Children with Intestinal Failure are at Risk for Psychopathology and Trauma.

OBJECTIVES: The objective of this study is to assess the psychopathology and medical traumatic stress in children with intestinal failure (IF) and identify associated risk factors. METHODS: Two-center study, performed from September 2019 until April 2022 (partly during COVID-19 pandemic), including children (1.5-17 years) with IF, dependent on parenteral nutrition (PN) or weaned off PN, treated by a multidisciplinary IF-team. Psychopathology in children was evaluated with a semi-structured interview assessing psychiatric classifications and validated questionnaires assessing emotional (internalizing) and behavioral (externalizing) problems. Medical traumatic stress was assessed with a validated questionnaire. Problem scores were compared with normative data. Associations between clinical characteristics and outcomes were analyzed with linear regression analyses. RESULTS: Forty-one (of 111 eligible) children were included [median age 8.9 years (interquartile range, IQR 5.5-11.8), 54% female, 73% born preterm]. Median PN-duration was 17.3 months (IQR 6.9-54.0); 17 children (41%) were still PN-dependent. One third of the children met criteria for at least 1 psychiatric classification (compared with 14% in age-matched general population). Anxiety disorders and attention deficit hyperactivity disorder were most common. In school-aged children (n = 29, 6-17 years), significantly increased emotional problems were consistently reported by children ( P = 0.011), parents ( P < 0.001), and teachers ( P = 0.004). In preschool children (n = 12, 1.5-5 years), no significant differences with normative data were found. Subclinical or clinical emotional problems were reported in 19 children (46%). Medical traumatic stress was present in 14%, and 22% of children had received psychological help for trauma before. Lower gastrointestinal related quality of life was associated with more emotional problems, but not PN-duration. CONCLUSIONS: Children with IF, particularly school-aged children, are at risk for psychological problems which is reflected by the high rate of received psychotherapy and the high rate of emotional problems and psychiatric classifications.

Challenges in body composition assessment using air-displacement plethysmography by BOD POD in pediatric and young adult patients.

BACKGROUND & AIMS: Air-Displacement-Plethysmography (ADP) by BOD POD is widely used for body fat assessment in children. Although validated in healthy subjects, studies about use in pediatric patients are lacking. We evaluated user experience and usability of ADP measurements with the BOD POD system in healthy children and pediatric and young adult patients. METHODS: Using the experiences of seven cohort studies, which included healthy children and patients aged 2-22 years, we retrospectively evaluated the user experience with the User Experience Questionnaire (UEQ) (n = 13) and interviews (n = 7). Technical performance was studied using the quality control data collected by the ADP-system. RESULTS: From 2016 to 2022, 1606 measurements were scheduled. BOD POD was mostly rated 'user-friendly', with a generally neutral evaluation on all scales of the UEQ. However, questionable reliability and validity of the results were frequently (86%) reported. We found a high technical failure-rate of the device, predominantly in stability (17%) and accuracy of the measurement (12%), especially in the 'pediatric option' for children aged <6 years. Measurement failure-rate was 38%, mostly due to subject's fear or device failure, especially in young and lean children, and in children with physical and/or intellectual disabilities. CONCLUSION: We conclude that ADP by BOD POD in children and young adults is non-invasive and user-friendly. However, in specific pediatric populations, BOD POD has several limitations and high (technical) failure-rates, especially in young children with aberrant body composition. We recommend caution when interpreting body composition results of pediatric patients as assessed with BOD POD using the current default settings.

Venous Thromboembolic Complications in Pediatric Gastrointestinal Diseases: Inflammatory Bowel Disease and Intestinal Failure.

In children with gastrointestinal disorders such as inflammatory bowel disease (IBD) and intestinal failure (IF), the risk of venous thromboembolism (VTE) is increased. VTE may lead to pulmonary embolism, sepsis and central line infection, stroke and post-thrombotic syndrome. The purpose of this review is to summarize current knowledge and recent advances around VTE management in pediatric gastroenterology with a focus on IBD and IF. The VTE incidence in children with IBD is reported to be around 4-30 per 10,000 patient-years, with higher incidences for hospitalized children. While in general, IF is less common than IBD, the VTE incidence in children with IF is around 750 per 10,000 patient-years. The most common risk factors for development of VTE involve deviations leading to Virchow's triad (endothelial damage, stasis, and hypercoagulability) and include active inflammation, particularly with colonic involvement, presence of a central venous catheter, underlying thrombophilia, reduced mobility, surgery, and hospitalization. Classes of anticoagulants used for treatment of VTE are low molecular weight heparins and vitamin K antagonists. However, the use of direct oral anticoagulants for treatment or prevention of VTE has not been studied in this pediatric population yet. Pediatric gastroenterologists apply different VTE prevention and treatment strategies due to lack of literature and lack of consensus. We discuss the role of primary and secondary prophylactic use of anticoagulants, and provide tools and recommendations for screening, prevention and management for the specific pediatric populations.

Ghrelin Levels in Children With Intestinal Failure Receiving Long-Term Parenteral Nutrition.

Background: Children with intestinal failure (IF) require parenteral nutrition (PN). Transition to oral and enteral nutrition (EN) can be difficult also due to abnormal gastrointestinal motility. The gut hormone ghrelin is increased in states of negative energy balance, functioning to preserve euglycemia, and also has appetite stimulating and prokinetic properties. We aimed to evaluate and compare ghrelin levels in children with IF, and to assess the relationship with PN-dependency. Methods: In this exploratory prospective multicenter study, plasma acylated (AG) and unacylated (UAG) ghrelin levels were measured in children with short bowel syndrome (SBS) and with functional IF (pseudo-obstruction or any enteropathy) and compared with healthy control subjects. Spearman's rho (rs) was used to assess correlations of AG and UAG with PN-dependency (%PN) and parenteral glucose intake. Results: Sixty-four samples from 36 IF-patients were analyzed. Median baseline AG and UAG levels were respectively 279.2 and 101.0 pg/mL in children with SBS (n = 16), 126.4 and 84.5 pg/mL in children with functional IF (n = 20) and 82.4 and 157.3 pg/mL in healthy children (n = 39). AG levels were higher in children with SBS and functional IF than in healthy children (p = 0.002 and p = 0.023, respectively). In SBS, AG positively correlated with %PN (rs = 0.5, p = 0.005) and parenteral glucose intake (rs = 0.6, p = 0.003). These correlations were not observed in functional IF. Conclusion: Children with IF had raised AG levels which could be related to starvation of the gut. The positive correlation between AG and glucose infusion rate in SBS suggests an altered glucoregulatory function.

Cognitive Outcomes in Children With Conditions Affecting the Small Intestine: A Systematic Review and Meta-analysis.

OBJECTIVES: The aim of the study was to assess cognitive outcomes in children with intestinal failure (IF) and children at high risk of IF with conditions affecting the small intestine requiring parenteral nutrition. METHODS: EMBASE, Cochrane, Web of Science, Google Scholar, MEDLINE, and PsycINFO were searched from inception to October 2020. Studies were included constituting original data on developmental quotient (DQ), intelligence quotient (IQ) and/or severe developmental delay/disability (SDD) rates assessed with standardized tests. We used appropriate standardized tools to extract data and assess study quality. We performed random effects meta-analyses to estimate pooled means of DQ/IQ and pooled SDD rates (general population mean for DQ/IQ: 100, for percentage with SDD: 1.8%) for 4 groups: IF, surgical necrotizing enterocolitis (NEC), abdominal wall defects (AWD), and midgut malformations (MM). Associations of patient characteristics with DQ/IQ were evaluated with meta-regressions. RESULTS: Thirty studies met the inclusion criteria. The pooled mean DQ/IQ for IF, NEC, AWD, and MM were 86.8, 83.3, 96.6, and 99.5, respectively. The pooled SDD rates for IF, NEC, AWD and MM were 28.6%, 32.8%, 8.5%, and 3.7%, respectively. Meta-regressions indicated that lower gestational age, longer hospital stay, and higher number of surgeries but not parenteral nutrition duration, were associated with lower DQ/IQ. CONCLUSIONS: Adverse developmental outcomes are common in children with IF and NEC, and to a much lesser extent in children with AWD and MM. It is important to monitor cognitive development in children with conditions affecting the small intestine and to explore avenues for prevention and remediation.

Necrotizing Enterocolitis in a Dutch Cohort of Very Preterm Infants: Prevalence, Mortality, and Long-Term Outcomes.

INTRODUCTION: To improve counseling of parents and to guide care strategies, we studied the disease course and outcomes of necrotizing enterocolitis (NEC) up to 2 years of corrected age (CA) from a multidisciplinary perspective. MATERIALS AND METHODS: This was a retrospective cohort study in preterm infants (birth weight < 1,500 g, gestational age < 32 weeks), diagnosed with NEC (Bell's stage ≥ II) from 2008 through 2020. Data on prevalence, mortality, surgery, intestinal failure (IF), growth, and neurodevelopment at 2-year follow-up were separately analyzed for medically and surgically treated children. RESULTS: Of 3,456 preterm infants, 200 (6%) were diagnosed with NEC, of whom 135 developed an indication for surgery within 7 days after the diagnosis; 28/135 died before surgery, and 37/107 died after an open-and-close procedure. An enterostomy was constructed in 62 patients and an end-to-end anastomosis in 15. The postoperative course was described for 77 patients, of whom 23 developed surgical complications (12/23 incisional hernias, 9/23 anastomotic strictures), 13/77 a short bowel, and 25/77 IF. Sixty-day survival after birth for medical NEC patients was 88% (hazard ratio [HR]: 0.698; p = 0.318), and for surgically treated NEC patients was 40% (HR: 3.729; p < 0.001). At 2-year follow-up, one patient received parenteral nutrition. Severe delay in weight for age, motor, and cognitive development was seen in 3, 6, and 2%, respectively. CONCLUSION: In this cohort, the mortality rate was high, especially in surgically treated NEC patients. The surgical complication rate is comparable to previous studies, but in surviving patients, persisting IF and severe delay in growth and neurodevelopment at 2 years CA were relatively rare.

Anthropometrics and fat mass, but not fat-free mass, are compromised in infants requiring parenteral nutrition after neonatal intestinal surgery.

BACKGROUND: Children with intestinal failure (IF) receiving long-term parenteral nutrition (PN) have altered body composition (BC), but data on BC changes from start of PN onwards are lacking. OBJECTIVES: We aimed to assess growth and BC in infants after neonatal intestinal surgery necessitating PN and at risk of IF, and to explore associations with clinical parameters. METHODS: A prospective cohort study in infants after intestinal surgery. IF was defined as PN dependency for >60 d. SD scores (SDS) for anthropometry were calculated until 6-mo corrected age. In a subgroup, fat mass (FM) and fat-free mass (FFM) were measured with air-displacement plethysmography at 2- and 6-mo corrected age. SDS for length-adjusted FM index and FFM index were calculated. Associations between cumulative amount of PN and BC parameters were analyzed with linear mixed-effect models. RESULTS: Ninety-five neonates were included (54% male, 35% born <32 wk) and 39 infants (41%) had IF. Studied infants had compromised anthropometric parameters during follow-up. At 6-mo corrected age, they remained smaller (median weight-for-age SDS -0.9 [IQR -1.5, 0.1], P < 0.001) than the normal population. In 57 infants, 93 BC measurements were performed. FM index SDS was lower than in healthy infants at 2- and 6-mo corrected age (-0.9 [-1.6, -0.3], P < 0.001 and -0.7 [-1.3, 0.1], P = 0.001, respectively), but FFM index SDS did not differ. A higher cumulative amount of PN predicted a higher FM index in female infants but lower FM index in male infants. CONCLUSIONS: In this cohort of infants receiving PN after intestinal surgery, compromised anthropometrics, decreased FM, and adequate FFM were observed during the first 6 mo. Male and female infants seemed to respond differently to PN when it comes to FM index. Continuing growth monitoring after the age of 6 mo is strongly recommended, and further research should explore the benefit of incorporating ongoing BC monitoring during follow-up.

Longitudinal Development of Health-related Quality of Life and Fatigue in Children on Home Parenteral Nutrition.

OBJECTIVES: The aim of the study was to describe the longitudinal development of health-related quality of life (HRQOL) and fatigue in children with chronic intestinal failure (CIF) on home parenteral nutrition (PN) and compare these children to the general population. METHODS: Prospective, observational study conducted over 7 years in patients suffering from CIF receiving home PN from 2 tertiary hospitals in the Netherlands. Every 6 months, parents (if child <8 years old) or patients (if child ≥8 years old) completed 2 questionnaires: Pediatric Quality of Life Inventory 4.0 (PedsQL) Generic and Fatigue on the KLIK (kwaliteit van leven in kaart [Dutch Acronym for Quality of Life in Clinical Practice]) Patient Reported Outcome Measures portal, which were compared with the general population. Linear mixed models (LMMs) were constructed to investigate the course of HRQOL over time. RESULTS: Thirty-five patients were included (40% girls). At time of last KLIK contact, patients received HPN for a median of 5.3 years (interquartile range [IQR]: 2.9-9.7). In total, 272 questionnaires were completed. PedsQL generic total score for ages 5 to 7 and 8 to 12 years was significantly lower than the general population (P < 0.01 for both age groups) with effect sizes of 0.73 and 0.71, respectively. PedsQL fatigue total score for ages 5 to 7 years was also significantly lower (P = 0.01; effect size 0.70). LMMs for PedsQL Generic and Fatigue total score 2 to 7 and 8 to 18 years showed no significant coefficient for duration of home PN. CONCLUSIONS: Children suffering from CIF receiving home PN ages 5 to 12 years report lower HRQOL scores than the general population. HRQOL and fatigue do not change during long-term treatment with home PN in these children.

The Role of a Nutrition Support Team in the Management of Intestinal Failure Patients.

Parenteral nutrition (PN) is a complex and specialized form of nutrition support that has revolutionized the care for both pediatric and adult patients with acute and chronic intestinal failure (IF). This has led to the development of multidisciplinary teams focused on the management of patients receiving PN: nutrition support teams (NSTs). In this review we aim to discuss the historical aspects of IF management and NST development, and the practice, composition, and effectiveness of multidisciplinary care by NSTs in patients with IF. We also discuss the experience of two IF centers as an example of contemporary NSTs at work. An NST usually consists of at least a physician, nurse, dietitian, and pharmacist. Multidisciplinary care by an NST leads to fewer complications including infection and electrolyte disturbances, and better survival for patients receiving short- and long-term PN. Furthermore, it leads to a decrease in inappropriate prescriptions of short-term PN leading to significant cost reduction. Complex care for patients receiving PN necessitates close collaboration between team members and NSTs from other centers to optimize safety and effectiveness of PN use.