instead, toilet training should stop and not be resumed until the child has a normal stool pattern and is not resistant to sitting on the toilet. Furthermore, medication should not be discontinued until the child has successfully mastered toilet training (
      • Tabbers M.M.
      • Di Lorenzo C.
      • Berger M.Y.
      • Faure C.
      • Langendam M.W.
      • Nurko S.
      • Benninga M.A.
      Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN.
      ).
      Unhurried use of the toilet and privacy are important parts of therapy. Older children should be instructed to sit on the toilet and attempt to defecate 20 to 30 minutes after meals to take advantage of the gastrocolic reflex. This physiologic response occurs after a meal or after awakening and refers to the high-amplitude colonic contractions from the proximal to distal sigmoid colon that push stool into the rectum (
      • Lewis G.
      • Rudolph C.
      Practical approach to defecation disorders in children.
      ). Having a daily scheduled toilet sitting time also allows for the parents to verify their child's stool consistency, frequency, and amount. Proper positioning helps facilitate defecation. Children should have foot support if their feet do not touch the floor when sitting on the toilet. This helps flatten the anorectal angle and aids in complete emptying of the rectum (
      • Benninga M.A.
      • Voskuijl W.P.
      • Taminiau J.A.J.M.
      Childhood constipation: Is there new light in the tunnel?.
      ).

      Intractable Constipation

      Children who have been constipated for at least 3 months and are not responding to maximum medication therapy have intractable constipation. For these children, it is recommended that cow's milk protein be removed from their diet for 2 to 4 weeks. Experts also recommend antegrade enemas for select children (
      • Tabbers M.M.
      • Di Lorenzo C.
      • Berger M.Y.
      • Faure C.
      • Langendam M.W.
      • Nurko S.
      • Benninga M.A.
      Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN.
      ). The Malone Antegrade Continence Enema (MACE) surgery is an appendicostomy typically hidden within the umbilicus or placed in the right lower quadrant. Antegrade enemas can then be given to prevent constipation and fecal incontinence. Appropriate candidates for MACE surgery are children who have intractable constipation with significant social and emotional disruption. Occasional fecal soiling, leakage from the MACE, and granulation tissue can be complications after the MACE. This surgery can be a beneficial treatment option for children with intractable constipation and can improve their quality of life (
      • Har A.F.
      • Rescorla F.J.
      • Croffie J.M.
      Quality of life in pediatric patients with unremitting constipation pre and post Malone antegrade continence enema (MACE) procedure.
      ).

      Recovery

      Research shows that children will recover faster and are less likely to have constipation relapses when they receive early treatment. In the primary care setting, constipation may be viewed as something the child will outgrow, and this can delay treatment. Referral to a pediatric gastroenterology specialist is recommended when treatment is unsuccessful, there is concern of organic disease, or management is complicated (
      • Baker S.
      • Liptak G.
      • Colletti R.
      • Croffie J.
      • Di Lorenzo C.
      • Ector W.
      • Nurko S.
      Evaluation and treatment of constipation in infants and children: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
      ). At least one relapse will occur in 50% of children within the first 5 years after treatment (
      • van Ginkel R.
      • Reitsma J.B.
      • Buller H.A.
      • van Wijk M.P.
      • Taminiau J.A.
      • Benninga M.A.
      Childhood constipation: Longitudinal follow-up beyond puberty.
      ). As many as 25% to 50% of children will remain constipated into early adulthood (
      • Bongers M.E.J.
      • van Wijk M.P.
      • Reitsma J.B.
      • Benninga M.A.
      Long-term prognosis for childhood constipation: Clinical outcomes in adulthood.
      ,
      • Michaud L.
      • Lamblin M.
      • Mairesse S.
      • Turck D.
      • Gottrand F.
      Outcome of functional constipation in childhood: A 10-year follow-up study.
      ). Regular follow-up visits for at least 1 year after resolution of constipation are suggested to prevent relapse (
      • van Ginkel R.
      • Reitsma J.B.
      • Buller H.A.
      • van Wijk M.P.
      • Taminiau J.A.
      • Benninga M.A.
      Childhood constipation: Longitudinal follow-up beyond puberty.
      ).

      Summary

      Functional constipation is common during childhood and most often develops because of painful defecation. Medications are a critical part of therapy, as supported by the most current evidence-based guidelines. Successful management includes thorough parent education and toileting strategies. Children have a better prognosis when vigorous treatment is not delayed and close monitoring occurs.

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      Biography

      Lisa Philichi, Pediatric Gastroenterology Nurse Practitioner, Mary Bridge Children's Hospital and Health Center, Pediatric Gastroenterology Clinic, Tacoma, WA.

      Linked Article