Weber, Thabata K.*; Toporovski, Mauro S.†; Tahan, Soraia*; Neufeld, Clarice B.†; de Morais, Mauro B.*
Chronic constipation (CC) is a common symptom in pediatric populations (1). Treatment involves various educational measures concerning appropriate intestinal habits; when necessary, fecal impaction is treated with disimpaction therapy, and maintenance therapy is initiated to avoid recurrences (2,3). The maintenance therapy involves the continued use of stool softeners, correcting eating habits and adopting a fiber-rich diet (3).
The modulation of a number of intestinal functions is a physiological effect attributed to dietary fiber (4). Diets that contain sufficient fiber can increase the number and volume of bowel movements, soften stool texture, and decrease intestinal transit time (5). The preferential consumption of foods with higher fiber content is not always sufficient to attain an adequate dietary fiber intake (6). Therefore, individuals can increase their fiber consumption using dietary fiber supplements. Despite indications that increased fiber consumption aids in the treatment of constipation (2,3,7), few clinical trials (8–12) have evaluated the efficacy of increased fiber intake. These trials have demonstrated little evidence that fiber supplements are more effective than placebo, and in the majority of cases, the effect of only a single type of fiber was evaluated. Each type of dietary fiber presents particular characteristics that determine its action, mechanism, and performance in different parts of the colon (13). Therefore, the combination of different types of fibers into a single product for fiber supplementation may result in greater effectiveness.
Owing to the lack of well-designed, randomized clinical trials targeting nonpharmacological treatment for constipated children (14), we designed a clinical trial to evaluate the clinical efficacy and effect of a dietary fiber mixture on colonic transit time (CTT) in pediatric patients with controlled CC.
Children between the ages of 4 and 12 years were included in the study. The initial diagnosis of functional CC was based on the Rome III criteria (1). The children were treated at the Pediatric Gastroenterology Outpatient Clinics of the Santa Casa de Misericórdia Hospital and the Federal University of São Paulo, Brazil, which are located in the city of São Paulo. All of the patients had controlled CC and had received maintenance therapy with low doses of stool softeners (<1.0 mL/kg of magnesium sulfate, mineral oil or lactulose or <0.5 g/kg of polyethylene glycol 3350). The controlled CC was defined by at least 1 evacuation every 2 days and the absence of fecal incontinence or fecal impaction for >1 month. In addition to this, the patients were in the gradual removal phase of the softener and working toward the goal of complete suspension of the medication.
The exclusion criteria included the following: organic causes of constipation, metabolic illnesses, regular use of fiber and probiotic supplements in the 4 weeks before admission to the study, use of medications that could cause constipation, a family that was unable to record the protocol information, and absence of a fixed or mobile telephone.
Study Design and Intervention
This study was a randomized, parallel, double-blind, placebo-controlled trial that followed the standards proposed by the Consolidated Standards of Reporting Trials (15). The randomization was generated using a random number table produced by a clinical research company (Invitare, São Paulo, Brazil). Blocks of 6 patients were allocated at a 1:1 ratio into the study and control groups.
For the clinical evaluation, we assessed the patients’ prior and present history of constipation. We paid special attention to the abdominal and rectal evaluations to verify the absence of fecal impaction. Upon admission to the study, the child's parents were instructed to suspend the use of stool softeners and to administer the supplied supplement or placebo. They were informed about maintaining daily toilet training and regular water ingestion. A daily diet inquiry and 24-hour recording methods were used to determine the child's dietary consumption. Energy, fat, carbohydrate, and protein levels were measured using the Nutritional Decision Support System (version 2.5) software (São Paulo, Brazil) (16). The Brazilian food composition table was used to quantify the intake of dietary fiber from food sources (17).
The patients were evaluated once weekly during the 4-week study period. The first (day 7) and third (day 21) evaluations were performed over the telephone, and the second (day 14) and fourth (day 28) evaluations were conducted at the ambulatory outpatient clinic. At home, the individual responsible for administering treatment completed 2 specific questionnaires: first, a daily defecation frequency and type of feces eliminated questionnaire based on the Bristol Stool Form Scale (18) (stools were rated based on water content; a score of 1 represented hard stools and a score of 7 represented liquid stools), and, second, a questionnaire addressing symptoms related to constipation and the use of the supplement provided.
Dietary Fiber Mixture
During the 4-week study period, the patients received the fiber mixture or the maltodextrin placebo. The fiber mixture used in this study (Stimulance; Milupa, Friedrichsdorf, Germany; imported and distributed by Support Produtos Nutricionais, São Paulo, Brazil) was selected because it had been successfully used in hospitalized adults who required enteral nutrition (19). Additionally, its various components are digested in different portions of the colon (proximal and distal); therefore, the combined use of these fiber types was expected to be more effective than the use of single-fiber products. It should be emphasized that several of the components (10.5% fructooligosaccharides, 12.5% inulin, 24% gum arabic, 9% resistant starch, 33% soy polysaccharide, and 12% cellulose) are considered prebiotics.
Dietary fiber and fiber supplements are often recommended for both the treatment and prevention of constipation; however, there is no specific therapeutic dose (14,20), according to the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition guideline (3). The product manufacturer suggests a variable dose for both children (1/2–3, 3.8-g/day) and adults (1–3 g/day). In this context, we decided to use a lower dose for children <18 kg of weight and a higher dose for children weighing >18 g. The dose was defined according to body weight: 3.8 g of fiber or placebo (1 tablespoon) diluted in 200 mL of a chocolate milk drink was given twice a day to children weighing up to 18 kg, and 7.6 g of fiber or placebo (2 tablespoons) was given in the same form to children weighing >18 kg.
The parents were instructed on how to adequately prepare the fiber mixture or the placebo with the chocolate milk drink. Therapeutic compliance with the prescription was based on the weight of the product tins, which were delivered unopened to the researchers. The labeling was standardized, and the products resembled each other and were administered in an identical manner.
The primary outcome was defined as therapeutic failure. Therapeutic failure was defined as a patient who experienced hardened stools, defecation with pain or difficulty, a greater interval between evacuations compared with the previous day, the appearance of fecal incontinence and fecal impaction, or when the patient required a stool softener during the study period. Therapeutic success was defined as a patient maintaining normal bowel habits without the use of stool softeners or enemas.
Secondary outcomes were defined as the defecation frequency (as stated in the bowel movement records); the form and consistency of the stool, for which hardened stools included types 1, 2, and 3 and nonhardened stools included types 4, 5, 6, and 7, according to the Bristol Stool Form Scale (18); the CTT; the palatability level, based on palatability scores (1 = good, 2 = reasonable, and 3 = poor); and the occurrence of adverse effects.
The total and segmental CTTs were evaluated during the last week of the study using the method proposed by Bouchoucha et al (21), although with several modifications (22). Radiopaque markers (Sitzmarks; Konsyl Pharmaceuticals, Easton, MD) were reencapsulated to contain 12 markers in each capsule. A capsule containing 12 radiopaque markers was ingested on 6 consecutive mornings (at 9:00 AM). An abdominal radiograph was obtained on day 7. To determine the segmental transit time (right, left, and rectosigmoid), the topographic regions proposed by Gutierrez et al (22) were used. Based on the number of markers counted in each region, the CTTs were calculated using the following formula: CTT = (sum of the markers × [time between administrations/number of markers per capsule]).
We obtained written informed consent for each patient before the patients were admitted into the clinical trial. The ethics committees from both research centers approved the study.
The sample size was calculated based on the primary outcome (therapeutic failure). We assumed a 30% failure rate for the intervention group and a 70% failure rate for the control group. With α = 0.05 and β = 0.20 (power = 0.80), each group would ideally comprise 28 patients.
To compare the mean and median values of the 2 study groups, we used a parametric (the Student t test) or a nonparametric test (the Mann-Whitney U test) in accordance with the variable distribution. The paired t test was performed to compare intragroup averages. To determine proportions, we used the χ2 test or the Fisher exact test. We performed the calculations using SigmaStat 3.1 (Jandel Corporation, Richmond, CA) (23) and EpiInfo (24) software. To calculate the risk ratio (RR) and 95% confidence intervals (CIs), we used the EpiInfo program. To calculate the number needed to treat, we used the inverse of the absolute risk reduction. The difference between the study groups was considered significant when P < 0.05 or when the 95% CI for the risk ratio did not exceed 1.0 (equivalent to P < 0.05).
Between February 2008 and January 2009, 60 children were eligible for the study, and 57 patients were randomized into 2 groups. The experimental group (n = 27) received the dietary fiber mixture, and the control group (n = 30) received the placebo. No statistically significant differences were found between the groups at the time of their admission to the trial (Table 1). During the treatment period, 2 patients from the control group were excluded from the analysis; 1 patient was excluded for consuming products containing probiotics, and the other patient was excluded for not attending the consultations. One patient in the dietary fiber mixture group discontinued intervention because he did not want to drink the chocolate milk and was therefore not consuming the fiber treatment. In total, 54 patients were evaluated, 26 from the dietary fiber mixture group and 28 from the control group. Six patients in the dietary fiber mixture group (6/26) and 4 patients in the control group (4/28) interrupted their treatment (because of the need for stool softeners or enemas to manage fecal impaction) during the intervention period (P = 0.254). Twenty patients from the dietary fiber mixture group (20/26) and 24 patients from the control group (24/28) completed the entire 4-week protocol (Fig. 1). Three patients in the intervention group and 6 patients in the control group were, however, designated as therapeutic failures during the last evaluation.
The analysis of the primary outcome followed the intention-to-treat principle. Therefore, all 54 of the patients included in the study were considered. The evaluation of the secondary outcomes (defecation frequency, stool consistency, and CTT) was based on the data from the 44 patients who completed the 4-week study period.
Therapeutic failure was similar between the 2 groups. In total, 9 (9/26, 34.6%) patients from the dietary fiber mixture group and 10 (10/28, 35.7%) patients from the control group were considered to present therapeutic failure (Table 2).
Defecation Frequency and Stool Consistency
Taking into account the secondary outcomes, a greater increase in defecation frequency per day (final − basal value) was observed for patients in the dietary fiber mixture group (0.529 ± 0.423) compared with those in the control group (0.232 ± 0.350, P = 0.014; Table 3). The recording of the form and consistency of the stool according to the Bristol Stool Form Scale permitted the identification of the predominant type of stool passed. Hardened stools included types 1, 2, and 3, and nonhardened stools included types 4, 5, 6, and 7 based on the Bristol Stool Form Scale. Hardened stools predominated among the control group patients, whereas nonhardened stools predominated among the patients in the dietary fiber mixture group. This association was statistically significant (Table 4).
Consumption of Fiber, Energy, and Macronutrients
The median dietary fiber intake was similar for both groups before the start of the clinical trial (13.8 g/day in the dietary fiber mixture group and 14.10 g/day in the control group, P = 0.993). In addition to this, the median energy and consumption of macronutrients were similar between the groups. During the study period, the children maintained their normal and expected body mass index values (data not shown).
We did not perform an abdominal radiograph on 1 patient in the dietary fiber mixture group. Table 5 presents the total and segmental CTTs during the fourth week of the clinical trial. These times were similar for the 2 groups.
The median (25th and 75th percentiles) palatability scores for the dietary fiber mixture and the placebo (maltodextrin) were 1.25 (1.00–1.67) and 1.00 (1.00–1.25), respectively (P = 0.007). Nevertheless, the compliance of the dietary fiber mixture group with the prescribed dosage was satisfactory.
A total of 81% of the children in the fiber mixture group consumed >80% of the prescribed dosage. No child failed to take the supplements on consecutive days throughout the study. Serious adverse events were not observed for either group, and the products were well tolerated.
This clinical trial demonstrated that the ingestion of a dietary fiber mixture can contribute to increased defecation frequency and increased stool softness in pediatric patients with controlled CC and those who have been withdrawn from stool softener therapies. The dietary fiber mixture was the sole therapeutic intervention used in this study.
The admission data demonstrated that the children in both treatment groups defecated at least once every 2 days. Despite this frequency of defecation, the consumption of dietary fiber increased the daily defecation rate. This increase was more evident in the patients who completed the 4-week study. The mean rate of defecation was approximately once per day in the group treated with the fiber mixture, which is similar to the normal defecation rate for children >3 years of age (3,25).
Previous clinical trials evaluated stool consistency using different methods, including subjective evaluations from the child's parents (11), 5 different scores (8,10), and the Bristol Stool Form Scale (12). We used the Bristol Stool Form Scale to verify that the individuals in the dietary fiber mixture group produced softened stools and that those in the control group predominantly produced hardened stools. Furthermore, stools in the form of round balls (sausage-shaped but lumpy, type 2) were more frequent among patients who had received the placebo. Smooth, thin stools (type 4) were more frequent among individuals in the dietary fiber mixture group (P < 0.05; data not shown).
In adults with a polymeric enteral diet, increased production of short-chain fatty acids and an increase in the total number of bacteria have been observed (19). In addition to this, these patients demonstrated decreased CTTs (26). Fatty acid production is known to favor bacterial proliferation (13). This increase in bacteria and the resulting high percentage of water create a moist stool with a soft consistency (5) that is more easily excreted (27). Although they do not directly address the research subject being presented, these results support the hypothesis that this fiber mixture can benefit the intestinal function of constipated children and can promote better stool consistency and increased defecation frequency, despite the fact that our patients ate a regular diet and not a special polymeric enteral diet.
No statistically significant difference was found in terms of the proportion of therapeutic failure and success between the 2 groups. It is worth noting that patients with hard stools and those with pain during defecation, fecal inconsistency, or the need for stool softeners and enemas were, however, considered therapeutic failures in this study. These failure criteria were rigorously compared with those reported in the published literature. Loening-Baucke et al (10) observed a 68% therapeutic success rate for constipated patients without encopresis using glucomannan and a 13% success rate for patients using a placebo. The definition of therapeutic success from the study permitted the occurrence of up to 1 episode of fecal incontinence in 3 weeks and the use of stool softeners (10), a definition used in other studies (8,12). The present study, however, used a stricter definition of therapeutic success. Nevertheless, the dietary fiber group achieved a therapeutic success rate (65.4%) that approximated the expected value for this sample size (70.0%). The placebo effect (64.3%) was higher in this study than the expected level of 30.0% observed in other clinical trials (9,10). It should be noted that the high success rate of the placebo has been shown in clinical trials involving children and adults with functional gastrointestinal disorders (28).
The patients’ total and segmental CTTs were similar for both groups. The median total CTT (50 hours in both groups) was shorter than the normal upper limit of 62 hours recommended in the literature (29). This value (45.7 hours) was longer than the mean time and 2 standard deviations measured for 30 Spanish children without constipation (29.1 ± 8.3 hours). Thus, in the last week of our clinical trial, the total CTTs of both the dietary fiber mixture group and the control group were longer than the reference values observed in normal children. The median transit time of 50 hours was also longer than the values observed during the sixth week of mineral oil treatment for 33 patients with severe constipation (median, 37 hours) (30). Thus, the exclusive use of the dietary fiber mixture did not result in the same transit times that were demonstrated for the mineral oil treatment.
The short duration of our study (4 weeks) may have been insufficient to show a greater difference between the groups, given that CC is a condition marked by frequent improvements and then relapses. Another limitation relates to a greater increase in defecation frequency per day. Although we found significant differences between the 2 groups regarding this variable, it is important to consider that constipated patients can often have daily bowel movements without fully emptying their rectums, which may lead to increased stool accumulation. This factor could explain why we found no difference in intestinal transit times between the patients who received placebo and those who consumed fiber. The results may have been better understood if the transit time had been evaluated upon admission to the trial. Measures such as an outlet dysfunction evaluation (31) would have highlighted the presence of disorders that would not have been expected to improve with the addition of fiber alone. Thus, the failure to rule out complicating disorders before patients were enrolled could be considered another limitation of the study. The relation between the effects of administered dietary fiber, its ingestion time, and the CCT of constipated children should be explored in future studies.
In conclusion, the use of a mixture containing 6 different types of dietary fiber did not prevent the need for stool softeners or enemas during the dietary fiber intervention nor did it reduce CTT in constipated patients who were in the suspension phase of treatment with stool softeners. The increase in defecation frequency and the improvement in stool consistencies observed in the children who finished the study without using stool softeners were, however, important findings concerning the prevention of recurring constipation symptoms. These findings cannot be extrapolated to those children who present with severe constipation because our study population included only patients who used low-dose stool softener therapies and had controlled CC.
The authors are thankful for the support from Support Produtos Nutricionais and for the collaboration of residents in pediatric gastroenterology, namely Cristina Marino, Fernanda Miyamoto Barreto (Santa Casa de Misericórdia, de São Paulo), Sabrina Bortolin Nery, and Juliana Okamoto (Federal University of São Paulo).
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