An open-label, randomized, parallel-group controlled clinical trial was conducted, within the time frame of July 2007 and July 2015, at the gastroenterology outpatient department of the Hospital Infantil de México Federico Gómez.

The study population was made up of outpatients seen at a tertiary care hospital in Mexico. After the parents gave their informed consent and the patients above the age of 7 years signed the statements of informed consent, patients from 6 months to 18 years of age were enrolled in the study. The patients had not taken either of the study medications for at least one month and they met the Rome III diagnostic criteria for FC:23,24

• a)

  From infancy to 4 years of age: the presence, for at least one month, of two or more of the following manifestations:

  • 1)

    ≤ 2 bowel movements per week.

  • 2)

    ≥ 1 episode per week of encopresis, after having achieved anal sphincter control.

  • 3)

    A history of excessive fecal retention.

  • 4)

    A history of hard or painful bowel movements.

  • 5)

    The presence of a large fecal mass in the rectum.

  • 6)

    A history of large-diameter bowel movements that may clog the toilet.

• b)

  Children ≥ 4 years of age: the presence at least once a week for ≥ 2 months before diagnosis, of two or more of the following manifestations:

  • 1)

    ≤ 2 bowel movements in the toilet per week.

  • 2)

    ≥ 1 episode per week of encopresis, after having achieved anal sphincter control.

  • 3)

    A history of retentive posturing or excessive voluntary stool retention.

  • 4)

    A history of hard or painful bowel movements.

  • 5)

    The presence of a large fecal mass in the rectum.

  • 6)

    A history of large-diameter bowel movements that may clog the toilet.

The exclusion criteria were patients with a diagnosis of irritable bowel syndrome, secondary constipation, abdominal surgery, an anatomic abnormality of the gastrointestinal tract, or a comorbidity that could affect treatment results. Those criteria were maintained throughout the study, with no modifications.

Sample size for comparing two proportions was calculated using the STATA 9.2 (College Station, Texas 77845 USA) program. Taking into account an α of 0.05 (two-tailed test) and a power of 90%, with a p1 = 0.05, p2 = 0.35, and N2/N1 = 1.00, produced 42 patients per treatment group. After calculating a 10% loss of patients, the final number per group was 46.

At the initial visit, the patient’s suitability to be enrolled in the study was corroborated. If fecal impaction was detected, rectal disimpaction was carried out, utilizing soap suds enemas. Patients were then assigned to a treatment group, using the randomized block method, to have balanced groups in three different age subgroups (6 months to 4 years, > 4 years to 12 years, and > 12 years to 18 years). A table of randomized numbers created with the Excel program by a third party that did not participate in patient enrollment was utilized. The intervention maneuver could not be blinded due to the difference in the physical characteristics and presentation of the two interventions. The data were analyzed by an independent researcher that had no direct contact with the patients.

The decision was made to have different age subgroups, to evaluate whether patient age influenced the efficacy, safety, and acceptance of each of the laxatives, especially for MH, given its poor palatability. Taking into account that doses would be weight-based, older patients would ingest a larger volume of MH, potentially making its acceptance more difficult. Therefore, three subgroups were established. The first subgroup corresponded to the ages of 6 months to 4 years, according to the Rome III criteria for the classification of FC; the second subgroup was from 4 to 12 years of age; and the third subgroup included only adolescents. Adolescents are generally more difficult to treat due to low treatment adherence, especially if treatment is long, as well as to the fact that they are the group that has to take the higher doses of laxative, given their weight.

The treatment goal, which was to achieve one to three daily bowel movements of soft consistency, no abdominal pain, and no fecal incontinence (FI), was verbally explained to the parents. They were told how to increase or decrease the doses of the medications to reach the goal and were given an instruction sheet containing the written indications. All patients that had anal sphincter control were instructed to sit on the toilet after each meal.

After the initial visit, clinical controls were carried out at 1, 3, 6, 9, and 12 months of treatment, at which the following aspects were evaluated: bloating, palpable masses in the abdomen, pain upon abdominal palpation, fecal impaction (hard stools in the rectum or the lower abdomen), and stools in the perianal region and/or on the underwear. Blood samples of approximately 5 ml were taken for the baseline laboratory tests and at 3, 6, 9, and 12 months of treatment: complete blood count, ureic nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, and serum electrolytes (Na, K, Cl, Ca, P, and Mg).

The parents were instructed to keep a diary, during the entire study, registering:

• 1)

  The daily dose of PEG (g/day) or milk of magnesia (ml/day), according to the laxative utilized.

• 2)

  The number of medication doses rejected per day: the number of doses of the laxative that the patient refused to take in 24 h.

• 3)

  The use of another laxative/day (yes/no): the added use of any other laxative in 24 h.

• 4)

  The number of doses of the other laxative/day: the number of doses of the added laxative in 24 h.

• 5)

  Enemas/day (yes/no): the use of rectal washouts in 24 h.

• 6)

  The number of enemas/day: number of rectal washouts performed in 24 h.

• 7)

  The number of bowel movements/day: the number of bowel movements in the toilet or diaper that the patient had in 24 h.

• 8)

  Stool consistency:

  • a)

    Hard stool (HS), any shape, with a rock-hard consistency, very difficult to pass and impossible to press.

  • b)

    Soft stool (SS), any shape, soft, easy to pass, easily pressed.

  • c)

    Mushy stool (MS), no shape, like a thick soup.

  • d)

    Liquid stool (LS), an abundance of liquid, with solid residues.

• 9)

  The number of episodes of retentive FI/day: the number of events of soiling underwear in 24 h, with or without hard stools in the toilet.

• 10)

  The number of episodes of abdominal pain/day: the number of times the patient complained of abdominal pain in 24 h.

• 11)

  Adverse events/day (yes/no): cramps, gases, abdominal pain, diarrhea, non-retentionist FI (presence of stool on underwear and liquid stools in the toilet), vomiting, dehydration, and others, with their specification.

The physicians in charge of the study kept a register of the baseline clinical data and at months 1, 3, 6, 9, and 12 of treatment; it included evidence of fecal impaction and manifestations of the autism spectrum. The data obtained from the daily registers of the patients, the consultations, and the laboratory were collected on an Excel sheet for their analysis.

At the end of 12 months, the following results were considered:

• 1)

  Success: ≥ 3 bowel movements/week in the toilet (for the patients with anal sphincter control) or in the diaper (for patients with no anal sphincter control), with no episodes of FI, fecal impaction, or abdominal pain, and no need for another laxative.

• 2)

  Partial improvement: ≥ 3 bowel movements/week in the toilet (for the patients with anal sphincter control) or in the diaper (for patients with no anal sphincter control), ≤ 2 episodes of FI per month, with no fecal impaction, no abdominal pain, and no need for another laxative.

• 3)

  Failure: ≤ 2 bowel movements/week in the toilet (for the patients with anal sphincter control) or in the diaper (for patients with no anal sphincter control), with > 2 episodes of FI/month and/or ≥ 1 event of fecal impaction or the need for another laxative.

A researcher blinded to the treatment assignment performed the statistical analysis. Hypothesis testing was carried out to evaluate normality in the distribution of the variables to be compared. The analytic focus of intention-to-treat was utilized. The significance of the differences between groups was determined for the primary and secondary cutoff points through the chi-square test or the Fisher’s test, for the qualitative variables, and through the Student’s t test or Mann-Whitney U test, for the quantitative variables. All the procedures were performed using the SPSS version 13.0 program. A two-tailed p value of 0.05 was considered statistically significant for all the comparisons.

The study protocol was approved by the Local Research and Ethics Committee of the Hospital Infantil de México Federico Gómez (HIMFG) (HIM/2007/032/SSA-759 and 1062) and registered in the archives of said committee. There were no protocol modifications, once the study was registered and begun. All parents of the enrolled patients gave their informed consent and patients above 7 years of age signed statements of informed consent. The authors declare that this article contains no personal information that could identify the patients.

Within the time frame of July 2007 and July 2015, 83 patients were included in the study: 41 in the PEG group and 42 in the MH group. Fifty-three percent of the patients were females. There were no differences in the number of patients assigned to each age subgroup between the two treatment options. Table 1 shows the baseline demographic characteristics. Sixty-five patients (78%) completed the study at 12 months. Eighteen patients (9 from each group) suspended treatment before the 12 months, for different reasons: 4 due to family problems, 2 due to rejecting the medication, 2 due to intercurrent diseases, one due to psychologic problems, one due to fecal impaction, one due to diarrhea, and 7 due to no specific cause (Fig. 1).

Figure 1.

Flowgram of patients.

MH: magnesium hydroxide; PEG: polyethylene glycol.

(0.19MB).

Of the 83 patients, 66 (79.5%) met the success criteria at the first month of treatment, 12 (14.5%) at 3 months, 2 (2.4%) at 6 months, and one at 9 months. Two patients (2.4%) (one from each group) were eliminated from the study. No significant differences were found in the general population, when comparing the baseline biochemical test results with those taken after the intervention. No severe adverse events were registered. The most frequent adverse events were gases, cramps, FI, and diarrhea. Twenty-nine patients (34.9%) rejected a medication dose.

No differences were found in the weekly number of bowel movements or FI episodes by group at 1, 3, 6, 9, or 12 months of follow-up. Only one patient presented with fecal impaction after one week of treatment with PEG and was immediately removed from the study. No patients needed to take extra laxatives or have enemas. The required maintenance dose for achieving the treatment goal (1 to 3 bowel movements of soft consistency per week, and no abdominal pain or FI) was 0.91 ± 0.37 g/kg/day of PEG and 1.83 ± 0.39 ml/kg/day of MH.

Due to the different forms of presentation and textures of PEG (powder) and milk of magnesia or MH (liquid), conducting a blinded study was not possible. Another limitation was that 9 patients from each group abandoned the study before its completion. But importantly, 8 of the 9 patients that abandoned the study before it ended met the success criteria at the time of abandonment, in each treatment group, and so cannot be considered treatment failures.