Colonic dysmotility in children with functional constipation and psychiatric and developmental disorders

Functional constipation (FC) is common and can cause significant impairments in quality of life. ¹ An association between FC and psychiatric and developmental disorders, including autism spectrum disorder (ASD), anxiety, depression, attention‐deficit hyperactivity disorder (ADHD), and developmental delay (DD), has been reported. A survey showed that up to 85% of children with ASD had constipation and that children with ASD have more emergency department (ED) visits and hospital admissions for constipation compared to those without. ² , ³ Prevalence of constipation and healthcare visits for constipation are higher in individuals with ADHD, anxiety or depression, and intellectual disability. ⁴ , ⁵ , ⁶ , ⁷

In children with constipation who have failed conventional management, colonic manometry is used to evaluate colonic motility and can be used to guide subsequent treatment. ⁸ , ⁹ A previous study found that the likelihood of abnormal colonic motility was similar between patients with constipation with ASD versus without. ¹⁰ Our study aimed to investigate a similar question including the following diagnoses of interest: ADHD, ASD, anxiety, depression, and DD. Patients with these psychiatric and developmental disorders may have challenges with medical or behavioral management, delayed presentation to care, and therefore more severe constipation. We hypothesized that having a psychiatric or developmental comorbidity is associated with colonic dysmotility in children with FC.

We reviewed colonic manometry studies performed in children with FC from May 2015 to May 2022 at Nationwide Children's Hospital. Children with FC were identified via International Classification of Diseases, Ninth Revision (ICD‐9) codes. Charts were reviewed by the research team. Diagnoses were recorded when documented in the medical record and were not verified to have been confirmed by specialists (e.g., ASD confirmed by a developmental behavioral pediatrician). Colonic manometry studies in children with organic causes of constipation were excluded. We recorded patient demographics; medical history including prior diagnosis with ADHD, anxiety or depression, ASD, and DD; surgical history; and manometry results.

Our colonic manometry protocol involves placement of a catheter under anesthesia either colonoscopically or using fluoroscopy. Most studies were performed using high‐resolution solid‐state manometry catheters (Unisensor AG, Attikon), although some used water‐perfused catheters (Medical Measurement Systems [MMS]). Colonic manometry was performed the day of catheter placement but several hours afterwards to account for potential anesthesia effects. Our protocol consists of the fasting phase, postprandial phase, and the provocative phase. During the provocative phase, stimulant laxatives (bisacodyl or glycerin) are given through the catheter into the proximal colon to stimulate colonic motor activity. Studies were considered normal if high‐amplitude propagating contractions (HAPCs) progressing from the proximal colon through the sigmoid colon were observed. If fully propagating HAPCs were only observed after three or more doses of stimulant laxative, studies were categorized as showing normal colonic motility with high‐dose stimulant. Studies were categorized as showing distal, proximal, or total colonic dysmotility if HAPCs terminated prematurely, were only found in the distal colon, or were not present for the duration of the study, respectively.

We compared the proportion of studies showing normal colonic motility between children with FC with and without each diagnosis of interest. We also compared the likelihood of specific colonic dysmotility findings between diagnoses of interest and evaluated the effect of multiple comorbid diagnoses. Analyses were performed using Fisher's exact test using Stata (StataCorp LLC). A p‐value of <0.05 was considered statistically significant.

We identified 395 colonic manometry studies performed in 360 children (mean age 10 years, range 2 months to 23 years, 52% female). Comorbid diagnoses included anxiety or depression (151, 38%), ADHD (103, 26%), ASD (56, 14%), and DD (94, 24%). Comparisons of patient characteristics by comorbid diagnosis are shown in Table 1. Children with FC and ADHD, anxiety or depression, or ASD were older than children with FC alone (all p < 0.05). In our studies, 228 (58%) used solid‐state catheters, 159 (40%) used water‐perfused catheters, and 8 (2%) used both (e.g., one antegrade via cecostomy or appendicostomy and one retrograde). Catheters were placed retrograde (357, 90%), antegrade through a cecostomy or an appendicostomy (24, 6%), or via both (13, 3%).

Table 1.

Patient demographics at time of first colonic manometry test by diagnosis (N = 360).

Diagnosis	Male	Female	Mean age (years)
FC alone	62 (41%)	89 (59%)	9.7 ± 4.5
FC with attention deficit hyperactivity disorder	57 (66%)	29 (34%)*	11.3 ± 3.8*
FC with anxiety or depression	55 (43%)	73 (57%)	11.6 ± 4.2*
FC with autism spectrum disorder	34 (69%)	15 (31%)*	11.5 ± 4.5*
FC with developmental delay	51 (59%)	35 (41%)*	9.8 ± 4.6

Abbreviation: FC, Functional constipation.

^* p < 0.05 when compared to FC alone group.

As shown in Figure 1, the likelihood of an abnormal study was higher in children with FC and ADHD compared to FC alone (54% vs. 41%, p = 0.02), FC and anxiety or depression compared to FC alone (54% vs. 39%, p = 0.005), FC and ASD compared to FC alone (57% vs. 42%, p = 0.04), and FC and DD compared to FC alone (56% vs. 41%, p = 0.01). Patients with two or more comorbid diagnoses were not any more likely to have colonic dysmotility when compared to patients with one comorbid diagnosis. Distal colonic dysmotility was the most common abnormality in all patients with FC and for patients with FC and each comorbid psychiatric or developmental diagnosis (all p < 0.05) (Figure S1).

Figure 1.

Percent of abnormal colonic manometry studies by diagnosis.

Of the 360 children included, 31 patients had a repeat colonic manometry and 4 had a third colonic manometry. Six of the 31 patients had FC alone while 19 had anxiety/depression, 14 had ADHD, 8 had DD, and 5 had ASD. In the first colonic manometry, 12/31 showed distal colonic dysmotility, 12/31 showed normal motility, 5/31 showed total colonic dysmotility, 1/31 showed proximal colonic dysmotility, and 1/31 showed normal motility with high‐dose stimulant. At second colonic manometry, 14/31 showed distal colonic dysmotility, 12/31 showed normal motility, and 5/31 showed total colonic dysmotility. Five that were abnormal initially were normal by their second study. Five were normal initially but were abnormal by their second study.

In conclusion, we found that children with FC who had a psychiatric or developmental comorbidity were more likely to have colonic dysmotility. Distal colonic dysmotility was the most common abnormality observed. Having more than one comorbid diagnosis was not associated with higher likelihood of colonic dysmotility. Our findings expand upon our understanding of FC in children with psychiatric and developmental disorders. Colonic dysmotility should be suspected as contributing to refractory constipation in children with psychiatric and developmental disorders, and may influence the management of their constipation.

Whether the colonic dysmotility observed in these patients is due to a primary or secondary colonic neuromuscular disorder remains a question. Since distal colonic dysmotility was the most common abnormality seen in all patients regardless of comorbid diagnoses, it seems unlikely that a primary disorder is responsible. In most children with chronic constipation, the finding of a dilated distal colon is secondary to incomplete evacuation and ongoing stool retention. Perhaps children with psychiatric or developmental disorders are prone to more chronic or severe fecal retention, leading to prolonged colonic distention. Possible mechanisms include altered communication between the enteric and central nervous systems, impaired sensation, pelvic floor dyssynergia, inability to communicate and act on defecatory urges, or diets lacking fluids or fiber.

Children with ASD who display more severe rigid compulsive behaviors have a higher likelihood of FC. ¹¹ Language delay, younger age, and increased social impairment are also associated with constipation in children with ASD, ² raising concern that children with ASD have decreased ability to communicate or act on defecatory urges. The behavioral challenges seen in patients with ASD can also impact adherence with treatment, ³ making them prone to chronic stool retention. Children with ADHD have been shown to have higher rates of dysfunctional urinary voiding and nocturnal enuresis, perhaps due to a failure to detect bladder signals or decreased alertness to a full bladder. ¹² It is plausible that a similar inability to act on a stool‐filled rectum could apply to children with FC and ADHD.

Our study has several limitations. As it was done in a tertiary care hospital, there is potential selection bias for patients with more severe phenotypes of these psychiatric and developmental disorders and constipation. Given the retrospective nature of this study, it was limited by its reliance on accurate documentation of comorbid diagnoses by medical providers. We did not assess the severity, duration, and status of treatment of constipation at the time of manometry study. This data would be challenging to accurately determine given the retrospective nature of this study, but warrants future prospective evaluation. Since our patients with ADHD, anxiety or depression, and ASD were older than patients with FC alone, it is plausible that having these comorbidities leads to delayed presentation and management of their constipation. Finally, we did not record anorectal manometry findings, which could identify rectal evacuation disorders responsible for subsequent distal colonic dilation.

Our findings highlight both the importance of screening for psychiatric and developmental comorbidities in children with constipation and the potential need for more comprehensive medical, behavioral, and psychological management in children with refractory constipation. Prospective studies are needed to understand the relationship between constipation severity and colonic motility in these populations, evaluate for concurrent rectal evacuation disorders that may influence distal colonic motility, and assess if adequate management of comorbid diagnoses influences colonic motility.

CONFLICT OF INTEREST STATEMENT

The authors decalre no conflicts of interest.

ETHICS STATEMENT

The study protocol was approved by the Nationwide Children's Hospital Institutional Review Board (STUDY00000933). The requirement for informed consent was waived given the retrospective nature of the study.

Supporting information

Supplemental Figure: Colonic manometry findings in patients with functional constipation by comorbid diagnosis.