REVIEW ARTICLE
Hippokratia 2015, 19(1):11-19
Xinias I, Mavroudi A
3rd Pediatric Department, Hippokratio Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
Abstract
Objective: Constipation is a frequent problem in childhood and may be defined as delay or difficulty in defecation that persists for longer than two weeks. It is one of the ten most frequent pathological conditions that a general paediatrician deals with. The aim of this review is to provide the general paediatrician an overview of constipation in children discussing the etiology, differential diagnosis, signs and symptoms and patient evaluation.
Methods: We provide an overview on the pathogenesis, the diagnostic approach and the management of constipation based on electronic literature searches using the best available evidence from PubMed, Medline, Google Scholar, the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN).
Results: The most common type of constipation is functional accounting for 90-95% of all cases. In a small percentage of children, who may have an organic cause of constipation, an appropriate laboratory investigation and imagine studying is warranted.
Conclusions: Functional constipation remains a frequent problem in childhood. Treatment options differ between infants and children. Emphasis on recommended regimens for maintenance and how to reduce medication will help to improve the long-term outcome. Moreover, it is of great importance to follow constipated children closely and restart medication promptly. On treatment failure or on suspicion of organic disease the patient should be referred for further evaluation. Hippokratia 2015, 19 (1): 11-19.
Key words: Constipation, children, gastroenterology, nutrition, evaluation, management
Corresponding author: Ioannis Xinias, Pediatrician, Assistant Professor of Pediatrics – Pediatric Gastroenterology, 62 Protomagias St, 54352, Thessaloniki, Greece, tel: +302310992877, +306945251600, fax: +302310992981, e-mail: xinias@auth.gr
Introduction
Constipation is typically characterized by lack of periodicity in defecating, bulky stools and difficulty or pain during defecation. Constipation is one of the ten most frequent problems that a general pediatrician deals with, accounting for 25% of referrals to pediatric gastroenterologists worldwide1. According to the diagnostic criteria for constipation, a patient must have experienced less than 3 bowel movements per week. Prevalence rates of constipation range from 0.7% to 29.6% of the worldwide general population. Up to 84% of functionally constipated children suffer from fecal incontinence, while more than one third of children present with behavioral problems primary or secondary due to constipation2,3. Most studies do not report prevalence difference between boys and girls or correlation with socio-economic factors4. The Northern American Society of Gastroenterology, Hepatology and Nutrition (NASPGHAN) defines constipation as a delay or difficulty in the defecation present for two weeks or more5.
The frequency of defecation depends on the child’s age. In the neonatal period and early infancy, defecation may occur more than 4 times a day and progressively decreases to 1-2 per day, at the age of 4 years, in which 98% of the children have gained voluntary control of the sphincter. The normal frequency of bowel movements is correlated to age. According to literature neonates and infants up to 3 months use to have 2.0 to 2.9 bowel movements per day. Older infants and children up to 3 years have 1.8 and 1.4 defecations/day respectively. Children over 3 years have about 1.0 defecation per day6. Terms which have been used to describe constipation, such as fecal leakage, fecal soiling and encopresis, do not describe the condition accurately. Fecal leakage may occur without co-existing constipation and can be either voluntary or involuntary. Encopresis is defined as voluntary or involuntary passage of stools in inappropriate places7. The terms encopresis and fecal leakage are often replaced by the term incontinence.
The Paris consensus on childhood constipation terminology8 includes a number of specific criteria that have been developed and complete the Rome III diagnostic criteria9,10. These criteria include, among else, bowel movement frequency, stool consistency and fecal incontinence (Table 1).
The term infantile dischezia is used to describe a pathological disorder, relatively often seen in infants by the pediatrician, characterized by pelvic floor dysfunction resulting in loose or watery stool and difficulty in defecating, often accompanied by irritability and crying. These babies are unable to coordinate the increased intra-abdominal pressure with the relaxation of the pelvic floor. This type of defecation may occur several times a day and last up to 20 minutes each time. The first signs of symptoms begin in the neonatal period and resolve automatically when muscle coordination is achieved. Parents can be reassured that this phenomenon is part of the learning process of the child and that does not require any additional intervention9-11.
Etiology
The majority of children with constipation have functional constipation, accounting for 95% of cases1,12. The peak incidence of constipation occurs between 2 and 4 years of age, when the toilet training starts11.
Available research suggests that several factors may contribute to constipation, such as lower parental educational level, increased body weight, reduced physical activity, a low fiber diet, positive family history and psychological factors3,13,14. The etiology of functional constipation is shown in Table 2. It relates mostly to fecal retention, when a child is trying to avoid an unpleasant defecation7.
However, only a small percentage of children (5%) experiences an organic cause of constipation, such as neuromuscular diseases, drug side effects, food allergies, celiac disease, etc (Table 2)7,15,16.
Hirschsprung’s disease must be differentiated from idiopathic constipation. Hirschsprung’s disease is a colonic motility disorder, resulting from segmental colonic aganglionosis. It is believed to account for 20 to 25 per cent of all cases of neonatal intestinal obstruction9. It can lead to severe enterocolitis with fever, diarrhea, and severe prostration, which may be fatal if the diagnosis is not made early. Most affected infants develop difficulties with defecation during the first few weeks of life. Other signs and symptoms associated with the condition include abdominal distention, refusal to feed, and bilious vomiting. In the older infant or child, in whom the diagnosis is not made early in life, there may be persistent abdominal distention, recurrent fecal impaction, and failure to thrive. In some patients with short segment or ultra short segment Hirschsprung’s disease, the diagnosis may not be made until later in life. Those patients have long periods of chronic constipation and may have normal ganglion cells in rectal biopsy, despite anorectal manometric findings consistent with Hirschsprung’s disease.
Magnetic resonance imaging (MRI) of the lumbosacral spine and colonic manometry may be necessary to identify occult spine abnormalities and occult myopathy or neuropathy of the gastrointestinal tract16,17.
Risk factors
Several risk factors have been identified in association with pediatric constipation. Low consumption of dietary fiber has long been considered as one of the leading risk factors. Undigested fibers in the colon are thought to increase the colonic transit and increase stool output. Lee et al18 found that kindergarten children with constipation took significantly lower median dietary fiber than non-constipated children. Furthermore, fruits and total plant food intake were significantly lower in the constipated group18. Two other studies, among older children, also noted that children with constipation consume significantly less amount of dietary fiber than controls19,20. Studies from Asia also show that fiber consumption in Asian countries such as Hong Kong18,21 and Maldives22 is lower than the recommended values.
Several studies have demonstrated its relationship with psychological factors. Inan et al23 has shown that physical or psychological trauma and personal health problems were associated with constipation, in school-aged children. Furthermore, they have found that abnormal oral habits (which were considered to correlate with psychological stress) also showed a significant association with constipation23. A study from Sri Lanka, involving school age children (10-16 years old), noted that school-related stressful events such as separation from best friend, bullying at school, failure of exam and family-related events, such as severe illness of family member, parents’ job loss and frequent punishment by parents, were predisposing them to develop constipation24. Psychological factors including emotional stress are likely to modulate colonic and rectal functions, through the brain gut axis, leading to constipation.
Cow’s milk protein allergy is considered as a risk factor for constipation. Several studies have reported reduction of constipation by elimination of cow’s milk from diet25,26. However, further studies are needed to confirm this association and to introduce cow’s milk-free diet to infants and children with constipation. Others demonstrated risk factors are extreme low birth weight27, positive family history19,28 and living in urban areas28,29. High consumption of junk foods with low fiber content and sedentary life style might have contributed to the higher prevalence of constipation, reported in children living in urban areas.
Pathophysiology
The pathophysiology of constipation in children is multi-factorial and is associated with interactions of many risk factors. Many organic diseases cause constipation. However, the majority of patients with constipation secondary to organic conditions, usually have other clinical features suggestive of the relevant underlying organic disease. Organic diseases presenting as isolated constipation are rather uncommon.
Borowitz et al30 reported painful defecation as the commonest factor for constipation. If there is pain during defecation, children usually withhold stools. During the withholding, rectal mucosa absorbs water from the fecal mass, which becomes harder and larger as the time passes and ultimately defecation becomes difficult. Therefore, when the desire to pass stools comes, children adopt retentive posture, hide from parents till the urge pass off. Passage of this fecal mass is painful and sometimes results in anal fissures, which further aggravate pain and precipitate stool withholding. This sets up a vicious cycle of stool retention.
Accumulation of stools in rectum causes gradual dilatation leading to megarectum resulting in loss of rectal sensation and urge for defecation. It had been shown that children with megarectum have high sensory threshold for rectal sensation31,32. Several studies have demonstrated slow colonic transit in 25%-69% of children with constipation33-35. Furthermore, those with slow transit constipation had more severe symptoms, including night time soiling33. Laparoscopic biopsies of the colon have shown deficiency of neurotransmitters such as substance P in some children36,37. Furthermore, it was shown that number of antegrade pressure waves in the colon was significantly decreased in children with slow transit constipation38,39.
Symptoms
Signs and symptoms may vary according to the age of the child. Infants may present with clinical features, such as straining, turning red in face and crying. Toddlers may present with passing painful and hard stool that may be associated with bleeding per rectum, secondary to a small tear in the anal canal which leads to further withholding. Parents may note that the child resists the urge to defecate.
Patients may also present with retentive fecal soiling secondary to withholding that can be mistaken as diarrhea and will force parents to seek medical care. Other manifestations include abdominal pain, distention, and feeling of incomplete disimpaction causing nausea and decreasing appetite. Some patients also present with enuresis and urinary tract infections, because stool masses press on the urinary tract and block normal urinary flow40.
Diagnosis and differential diagnosis
The approach to making diagnosis includes the patient’s medical history, physical examination and an appropriate laboratory investigation41.
Although the most common type of constipation is functional constipation, an underlying pathology should be excluded. The physical findings distinguishing organic constipation from functional constipation (Table 3).
The most important step of the diagnostic approach to constipation is a thorough medical history, including a constipation diary and a careful physical exam.
A complete medical history should include information regarding the symptom onset (age, duration, severity), description of bowel movements (frequency, stool composition and volume, co-existing symptoms), use of medication, psychological state, dietary habits, the existence of a positive family history, co-morbidities and possible related etiologic factors43-45.
On clinical examination, the child’s somatometric features should be obtained and possible systemic or neurological diseases (skin, facial features, etc) should be sought. An examination of the thorax, the abdomen, the lumbosacral part of the vertebral column and the perineum should be performed as well. A digital rectal examination is also required and the cremasteric reflex, as well as the lower extremity reflexes, should be tested.
Most children with functional constipation only need a thorough history and physical exam and do not require laboratory investigation. If the patient does not respond to initial treatment, further laboratory tests need to be performed, which include thyroid function test, serum electrolytes (calcium, potassium), lead level and celiac disease antibodies.
If the initial laboratory investigation is negative, the treatment for constipation has failed and an organic cause of constipation is suspected, then further laboratory testing is required, as shown in Table 47.
Plain radiographs of the abdomen may be necessary to establish fecal impaction in a child who refuses rectal examination, and in the obese child when abdominal and rectal examinations are suboptimal to assist fecal load16. Barium enema on unprepared colon, rectal biopsy, and anorectal manometry study are performed in case of suspicion of Hirschsprung’s disease. Anorectal manometry is also helpful to identify functional abnormalities in some children with chronic idiopathic constipation, including an increased rectal sensory threshold, decreased rectal contractility on attempted defecation and paradoxical contraction of the external anal sphincter and puborectalis muscles, during attempts at defecation16,46.
Warning signs for organic causes of constipation are also shown in Table 41,7,11,12.
Management of constipation in infants and children
Treatment of constipation includes close medical supervision, dietary instructions, behavioral changes and instructions regarding toilet training (most preferably after meals). An algorithm for evaluation of pediatric constipation (organic or functional) is shown in Figure 1 and a treatment algorithm for pediatric functional constipation is shown in Figure 242. Treatment differs between infants and children.
Figure 1. Algorithm for evaluation of pediatric constipation (organic or functional) (based on current literature)12,27,42.
Figure 2. Treatment algorithm for pediatric functional constipation. (based on current literature)12,27,42.
Infants
Babies (3-12 months) are offered juices which contain sorbitol, diluted with water, twice a day (Table 5). Honey and syrup of plant origin should be avoided5,11. Some infants may benefit from avoidance of cow’s milk. Breastfed infants may benefit from a cow’s milk restricted diet followed by the mother25.
According to a recent study, the use of an infant formula with a high proportion of Sn-2 palmitate [palmitic acid is esterified in the sn-2 (b) position of triglycerides], may lead to softer stools in constipated infants because free palmitic acid may form insoluble calcium fatty acid soaps, which are excreted via the feces, resulting in firmer stools. Stool hardness has been positively associated with the presence of calcium fatty acid soaps in the stools. In human milk however, palmitic acid, esterified at the Sn-2 position of the triacylglycerol molecule, is well absorbed as 2-monopalmitin, since it readily forms mixed micelles with bile acids48. However, further investigation is necessary to generalize this recommendation.
For infants older than 6 months of age adequate dietary intake of fiber, according to the age, is recommended. Increase in cooked and pureed fruits and vegetables, as so as cereals, may be an option. If needed, addition of guar powder (rich in fiber, available in developed countries), may be also useful. Moreover, increased fluid intake, particularly of juice containing sorbitol, such as prune, pear and apple, are very helpful25. Wherever dietary interventions have failed, osmotic stool softeners, such as lactulose, lactitole and sorbitol may be needed. Rectal disimpaction has been effectively performed in infants by using glycerine suppositories46.
Excessive administration of phosphate enemas may result in systemic absorption and leads to symptoms associated with hyperphosphatemia and hypocalcemia and even death, particularly in very young infants and in patients with Hirschsprung’s disease49,50. If treatment fails, or the infant has delayed passage of meconium, or the presence of red flags such as fever, vomiting, bloody diarrhea, failure to thrive, distention, or tight empty rectum, further evaluation is required to exclude Hirschsprung’s disease. If the patient has delayed passage of meconium and Hirschprung’s disease is excluded, sweat test to rule out cystic fibrosis, is recommended42.
Children
The goals of treating constipation in childhood are to produce soft, painless stools and to prevent the re-accumulation of feces. These outcomes are achieved through a combination of education, behavioural modification, daily maintenance stool softeners and dietary modification. Fecal disimpaction may be necessary at the outset of treatment. Initial laboratory and radiographical investigations are not necessary, unless history and examination suggest organic disease47,51. Treatment in children usually consists of 3 phases (Table 5). The first phase in constipation treatment for older children (>12 months) is the clean-out phase, with a goal of clearing out the hard, chronically accumulated stool. Fecal impaction is identified by the presence of a large and hard mass in the abdomen or dilated vault filled with stool on rectal examination, and often substantiated by a history of overflow incontinence (an abdominal radiograph is not necessary to diagnose fecal impaction). Fecal disimpaction can be accomplished with oral use of osmotic agents and laxatives, as well as, in some cases with the need of enemas and/or suppositories. This phase lasts a couple of days. In phase II, which lasts between 2 and 6 months, treatment aims to restore muscle tone to the sphincter and the return of the gut diameter to its normal size. The previous therapeutic targets are achieved by stool softeners, hyperosmotic laxatives, non-absorbable salts or combinations. Management also includes keeping a stool diary, dietary instructions for constipation and instructions for toilet training.
In phase III, which lasts between 4-6 months, therapeutic targets are to restore regular bowel movements and avoidance of relapses. These goals can be achieved by cutting down laxative use and by increasing daily fiber and fluid intake52-54. Commonly used drugs for pediatric constipation, drug dosage and drug side effects are shown in Tables 5 and 6.
A high dose of mineral oil and polyethylene glycol solution (PEG) has found to be effective, as an oral medication for disimpaction55. Disimpaction can be achieved by either oral or rectal medication. In a double-blind uncontrolled study, Youssef et al56 showed that the three-day administration of PEG 3350, at a dose of 1 g/kg/day to 1.5 g/kg/day (maximum dose 100 g/day), successfully disimpacted 95% of children and was well tolerated56. Another study showed that a regimen of daily enemas, for six days, was equally effective as PEG 3350 (1.5 g/kg/day) in relieving disimpaction, but may be less well-tolerated57. Patients who do not respond to enema or oral polyethylene glycol solution, may need manual disimpaction, under general anesthesia16,58.
Once the impacted stool has been removed, the focus of the treatment should be on preventing recurrence. Maintenance therapy should be started immediately after disimpaction, to prevent re-impaction. Medications have been shown to be more effective than behavioural change alone in the treatment of constipation59. A systematic review of laxative treatments for childhood constipation has been recently published, and acknowledges the relative paucity of well-designed trials for laxatives in children and the resultant difficulty in establishing first-line therapy60. Available medication includes lubricants such as mineral oil, osmotic laxatives such as lactulose, sorbitol and PEG.
Mineral oil has a risk of aspiration and should be avoided in infants and in children who resist taking it or have dysphagia or vomiting. Mineral oil, lactulose or sorbitol is equally efficacious, the choice among these being based on safety, cost, the child’s preference and the practitioner’s experience42,58.
There is growing evidence to support the efficacy and safety of PEG 3350 in the maintenance treatment of children with constipation61. PEG 3350 without electrolytes is a tasteless, odourless, osmotic laxative. It is available in powder form, and dissolves well when mixed in juice or water. It is absorbed only in trace amounts from the gastrointestinal tract and, unlike other colonic lavage solutions, carries no risk of electrolyte imbalance. The effects of PEG 3350 start within the first week of treatment. It has been reported that PEG is a safe and effective laxative in a dose of 0.8 g/kg/day with fewer side effects than lactulose. PEG did not cause persistent gas, abdominal pain, or perianal irritation in children62,63. PEG has been shown to be equally as effective as milk of magnesia, although better tolerated64. Dose-finding studies for PEG 3350 used starting doses of 0.4 to 0.8 g/kg/day, as either a single or twice-daily dose and, when tailored to effect, a range of doses from 0.27 to 1.4 g/kg/day65, and 0.3 to 1.8 g/kg/day66 were reported. Maintenance doses of 0.4 to 1.0 g/ kg/day have been shown to be effective and well tolerated63,65,66. A common reason for the lack of response to stool softening therapy is inadequate dosing; physicians should not hesitate to start PEG therapy at a higher dose of 1.0 g/kg and then decrease as necessary. The safety profile for PEG 3350 has been favourable. Clinical adverse effects are minor and can include bloating, flatulence, abdominal pain and loose stools61,63,65-67. In none of the aforementioned trials was PEG 3350 discontinued due to side effects related to the medication.
The prolonged use of stimulant laxatives such as senna is not recommended, but they may be used intermittently as a rescue therapy to prevent re-impaction. The patient should be weaned away from stimulant laxatives, as early as possible, to prevent dependence16,42.
General aspects of constipation management
Behavioral Modification
Time dedicated for defecation, as part of toilet training, is valuable. Most people who have normal stooling habits, tend to defecate at the same time each day47. The reflex of defecation tends to occur within 1 hour of eating, and usually during morning hours. A constipated child should have a routine scheduled toilet sitting for three to ten minutes (age dependent), once or twice a day. Ensure that the child has a footstool on which they can support their legs to effectively increase intra-abdominal pressure (valsalva manoeuvre). There should be no punishment for not stooling during the toileting time; praise and reward for stooling and the behaviour of toilet sitting, can be offered. It is helpful if children and their caregivers keep a diary of stool frequency to review at the next appointment. Regular physical activity can be recommended, although its role in treating constipation remains unclear23.
Dietary Modification
A balanced diet that includes grains, fruits and vegetables is recommended as part of the treatment of constipation in children5. Carbohydrates (especially sorbitol) found in prune, pear and apple juices can cause increased frequency and water content in stools5. The American academy of pediatrics recommends a fibre intake of 0.5 g/kg/day (to a maximum of 35 g/day) for all children68. Fibre intake below the minimum recommended value has been shown to be a risk factor for chronic constipation in children20,18.
Although excessive milk intake may exacerbate constipation, there is insufficient evidence that eliminating it from the diet improves refractory constipation. For children unresponsive to adequate medical and behavioural management, consideration could be given to a time-limited trial of a cow’s milk-free diet5. Intolerance to cow’s milk, particularly in children with atopy, has been associated with chronic constipation25.
Probiotics in Constipation
Two studies have addressed the use of probiotics in treating constipation in children. The addition of Lactobacillus rhamnosus GG in the first study, showed that it was not an effective adjunct to lactulose in treating constipation69. The second study’s sample size was too small, to draw any meaningful conclusion70. Currently there is no sufficient evidence for recommending probiotics as a treatment option for children suffering from constipation.
Prognosis
Parents should be informed that there is a risk of constipation recurrence in 50% of all cases. The prognosis for full recovery, defined as no soiling and no constipation while off medication, has been reported as 48% at 5 years follow up16. Treatment failures are reported in 20% of children. Early onset of symptoms during the first year, family history of constipation, poor self esteem and prior sexual abuse are associated with poor prognosis16,71. In case of recurrence the treatment protocol will have to be repeated.
Conclusions
Constipation remains a frequent problem in childhood. The most common type of constipation is functional. A small percentage may have an organic cause and appropriate laboratory investigation is warranted. A complete medical history and clinical examination are important to guide the practitioner to the diagnosis and further work-up or referral to a specialist. Treatment of constipation includes close medical supervision, dietary instructions, behavioral changes and instructions regarding toilet training. Patients who do not respond to treatment, should have further evaluation to exclude an organic etiology.
Conflict of Interest
The authors report no conflict of interest.
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