Autistic Spectrum Disorder, Constipation
Conditions
Keywords
Autism, 4-cresol, anxiety, autism spectrum disorder, biomarkers, constipation, microbiota
Brief summary
Many autistic children suffer from chronic constipation. Gut mobilization was obtained administering polyethylene glycol (PEG) at the dose of 6.9 g/d once a day for 6 months in an open trial involving 21 chronically constipated autistic children 2-8 years old, followed prospectively for 6 months. Children diagnosed with Autism Spectrum Disorder by DSM-5 and confirmed by ADOS-2 criteria, were evaluated before (T0), 1 month (T1), and 6 months (T2) after intestinal mobilization, recording Bristol stool scale scores, urinary p-cresol concentrations, and behavioral scores for social interaction deficits, stereotypic behaviors, anxiety, and hyperactivity.
Detailed description
Chronic constipation is common among children with ASD and is associated with more severe anxiety, hyperactivity, irritability and repetitive behaviors. Young autistic children with chronic constipation display higher urinary and foecal concentrations of p-cresol, an aromatic compound produced by gut bacteria, known to negatively affect brain function. Acute p-cresol administration to BTBR mice enhances anxiety, hyperactivity and stereotypic behaviors, while blunting social interaction. This study was undertaken to prospectively assess the behavioral effects of gut mobilization in young autistic children with chronic constipation, and to verify their correlation with urinary p-cresol. To this aim, 21 chronically constipated autistic children 2-8 years old were evaluated before (T0), 1 month (T1), and 6 months (T2) after intestinal mobilization, recording Bristol stool scale scores, urinary p-cresol concentrations, and behavioral scores for social interaction deficits, stereotypic behaviors, anxiety, and hyperactivity. Gut mobilization was obtained administering PEG (6.9 g/d once a day) for 6 months. A progressive, statistically significant decrease in all behavioral symptoms was recorded over the six-month study period. Urinary p-cresol levels displayed variable trends, mainly increasing at T1 and decreasing at T2. These results support gut mobilization as a simple strategy to at least partly ameliorate ASD symptoms, as well as comorbid anxiety and hyperactivity, in chronically constipated children. These beneficial effects likely involve multiple mechanisms.
Interventions
DIETARY_SUPPLEMENTGut mobilization
Polyethylene Glycol (PEG) at the Dose of 6.9 g/d Once a Day for 6 Month. Children were observed and tested at baseline (T0), 1 month (T1) and 6 months (T2) after gut mobilization.
Sponsors
University of Messina
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
In this open trial, each child underwent gut mobilization using a standard protocol with oral administration of PEG (6.9 g/d once a day) for 6 months. Children were observed and behaviorally tested at baseline (T0), 1 month (T1) and 6 months (T2) after gut mobilization. At the time of recruitment, Intellectual Quotient (IQ) or Developmental Quotient (DQ) were determined using the Leiter International Performance Scale-Third Edition or the Griffith Mental Development Scales, respectively. Autistic behaviors were assessed using the ADOS-2, and the Children Autism Rating Scales (CARS). Adaptive functioning was assessed using the Vineland Adaptive Behavior Scales-Second Edition
Eligibility
Sex/Gender
ALL
Age
2 Years to 8 Years
Healthy volunteers
No
Inclusion criteria
* Fulfilling DSM-5 diagnostic criteria for Autism Spectrum Disorder * Chronic constipation, namely unsatisfactory defecation characterized by difficult and infrequent passage of lumpy and hard stools during at least the previous 3 months, as reported by parents based on the Bristol Stool Scale
Exclusion criteria
* ASD constipated children already treated with laxatives
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in stool quality | At baseline (T0) prior to gut mobilization; 1 month (T1) and 6 months (T2) after gut mobilization | Stool quality was assessed by parental report using the Bristol Stool Scale (score ranges from 1 to 7, where 1 is lumpy constipation and 7 is liquid diarrhoea). |
| Change from baseline urinary concentrations of total p-cresol | First-morning urines were collected at home by parents at baseline (T0), 1 month (T1) and 6 months (T2) after gut mobilization | Urinary concentrations of total p-cresol, encompassing on average 95% p-cresylsulfate, 3%-4% p-cresylglucuronide and 0.5%-1% of unconjugated free p-cresol, were measured by HPLC three times, averaged and normalized by urinary specific gravity. |
| Change in Childhood Autism Rating Scale (CARS) | At baseline (T0), 1 month (T1) and 6 months (T2) after gut mobilization | The Childhood Autism Rating Scale is a clinical rating scale for the trained clinician to rate the presence and severity of signs and symptoms of ASD by direct observation of the child. Scores can range from 15 to 60: below 30, non autistic; 30-36.5 mild to moderate autism; 37-60, severe autism |
| Change in Repetitive Behavior Scale-Revised (RBS-R) | At baseline (T0), 1 month (T1) and 6 months (T2) after gut mobilization | 44- item questionnaire used to assess repetitive behaviors. Scores range from 0 to 3 (0 = the behavior does not occur, 3 = the behavior is present and severe). Overall rating (last question) ranges from 0 to 100, indicating that the set of behaviors described in the questionnaire do not represent a problem at all (0) or instead represent an extremely severe problem (100). |
| Change in Conners' Parent Rating Scale - Revised (CPRS-R) | At baseline (T0), 1 month (T1) and 6 months (T2) after gut mobilization | 48-item rating scale used to evaluate through parental reports the presence of childhood hyperactivity/inattention, impulsivity and externalizing behaviors (scores for each item range from 0=not true, never, rarely to 4=very true, very often or very frequent; diagnostic threshold score = 60). |
| Change in Social Responsiveness Scale (SRS) | At baseline (T0), 1 month (T1) and 6 months (T2) after gut mobilization | 65-item questionnaire used to assess social impairment, communication deficits and repetitive behaviors (T scores: \<60, normal range; 60-65, mild deficits; 66-75, moderate deficits; 76 or above, severe deficits in reciprocal social behavior). |
Countries
Italy
Outcome results
None listed