Constipation is a common problem in children. In a study by Issenman et al. (1), 16% of parents of 22-month old children reported constipation in their toddlers. Constipation is defined in a medical position statement from the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) as a delay in defecation present for two or more weeks and sufficient to cause significant distress to the patient (2). Functional constipation in infants and toddlers is often characterized by passage of firm or hard stool, stool withholding maneuvers and pain or blood with the defecation with no underlying anatomic or medical cause. Functional constipation in infants is usually treated with fruit juices, formula changes or corn syrup. If despite these changes, the stool is still hard and painful to evacuate, then laxatives, such as milk of magnesia, lactulose or sorbitol, are given.
Polyethylene glycol 3350 without electrolytes (PEG) has been used short-term (3,4) and long-term (5-8) as a laxative in constipated children. PEG is a chemically inert, tasteless, odorless powder that has no grit when stirred in juice, Kool-Aid or water for several minutes. PEG is not degraded by bacteria and is not readily absorbed and thus acts as an excellent osmotic agent.
Little information is available on the safe and efficient use of PEG in infants and toddlers (8). Therefore, we retrospectively evaluated the records of all children less than 2 years of age who were treated with PEG for functional constipation.
MATERIALS AND METHODS
Retrospective chart review was performed of all children with functional constipation, <2 years of age at start of PEG therapy. These children were seen initially in our general pediatric and pediatric gastroenterology clinics between January 2000 and August 2003. Children with Hirschsprung's disease, chronic intestinal pseudo-obstruction or previous surgery of the colon or anus were excluded, as were children with disease states that placed limitations on the act of defecation such as hypotonia, cerebral palsy and severe mental retardation. The retrospective chart review revealed that we had treated 75 children with functional constipation with PEG who were otherwise healthy. Their symptoms fitted the NASPGHAN criteria for constipation (2).
This study was approved by the Institutional Human Research Review Committee.
The treatment of functional constipation in infants and toddlers consisted of education, (rarely) an initial fecal disimpaction, dietary changes and PEG to prevent re-impaction. Dietary advice was to decrease excessive milk intake but not eliminate milk from the diet. Parents were told that constipation is not life threatening but would require many months of treatment. PEG 3350 without electrolytes (MiraLax®, Braintree Laboratories, Inc., Braintree, MA) was started at an average dose of 1 g/kg body weight/d and parents were asked to adjust the dose to yield 1 to 2 soft painless bowel movements (BMs) per day. Verbal and written instructions were given to parents about PEG, its dose and how to mix and adjust the dose. Parents were instructed to dissolve 17 g of PEG powder in 240 ml milk, juice or a beverage of the patient's choice and to give the appropriate dose. Re-evaluation was planned initially to be monthly and less frequently later in treatment.
During follow-up, stool records were reviewed and the examination repeated to assure that constipation was adequately controlled. If necessary, the dose of PEG was adjusted and the parents were encouraged to continue with the regimen. After several months of regular bowel habits, the medication dose was gradually decreased to a dose that maintained one soft bowel movement daily and prevented withholding behavior and rectal bleeding. After several months, further reduction and discontinuation of the medication was attempted. Treatment resumed if constipation recurred. These 75 children were treated in our clinics by many pediatricians, and follow-up was occasionally planned at different times. In addition, parents did not always keep scheduled follow-up appointments. Therefore, we evaluated the records of the children for a 4-month or shorter period (short-term PEG) and for a 6-month or longer period (long-term PEG).
Data collected at each visit included age, weight, duration of constipation, symptoms and signs of constipation such as BM frequency, BM consistency (scale: 1 = hard, 2 = formed, 3 = soft, 4 = loose, and 5 = watery), presence of pain, fear/withholding or blood with BM, presence of rectal impaction and abdominal fecal mass, PEG dose and any adverse effects of PEG.
Data obtained during the initial visit (Pre-PEG) were compared to similar parameters on short-term and long-term PEG therapy. The statistical analysis included Student's t-tests and χ2 tests with significance accepted at the 5% level. Results were expressed as mean ± SD or percent.
Seventy-five infants and toddlers (39 girls and 36 boys) received PEG for functional constipation. Of these, 20 infants were < 1 year of age. Mean age was 17 ± 7 months (range, 1 to 24 months) at start of PEG therapy. The mean duration of constipation was 10 months (range, 0.5 to 23 months). All children were symptomatic when PEG was started. These children had failed dietary modification. In children less than 1 year of age, these suggestions had included the addition of solids such as pureed fruits and vegetables and often a change in infant formula. In toddlers, several servings daily of fiber-rich foods and juices had failed. Many children had been treated unsuccessfully with laxatives previously (18 had taken milk of magnesia, eight Karo syrup, four mineral oil, four lactulose and two senna). Many had received intermittently glycerin suppositories or phosphate enemas. As can be seen in Table 1, by their mothers' report, 85% of children had hard bowel movements, 73% had painful bowel movements, 69% had stool withholding behavior and 40% had blood in the stools. Only 77% of children underwent a rectal examination at the initial visit. In these, rectal impaction was documented in 53%. An abdominal fecal mass was felt in 21% of the children. The mean number of outpatient visits for constipation was 3, range 2 to 7.
Seventy-one children came at least once for follow-up within 4 months, mean follow-up was 2.3 ± 1.3 months (range, 1 to 4 months). Table 1 gives the findings from history and physical examination at the short-term follow-up visit. BM frequency increased, BM consistency improved and pain, fear/withholding and blood in the stool decreased significantly (P < 0.001). The presence of a rectal impaction and of an abdominal fecal mass decreased significantly with PEG treatment (P < 0.001). Table 2 gives the PEG doses and side effects. The mean effective short-term PEG dose was 1.1 g/kg body weight daily, range 0.4 to 2.3. One mother had not complied with treatment, giving PEG only intermittently, and 10 children were improved but still had abnormal defecation patterns. These 10 children were still withholding hard stools, had blood in the stool or painful stools and/or had <3 bowel movements/wk. The mothers of these children were instructed to increase the dose and to give PEG daily. An additional 16 parents (21%) had stopped and restarted PEG because of recurrence of constipation. None of the children refused PEG.
Forty-seven children came for follow-up at least 6 months (range, 6 to 37 months) after having been started on PEG therapy. These children included four who did not come for a follow-up visit during the first 4 months of treatment. We used the longest follow-up because we were interested to evaluate the safety of long-term PEG use in this age group. As shown in the Table 1, significant improvement in all parameters was achieved with long-term PEG therapy as compared with the Pre-PEG period. The improvements were similar to improvements achieved at short-term follow-up except stool frequency was less than during the short-term PEG period (P < 0.05). Table 2 gives the PEG doses and side effects. The long-term PEG dose was 0.8 g/kg body weight daily (range, 0.3 to 2.1 g/kg body weight daily). Four children were improved but still had abnormal defecation patterns. One parent was noncompliant and three children were still withholding hard stools. The mothers of these children were instructed to increase the PEG dose. Eighteen parents (38%) had stopped and restarted PEG because of recurrence of constipation. None of the children refused PEG.
No serious adverse effects of PEG 3350 were seen in the infants and toddlers. At the short-term follow-up visit, five children had runny stools and at the long-term follow-up, one child had watery stools (he was only brought by his mother for a 6-month follow-up). The diarrhea disappeared after lowering the dose of PEG. Parents did not report increased flatus, abdominal distention, vomiting or new onset abdominal pain. None stopped PEG because of adverse effects. Complete blood counts (in 24 children), electrolytes (in nine children), renal functions (in eight children) and liver functions (in eight children) were occasionally done in children on long-term PEG treatment, and all were within normal limits.
Our report shows that PEG is effective and appears safe for the treatment of functional constipation in children less than 2 years of age. PEG was effective in relieving the constipation with associated symptoms in 85% of infants and toddlers at short-term follow-up and in 91% at long-term follow-up. With PEG therapy, the bowel movement frequency increased, stool consistency improved, and the percent of children with pain, fear/withholding and blood in the stool decreased significantly. We think the overall good treatment results are attributable to the osmotic laxative property of PEG and the taste characteristics, which produced good compliance.
Constipation in early life is a special situation because of the possibility of rare but serious congenital disorders, such as Hirschsprung's disease and anatomic defects of the spinal cord or anorectum. The most common cause of constipation in children is an acquired behavior that occurs when a child begins to delay defecation after experiencing a painful or frightening defecation. Fear of defecation then leads to voluntary withholding of stool. Retentive behavior was present in 69% of our infants and toddlers. The choice of treatments in infants and toddlers with retentive behavior is limited. Juices, Karo syrup and dietary changes are seldom helpful. Mineral oil has been associated with aspiration and lipoid pneumonia in infants less than 1 year of age (9). Lactulose and milk of magnesia have been used successfully in this age group (10,11). PEG is effective and appears to be safe for the treatment of constipation in infants and toddlers and can be added to the list of laxative agents useful for the treatment of constipation in infants and toddlers.
Constipation is often a chronic problem. In this study, 34 parents stopped giving PEG to their children and constipation returned immediately; this is very similar to our previous report of children <4 years of age, in which 37% of children continued to have symptoms of constipation 3 to 12 years after the initial diagnosis (11).
Because of the young age of our patients, intolerance to cow's milk protein was considered. Iacono et al. (12) highlighted the role of cow's milk protein intolerance in intractable constipation in young children. However, Miele et al. (13) studied 2594 children 0.5 to 6 years of age who were drawn from six primary pediatric care practices in the Campagna region of Italy. They found 28 constipated children (1.1%), and only two had refractory constipation and atopy. Both failed to respond to 4 weeks of cow's milk protein elimination. None of our infants and toddlers had a history of cow's milk sensitivity. We decreased the amount of cow's milk in the diet of a few constipated children who had a large milk intake but did not eliminate cow's milk.
There is no set dosage for any laxative, including PEG. There is only a starting dose for each child that must be adjusted to achieve the desired therapeutic result. The mean dose of PEG for the initial treatment of functional constipation in infants and toddlers was 1.1 g/kg body weight daily and was higher than in school-aged children (0.6 g/kg body weight daily) (5). The average effective dose at long-term follow-up in our infants and toddlers was 0.8 g/kg body weight/d, still higher than the 0.4 g/kg body weight dose required at 12-month follow-up in the older children (5).
PEG was well tolerated and appeared to be safe in our study. We did not see any major clinical adverse effects related to PEG in this study. Laboratory evaluation was normal but was only done in a small number of children. More studies are required to ensure safety of PEG in this age group. In our previous study of PEG in children 2 years and older, long-term PEG therapy was found to be safe without any changes in serum electrolytes, liver or renal function (7). Absorption of PEG in the gastrointestinal tract is negligible, and therefore, systemic toxicity is very unlikely (14). Post-marketing safety information from Braintree Laboratories reported rare allergic reactions in the form of a rash but no other serious adverse effects.
We have shown in our retrospective study that the polyethylene glycol 3350 without electrolytes is a new alternative therapy in the management of infants and toddlers with functional constipation. PEG 3350 was effective and palatable and appeared safe in this age group.
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