OBJECTIVE. Our aim was to compare 2 laxatives, namely, polyethylene glycol 3350 without electrolytes and milk of magnesia, evaluating the efficacy, safety, acceptance, and 1-year outcomes.
METHODS. Seventy-nine children with chronic constipation and fecal incontinence were assigned randomly to receive polyethylene glycol or milk of magnesia and were treated for 12 months in tertiary care pediatric clinics. Children were counted as improved or recovered depending on resolution of constipation, fecal incontinence, and abdominal pain after 1, 3, 6, and 12 months. An intent-to-treat analysis was used. Safety was assessed with evaluation of clinical adverse effects and blood tests.
RESULTS. Thirty-nine children were assigned randomly to receive polyethylene glycol and 40 to receive milk of magnesia. At each follow-up visit, significant improvement was seen in both groups, with significant increases in the frequency of bowel movements, decreases in the frequency of incontinence episodes, and resolution of abdominal pain. Compliance rates were 95% for polyethylene glycol and 65% for milk of magnesia. After 12 months, 62% of polyethylene glycol-treated children and 43% of milk of magnesia-treated children exhibited improvement, and 33% of polyethylene glycol-treated children and 23% of milk of magnesia-treated children had recovered. Polyethylene glycol and milk of magnesia did not cause clinically significant side effects or blood abnormalities, except that 1 child was allergic to polyethylene glycol.
CONCLUSIONS. In this randomized study, polyethylene glycol and milk of magnesia were equally effective in the long-term treatment of children with constipation and fecal incontinence. Polyethylene glycol was safe for the long-term treatment of these children and was better accepted by the children than milk of magnesia.
- polyethylene glycol
- milk of magnesia
- functional constipation
- fecal incontinence
- long-term treatment
Functional constipation and fecal incontinence (encopresis) represent common problems in childhood.1 Constipation often is associated with fecal incontinence, often lasts for years, and can persist beyond puberty.2–7
Children with chronic functional constipation and fecal incontinence benefit from a precise, well-organized, treatment plan designed to clear the fecal retention, to prevent future fecal retention, and to promote regular bowel habits.2–11 After the initial bowel cleanout, increases in dietary fiber, several toilet sittings daily, and long-term daily laxative therapy are started. Osmotic laxatives such as milk of magnesia (MOM), lactulose, and sorbitol and the lubricant mineral oil are used most commonly by different centers. These laxatives have been used successfully on a long-term basis for children with functional constipation and incontinence and have very good safety profiles, but they are often refused by children because of their taste.4,6,10 Polyethylene glycol (PEG) 3350 without added electrolytes (MiraLax; Braintree Laboratories, Braintree, MA) is a chemically inert polymer and has been introduced as a new laxative in recent years. PEG has been shown to be effective in the treatment of constipation among infants, toddlers, preschool-aged children, and school-aged children.11–19
The use of PEG in subspecialty and primary care practices is increasing greatly. Parents often question the safety of PEG after reviewing information on the company Web site and noticing precautions for children receiving PEG for an extended period. The information from this study should help to address this problem.
Despite the availability of different laxatives, there are very few published studies among children comparing different laxatives with respect to efficacy or safety.11,13,18 Therefore, we designed a prospective, randomized study to compare the efficacy, safety, and patient acceptance of PEG versus MOM over 12 months.
All new children (≥1 per week) who were referred to the Children’s Hospital of Iowa (Iowa City, IA) for treatment of functional constipation with fecal incontinence, in August 2001 to September 2004, were eligible for the study. Children and their families were recruited by the 2 authors. Inclusion criteria were age of ≥4 years and presence of functional constipation with fecal incontinence. Functional constipation was defined by a duration of ≥8 weeks and ≥2 of the following characteristics: frequency of bowel movements of <3 stools per week, >1 episode of fecal incontinence per week, large stools noted in the rectum or felt during abdominal examination, passing of stools so large that they obstructed the toilet, and retentive posturing (withholding behavior). These criteria are similar to the recently proposed Paris Consensus on Childhood Constipation Terminology criteria20 and the new Rome criteria.21 The previous Rome criteria22 were too restrictive and excluded many children who had functional constipation.23,24 Children with stool toileting refusal, children with fecal incontinence but no constipation, children who had refused previously 1 of the study medications, children who came from far away for a second opinion, and children with Hirschsprung’s disease, chronic intestinal pseudo-obstruction, or previous surgery involving the colon or anus were not recruited.
The study was approved by the institutional review board of the University of Iowa. Children ≥7 years of age gave written assent, and all parents gave written informed consent.
Randomization, Treatment, and Follow-up Monitoring
Before the first appointment, parents were mailed a detailed questionnaire developed by Levine and Bakow,25,26 which included questions on stooling habits and fecal incontinence. This questionnaire was reviewed with the parents. All children were assessed by 1 of the authors. A short evaluation form that has been used for many years in our clinics was completed by the physician during the interview and after the examination. This form included questions about age at the time of development of constipation, whether the child was ever toilet trained for stool and at what age, presence of retentive behavior, frequency of fecal incontinence per week (smear, small bowel movement, or large bowel movement in underpants), frequency, size, and consistency of stools defecated into the toilet, passage of bowel movements that obstructed the toilet, presence of abdominal pain, urinary incontinence during the day or night, previous treatments, and presence of an abdominal fecal mass and/or rectal mass.
Randomization was performed by children drawing a sealed envelope with an enclosed assignment. The investigators, the children, and their parents were aware of the study group assignment. Children received initially either 0.7 g/kg body weight PEG daily11 or 2 mL/kg body weight MOM daily. Large dosages could be divided into 2 doses. A capful of PEG (17 g) was mixed in 8 oz of a beverage (such as juice, Kool-Aid, Crystal Light, or water), making a solution of ∼2 g/30 mL. Plain MOM could be mixed into applesauce or milkshakes, or chocolate and other flavorings could be added. Children were disimpacted with 1 or 2 phosphate enemas in the clinic on the day of the visit, if necessary, and started laxative therapy that evening. Parents were provided with written instructions regarding how to adjust the dosage of medication and children were treated with the minimal effective dosage of PEG or MOM, allowing for a daily stool and preventing abdominal pain and fecal incontinence. The written instructions said that we aim for 1 or 2 stools of milkshake consistency each day. Parents were asked to increase the dosage if the stools were too hard or not frequent enough and to decrease the dosage if the stools were watery or too numerous. Small changes, such as 2 oz of PEG or 0.5 tbsp of MOM every 3 days, were recommended. Regular stool sittings for 5 minutes after each meal were required initially. Toilet sitting frequency was reduced after the children recognized the urge to defecate and initiated toilet use themselves. Parents were instructed to keep a stool diary for the duration of the study, recording each bowel movement’s amount and consistency, episodes of fecal incontinence, abdominal pain, and medication use. Stool diaries were obtained rarely from patients who did not come for a follow-up visit. Data from parents’ verbal reports were accepted.
Return clinic visits were planned at 1, 3, 6, and 12 months after enrollment. A follow-up call was made at 9 months. At each visit, the interim history was assessed, stool diaries were reviewed and discussed, and a physical examination, including a rectal examination, was performed. Clinical progress, compliance with the treatment program, stool frequency, frequency of fecal incontinence episodes, occurrence of abdominal pain, and medication compliance were assessed from the stool diaries and history. A predesigned script, which had been approved by the institutional review board, was used during each visit or telephone call. The laxative dosage was adjusted as necessary, an enema was given if the child was impacted, and the stimulant laxative senna was added to the treatment program if the child was retaining liquid stools. If a child did not return for a planned follow-up visit, then the follow-up data were obtained through a telephone call by the authors, who gave advice regarding dose adjustment, toilet sitting, and a reward system and encouraged the parent to come for a follow-up visit if the child had not already recovered. If the family could not be reached by telephone, then a questionnaire was mailed to the last known address.
During each visit, patients and their parents were questioned with respect to diarrhea, ease of passage of stools, cramps, flatus, or any other adverse effects. Laboratory tests were optional, but children were encouraged to have blood drawn for measurement of serum sodium, potassium, chloride, blood urea nitrogen, creatinine, alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), hemoglobin, and hematocrit levels, platelet count, red blood cell count, and white blood cell count during the initial, 3-month, 6-month, and 12-month visits.
Improvement was defined as ≥3 bowel movements per week, ≤2 episodes of fecal incontinence per month, and no abdominal pain, with or without laxative therapy.5–7,11,24 Recovery was defined as ≥3 bowel movements per week, ≤2 episodes of fecal incontinence per month, and no abdominal pain, with no laxative treatment for ≥1 month.5–7,11,24 Children were counted as not improved and not recovered from the time of the refusal if they refused their study medication consistently and needed to be switched to a different laxative, if they discontinued participation in the study, if they were lost to follow-up monitoring, or if they were allergic to the study medication. Children who received additional senna treatment were counted as not improved and not recovered during the time they were receiving senna treatment.
Other outcomes studied were (1) improvement in stool frequency per week, improvement in episodes of fecal incontinence per week, and resolution of abdominal pain; (2) safety profile; and (3) patient’s acceptance and compliance.
We hypothesized that PEG would be as successful as MOM in treating chronic constipation and fecal incontinence. Our previous study showed that 33% of children refused to take MOM during the first 12 months of treatment.11 We estimated that 38 subjects were required in each group to be able to detect a difference in failure rates between the 2 groups of 30% in 12 months (40% vs 10%), at the .05 significance level with .80 power.
Data were entered into Excel (Microsoft, Redmond, WA), and analyzed. Efficacy analyses (improved and recovered) were performed with the intent-to-treat population, defined as all children assigned randomly. Bowel movement frequency, frequency of fecal incontinence episodes, and presence/absence of abdominal pain were calculated from the available follow-up data. Comparisons were made between the initial data and the follow-up data, between the 1-, 3-, 6-, and 12-month follow-up data, and within groups. Statistical analyses included determination of means and SDs, t test, χ2 test, and Fisher’s exact test, with significance accepted at the 5% level. Results are expressed as mean ± SD or percentage.
Initial Patient Characteristics
A total of 137 children and their families were asked to participate in our study. Seventy-nine children (65 boys and 14 girls; age range: 4–16.2 years; mean ± SD: 8.1 ± 3.0 years; median: 7.4 years) and their families agreed to participate and were enrolled in the study. A detailed flow diagram of the children’s progress through the study is presented in Fig 1. Thirty-nine children (31 boys and 8 girls) were assigned randomly to receive PEG 3350 without electrolytes. Forty children (34 boys and 6 girls) were assigned randomly to receive MOM. Initial patient characteristics of the children who received PEG and MOM are shown in Table 1. The baseline characteristics of the 2 groups were not statistically different (P > .07), with respect to demographic features and various parameters of constipation and incontinence. The frequency of bowel movements per week was higher than expected in both groups, but many children came to our clinic because of chronic continuous problems with constipation and fecal incontinence, often while receiving some form of treatment.
One-Month Follow-up Findings
In the PEG group, 33 children returned for the 1-month follow-up visit and 5 families were contacted by telephone. One child discontinued participation in the study because of an allergic skin rash, which reoccurred after rechallenge with PEG. In the MOM group, 27 children came for the 1-month follow-up visit and 10 families were contacted by telephone. Three children refused to take the MOM after a few days. Results of the 1-month follow-up visit are shown in Fig 2 and Table 2. Improvement was seen for 49% of children in the PEG group and 55% of children in the MOM group (P > .6) (Fig 2). In both groups, bowel movement frequency increased and fecal incontinence frequency and abdominal pain decreased significantly from baseline (Table 2).
Three-Month Follow-up Findings
In the PEG group, 29 children came for the 3-month follow-up visit and 9 families were contacted by telephone. In the MOM group, 26 children returned for the 3-month follow-up visit, 10 families were contacted by telephone, and 1 child was lost to follow-up monitoring. Four additional children refused to take the MOM, and 1 child experienced relapse and was switched to PEG by his primary practitioner. The rates of improvement and recovery were similar for the 2 groups (Fig 2). Improvement in the constipation parameters was significant for both groups, compared with baseline (P < .001) (Table 2).
Six-Month Follow-up Findings
In the PEG group, 21 children returned for the 6-month follow-up visit, 16 families were contacted by telephone, and 1 child was lost to follow-up monitoring. One child had refused PEG permanently, and 3 children needed senna. In the MOM group, 16 children came for the 6-month follow-up visit and 15 families were contacted by telephone. Three additional children had refused MOM, and 2 children had discontinued participation in the study. By 6 months, a total of 10 children (25%) had refused MOM. The 6-month outcome data (Fig 2 and Table 2) were not significantly different between the 2 treatment groups, remained significantly improved, compared with the initial data (P < .001), and were similar to the 1- and 3-month data (P > .1).
Twelve-Month Follow-up Findings
In the PEG group, 16 children returned for the 12-month follow-up visit, 19 families were contacted by telephone, and 1 child was lost to follow-up monitoring. Two of the 3 children who were receiving senna at the 6-month follow-up visit were still receiving daily senna. One child had refused PEG. After 12 months, a total of 2 children were lost to follow-up monitoring, 2 children (5%) had refused PEG, 1 child was allergic to PEG, and 2 children were receiving senna. These 7 children were counted as not improved and not recovered. In the MOM group, 8 children came for the follow-up visit, 17 families were contacted by telephone, and 1 child was lost to follow-up monitoring. Four additional children had refused to continue with MOM. By 12 months, 2 children were lost to follow-up monitoring, 3 children had discontinued study participation, 14 children (35%) had refused to take MOM, and 1 child was receiving senna.
The percentages of children who experienced improvement were similar in the PEG group (62%) and the MOM group (43%; P < .086) (Fig 2). The recovery rates were similar for children in the PEG group (33%) and the MOM group (23%; P = .283) (Fig 2). The 12-month data for frequency of bowel movements, frequency of episodes of fecal incontinence, and percentage of children with abdominal pain were not significantly different between the PEG and MOM groups (Table 2).
The mean PEG treatment dose at the 1-month follow-up evaluation was 0.7 ± 0.2 g/kg body weight daily and that at the 3-month follow-up evaluation was 0.6 ± 0.3 g/kg body weight daily. The mean PEG doses were similar for children who had and had not experienced improvement.
The mean MOM treatment dose at the 1-month follow-up evaluation was 1.2 ± 0.7 mL/kg body weight daily and that at the 3-month follow-up evaluation was 1.2 ± 0.8 mL/kg body weight daily. The mean MOM doses were similar for children who had and had not experienced improvement. There were 3 children who received the stimulant laxative senna in addition to PEG and 1 child who received it in addition to MOM at some point during the study (P > .29).
One child was allergic to PEG. No other significant clinical adverse effects were reported with either PEG or MOM except for transient diarrhea, which disappeared with dose reduction. There were no complaints of increased flatus, abdominal distention, or new onset of abdominal pain. The children in both groups who came for follow-up evaluations continued to grow in weight and height, along their growth curves, during the 12 months. There were no new abnormal physical findings on examination.
Most laboratory test results were within normal limits for the 30 children who had their blood evaluated before starting PEG treatment. Four children had elevated platelet counts (402000–492000 platelets per mm3; normal: <400000 platelets per mm3), and 2 had elevated AST levels (46 and 56 U/L; normal: ≤40 U/L) with elevated ALT levels (77 and 32 U/L; normal: ≤30 U/L). Twenty-seven children had 41 follow-up blood tests while receiving PEG; 17 children had 3-month follow-up blood tests, 15 had 6-month tests, and 9 had 12-month tests; 11 had 1 follow-up blood test, 9 had 2 tests, and 7 had 3 tests. Only 1 of the 4 children with elevated platelet counts showed an elevated platelet count; 1 blood test showed a decreased sodium level (133 mEq/L; normal: 135–145 mEq/L) at the 6-month follow-up evaluation, but the level was normal at 12 months. All children had normal ALT and AST values at follow-up evaluations.
Of 25 children who underwent laboratory testing before starting MOM, 1 had an elevated platelet count (453000 platelets per mm3) and 2 had mildly decreased serum potassium levels (3.3 mEq/L; normal: 3.5–5 mEq/L). Twenty children had 30 follow-up blood tests while receiving MOM, 15 children at 3 months, 10 at 6 months, and 5 at 12 months; 12 children had 1 follow-up blood test, 6 had 2 tests, and 2 had 3 tests. One child had a high platelet count (563000 platelets per mm3), 1 child had a low serum sodium level (134 mEq/L), 1 child had an elevated AST level (43 U/L), and 1 child had an elevated ALT level (48 U/L).
Several children complained about the taste of PEG and MOM. Only 2 children (5%) continued to refuse PEG, whereas 14 children (35%) continued to refuse MOM during the 12 months of the study (P < .001) (Fig 1).
In this prospective, randomized study, we found that PEG was similar in efficacy to MOM for the long-term treatment of children with functional constipation and fecal incontinence. At the 1-month, 3-month, 6-month, and 12-month follow-up evaluations, similar improvement and recovery rates were seen for the PEG and MOM groups, with a significant increase in bowel movement frequency, a significant decrease in the frequency of fecal incontinence episodes, and resolution of abdominal pain. At the 12-month follow-up visit, 62% of children in the PEG group and 43% of children in the MOM group showed improvement and 33% of children in the PEG group and 23% of children in the MOM group had recovered (not significant). In this study, we could not demonstrate superior efficacy of one medication over the other.
Similar to our study, previous studies showed that MOM and PEG were not associated with any significant clinical adverse effects. In 1 study, minimal abnormalities in liver function tests (AST and ALT) were noted for 11% of children receiving PEG therapy, but no laboratory evaluation was performed before PEG initiation.15 In the present study, 9 children had minor laboratory abnormalities before randomization, including 2 children with elevated AST and ALT levels. However, all children had normal values for AST and ALT levels while receiving PEG. One child each had minor AST or ALT elevation while receiving MOM. It seems that both PEG and MOM are safe for long-term use among children.
Compliance with taking the prescribed laxative was clearly superior for PEG-treated children (95%), compared with MOM-treated children (65%), during the 12-month study. One advantage of PEG is that it can be mixed in a beverage of the patient’s choice. MOM does not have good palatability, however, and its taste is difficult to hide even when it is mixed with different foods. Patient acceptance is an important factor for successful long-term resolution of constipation.
Although constipation is a common chronic problem, there are very few studies with children comparing different laxatives. In 1 randomized, crossover trial, PEG was found to be as effective as lactulose for 37 children with constipation, over a 2-week study period.13 In 2 randomized trials, PEG with electrolytes was shown to be more effective than lactulose for 91 children over 8 weeks of therapy18 and for 51 children over a 3-month period.19 In our previous, pilot, nonrandomized study, PEG was as effective as MOM for 49 children over 12 months.11 All of those studies had limitations of short follow-up periods, small sample sizes, or lack of randomization.
Compared with previous studies, our study has multiple strengths. Our study was a randomized, clinical trial comparing PEG and MOM in 2 large, well-matched groups of children, with well-defined outcome measures. It was not possible to perform a blinded study because these 2 medications are administered to children in different ways. In this study, we examined children and gathered data at frequent intervals and for long periods. We also studied the safety profiles and patient acceptance, which are 2 important factors, in addition to efficacy, in consideration of an appropriate laxative for children.
Limitations of our study include a relatively high dropout rate, because of loss to follow-up monitoring and refusal of medication. We tried to adjust for this problem by analyzing our data on an intent-to- treat basis. Loss to follow-up monitoring occurred in both groups and could be attributable to difficulties with money, insurance policies, or time, unhappiness with the treatment or perceptions that improvement was too slow, recovery of the child, or parents’ satisfaction with the degree of improvement. Another limitation is that we did not measure biochemical profiles for all children, because mandatory blood testing would have affected recruitment and not all children were brought for the agreed-upon follow-up visits. Our patients were treated in a tertiary care center, with 68% having undergone previous unsuccessful treatment. It could be postulated that outcomes would be better in primary care practices and for children whose constipation has not progressed to fecal incontinence.
At the time of recruitment into this study, we used phosphate enemas for disimpaction in our clinic. Youssef et al27 reported excellent disimpaction results with 1.5 g/kg body weight PEG daily for 3 days. Currently, we use enemas rarely and we achieve good results with oral disimpaction therapy.
Studies showed that most constipated children, with or without fecal incontinence, experienced improvement regardless of the type of laxative chosen, with 1-year recovery rates ranging from 31% to 59%.5–7,9 Recovery rates 4 years after the start of treatment were reported to be 65%, those 5 years later to be 48% to 75%, and those 8 years later to be 70%.3,5–7 As the data from the long-term study with lactulose by van Ginkel et al6 illustrate, relapse is frequent among these children. It is clear that a well-accepted laxative is needed for long-term treatment for these children, because follow-up data after 7 and 8 years showed that ∼30% of children were still experiencing difficulties with constipation and/or fecal incontinence, even in adolescence.6
This randomized, controlled trial confirms that both PEG and MOM are effective and safe in the long-term treatment of children with constipation and fecal incontinence. PEG had better patient acceptance than did MOM. Whether better follow-up monitoring for these children would have resulted in better outcomes requires study.
Braintree Laboratories (Braintree, MA) supported this study with an unrestricted research grant. The funding source had no involvement in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.
- Accepted March 23, 2006.
- Address correspondence to Vera Loening-Baucke, MD, Children’s Hospital of Iowa, JCP 2555, 200 Hawkins Dr, Iowa City, IA 52242. E-mail:
The authors have indicated they have no financial relationships relevant to this article to disclose.
- ↵Abi-Hanna A, Lake AM. Constipation and encopresis in childhood. Pediatr Rev.1998;19 :23– 30
- ↵Loening-Baucke V. Constipation in early childhood: patient characteristics, treatment, and long-term follow up. Gut.1993;34 :1400– 1404
- ↵Loening-Baucke V. Biofeedback treatment for chronic constipation and encopresis in childhood: long-term outcome. Pediatrics.1995;96 :105– 110
- ↵Gremse DA, Hixon J, Crutchfield A. Comparison of polyethylene glycol 3350 and lactulose for treatment of chronic constipation in children. Clin Pediatr (Phila). 2002;41 :225– 229
- Pashankar DS, Bishop WP, Loening-Baucke V. Long-term efficacy of polyethylene glycol 3350 for the treatment of chronic constipation in children with and without encopresis. Clin Pediatr (Phila). 2003;42 :815– 819
- ↵Voskuijl W, de Lorijn F, Verwijs W, et al. PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomized, controlled, multicenter trial. Gut.2004;53 :1590– 1594
- ↵Rasquin-Webber A, Hyman PE, Cucchiara S, et al. Childhood functional gastrointestinal disorders. Gut.1999;45(suppl II) :1160– 1168
- ↵Fishman L, Rappaport L, Schonwald A, et al. Trends in referral to a single encopresis clinic over 20 years. Pediatrics.2003;111 (5). Available at: www.pediatrics.org/cgi/content/full/111/5/e604
- ↵Levine MD, Bakow H. Children with encopresis: a study of treatment outcome. Pediatrics.1976;58 :845– 852
- Copyright © 2006 by the American Academy of Pediatrics