Childhood Constipation: Is There New Light in The Tunnel?

Introduction Constipation is a common phenomenon in childhood worldwide. The symptoms vary from mild and short-lived to severe and chronic with faecal impaction and encopresis. Although our understanding of pathophysiology has grown rapidly in recent decades, the causes and management of constipation in childhood remain obscure. This review begins with the current opinion concerning the definition of constipation as stated by a group of experts in the field of paediatric gastroenterology. Physiology of normal defecation, pathophysiological mechanisms, clinical features, and diagnostic work up for constipation then are addressed. Finally, an extensive overview is given concerning the treatment options and long-term outcome in these children. Definition One of the key problems in studies concerning the management of childhood constipation is the lack of a generally accepted definition for paediatric constipation. This derives mainly from the fact that constipation is a symptom rather than a disease. Constipation is often differently interpreted by patients and physicians (1). In children it is even more difficult to define, because, the physician must rely upon the interpretation of symptoms as told by the parents (2). In the last two decades, the Iowa-criteria (3) have often been used in large randomised controlled trials. These criteria are based on the most common features of childhood constipation, i.e. infrequent defecation, large stools, encopresis and faecal impaction found on physical examination. The criteria are straightforward, easy to work with and useful in evaluating endpoints of various treatment regimens. However, they do not include the whole spectrum of childhood defecation disorders. Recently a group of experts in the field of paediatric gastroenterology categorized childhood functional gastrointestinal disorders using symptom-based diagnostic criteria (4). These Rome-II criteria define defecation disorders in childhood based on presenting symptoms including infant dyschezia, functional constipation, functional retention and functional non-retentive faecal soiling (FNRFS) (Table 1). These criteria should help clinicians to standardize the definitions used to categorize constipation and encourage researchers from various fields to study the (patho-) physiology and treatment of similarly defined disorders from different points of view.TABLE 1: Childhood functional defecation disorders: ROME II-criteria (4)Functional non-retentive faecal soiling is a separate entity defined as encopresis in the absence of other clinical and physical signs of constipation. These children have normal total and segmental colonic transit time and normal rectal sensation on anorectal function testing (5). The treatment of these patients consists of a strict toilet training regimen only, without the use of laxatives (6). In this review on constipation, FNRFS will not be further discussed. The universally accepted definition for encopresis (from kopros, Greek for stool) is the repeated expulsion of a normal bowel movement, whether involuntary or intentional, in inappropriate places (e.g. clothing, floor) in a child at least four years of age (or equivalent developmental level) (DSM-IV). In a recent study, the prevalence and applicability of the definitions of defecation disorders in childhood according to the paediatric Rome II criteria and according to criteria developed by Dr. Loening-Baucke were evaluated in children with defecation disorders (7). According to the Rome-criteria, 64% and 18% of the patients fulfilled the criteria for functional constipation and functional faecal retention respectively, whereas 74% fulfilled Loening-Baucke's criteria for paediatric constipation. The low prevalence of FFR was recently confirmed by others (8). The low incidence of functional faecal retention might be a result of the subjectivity of the symptom of retentive posturing. Parents are often not able to determine reliably whether their child exhibits stool-withholding behaviour. Moreover, accuracy of responses depends greatly on the way questions are formulated by physicians and the way responses of parents are interpreted. We agree with Nurko that the current Romecriteria are too restrictive and exclude too many children with constipation (9). The next Rome criteria should include consideration of encopresis, the most important feature of constipation, which is present in 84% of the patients. Uniform application of adequate definitions will allow for better understanding the pathophysiology of constipation, will enhance treatment monitoring and will allow comparison of the outcome of different treatment regimens. International collaboration is necessary to develop and validate standard constipation-questionnaires in which hard to quantify items as amount of stool, consistency of stool and retentive posturing are defined. Epidemiology Population based studies in adults in westernized societies and in Asia have estimated that approximately 10-20% of otherwise healthy people report one or more symptoms of constipation (10-13). Little is known about the prevalence of constipation in developing countries (14,15). To date, the worldwide prevalence figures for constipation in children varies widely and is estimated to range between 0.3-28% (16-19). This large range is likely due to the differing criteria used to define constipation and to differing cultural norms regarding acceptable bowel habits. Thirty-four percent of British children 4-11 years of age are reported to have had constipation. Of these, 5% had complaints for more than 6 months(20). TABLETABLE 2: "The Loening-Baucke criteria" (3)The prevalence of childhood constipation seems to be rising in the last decades (10). In one study of children between 0-9 years of age, the increase in physician visits for constipation was most marked in children less than 2 years of age (21). Whether this was a true increase in prevalence or a result in differences in the rate of seeking medical advice is unclear (22). Others have suggested that the increase in constipation in childhood is due to a decreased fibre intake (23). Constipation is diagnosed in 3% of all children referred to a general paediatrician (24,25). This percentage increases to 25% of all children referred to a paediatric gastroenterologist (26-28). Approximately 45% of children referred for gastrointestinal problems to our tertiary hospital in The Netherlands have constipation. In children with cerebral palsy or autism constipation is reported in from 26%-74% (29,30). In very low birth weight infants (< 750 g) constipation is very common (32%). When evaluated between 10-14 years of age, these children ontinue to experience higher rates of toileting problems such as encopresis and withholding behaviour, and neuro-developmental impairment when compared with age matched children of higher birth weight (31). Constipation is usually reported to be more common in boys than in girls, with a 2:1 ratio (32,33). Some studies report an equal prevalence between the sexes (10,19,34,35). In adults, significantly more women than men suffer from constipation and the ratio of women to men increases with age (36,37). In a large population based study from Australia, low-socio-economic status was strongly related to symptoms of constipation (38). Encopresis is reported in 1.5-2.8% of children older than 4 years. In 10-30% of these children, encopresis is not secondary to constipation but is a manifestation of functional non-retentive faecal soiling (FNRFS) (4). Boys are more likely to experience this frustrating symptom than girls at a ratio of 9:1 (6,39). Physiology of Defecation Normal anorectal function depends on the complex interplay between muscles of the pelvic floor, the autonomic and somatic nervous system and the group of muscles controlling the anal sphincters. Defecation is elicited by presence of faecal material in the rectumdue to peristaltic propagation. Sensory stimuli in the anal canal provoke a sudden drop in the tone of the internal anal sphincter, the recto-anal inhibitory reflex (RAIR). Recently studies in term and preterm infants have shown that the RAIR is present in infants older than 26 weeks postmenstrual age (40). The voluntary defecation process is initiated by relaxation of the puborectalis and levator ani muscles. Rectal distension induces contractions of the rectum and defecation can be completed by voluntary increase in intra-abdominal pressure. Triggering of receptors in the anal canal by faeces will result in the sensation of imminent faecal loss, giving the person the ability to prevent this loss of faeces by contracting the pelvic floor muscles. When defecation is not desirable, the external sphincter complex, with the help of the pelvic floor, remains contracted, until (due to rectal compliance) the rectal wall has adapted (distension) to the increased rectal volume. Many children achieve voluntary bowel control around 18 months, but the age at which complete control is attained is variable. Around the age of 3 years, 98% of children are toilet trained (41). Girls appear to attain both bowel and bladder control earlier than boys (41). Development of bowel and bladder control is a maturational process, which cannot be accelerated by early onset and high intensity of potty-training (42). The child's initiative proves to be a reliable indicator that the child is developmentally capable of being clean and dry. In one study, bowel and bladder control in term and prematurely born infants were attained at the same age (corrected for prematurity) and the timing was not affected by adverse perinatal events or mild to moderate neurologic impairment or psychomotor development (43). More than 99% of term infants pass the first stool within 48 hours (44). Weaver et al found an inverse relation between gestational age and the day of the first bowel movement. In contrast to term infants, 35% of infants with birth weight between 1000-1500 g had delayed passage of the first stool (45). Stool frequency declines from more than four per day during the first week of life to 1-2 per day at four years of age with a corresponding increase in stool size and weight (46). Approximately 97% of 1-4 year old children pass stool from .5 to 3 three times daily (47). Black children show higher defecation frequencies and shorter transit times than white children (48). Another study indicates that defecation frequency in children is highly variable, ranging from 1.4 to 4 times daily in the first weeks of life to 1.2 times daily at 4 years of age (49). In the first year, the defecation frequency is higher in breastfed children and children on a diet rich in fibre (45). This is probably due to a difference in fat digestion and absorption between breast and formula fed infants (50). By 16 weeks of age however, both breast-fed and formula-fed children pass an average of 2 stools per day (46,51). The slow decrease in defecation frequency with increasing age suggests a maturation of the water conserving ability of the colon (52). In a sample of 350 children (1-4 years) from a general practice, 85% of children defecated once or twice daily and 96% fell in the range between 3 times per day to once every other day with a mean stool volume of 25 ml (53). In healthy African children aged 6 months to 5 years, 95% defecated one to three times a day with a mean volume of 50-75 ml per stool (54). In comparison to western children, non-western children pass larger, softer, and more frequent stools (54-56). Generally, at the age of 4 years the defecation frequency of children equals that of adults and ranges from three bowel movements per day to 3 per week (46,57). Pathogenesis The pathophysiology of functional constipation is undoubtedly multi-factorial, and not well understood. Difficulties with defecation can result from abnormal function of the different players involved, including the colon, the rectum and the sphincter complex and not least the will of the child. Severe behavioural problems do occur in constipated children, but they are usually mild and seem to be secondary to bowel dysfunction (58-60). Table 4 summarizes the most common causes of constipation in infants, toddlers and adolescents. In more than 90% of all age groups no obvious cause can be identified. In some babies, an acute episode of constipation may occur associated with a change in diet (i.e. human to cow's milk) (61). Passage of dry and hard stools may cause anal fissures and pain. In "infant dyschezia" it is hypothesized that neonates fail to coordinate increased intra-abdominal pressure with relaxation of the pelvic floor (4). This phenomenon is part of the child's learning process for which no intervention is indicated. Genetic predisposition may play a role since constipation often dates back to the first months of life, and many patients have a positive family history of constipation (62-65). Recently, delayed maturation of the interstitial cells of Cajal was suggested to be involved in two neonates with constipation and abdominal distension (66). The most common condition in infancy that must be differentiated from idiopathic constipation is Hirschsprung disease (66).TABLE 4: Etiology of constipationRetentive posturing is probably the major cause for the development and/or persistence of constipation in toddlers (17). The time of toilet training is an especially critical period when constipation may occur as a consequence of a struggle between child and parents (67). Interestingly, Borowitz, et al. found no association between the development of early childhood constipation and the timing, style or techniques used for toilet training (68). Other causes of stool withholding are: 1) the previous passage of large, hard or painful stools, 2) anal fissures, 3) significant behavioural problems, 4) lack of time for regular toileting and 5) distaste for toilets other than the child's own (22). When the retentive toddler experiences the urge to defecate, he assumes an erect posture and holds the legs stiffly together to forcefully contract the pelvic and gluteal muscles. Consequently the rectum accommodates to its content and the urge to defecate disappears. The retained stools become progressively more difficult to evacuate leading to a vicious circle in which the rectum is increasingly distended by large faecal contents. Finally chronic rectal distension may cause overflow soiling, loss of rectal sensitivity and, in the end, loss of normal urge to defecate. This aberrant behaviour may lead to the unconscious contraction of the external sphincter during defecation (also known as anal sphincter dyssynergia) (32). Approximately 50% of children and adults with constipation have this abnormal defecation pattern. This paradoxical contraction of the anal sphincter complex has been considered by some to be the major pathophysiological mechanism of childhood constipation. However, normalization of this pattern with biofeedback training does not correlate with successful treatment outcome (32,69). It is not clear that chronic postponement of defecation with rectal accumulation of faeces actually produces subsequent abnormalities in rectal sensation, compliance and motility, or whether these abnormalities are primary to the condition (69). An overall delay in colonic transit time, slow transit constipation, objectified by colonic transit time measurements, is described in a minority of young women and adults with chronic constipation (70,71). This might be due to dysfunction of the muscles of the colonic wall (resulting in non-powerful contractions) or to dysfunction of the enteric nervous system (resulting in non-coordinated motor activity) (72). In children however, it might also be possible that delay in colonic transit time is also a phenomenon secondary to massive chronic faecal retention in the rectum. Some histopathologic studies in adults with slow transit constipation have suggested that decreased numbers of argyrophilic neurons are found in colon tissue. Other studies have suggested that there is dysfunction of the intrinsic neural control secondary to alteration of the colonic cholinergic activity or to non-specific abnormalities of axonal structures, ganglion cells and the neuronal plexus (73,74). Recently, a reduction in the number of interstitial cells of Cajal was suggested to play a role in the pathophysiology of gastrointestinal motility in adults with slow transit constipation and in one child with severe constipation (75-77). However, Hasler suggested that the reduction of ICC's might be secondary to an undefined injury and not the cause of slow transit constipation (78). Clinical Signs and Symptoms of Constipation The majority of children with constipation have reduced frequency of defecation, in combination with encopresis, passage of large stools, hard stools, retentive posturing, and painful defecation (21,71,79,80)(Table 3). The involuntary leakage of faeces may occur several times a day and in some severe cases with large rectal impactions it may also occur at night (71). Encopresis is a source of considerable embarrassment for the child who must deal with taunting by peers (80). Parents often feel that the child is to blame for encopresis citing such behavioural aspects as laziness, carelessness, immaturity and emotional problems as important factors. Encopresis is associated in the child with low self-esteem, depression, social withdrawal, shame, fear of discovery and anger. Although children chronically deny the problem, recent reports indicate that overt denial is decreasing and that fewer children hide their soiled underwear (80). It is not surprising that children with constipation and encopresis have more behavioural problems than healthy controls. The behavioural problems, however, are usually mild, and referral to mental health services is rarely needed. Moreover, behavioural profiles in these children significantly improve after successful treatment (39).TABLE 3: Common clinical presentation of constipation (21, 33, 57, 71, 79, 207)In children with very infrequent passage of stool, there may be a pattern of intermittent passage of huge volume stools which may obstruct the toilet. The evacuation of these large stools is often preceded by an increase in encopresis frequency and by complaints of abdominal pain and poor appetite. These symptoms disappear immediately after defecation. Between 10-70% of children with constipation complain of non-specific abdominal pain (32). Urinary tract infection and enuresis are reported in 30% of constipated children. The majority of constipated children have palpable abdominal masses and/or faecal impaction of the rectal on physical examination (7). Although at least one digital examination is recommended by experts in the field, this procedure is not performed routinely since many paediatricians consider repeated rectal examinations invasive and unethical (81,82). Investigations A careful medical history together with a thorough physical examination is all that is needed for diagnosis and treatment of most children with constipation. Symptom diaries (for diagnostic evaluation and monitoring treatment); colon transit studies (to confirm the patient's complaints and to assess slow transit and regional delay) and anorectal (to exclude are In a recent study, of the in constipated children abnormalities in of these children that constipation after treatment The medical history of children with constipation should include questions about the time after birth of the first bowel to functional constipation from disease. one a history of constipation when an infant was from breast to a infant age of onset of bowel problems, stool the consistency and size of stools, whether defecation is whether has been present on the stool or the toilet and retentive posturing are to be about the encopresis the time of and/or and the in which encopresis the when is of major loss of tract problems, weight loss or poor weight development and or behavioural problems should be history and the history of previous treatment for constipation should also be Finally, it is to for life such as in the birth of a problems and which might to the development of retentive A stool is to reliable from the the of the of bowel is One study in children with constipation suggested that the of the child and/or the is adequate and a to treatment physical and neurologic examination should be performed in all children with defecation disorders. examination concerning accumulation of or about the of the fissures, and The anorectal digital examination sensation, anal the size of the the amount and consistency of stool in the the voluntary contraction and relaxation of the anal sphincter and the presence of an anal in the anorectal and is used to concerning anorectal Many these but lack of in pressure has in The to is to the presence of the recto-anal inhibitory reflex (RAIR). The presence of the RAIR of the internal sphincter by distension of the disease. positive may be due to such as of the or an of the in the sphincter The RAIR may also be in children with In infants, are common and should be interpreted with the absence of the RAIR in the presence of ganglion cells is of internal anal sphincter to functional constipation children with internal anal sphincter have less encopresis and less withholding behaviour. In this group of children, per may be a and using anorectal have shown an increased for rectal sensation in up to of constipated children, with The that the from the rectum is abnormal in constipated children further that rectal sensation should be considered an important pathophysiological mechanism in childhood constipation of the rectum and the age of the child will significantly the for sensation as volume. children with an increased rectal compliance will be considered to have an increased for The rectal volume at which sensation is strongly depends on rectal A recent rectal study using pressure controlled distension decreased rectal sensation in of the children with constipation More than 50% of these children had an abnormal rectal faecal impaction was not of abnormal rectal Some studies have found no significant difference in the anal sphincter tone of constipated children and others have found a significantly higher or significantly anal sphincter tone in constipated children anal sphincter change during expulsion of an anorectal can be used to the of pelvic floor floor in more than 50% of the constipated children It however, whether a pattern of is a diagnostic In a study in adults, when was in in of patients. the when normal confirm this in of the time between and colonic transit times or complaints of infrequent defecation or was found in a study in constipated children Although colonic is no an and is considered an diagnostic for childhood defecation one paediatric group has experience with this procedure can be used to between functional and the causes of severe and constipation for normal motility are the presence of high contractions and the presence of a to a are well peristaltic important in the of colonic contents. In patients with functional constipation, colonic motility is with or colonic in the absence of colonic are more likely to have a colonic In patients with colonic the is and are or In children with chronic defecation 4 for colon were the pathophysiology of symptoms in general the pathophysiology of symptoms after for of the diagnosis of and about of a colon on the of the colonic to were in of these patients. A possible of colonic in paediatric patients is the lack of colonic motility in healthy children. In the procedure a of experience which cannot be in and concerning the of an abdominal in the diagnosis of constipation. to assess faecal in constipated children has been in studies using to retention Although all studies were performed by paediatric and and paediatric the interpretation of are difficult and An abdominal might be when there is about whether a is in a child who is or who a rectal or in there are such as that rectal examination inappropriate and of total and segmental colonic transit time using more and reliably about motor function in defecation disorders The is used to the delay in colonic transit and is bowel history is In adults as well as in children, a is found between symptoms of constipation and colonic transit time We use the in which a segmental and total is from on day after of on the previous 6 transit time is by the number of in the of numbers of hours in a day by the number of the study, the child should be on a high fibre diet but should not or rectal laxatives that may bowel studies have reported normal for in healthy children studies reported for the for total based on the mean 2 and whereas a recent study from the using the reported hours as in adults and children with constipation show different colonic transit 1) normal colonic transit transit all colonic 2) transit the anorectal and 3) slow transit transit the Normal are found in to of constipated children The most common of delayed in children at the of the rectum The is useful to between children with constipation and children with functional non-retentive faecal soiling (4). percent of children with FNRFS have a normal and have normal upon anorectal A normal