This questionnaire was developed in ten steps, according to literature recommendations.10–12

Step 1. “Constipation”, “HRQoL” and “Questionnaires” were used as keywords to search related terms on Pubmed and Scielo databases.

Step 2. A literature review related to these terms was conducted to generate 420 phrases. Translation from English into Portuguese was done considering the cultural adaptation, by authors of the study with fluency in English and Portuguese.

Step 3. The list of phrases was converted in the Preliminary Questionnaire (PQ) 1, with 57 questions divided into five domains: physical, emotional, social, school and family; including a general health question and a question about the children's behavior. The questions were directed to events of the last four weeks, considering the diagnosis of PFC through the Rome IV Criteria.13 The answer options were organized on a four-point Likert scale format assessing frequency (0 = never; 1 = occasionally; 2 = frequently; 3 = always), intensity (0 = nothing; 1 = little; 2 = quite; 3 = extremely), agreement (0 = completely disagree; 1 = partially disagree; 2 = partially agree; 3 = completely agree) and quality/rating (0 = very poor; 1 = poor; 2 = good; 3 = very good).

Step 4. On PQ 2, redundant, inappropriate words or questions were eliminated. All steps were discussed between the authors of the study and two more guests (a general pediatrician with experience in treating children with constipation and a child psychologist who works in specific constipation outpatient clinics). The meetings were specific and discussed until consensus was reached on the topic to be excluded, included, or modified in the questionnaire. In addition, terms that induce a specific response, negative phrases, vague words, double meaning, and indefinite questions were avoided, resulting in 37 questions.

Step 5. On PQ 3 the quality of the questions was improved, organized from the easiest to the most difficult, from concrete to abstract, from least to most sensitive. In addition, short sentences and straightforward words were used to the level of respondents. Besides, were emphasized essential words, using bold, and the number of the questions reduced, considering an ideal literature number from 15 to 30 questions.

Step 6. PQ 4 was a semi-structured questionnaire with 26 questions and submitted simultaneously to 11 health professionals experienced in pediatric care in order to improve the clarity of the questionnaire.

Step 7. On PQ 5 the domains were renamed to Physical, Behavioral (formerly Emotional), Social (including questions from the previous "Family" domain), and School, with 26 questions. The answer options, organized on a four-point Likert scale format, were interspersed with standardization for even and odd questions.

Step 8. PQ 5 was administrated to 45 parents/caregivers (40 mothers, 01 father and 04 caregivers), and a semi-structured interview was conducted, to assess the acceptability, comprehensiveness, clarity of writing, relevance, and ambiguity of items. Test-retest reliability was evaluated at this step in nine mothers with 7 to 14 days between requests. There was no statistical difference between responses for the total score and Items (p > 0.05).

Step 9. After a few adjustments in language, the specific HRQoL questionnaire was titled "The PFCQuestionnaire - Parent Report" (PedFCQuest-PR), consisting of 26 questions considering four domains: Physical, Behavioral, Social and School; including a general health question and a question about the child's behavior. The answers were organized in a four-point Likert scale, assessing frequency, intensity, agreement, and quality.

Step 10. The Questionnaire PedFCQuest-PR was qualified in forty-five parents/caregivers in a preliminary study.

After questionnaire development, a single-center, observational, cross-sectional study for the validation of PedFCQuest-PR applied to parents/caregivers of a convenience sample of consecutive cases of children/adolescents, referred from 2018 to 2019, from the same geographic area to a tertiary outpatient Pediatric Gastroenterology Clinic of the Brazilian Public Health System (SUS).

Inclusion criteria for parents/caregivers were aged over 18 years, able to understand and answer the questionnaire alone, knowledge of the children's clinical condition, living in the same home as the patient, and sign the Informed Consent Form. Inclusion criteria for children were age between 5 and 15 years old, diagnosis of PFC according to the Rome IV Criteria[13] and toilet trained. Exclusion criteria were chronic health problems (neurological, genetic, psychiatric, surgical, growth, and development disorders). The Ethics Committee (CAAE 90158218.0.0000.5411) approved this study.

The sociodemographic and anthropometric data were collected on a standardized clinical form developed according to the Rome IV criteria for pediatric Functional Gastrointestinal Disorders. Stool characteristics were obtained with Bristol Stool Consistency Scale translated and adapted for the Brazilian Portuguese.14 Experienced pediatric nurses obtained anthropometric measurements at the first visit, according to the World Health Organization (WHO) guidelines.15 BMI (kg/m2) and z score were evaluated according to the WHO growth standards adjusted for sex and age.16,17

PedsQLTM 4.0 Generic Cores Scales Parent Proxy-Report (PedsQL 4.0)18,19 have age-appropriate questionnaires for the young child (5–7y), child (8–12y), and adolescent (13–18y). The instrument encompasses 23 items in four domains: Physical Functioning (8 items), Emotional Functioning (5 items), Social Functioning (5 items), and School Functioning (5 items). This instrument was adapted cross-culturally and validated for use in Brazilian Portuguese exhibiting good psychometric properties.20 PedsQL 4.0 was used for validation of PedFCQuest-PR, and permission was obtained from the Mapi Research Trust.

Both questionnaires, PedFCQuest-PR (Supplementary Material A) and PedsQL 4.0, were self-administered simultaneously in a printed form during the first visit, in a private room, and before medical treatment. If the parent/caregiver did not understand the meaning of any question, the researcher read the question slowly, without using synonyms or giving explanations. After receiving the questionnaire already answered, the researcher checked that there is no more than one answer per question. In both questionnaires, the items were reverse-scored and linearly transformed to a 0 to 100 scale. The sum of the values attributed to each item was calculated as a total score, and the lowest values indicated HRQoL impairment.

The analysis was performed with GraphPad Prism version 8.4.0 for Windows (GraphPad Software, USA). The normality of data was tested with the Kolmogorov-Smirnov test. Continuous variables were analyzed with the Mann-Whitney test and the categorical data with Fisher's exact test. The Validity of the PedFCQuest-PR was analyzed using Spearman's correlation coefficient. Value of r (positive or negative) can be interpreted as a magnitude correlation between variables, and r values are designated as small (0.10), medium (0.30), and large (> 0.50). The statistical tests were two-tailed, and the level of significance was set at p < 0.05.

Supplementary Fig. 1 presents the flow diagram of 142 parents/caregivers of children with FC involved in the study. Forty-five participate in the Questionnaire development, and 87 in the Questionnaire validation. The PedFCQuest-PR and PedsQL 4.0 were self-administered, highly suitable with low refusal or difficulty in answering (only 04 parents/caregivers). There were no missing item responses.

Table 1 presents the baseline characteristics of the participants on questionnaire validation. The results demonstrate small families, mothers as respondents, and schoolchildren with prolonged duration of symptoms. Comparison analysis of total score of PedFCQuest-PR for the presence/absence of different Rome IV criteria demonstrated a significantly lower score for the children with ≤ 2 bowel defecations/week (p < 0.0001), fecal incontinence ≥1/week (p < 0.0001), retentive posturing (p < 0.01), large fecal mass in the rectum (p < 0.04), and large-diameter stools which can obstruct the toilet (p < 0.006). In a similar analysis using the PedsQL 4.0 total score, only the children with fecal incontinence ≥1/week showed a significantly lower score (p < 0.001). There was no statistical difference in comparison the total score of both questionnaires for sex, children age (< 8 vs > 8.3 years), duration of constipation (< 71 vs > 71 months), blood in the stool, and the presence of enuresis. There was a statistical difference in the presence of abdominal pain in both PedFCQuest-PR (p = 0.02) and PedsQL 4.0 (p = 0.03). No baseline characteristics of children and responders differed between the Questionnaire development (n = 45), and Questionnaire Validation (n = 87).

Table 2 presents PedFCQuest-PR results of ceiling effects in all domains. The Physical domain presents items with the lowest score values. The Cronbach's alpha was very adequate for all Items.

The reliability analysis was analyzed using Cronbach's alpha coefficients (Table 2) for the different items of PedFCQuest-PR, which were between 0.84 and 0.86, with a median of 0.85. Table 3 presents a statistically significant positive correlation coefficient between the total score and different domains and inter domains of PedFCQuest-PR. All correlations were positive, statistically significant and with medium (r > 0.30) and large (r > 0.50) values. In particular, Physical, Social, Behavior and Total scores are large. Table 4 presents the correlation between similar domains of PedFCQuest-PR and PedsQL 4.0. All results are positive, convergent and demonstrate a statistically significant medium value (r > 0.30), except for Physical domain (r = 0.25). On items correlation analysis between both questionnaires, all similar items correlations were statistically significant with moderate intensity (r > 0.30; p < 0.001). On different items, there were no statistically significant differences.

Content validity was evaluated, exposing the questionnaire to a group of pediatric specialists,22 and during the application of preliminary questionnaires (Steps 7 and 8), in order to construct the final questionnaire (PedFCQuest-PR). There was a minimum of suggestions for correction, suppression or addition of the items, as well as changes in domains. Criterion validity is rarely used due to the lack of a widely accepted criterion measure. This study is the first questionnaire in Brazilian Portuguese to evaluate the HRQoL of children with PFC. Consequently, there is no "gold standard" that can be used for comparison.