Disorders of Gut-Brain Interaction (DGBI)

Conditions that affect gastrointestinal (GI) function and motility can include symptoms of abdominal pain, nausea, distention, vomiting, and constipation and/or diarrhea. Functional and gastrointestinal motility disorders, now referred to as disorders of gut-brain interaction (DGBI), are estimated to affect approximately 25 million Americans and contribute to the morbidity observed in more than half of pediatric GI subspecialty visits. In addition, symptoms related to DGBIs can have a significant negative effect on school attendance, participation in extracurricular activities, and family relationships. A visual of the brain-gut axis can be found here.

Common DGBIs are addressed in this section, including:

• Functional Abdominal Pain

• Irritable Bowel Syndrome (IBS)

• Functional Constipation

• Gastroesophageal Reflux Disease (GERD)

Functional Abdominal Pain

Functional abdominal pain is defined by the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) as “abdominal pain without demonstrable evidence of a pathological (inflammatory or infectious) condition.” It is a clinical diagnosis that does not warrant extensive laboratory and/or radiographic investigation in the absence of alarm symptoms. More recently, Rome IV criteria have further characterized this disorder as “functional abdominal pain not otherwise specified”, indicating that it is distinct from other more distinctive functional disorders. Rome V criteria are currently in development.

Symptoms

Alarm symptoms that suggest organic pathology in patients with GI disease include the following:

• persistent right-upper-quadrant or right-lower-quadrant abdominal pain

• dysphagia or odynophagia

• persistent vomiting

• hematochezia

• unexplained (or supplement-refractory) iron-deficiency anemia

• nocturnal stooling

• perirectal disease

• involuntary weight loss

• deceleration of linear growth

• delayed puberty

• unexplained fever

Clinical symptoms in patients with functional abdominal pain can have a psychosocial basis. As such, treatments aimed at addressing these factors may include behavioral interventions including hypnotherapy and cognitive behavioral therapy (CBT), as well as the use of central and peripheral pain modulators (including selective serotonin-reuptake inhibitors [SSRIs]).

(Reference: Childhood Functional Gastrointestinal Disorders: Child/Adolescent. Gastroenterology 2016.)

Visceral hyperalgesia leading to disability is shown as the final outcome of sensitizing medical factors that are superimposed on a background of genetic predisposition and early life events.

Irritable Bowel Syndrome (IBS)

IBS is a subtype of functional abdominal pain in which patients experience both an alteration in bowel movements and abdominal discomfort.

Diagnosis and Etiology

Diagnosis of IBS is based on Rome IV criteria and requires the presence of all of the following symptoms for at least 2 months before diagnosis:

• Abdominal pain at least 4 days per month associated with one or more of the following:

  • related to defecation

  • a change in frequency of stool

  • a change in form (appearance) of stool

• In most children with constipation, the pain does not resolve with resolution of constipation (see functional constipation below).

• After appropriate evaluation, the symptoms cannot be fully explained by another medical condition.

• Etiology may be postinfectious in some cases. There are also significant familial (genetic and environmental) components.

Treatment

Treatment of IBS centers on managing the symptoms of diarrhea, abdominal discomfort, and/or constipation. Dietary management also has a role, and some studies have demonstrated a benefit from a low-FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet.

Functional Constipation

Functional constipation is an extremely common problem in childhood and affects 18% of children older than 4 years in the United States and 3% of children worldwide.

The cycle of constipation (see figure below) frequently occurs as follows:

• Constipation (for multiple reasons) leads to the passage of a painful stool that sensitizes the patient to withhold subsequent stooling and leads to fecal stasis with water resorption and increasingly larger and harder stools.

• The larger and harder stools cause progressive rectal dilation that results in a need for increasing stool caliber to activate stretch receptors sufficiently to trigger the urge to defecate.

• A reduced urge to defecate contributes to further stool retention, and the subsequent passage of even larger, harder, and more painful bowel movements.

Evaluation

Evaluation includes a thorough history of stool frequency and consistency. A review of the Bristol stool chart with children and families is helpful because they may have a different perception of constipation. The goal is for most bowel movements to be Bristol type 4 or 5.

(Source: Bladder and Bowel Dysfunction in Children: An Update on the Diagnosis and Treatment of a Common, but Underdiagnosed Pediatric Problem. Can Urol Assoc J 2017.)

Diagnosis

Diagnosis of functional constipation is based on the Rome IV criteria and requires the following:

• At least two or more of the following occurring at least one time a week, for a minimum of one month, with insufficient criteria to make a diagnosis of IBS:

  • two or fewer defecations per week

  • at least one episode of fecal incontinence per week (if toilet-trained)

  • history of retentive posturing or excessive stool retention

  • history of painful or hard bowel movements

  • presence of a large fecal mass in the rectum

  • history of large-diameter stools (that may obstruct the toilet in older children)

  • accompanying symptoms may include irritability, decreased appetite and/or early satiety, which may disappear immediately following passage of a large stool

• symptoms cannot be explained by another medical condition after appropriate evaluation

Symptoms

Alarm symptoms include those described for functional abdominal pain and symptoms concerning for an organic disorder, including the following:

• the onset of constipation before one month of age

• delayed passage of meconium

• abnormal neurological examination (low tone, loss of cremasteric reflex, decreased lower-extremity reflexes)

• lower-back findings including a sacral dimple, hair tuft, or anorectal anomalies

• poor response to treatment

• concern for hypothyroidism or other organic diseases associated with constipation

Evaluation: Current evidence of patients with suspected functional constipation does not support digital rectal examination, abdominal radiography, colonic transit studies, or rectal ultrasound.

Treatment and Management

The goal of management is the passage of soft-to-formed stools daily or no less frequent than every other day. It may take several months to years to wean treatment as a patient’s rectal vault that has been chronically dilated returns to normal size and sensitivity to stretch is restored.

Dietary interventions include the following:

• increased fiber

• decreased higher-residue foods (white-flour-based foods and rice)

• increased fluid intake

Medications include the following:

• osmotic laxatives (polyethylene glycol 3350

• lactulose and magnesium citrate

• stool softeners (docusate sodium, mineral oil)

• stimulant laxatives (senna, bisacodyl), often used for shorter periods as part of “rescue therapy”; some patients benefit from long-term use

• lubiprostone

• linaclotide

Disimpaction: Initial treatment frequently includes a “clean-out” or disimpaction phase followed by maintenance therapy. Disimpaction may necessitate the use of:

• high-dose osmotic laxatives in conjunction with the administration of a stimulant laxative

• rectal treatment including saline enema or glycerin/bisacodyl suppository

Behavioral modifications include scheduled toileting time after meals, good toilet posture (e.g., feet on a stool), and positive reinforcement (e.g., sticker chart or similar technique, depending on age). It is also important to address any other contributing behavioral issues or stressors.

The consensus algorithms for the evaluation and treatment of functional constipation in infants and children can be found here.

Gastroesophageal Reflux Disease (GERD)

Gastroesophageal reflux (GER) is defined as the passage of gastric contents into the esophagus with or without regurgitation, vomiting, or both. When this causes clinical symptoms or complications (e.g., esophagitis, strictures), it is defined as gastroesophageal reflux disease (GERD).

Symptoms

Symptoms and signs that may be associated with GERD in infants and children (aged 0 to 18 years) include:

• general: discomfort, irritability, failure to thrive, feeding refusal, dystonic neck posturing, dental erosion, anemia

• gastrointestinal: recurrent regurgitation, heartburn, chest pain, epigastric pain, hematemesis, dysphagia, esophagitis, esophageal stricture, Barret esophagus

• airway: wheezing, stridor, cough, hoarseness, apnea, asthma, recurrent pneumonia, recurrent otitis media

(Reference: Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2018.)

Diagnosis and Management

Diagnosis in infants: A gold-standard diagnostic tool does not exist for the evaluation of GER and GERD in infants or children.

• Symptoms of GERD in infants are varied. Nonspecific symptoms (e.g., excessive crying, back arching, spitting, irritability) can also be associated with colic, infection, cow’s milk-protein allergy, and even normal newborn behaviors.

• Uncomplicated infant GER is a normal physiological event and is characterized by recurrent spitting in the absence of GERD symptoms and alarm symptoms above. If an infant is growing well and does not have specific feeding issues, acid suppression or diagnostic evaluation are not needed.

• GERD exists when GER is associated with particular clinical symptoms (see table of Symptoms and Signs of GERD in Infants and Children).

• The identification of alarm features (see table of Red Flag or Alarm Symptoms and Signs That Suggest Disorders Other Than Gastroesophageal Reflux Disease) can help direct workup to rule out serious conditions that can present with symptoms of GER or GERD.

Management in infants: Primary management for GERD in infants includes the following:

• avoidance of overfeeding

• elimination of milk protein exposure (either by maternal dairy restriction or the provision of protein hydrolysate or amino acid-based formula)

• thickening of formula feeds (breast milk cannot be thickened with infant cereals)

  • General instructions for thickening formula: Add 1 to 3 teaspoons of infant cereal (rice or oat) per ounce of prepared infant formula. Mix gently and thoroughly until homogenous. Nipples that allow higher flow may be necessary. Note that some cereals contain soy ingredients. Encourage caregivers to look for products that just contain the grain.

• The evidence is unclear about the benefit of positioning therapy in infants (e.g., holding upright after feeds).

• See the Pediatric Gastroesophageal Reflux Clinical Practice Guidelines (Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition) for an algorithm for the management of symptomatic infants with GERD.

Diagnosis in older children: No gold-standard diagnostic tool exists for the evaluation of GER or GERD in children. Older children are more likely to present with classic symptoms such as heartburn and regurgitation.

Treatment and management in older children:

• First-line treatment for GERD is dietary modification to reduce triggers.

• A trial of acid suppression may be considered if dietary changes alone do not adequately improve symptoms. Some evidence suggests that the greatest clinical improvement occurs during the first 2 to 4 weeks of acid suppression therapy.

• Acid suppression, if deemed clinically helpful, may be continued for 4 to 8 weeks. If symptoms recur when the medications are tapered, further evaluation may include endoscopy, quantitative assessment of reflux burden, or both.

• Although positional therapy in older children has not been studied, head-of-bed elevation has been shown to be beneficial in adults with GER or GERD.

• See the Pediatric Gastroesophageal Reflux Clinical Practice Guidelines (Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition) for a diagnostic and therapeutic algorithm for typical reflux symptoms in the older child.

Imaging and Endoscopy

• No evidence supports the routine use of upper GI barium-contrast studies in the routine evaluation of otherwise healthy infants and children with GERD.

• Barium studies are useful to assess for suspected anatomical disorders that can present in the context of red-flag signs and symptoms. Similarly, barium fluoroscopy can be useful in identifying anatomic abnormalities in patients who have not responded as expected to treatment.

• Upper endoscopic evaluation may be considered in the evaluation of children who fail to respond to an adequate trial of proton pump inhibitor (PPI) therapy. Gross and histologic upper endoscopic study can identify patients with acid-peptic disease, as well as those with other conditions that may present with GERD-like symptoms, including eosinophilic esophagitis (see EoE), candida esophagitis (e.g., in children using inhaled glucocorticoids), or esophageal outlet obstruction.

• Additional testing includes BRAVO pH probe and pH impedance probes.