Pediatric Intestinal Pseudo-Obstruction: A Review

Clinicians may not be aware of pediatric intestinal pseudo-obstruction (PIPO), a rare, chronic, severe, and debilitating pediatric gastrointestinal motility disorder with an estimated incidence of approximately 1 per 40 000 live births. Furthermore, the diagnosis of PIPO can be difficult to make (resulting in delayed or underdiagnosis) due to its variable clinical presentation, presence of comorbidities and multiorgan involvement, and a lack of a single definitive diagnostic test or biomarker. Clinicians need to understand that treatment of PIPO remains challenging and requires a multidisciplinary approach, and that prognosis remains guarded with high morbidity/mortality as well as impaired functioning and health-related quality of life.After completing this article, readers should be able to: Describe the heterogeneous clinical presentations of PIPO.Recognize the need for increased awareness and correct diagnosis of PIPO.Describe the underlying pathophysiology and classification of PIPO subtypes.Describe the general diagnostic approach in the investigation of suspected PIPO.List the medical, nutritional, and surgical pillars of management of PIPO.Describe the roles of multidisciplinary team members in a holistic approach to PIPO management.Recognize the effect PIPO has on the quality of life of impacted patients and their families.Pediatric intestinal pseudo-obstruction (PIPO) is a rare but severely debilitating gastrointestinal (GI) motility disorder that affects children. PIPO is characterized by a chronic failure of the GI tract to propel its contents, therefore mimicking mechanical obstruction but in the absence of any lesion occluding the intestinal lumen.1 There are key differences in the adult and pediatric presentations of chronic intestinal pseudo-obstruction (CIPO), which prompted a 2018 proposal from the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) to refer to the occurrence of CIPO in children as PIPO.2The diagnosis of PIPO can be difficult to make due to its variable clinical presentation, presence of comorbidities and multiorgan involvement, and lack of a single definitive diagnostic test or biomarker. PIPO should be suspected in infants and children with feeding intolerance, bilious emesis, abdominal distension, and dilated loops of small bowel with air-fluid levels on imaging.PIPO can be congenital or acquired and further subdivided into primary, secondary, or idiopathic with 3 distinct subtypes (neuropathies, myopathies, and/or mesenchymopathies).2 A large proportion of children with PIPO have clinical symptoms that start in the first month of life and require prolonged parenteral nutrition (PN)3 and surgical interventions for feeding and decompression. Treatment remains challenging and requires a multidisciplinary approach. Despite advances in PN and intestinal transplant, the prognosis remains guarded with impairments in functioning and health-related quality of life (QoL).2,4–8This review highlights advances in our understanding of pathophysiology, genetic underpinnings, histopathology, diagnosis, and management of PIPO.PIPO is a rare disease with scarce epidemiological data on incidence, prevalence, or demographic risk factors. One study suggested that fewer than 100 infants are born with PIPO annually in the United States, yielding an estimated incidence of approximately 1 per 40 000 live births.2,9 However, a study in Japan demonstrated a prevalence of 3.7 in 1 000 000 children under 15 years of age. Among these children, 56.5% developed PIPO in the neonatal period (<1 month), 19.4% in infancy (1–12 months), 14.5% in childhood (1–7 years), and 9.7% in school age and beyond (7–15 years),2,10 which suggests an incidence lower than 1 in 40 000. While some adult studies indicate that CIPO is more frequent in females, this may be influenced by higher rates of secondary CIPO from conditions that are more common in females (eg, rheumatologic disorders). It is not yet known whether sex or race/ethnicity influence the epidemiology of PIPO.PIPO can be primary, secondary (as a manifestation of systemic disease), or idiopathic. Primary PIPO disorders are related to inflammatory degradation or atypical development of the enteric neuromusculature, which may be congenital or inherited. Primary PIPO disorders can be classified by their site of involvement as enteric neuropathies (enteric neurons), enteric myopathies (intestinal smooth muscle), and/or mesenchymopathies (interstitial cells of Cajal [ICC] network).4 PIPO is classified as idiopathic when neither a primary nor secondary cause has been identified. As advances in genetic sequencing continue to identify specific mutations associated with PIPO (Table 1), there may be a trend toward reclassification of prior idiopathic PIPO to primary PIPO.The neuromuscular composition of the GI tract is complex and comprised of intestinal smooth muscle, intrinsic enteric neurons (submucosal and myenteric plexuses) that make up the enteric nervous system (ENS), extrinsic afferent and efferent innervation of the gut, and the ICC networks (which mediate communication between the ENS and intestinal smooth muscle). Any single or combination of these components may be compromised in PIPO.Urinary tract involvement is common in PIPO and has been observed in up to 33% to 92% of cases, with a higher incidence in congenital myopathies.2,11 The most frequent urologic manifestation is megacystis with a hypocontractile detrusor and increased bladder capacity and compliance.11 Neurologic abnormalities are well defined in certain forms of PIPO, such as mitochondrial neurogastrointestinal encephalomyopathy in which patients may display peripheral neuropathy, generalized muscle weakness, ocular symptoms, deafness, and radiographic leukoencephalopathy.2,12 Cardiomyopathy and sinus node dysfunction may be present in other forms of PIPO.2 Some patients may have pancreaticobiliary involvement with hypocontractility of the gallbladder, predisposing to biliary colic and complications such as cholelithiasis, cholecystitis, choledocholithiasis, cholangitis, and gallstone pancreatitis.2,13The clinical presentation of PIPO depends on the age of onset and the affected region of the GI tract.14 Prenatal signs are detected in about 20% of patients, with 50% to 70% of patients presenting with symptom onset within the first month of life and 80% presenting symptom onset by 1 year of age. The remaining 20% will experience symptoms within the first 2 decades of life.5,15Dilated bowel is rarely noted on prenatal imaging.2,5,14 Rather, megacystis is the most commonly identified prenatal sign of PIPO, typically in patients with megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS). Megacystis diagnosed antenatally with urological signs and symptoms in the neonatal period should prompt consideration of MMIHS because these findings may precede GI symptoms of PIPO by several months. Other prenatal findings of other subtypes of PIPO may include hydronephrosis, polyhydramnios, and—less commonly—gastric distension.2,16In the neonatal period, the most common signs and symptoms include abdominal distension, vomiting (bilious and nonbilious), constipation, and delayed passage of meconium.2,5 Caution should be taken in diagnosing PIPO in premature infants because mature intestinal motor patterns do not emerge until 34 to 35 weeks' gestation.14,17The most prevalent sign of PIPO in infancy and childhood is abdominal distension that may be associated with nausea, vomiting, abdominal pain, anorexia, early satiety, constipation, and/or diarrhea.14,15 Dysphagia may be reported with lower frequency.15 Due to intestinal stasis, patients can present with diarrhea and steatorrhea in the setting of small intestinal bacterial overgrowth (SIBO). Late-onset PIPO is also associated with comorbid conditions.14,15Regardless of the age of onset, signs and symptoms often result in feeding intolerance and decreased oral intake.4,14,15 The impaired function of the GI tract can result in reduced intestinal absorption, increasing the risk for poor growth and undernutrition. Patients often require nutritional supplementation via a feeding tube, with more severe instances requiring PN.Signs and symptoms may be chronic with superimposed exacerbations that vary in severity. These episodes may occur during a time of illness, changes in environment, and physiologic and psychosocial stress. Patients may require bowel rest during exacerbations.2,18PIPO should be distinguished from other conditions that cause GI dysmotility. Pediatricians are more likely to encounter ileus, a temporary cessation of normal intestinal peristalsis that causes functional obstruction. Table 2 highlights differentiating features of common mimickers of PIPO. Other considerations include mechanical obstructions, such as Hirschsprung disease (which must be ruled out in all cases of suspected PIPO), intestinal atresia or stenosis, volvulus, adhesions, and intussusception. Importantly, patients with PIPO may also experience ileus or mechanical obstruction. There are also numerous systemic conditions that can affect GI motility and present with transient or chronic obstructive symptoms and may ultimately result in secondary PIPO (Table 1).Patients with PIPO have been found to have lower QoL compared with both healthy peers and peers with other chronic illnesses.4–8 Compared to healthy peers and peers with other chronic medical conditions, patients with PIPO experience greater impairments in academic and social functioning.7,8 Because children with PIPO demonstrate greater deficits even when compared to patients with other chronic GI diseases,8 these impairments may not solely be related to the presence of GI symptoms but rather other factors specific to PIPO.Although comparable to patients with other chronic illnesses and GI diseases, lower physical (difficulties with self-care and mobility) and emotional functioning have been found in PIPO.7,8 Less freedom from pain (ie, days without pain) (compared to healthy children and children with juvenile rheumatoid arthritis) may exacerbate these functional impairments.4,5,7,8However, despite overall impairments in functioning, QoL in PIPO may improve over time related to progressive adjustment and ability to manage medical concerns. In a study of children with intestinal failure (IF), including patients with PIPO, health-related QoL scores did improve with age but remained lower than healthy and chronically ill peers.8Patients with PIPO are at risk for psychiatric comorbidities. Compared to healthy peers, there are higher rates of anxiety and depression in PIPO.5,7 Patients with PIPO also exhibit increased rates of aggression, hyperactivity, and social withdrawal compared to patients with juvenile rheumatoid arthritis.7Caregivers of patients with PIPO are also significantly impacted. The time and effort necessary to care for these children are significantly greater than for healthy children, imposing a significant burden on caregivers, whose emotional resilience may be impacted.5,7 When compared to parents of healthy children, parents of children with PIPO reported increased worries regarding their child's health, functioning, pain levels, and well-being.7In 2018, a panel of experts led by ESPGHAN put forth consensus guidelines that established standards for the definition, diagnosis, and management of PIPO.2Figure 1 summarizes the diagnostic criteria and stepwise evaluation of PIPO.In suspected PIPO, the first screening test should be a plain abdominal x-ray to identify dilated bowel loops and air-fluid levels. Subsequently, a contrast study is necessary to rule out intestinal malrotation or other mechanical obstruction.Upper GI series with small bowel follow-through (UGISBFT) has long been considered the gold standard as it is universally available, easy to perform, and inexpensive. However, it delivers a high dose of radiation, and its utility may be limited in patients who are not able to tolerate a sufficient volume of enteral contrast.2,14 UGISBFT may demonstrate a markedly distended stomach and small bowel (mainly the first portion of the duodenum), slow transit through the intestine, and possible intestinal malrotation. Dilation of at least 1 region of the GI tract on contrast imaging ranges from 59% to 82% in PIPO, and intestinal malrotation may be seen in up to 36% of patients.2 Computed tomography and magnetic resonance enterography have emerged as advanced high-resolution studies that can provide detail on additional sources of obstruction, such as intestinal adhesions, and are surpassing UGISBFT as first-line imaging modalities.2,14 Cine-magnetic resonance imaging is a newer modality that allows for visual assessment of the entire small bowel and analysis of multiple parameters, including diameter measurements, bowel motility (fasted and fed state), displacement mapping, and GI tagging,2,14,19,20 but patients must tolerate the study without sedation because general anesthesia disrupts reliable interpretation of intestinal motility.Other radiologic studies demonstrate less consistency in the evaluation of PIPO. The use of radio-opaque markers is not routinely recommended due to its unreliable estimation of small bowel transit.2 Nuclear medicine gastric emptying scintigraphy may lend insight into the optimal route of enteral feeding, but it has not been studied specifically in PIPO.2Histopathology in cases of suspected PIPO may lend insight into prognosis and guide management of potentially treatable secondary cases.2 Full-thickness biopsy (FTB) allows histopathologic examination of the entire enteric neuromuscular complex. In 2009, an international working group at the World Congress of Gastroenterology proposed guidelines (now known as the London Classification) for diagnostic standardization of adult and pediatric GI neuromuscular pathology, including histopathologic techniques and reporting.21,22 The 2018 ESPGHAN PIPO consensus guidelines recommend that histopathology be performed at centers with sufficient expertise to execute and interpret a thorough neuromuscular analysis according to the London Classification.2While surgery is the current standard practice of obtaining an FTB, it is generally not advisable to perform surgery for the sole purpose of obtaining histopathologic samples given the increased risk of operative and postoperative complications in patients with PIPO. However, if therapeutic surgery is already being performed, this is an appropriate opportunity to obtain an FTB.2 An endoscopic FTB is of interest but requires further study of its safety and efficacy in PIPO.Endoscopic evaluation is best suited to assess for mucosal disease because biopsies are typically superficial and capture the mucosa and lamina propria. Esophagogastroduodenoscopy is helpful to rule out celiac disease or eosinophilic GI disease. Colonoscopy is less commonly used for PIPO evaluation, but, if performed, it can provide a therapeutic opportunity for transient decompression.14Manometry testing measures the pressures of various regions of the GI tract, which can be interpreted to characterize the region's motor function. The testing is performed by probing a small catheter, containing pressure transducers, through the mouth, nose, or anus into the lumen or sphincter of interest.Antroduodenal manometry (ADM) is particularly well-suited for evaluating PIPO. It can help confirm or rule out the diagnosis of PIPO. The small intestine is nearly always affected; therefore, normal study findings should prompt consideration of an alternative diagnosis.2,23 ADM can define the pathogenesis of PIPO (ie, classify PIPO as neuropathic and/or myopathic), which may aid in prognostication. Through provocative tests (eg, administering a meal or prokinetic medications to analyze the response or lack thereof), ADM can lend insight into clinical treatment uniquely tailored to each patient. Lastly, ADM is also part of the evaluation for intestinal transplant both in determining indication and, if necessary, which organs should be transplanted.23Of note, esophageal, colonic, and anorectal manometry are not always necessary in the evaluation of PIPO but may be used depending on the clinical presentation (eg, anorectal manometry to evaluate for Hirschsprung disease).Laboratory studies can aid in the evaluation of secondary forms of PIPO. At a minimum, a complete blood cell count, comprehensive metabolic panel, inflammatory markers, celiac serologies (note that this laboratory testing is only accurate if gluten is present in the diet, which generally excludes neonates and patients who are PN dependent), and thyroid studies should be obtained in all patients.2 Additional laboratory testing should be guided by clinical presentation (Table 1, Figure 1). With the increasing identification of pathogenic mutations linked to PIPO, genetic testing (including mitochondrial sequencing) and counseling will become increasingly important in the diagnostic evaluation.Except in secondary cases in which there is a treatable underlying etiology, there is no cure for PIPO. Management of PIPO typically comprises complementary therapeutic approaches, including pharmacotherapy, nutritional support, and surgical intervention (Table 3). A collaborative, multidisciplinary team is paramount to provide comprehensive care and support for children with PIPO and their families (Figure 2). Treatment goals are important to alleviate symptom burden, improve QoL (eg, avoiding hospitalization), promote growth and nutrition, minimize unnecessary surgery, and mitigate morbidities.4Targets of pharmacotherapy include enhancement of motility (prokinetics and other agents that modulate the GI tract), alleviation of symptoms such as nausea and pain, and treatment and prevention of SIBO (Table 3).Unfortunately, there is no medication that universally addresses the heterogeneous patterns of dysmotility in PIPO. Most of the data on medications for pseudo-obstruction come from adult CIPO literature, but recent studies have shown promising safety and efficacy of some of these agents in pediatric patients. For example, prucalopride was found to reverse symptoms of PIPO in 1 pediatric case series and has also successfully alleviated upper GI symptoms and improved feeding tolerance in the pediatric population.24,25 Additional therapies that have shown some effect include Japanese herbal medicines (eg, rikkunshito and daikenchuto, which are thought to work by enhancing GI motility and improving blood flow in the intestines) and fecal microbiota transplant, but further studies are needed to confirm these findings and demonstrate safety in a pediatric population.26,27Maintaining adequate nutrition is paramount but often very challenging. Most infants and children with PIPO require some degree of nutritional support in the form of enteral nutrition (EN) or PN, but some patients may tolerate varying degrees of oral nutrition. Beyond caloric requirements, it is important to ensure that patients receive adequate hydration, electrolytes, and micronutrients, which may require enteral and/or parenteral supplementation.Oral nutrition may be hindered by limited developmental oro-motor skills related to prolonged periods with nothing by mouth early in life and oral aversion related to negative associations with postprandial symptoms. Dietary measures that may help optimize tolerance of oral nutrition in PIPO are similar to those recommended in gastroparesis: small, frequent meals low in fat and fiber and avoidance of lactose (SIBO can lead to secondary lactose intolerance) and carbonated beverages (which can worsen gaseous distension and intraluminal pressure).28The route or site of delivery can impact the tolerance of EN in patients with PIPO. While gastric feeding is most physiologic and typically more straightforward for caregivers to administer, it may not be tolerated. Postpyloric feeds may be better tolerated because they can be administered continuously into the jejunum while simultaneously venting the stomach to alleviate obstructive symptoms. Hydrolyzed or elemental formula may improve tolerance of EN in some patients.2 However, despite modifications of the route and type of feeding, some patients may not tolerate EN due to excessive discomfort with obstructive symptoms. Even when oral or EN are tolerated clinically, stasis throughout the GI tract may impede the ability of macro- and micronutrients to reliably reach their sites of absorption, which may result in varying degrees of malnutrition.Patients with PIPO who are unable to tolerate sufficient EN to maintain their energy and volume needs and sustain life have IF and require PN.29 PN is a life-saving intervention in these scenarios and has vastly improved overall survival rates in pediatric IF.30 However, PN also carries risk of serious complications and morbidities, including central line-associated bloodstream infection (CLABSI), venous thrombosis, and intestinal failure-associated liver disease (IFALD). Ultimately, approximately one-third of patients with PIPO will tolerate oral feeding, another third will require EN, and the remainder will require either partial or total PN.2Patients with PIPO require close monitoring of hydration and electrolyte status. Those who are vented at 1 or more sites of their GI tract may lose a significant amount of GI fluid and electrolytes. Volume of output may vary day to day and may increase or decrease drastically from baseline during episodes of pseudo-obstruction. Even patients who are not vented may experience severe fluid shifts during exacerbations related to stasis and/or dumping of intestinal contents. Some patients may require a central line for intravenous fluid supplementation solely to maintain their fluid and electrolyte status, even if they are able to meet their nutritional needs enterally.Children with PIPO may experience worse surgical outcomes compared to the general population. These children are likely to undergo 1 or more lifetime surgeries for exploration, diagnosis, and/or treatment, with each intervention increasing the risk for adhesions and future mechanical obstruction. Underlying inflammatory or connective tissue disorders in some patients may also predispose them to adhesions. Prolonged postoperative paralytic ileus may lead to progressive deterioration of bowel function (ie, motility may not return entirely to preoperative baseline).2 Therefore, surgical decision-making should be thoughtful and judicious.The role of surgery in PIPO is primarily palliative, with a goal of decompressing the bowel to optimize motor function and relieve obstructive symptoms. Surgical decompression may be achieved with the creation of feeding gastrostomies and jejunostomies, as well as decompressive enterostomies (ileostomy, colostomy). These can be used for venting, which is the process of releasing gas or fluid from the GI tract to alleviate abdominal discomfort and distension. Decompressive enterostomies are almost uniformly beneficial in patients with PIPO with recurrent episodes of pseudo-obstruction and those who do not tolerate enteral feeds because they aid in alleviating obstructive symptoms, decreasing gaseous distension, reducing stasis of intestinal contents, and lessening PN reliance by enhancing EN tolerance.2As the only definitive treatment of PIPO, intestinal transplant may rescue patients with life-threatening PN-associated complications (recurrent CLABSI, loss of central access related to thrombosis, IFALD) or very poor QoL related to recurrent episodes of pseudo-obstruction.2 There are multiple types of intestinal transplants: isolated intestine, multivisceral (liver, small intestine with or without other abdominal organs), and modified multivisceral (small intestine and other abdominal organs, but no liver). While transplant carries its own host of morbidities and mortality, advances in surgical techniques and post-transplant medical treatment have improved outcomes and survival rates (89% at 1 year and 69% at 5 years in a large cohort of pediatric and adult patients with PIPO/CIPO).31Similar to the wide range of signs and symptoms found in children with PIPO, the disease course can be variable, leading to unpredictable prognoses and outcomes. Overall, primary or congenital forms of PIPO have a fairly guarded prognosis due to higher risks associated with prolonged PN dependence.2,32 Some children can experience significant improvement over time, while others have persistent symptoms. In secondary or acquired forms of the disease, the prognosis is more dependent on the underlying etiology of the dysmotility and disease progression. Children with milder forms of PIPO may have a better long-term outlook compared to those with severe and widespread involvement of the GI tract. Additionally, the effective response to management of symptoms and complications can significantly improve QoL.Common complications reported in PIPO include stoma prolapse, intestinal malrotation, recurrent pancreatitis, diversion colitis (inflammation of bypassed colon following surgery), and excessive fluid losses secondary to high ostomy output.2 Additionally, specific genetic mutations can be associated with various complications, including oncologic, cardiac, urologic, and neurodevelopmental issues.2 Psychiatric comorbidities should also be evaluated and addressed.4–8Historically, the mortality rate of PIPO was noted to be as high as 90% before 1 year of age. In more recent observational studies, mortality ranges from 4% to 32%,10,16,32 with several predictors of poor outcomes. While survival appears to be similar between neonatal-onset and late-onset PIPO, studies have demonstrated higher trends of PN dependence (with increased risk of CLABSI and IFALD) and surgical interventions (with increased risk of surgical complications) in neonatal-onset cases.10,33 Although generally less severe in presentation, this compares to increased risk of malnutrition in late-onset PIPO, which may indicate a more chronic and complex disease process.10,33Several other risk factors threaten a poor outcome. Perhaps the most significant are patients with myopathic forms of PIPO, esophageal dysmotility, urinary tract involvement, or concurrent intestinal malrotation.15,32,34 This is particularly true for patients with MMIHS, where survival rates can be as low as 20%.5On the other hand, patients who respond well to medical therapy generally show improved outcomes. This includes positive response to prokinetics, pain management, and treatment of other common risk factors, including SIBO. Surgical procedures, such as formation of a gastrostomy or enterostomy for venting of distended bowel, enabling enteral feeds, and management of emergencies (including severe bowel distension, perforation and ischemia) may be needed. Minimal response to such therapies may confer increased risk of poor outcome.Most pediatric deaths from PIPO are associated with complications of PN, including IFALD, CLABSI, and sepsis.32 In fact, the 1-, 5-, and 10-year survival rates in children with PIPO on home PN were 90%, 70%, and 60%, respectively.30 Despite these indicators of poor outcome, the long-term prognosis of patients who require significant medical (including PN) and surgical therapies far exceeds the prognosis of patients that ultimately require intestinal transplant. In these patients, 1-, 5-, and 10-year survival rates are as low as 75%, 57%, and 30%, respectively, due to infection, graft rejection, and multiorgan failure as primary causes of mortality.35,36 Thus, optimizing medical and surgical management to avoid intestinal transplant is vital to allowing children with PIPO to achieve optimal outcomes.While some children may experience improvement in symptoms as they grow older, potentially due to maturation of the ENS, this is not guaranteed. Ongoing treatment is typically required, including support and education for families and caregivers to effectively treat the child's condition and determining strategies to allow children to achieve a reasonable QoL despite physical and emotional challenges.Recent studies of pathophysiology, genetics, and potential therapies have advanced our understanding of PIPO and may lead to improving outcomes for children with PIPO.Current research has focused on illuminating the complex mechanism underlying PIPO, specifically attempting to better understand the roles of the ENS, smooth muscle function, and the ICC network. Contributions to the development of PIPO include disturbances to the ENS due to atypical neuronal density and altered neurotransmitter expression,37 mutations affecting smooth muscle contractility proteins (eg, actin and myosin) that result in impaired muscle contraction and relaxation cycles,38 and dysfunctional ICC, which disrupt typical rhythmic contractions of the GI tract.5Genetic studies have identified several mutations associated with PIPO (Table 1), providing insight into the hereditary nature of PIPO, implications for genetic counseling and family planning, and potential targets for gene therapy.Therapeutic modalities continue to evolve with newer medications, optimization of surgical interventions, and exploration of nonpharmacological interventions. While specific gene therapy targeting PIPO is not yet available, there is promising research in animals including zebrafish models of PIPO.39,40 Although stem cell transplantation is in its infancy, Hetz et al were able to show that human enteric neural crest cells transplanted into host tissue of immunodeficient mice could recreate a functional enteric neural network, leading to restored gut motility.41Ongoing research and clinical trials are crucial to enhance our limited understanding of PIPO, which is fundamentally unique from adult CIPO. Establishment of a collaborative research network to exchange clinical information and data would facilitate providers and scientists to elucidate genotype-phenotype correlations, unravel molecular mechanisms, provide targeted therapeutics, and ultimately improve outcomes for patients with PIPO.SummaryThere are key differences in the adult and pediatric presentations of intestinal pseudo-obstruction prompting the term PIPO when referring to children (level D, based on expert consensus).Emerging evidence continues to highlight the poorly understood and complex mechanisms underlying PIPO (level D, based on expert consensus).Using a collaborative, multidisciplinary treatment approach is paramount in providing comprehensive care and support for children with PIPO and their families (level D, based on expert opinion).Multiple complementary therapeutic approaches, including pharmacotherapy, nutritional support, and surgical interventions, are available to manage PIPO; however, it remains challenging to treat with significant lifelong comorbidities/complications, resulting in decreased functioning and impaired QoL (level D, based on limited pediatric evidence).Current evidence does not allow us to reliably predict clinical course or outcomes in patients with PIPO (level D, based on limited pediatric evidence).Existing literature provides multiple suggestions to address impaired QoL, decreased functioning, psychiatric comorbidities, and increased parental stress among patients with PIPO and their caregivers. It is important for these concerns to be addressed because psychological stress has been shown to exacerbate and trigger pseudo-obstruction symptoms.4,6 The most common recommendation is implementing a multidisciplinary team of physicians and allied health professionals (eg, psychologists, occupational and physical therapists, dietitians, and social workers). Adjunct treatments should focus on pain management, improving social, physical, and academic functioning, and providing support to parents.4,5,7,8To support the need for a multidisciplinary team, future quality improvement projects should focus on screening for impairments in QoL and functioning during patient visits. Screening should be performed regularly to target patients in need of more support early and increase their access to care.We propose the primary provider/team administer the Functional Disability Inventory42,43 and Pediatric Quality of Life Inventory44 at regular follow-up visits to evaluate the feasibility and utility of screening. Future quality improvement projects should focus on identifying appropriate referrals and interventions for these patients.