Functional constipation and fecal soiling (encopresis) are common problems in childhood. Many disorders can cause constipation. In children, functional disorders usually cause constipation. Constipation is rarely caused by organic and anatomical causes or by intake of medication. Practice guidelines of the North American Society for Pediatric Gastroenterology and Nutrition define constipation as a delay or difficulty in defecation severe enough to cause distress to the patient (1). Often encopresis accompanies long-standing constipation. Encopresis is defined as the involuntary loss of formed, semiformed, or liquid stool into the child's underwear after the child has reached a developmental age of 4 years (2).
Children with chronic constipation and encopresis benefit from a precise, well-organized treatment plan, designed to clear fecal retention, prevent future fecal retention, and promote regular bowel habits (1,3–9). After the bowel is cleaned out initially, patients begin taking increased dietary fiber, make several defecation trials daily, and often begin long-term laxative medication to achieve daily defecation and to prevent soiling. Osmotic laxatives, such as milk of magnesia (MOM), lactulose, or sorbitol, and the lubricant mineral oil, are used most commonly. The actual choice of medication is determined by the child's taste preference, and is not as important as an adequate dosage and the child's and parent's compliance with the treatment regimen. Milk of magnesia and mineral oil are unpalatable, and lactulose and sorbitol are too sweet. Therefore, children often refuse to take these medications for an extended period.
Polyethylene glycol electrolyte solutions are iso-osmotic and have been used in large quantities to cleanse the gastrointestinal tract for diagnostic and surgical procedures (10,11). They have been used daily in low volumes to treat chronic constipation in adults (12,13). However, these medications can lead to problems because of absorption of the electrolytes (14). Therefore, a new polyethylene glycol 3350 without added electrolytes (MiraLax; Braintree Laboratories, Inc., Braintree, MA, U.S.A.) has been developed and tested for daily use as a laxative in adults (15–17). MiraLax is a chemically inert polymer in powder form. It is tasteless, odorless, colorless; has no grit; and can be mixed in juice, Kool-Aid and water. Bacteria do not degrade MiraLax, and the drug is not readily absorbed and therefore acts as an excellent osmotic agent. The Food and Drug Administration has approved MiraLax for short-term treatment of constipation in adults. Abstracts and one manuscript have been published about the use of MiraLax for functional constipation in children for 2 weeks to 3 months (18–20).
In this study, we determined the efficiency, acceptability, and treatment dosage of MiraLax during a 12-month treatment period in children with functional constipation and encopresis.
PATIENTS AND METHODS
This observational study evaluated prospectively the effectiveness, acceptability, and dosage requirement of MiraLax in treating functional constipation with encopresis in children. Study subjects were children 4 years of age or older, who had been referred to and newly evaluated by the author for functional constipation and encopresis at the University of Iowa Hospitals and Clinics in Iowa City, Iowa, during September 1999 to May 2000. All children had functional constipation defined as delay or difficulty in defecation (1) and encopresis (≥1/week) for more than 1 year. The study began in September 1999 because the author first prescribed MiraLax at that time, and the study ended in May 2000 to allow evaluation of the medication after at least 12 months of treatment. Children younger than 4 years of age; children who refused the toilet for stooling but who had no constipation (21); or children with Hirschsprung disease, chronic intestinal pseudo-obstruction, or previous surgery of the colon or anus were excluded.
Twenty-eight children (20 boys and 8 girls) received MiraLax. Their ages ranged from 4.1 to 17.5 years, mean ± SD was 8.7 ± 3.6 years. These children started treatment with MiraLax after the initial evaluation. The results of these 28 children treated with MiraLax were compared with the results of all children who fit the entry criteria and who had initial evaluations during the same period. The comparison group consisted of 21 children (17 boys and 4 girls; 4.0 to 13.9 years of age, mean ± SD was 7.3 ± 3.0 years) who started treatment with MOM.
The Institutional Review Board of the University of Iowa approved the study.
Treatment was not randomized. Twenty-eight children received MiraLax. The parents of six of these children had reported the children's refusal to take MOM during previous treatment trials. MiraLax was given as a beverage, 17 g dissolved in 240 mL of a beverage such as juice or Kool-Aid. An initial dose of 0.5 g/kg daily was suggested for children whose rectums were loaded with stool but who had no fecal abdominal masses at the initial physical examination and no history of long intervals between huge bowel movements. Those with palpable abdominal fecal masses or history of infrequent huge bowel movements were started on 1 g/kg daily.
During the same time period, 21 children received MOM. Milk of Magnesia was given if the family could afford only the use of a cheaper laxative or if the child had previously received MOM without refusal. For these children, MOM was simply reintroduced or adjusted to an adequate dosage. Milk of Magnesia comes in various flavors, and parents were told how to improve the taste by mixing the child's preferred flavoring with plain MOM. An initial daily dosage of 1 mL/kg body weight was suggested for children with rectal fecal masses only at initial evaluation and if they had no history of infrequent large bowel movements. A dosage of 2.5 mL/kg was prescribed for those with fecal abdominal masses at the initial evaluation or history of huge, infrequent bowel movements.
Large laxative dosages were divided into two daily doses. Parents were told to adjust the dose of medication by 30 mL for MiraLax and by 7.5 mL (one-half tablespoon) for MOM every 3 days to a dosage that resulted in one to two soft bowel movements per day and prevented soiling and abdominal pain.
Regular stool sittings for 5 minutes after each meal were required for the initial months. The patients and their parents were provided with diary sheets to record each bowel movement, consistency of stools, soiling episodes, abdominal pain episodes, medication use, and daytime or nighttime urinary incontinence. A global assessment of whether the child was “doing well,” “improved,” or “not doing well” was recorded. Doing well, was defined as 3 or more bowel movements/week and 2 or fewer soiling episodes / month. Improved, was defined as 3 or more bowel movements / week and a more than 75% decrease in soiling but not more than 1 soiling / week. Not doing well was defined as fewer than 3 bowel movements / week, a less than 75% decrease in soiling frequency, use of senna, or refusal to take the assigned laxative. Recovered was defined as 3 or more bowel movements / week and 2 or fewer soiling episodes / month while not taking laxatives.
Children were reevaluated 1, 3, 6, and 12 months after the initial visit. If the child did not come to the follow-up visit, the information was obtained by telephone. At each visit, interim history was assessed, stool diaries were collected and discussed, and a physical examination that included a rectal examination was performed. If the child retained stools despite compliance with the assigned laxative, daily senna was added to the treatment.
During the initial follow-up visit, children were asked whether the MiraLax was tasteless, tasted okay, or tasted bad.
Data were entered into the software PC info (Retriever Data Systems, Seattle, WA), an analysis program for clinical data. Statistical analysis included the Wilcoxon 2-group rank sum test and signed rank test, and the Fisher exact test with significance accepted at the 5% level. Results were expressed as mean ± SD or percentage.
Table 1 shows the initial characteristics of the 28 children who received MiraLax and of the 21 children who received MOM. There were no differences between children who received MiraLax and MOM (P > 0.08). The frequency of bowel movements each week was higher than expected in both groups, but children often came to our clinic while taking some form of treatment.
Follow-up at 1 Month
One-month follow-up occurred as visits in 90% and by telephone contact in 10% of both groups. Figures 1 through 3 and Table 2 show results of the 1-month follow-up. Twelve children (43%) were doing well, 6 (21%) were improved, and 10 (36%) were not doing well. Three children (one pair of siblings) were not receiving the MiraLax daily. They continued to soil and had abdominal fecal masses present on examination. They received enemas for disimpaction, restarted MiraLax, and began taking daily senna. Frequency of bowel movements / week increased significantly (P < 0.001), and soiling episodes / week (P < 0.001) and abdominal pain decreased significantly (P < 0.01).
All children answered that MiraLax was tasteless or okay when stirred well into Kool-Aid, fruit juice, or soft drinks.
All 21 children in the MOM group were followed at 1 month (1.1 ± 0.1 month). Fourteen children (67%) were doing well; 6 (29%) were improved; and one child (5%), who did not take the MOM, was not doing well. Frequency of bowel movements / week increased significantly and soiling episodes / week decreased significantly (P < 0.002).
A similar percentage of children in both groups did well, but significantly fewer children in the MiraLax group (64%) were improved compared with the MOM group (95%, P < 0.01; see Fig. 1). Significantly more soiling episodes occurred in children in the MiraLax group than in the MOM group (P < 0.01; see Fig. 3).
Follow-up at 3 Months
The 3-month follow-up occurred as visits in 76% of children and by telephone contact in 22%. One child did not return for follow-up and could not be reached by phone. In the 27 children receiving MiraLax, this follow-up occurred at 3.3 ± 0.8 months. Figures 1 through 3 and Table 2 show the results of the 3-month follow-up. Fifteen children (56%) were doing well, six (22%) were improved, and six (22%) were not doing well. One patient had relapsed. Four patients were taking senna daily, two of them were improved and two were not doing well; all four were rated as not doing well. Their data were excluded from Fig. 2 and 3 and Table 2.
All 21 children in the MOM group were followed up at 3.4 ± 0.8 months. A total of 16 children (76%) were doing well, 4 (19%) were improved, and 1 (5%) was not doing well. One patient was taking daily senna and was not doing well (data excluded from Fig. 2 and 3 and Table 2). The 3-month outcome data did not differ significantly between the two groups (P > 0.1).
Follow-up at 6 Months
The 6-month follow-up occurred with visits in 73% of children and by phone contact in 27%. Figures 1 through 3 and Table 2 show results of the 6-month follow-up. All 28 children in the MiraLax group had follow-up at 6 months (6.6 ± 1.2 months). Fifteen children (54%) were rated as doing well, 4 of whom (14%) had recovered; 5 (18%) were improved; and 8 (29%) were not doing well. Two of the 4 children who were not doing well were siblings from a chaotic family in which compliance was poor. Two more children also required daily senna, neither of whom was doing well or had improved. The data of children on senna are excluded in Fig. 2 and 3 and Table 2.
All 21 children in the MOM group were observed at 6 months (6.9 ± 1.7 months). A total of 14 children (67%) were doing well with 7 (33%) having recovered, one (5%) was improved, and 6 (29%) were not doing well, including 2 children who were switched to MiraLax before the 6-month follow-up visit because of continued refusal to take MOM. At the 6-month follow-up visit, 3 more parents reported that their children refused to take MOM during the past months. These 3 children were switched to MiraLax at the 6-month visit. Therefore, a total of 5 children (24%) in the MOM group had refused MOM during the first 6 months of the study.
Six-month outcome data did not differ significantly between the two treatment groups (P > 0.1).
Follow-up at 12 Months
The 12-month follow-up occurred as visits in 55% of the children and by telephone in 45%. Figures 1 through 3 and Table 2 show results of the 12-month follow-up. All 28 children in the MiraLax group were observed at 11.9 ± 0.9 months. Seventeen children (61%) were doing well, 6 (21%) had recovered, and 11 (39%) were not doing well. Five children also received daily senna; none was doing well or had improved. Their data were excluded from Figs. 2 and 3 and Table 2.
All 21 children in the MOM group were observed at 12.4 ± 0.8 months. Fourteen children (67%) were doing well, 12 (57%) had recovered, and 7 children (33%) were rated as not doing well because they were taking MiraLax after having refused MOM (data excluded from Fig. 2 and 3 and Table 2).
The 12-month outcome data for the MiraLax and MOM groups did not differ significantly, except that the frequency of soiling was significantly higher in the MiraLax group (P < 0.01) (Fig. 3).
In the MiraLax group, the percentage of children complaining of abdominal pain had decreased significantly at each follow-up visit (P < 0.01), and none of the children in the MOM group reported abdominal pain at the 6-month and 12-month follow-ups (Table 2).
In both groups, the percentage of children with daytime wetting decreased (Table 2), but not significantly because of the small number of subjects in each patient group. The percentage of children with daytime wetting decreased significantly at 3-, 6-, and 12-month follow-ups when children in both groups were combined (P < 0.03, P < 0.03, and P < 0.01, respectively).
The percentage of children with nighttime wetting did not change significantly over time (Table 2).
The mean MiraLax dosage at 1 month for children who were doing well or improved was 0.6 ± 0.2 g/kg (range, 0.3 to 1.1 g/kg) and at 3 months was 0.6 ± 0.3 g/kg (range, 0.3 to 1.4 g/kg). The mean dosage did not differ significantly between children with or without initial palpable abdominal fecal masses. The mean MiraLax treatment dosage at 12 months for the 13 children who were doing well or improved and who still required MiraLax was 0.4 ± 0.1 g/kg (range, 0.1 to 0.7). None of the patients required an increased MiraLax dosage over time.
The mean MOM treatment dosage at 1 month for children who were doing well or improved was 1.4 ± 0.6 mL/kg (range, 0.6 to 2.6 mL/kg) and at 3 months was 1.2 ± 0.5 mL/kg (range, 0.6 to 2.4 mL/kg). The mean MOM dosage did not differ significantly between children with or without initial palpable abdominal fecal masses. At 12 months, only two children who were doing well still required MOM. Their dosages were 0.4 and 1.6 mL/kg, both less than the initial treatment dosage. None of the patients required an increased MOM dosage over time.
Five children received a stimulant laxative in addition to MiraLax, and one child received a stimulant laxative in addition to MOM (P > 0.2).
Clinically Significant Side Effects
MiraLax did not cause any significant clinical side effects. Some of the children in the MiraLax group had diarrhea, which may have been responsible for the more frequent soiling episodes as compared with the MOM group. None of the children in the MiraLax group became dehydrated. Children in both groups continued to grow in weight and height during the 12 months. Children receiving MiraLax and their parents did not report increased flatus, abdominal distention, or new onset of abdominal pain.
Noncompliance by children or their caregivers has been a well-known problem in children with functional constipation and encopresis. None of the children reported disliking the taste of MiraLax, and none of the parents reported that a child refused to take the MiraLax in juice or Kool-Aid, whereas 33% of children refused to take MOM. Children's noncompliance with other aspects of the treatment plan is more difficult to assess. Parental noncompliance with administering the laxative and supervising toilet use was a problem in 14% of children in the MiraLax group and in 4% of children in the MOM group.
In this prospective, observational study, we found that MiraLax was palatable, well tolerated, and efficient in the long-term treatment of children with functional constipation and encopresis. At the 1-month, 3-month, 6-month, and 12-month follow-ups, we saw significant improvement in the MiraLax and MOM groups (increased bowel movement frequency and decreased soiling frequency). At the 1- and 12-month follow-ups, children in the MiraLax group reported more soiling than did those in the MOM group (P < 0.01). At 12 months, 61% of children in the MiraLax and 67% of children in the MOM group were doing well (P = 1).
We have no explanation for why children in the MiraLax group had a significantly greater number of soiling episodes at the 1-month and 12-month follow-ups compared with the MOM group. We had observed a few children who developed diarrhea while receiving high doses of MiraLax. Similar observations have been made in initial study weeks when polyethylene glycol was compared with lactulose in constipated adults (22,23).
Abdominal pain decreased significantly, and daytime wetting decreased. Contrary to previous observations (24,25), we did not see a significant decrease in the percentage of children with nighttime wetting.
Recently, polyethylene glycol electrolyte lavage solutions have received increased attention for use as laxatives. Taken rapidly in large volumes, they do not cause net absorption or secretion of electrolytes (26,27). No intestinal absorption occurs at molecular weights exceeding 3,000 (28). No adaptation with consequent flatus or loss of efficiency occurred because no intestinal enzymatic degradation or bacterial metabolism occurred with polyethylene glycol (28). When taken daily in low volumes, polyethylene glycol electrolyte solution is effective, safe, well tolerated, and has no significant side effects in short-term (12) and long-term treatment (13) of constipation in adults. No net absorption or secretion was presumed for the use of smaller volumes, but recent work has shown that low-volume administration resulted in nearly complete absorption of the salt component of the solution, which could potentially lead to dangerous sequelae, especially for patients with renal impairment or congestive heart disease (14,15).
For many years, observational studies were believed to report stronger treatment effects than randomized, controlled trials. Recently, two studies found little evidence that estimates of treatment effects are either consistently larger than or qualitatively different from those obtained in randomized, controlled trials (29,30). However, a randomized, controlled trial comparing these two laxatives has been started, and electrolyte concentrations and hemograms will be checked regularly to evaluate further the efficacy and safety of polyethylene glycol in children with functional constipation and encopresis.
Our observational study shows that polyethylene glycol without electrolytes is a reasonable alternative in the long-term treatment of children with chronic constipation and encopresis. MiraLax did not cause any clinical significant side effects, there was no loss of efficiency during the 12-month study, and none of the children refused the medication because of taste. Soiling episodes decreased significantly over time. At the 12-month follow-up, soiling was more frequently observed in patients treated with MiraLax than in those treated with MOM. This may be because of differences in the patient groups, overtreatment, or noncompliance with all aspects of the treatment plan.
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