Measured resting energy expenditure by indirect calorimetry and energy intake in long-term growth hormone treated children with PWS.

INTRODUCTION: Severe obesity can develop in children with PWS when food intake is not controlled. Maintenance of body weight requires an energy balance, of which energy intake and energy expenditure are important components. Previous studies described a decreased resting energy expenditure (REE) in growth hormone (GH)-untreated children with PWS. In short-term studies, no difference in REE was found between GH-treated and untreated children with PWS. However, there are limited data on REE in children with PWS who were GH-treated for a long period. METHODS: This study describes measured REE (mREE), energy intake and body composition during long-term GH-treatment in children with PWS. Patients were treated with 1.0 mg GH/m2/day (~0.035mg/kg/day). REE was determined by indirect calorimetry; dietary energy intake was calculated using a 3-day dietary record. Body composition by Dual energy X-ray absorptiometry (DXA) scans. RESULTS: We included 52 GH-treated children with PWS with mean (SD) age of 8.53 (4.35) years and median (IQR) GH-treatment duration of 7 (4-11) years. mREE increased with age, but was not associated with GH-treatment duration. A higher LBM was associated with higher mREE. Mean energy intake was significantly lower compared to daily energy requirements (DER) for age- and sex-matched healthy children (p<0.001), ranging from 23-36% less intake in children aged 3.5-12 years to 49% less intake in children aged 12-18 years. Fifty percent of children had a normal REE, 17.3 % a decreased REE and 32.7% an elevated REE, according to predicted REE based on measured REE in a large group of healthy children. CONCLUSION: In children with PWS, mREE increases with age. GH-treatment duration is not associated, whereas LBM is an important determinant of mREE. Children with PWS have a low to very low energy intake compared to DER for age- and sex-matched children, with a declining intake when becoming older.

[Paediatricians report an increased demand for diagnostic tests for reassurance]. / Kinderartsen zien meer vraag naar diagnostiek ter geruststelling.

OBJECTIVE: Test decisions depend on the context in which health care is delivered. We interviewed paediatricians about perceived societal developments and their influence on diagnostic testing. DESIGN: Qualitative interview study. METHODS: Semi-structured in-depth interviews with 20 practicing Dutch paediatricians. RESULTS: Paediatricians associated societal developments, such as decreased risk acceptance, with perceived pressure from parents to perform tests. They were motivated to restrict unnecessary tests to avoid harming the child. CONCLUSION: Besides motivation and effort of health care providers, appropriate testing requires system-level actions, such as counteracting a culture of blame and considering societal interests in guideline recommendations.

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.

Cognitive function during 3 years of growth hormone in previously growth hormone-treated young adults with Prader-Willi syndrome.

CONTEXT: Most patients with Prader-Willi syndrome (PWS) have mild to moderate cognitive impairment. Growth hormone (GH) treatment has positive short- and long-term effects on cognition in children with PWS. Few studies, however, have investigated the effects of GH on cognitive functioning in adults with PWS. OBJECTIVE: To investigate the effects of 3 years of GH treatment on cognitive functioning and behavior in young adults with PWS who were treated with GH during childhood. DESIGN: Open-label, prospective study. SETTING: Dutch PWS Reference Center. METHODS: Patients were treated with 0.33 mg GH/m²/day (∼0.012 mg/kg/day; 33% of childhood dose). Cognitive functioning was measured by Wechsler Adult Intelligence (WAIS) tests. Behavior was studied by a developmental behavior checklist-parents/caregivers (DBC-P). RESULTS: Forty-six young adults with PWS with a median age of 19 (IQR 17-21) years were investigated. Estimated mean (95% CI) total, verbal, and performance IQ remained stable during 3 years of GH-treatment. Total IQ being 66 (63-69) at the start and 67 (64-71) after 3 years (P = .30); Verbal IQ being 65 (62-68) and 66 (62-70), respectively (P = .31) and performance IQ being 67 (63-70) and 67 (63-72) resp. (P = .42). Estimated mean Total DBC score did not significantly change during 3 years of GH-treatment, being 36.3 at start and 36.5 after 3 years (P = .94) (P50). CONCLUSIONS: Three years of GH-treatment in young adults with PWS with 33% of the pediatric dose, maintains total, verbal, and performance IQ. The emotional and behavioral disturbances remained stable and were similar compared to peers with other intellectual disabilities.

Diagnostic testing in children: A qualitative study of pediatricians' considerations.

AIMS AND OBJECTIVES: Studies in adult medicine have shown that physicians base testing decisions on the patient's clinical condition but also consider other factors, including local practice or patient expectations. In pediatrics, physicians and parents jointly decide on behalf of a (young) child. This might demand more explicit and more complex deliberations, with sometimes conflicting interests. We explored pediatricians' considerations in diagnostic test ordering and the factors that influence their deliberation. METHOD: We performed in-depth, semistructured interviews with a purposively selected heterogeneous sample of 20 Dutch pediatricians. We analyzed transcribed interviews inductively using a constant comparative approach, and clustered data across interviews to derive common themes. RESULTS: Pediatricians perceived test-related burden in children higher compared with adults, and reported that avoiding an unjustified burden causes them to be more restrictive and deliberate in test ordering. They felt conflicted when parents desired testing or when guidelines recommended diagnostic tests pediatricians perceived as unnecessary. When parents demanded testing, they would explore parental concern, educate parents about harms and alternative explanations of symptoms, and advocate watchful waiting. Yet they reported sometimes performing tests to appease parents or to comply with guidelines, because of feared personal consequences in the case of adverse outcomes. CONCLUSION: We obtained an overview of the considerations that are weighed in pediatric test decisions. The comparatively strong focus on prevention of harm motivates pediatricians to critically appraise the added value of testing and drivers of low-value testing. Pediatricians' relatively restrictive approach to testing could provide an example for other disciplines. Improved guidelines and physician and patient education could help to withstand the perceived pressure to test.

Interleukin-23 receptor signaling impairs the stability and function of colonic regulatory T cells.

The cytokine interleukin-23 (IL-23) is involved in the pathogenesis of inflammatory and autoimmune conditions including inflammatory bowel disease (IBD). IL23R is enriched in intestinal Tregs, yet whether IL-23 modulates intestinal Tregs remains unknown. Here, investigating IL-23R signaling in Tregs specifically, we show that colonic Tregs highly express Il23r compared with Tregs from other compartments and their frequency is reduced upon IL-23 administration and impairs Treg suppressive function. Similarly, colonic Treg frequency is increased in mice lacking Il23r specifically in Tregs and exhibits a competitive advantage over IL-23R-sufficient Tregs during inflammation. Finally, IL-23 antagonizes liver X receptor pathway, cellular cholesterol transporter Abca1, and increases Treg apoptosis. Our results show that IL-23R signaling regulates intestinal Tregs by increasing cell turnover, antagonizing suppression, and decreasing cholesterol efflux. These results suggest that IL-23 negatively regulates Tregs in the intestine with potential implications for promoting chronic inflammation in patients with IBD.

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.

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.

Gut microbiota and its diet-related activity in children with intestinal failure receiving long-term parenteral nutrition.

BACKGROUND: This study characterized gut microbiota and its diet-related activity in children with intestinal failure (IF) receiving parenteral nutrition (PN) compared with those of healthy controls (HC) and in relation to disease characteristics. METHODS: The fecal microbiota and short-chain fatty acids (SCFAs) were measured in 15 IF patients (n = 68) and 25 HC (n = 25). RESULTS: Patients with IF had a lower bacterial load (P = .003), diversity (P < .001), evenness (P < .001) and richness (P = 0.006) than HC. Patients with surgical IF had lower diversity (P < .039) than those with functional IF. Propionic acid and butyric acid (p < .001) were lower and d-lactate and l-lactate were higher (p < 0.001) in IF patients than in HC. The energy supplied by PN (%PN) was negatively associated with microbiota diversity and SCFA profile. IF patients had more Escherichia-Shigella (P = .006), Cronobacter (P = .001), and Staphylococcus (Operational Taxonomic Unit 14, P < .001) and less Faecalibacterium (P < 0.001) and Ruminococcus 1 and 2 (P < .001). Duration of PN (P = .005), %PN (P = .005), and fiber intake (P = .011) were predictive of microbiota structure. Higher intake of enteral nutrition was associated with microbiota structure and function closer to those of HC. CONCLUSIONS: Microbiota composition and its diet-related function are altered in IF, with depletion of beneficial SCFAs and species and supraphysiological increase of potentially harmful pathobionts. The influence of this compositional and functional microbial dysbiosis on patients' outcomes and management warrants further exploration.

Early diagnosis of coeliac disease in the Preventive Youth Health Care Centres in the Netherlands: study protocol of a case finding study (GLUTENSCREEN).

Introduction: Coeliac disease (CD) occurs in 1% of the population, develops early in life and is severely underdiagnosed. Undiagnosed and untreated disease is associated with short-term and long-term complications. The current healthcare approach is unable to solve the underdiagnosis of CD and timely diagnosis and treatment is only achieved by active case finding. Aim: to perform a case finding project to detect CD children who visit the Youth Health Care Centres (YHCCs) in a well-described region in the Netherlands to evaluate whether it is feasible, cost-effective and well accepted by the population. Methods/analysis: Prospective intervention cohort study. Parents of all children aged 12 months and 4 years attending the YHCCs for a regular visit are asked whether their child has one or more CD-related symptoms from a standardised list. If so, they will be invited to participate in the case finding study. After informed consent, a point of care test (POCT) to assess CD-specific antibodies against tissue transglutaminase (TG2A) is performed onsite the YHCCs. If the POCT is positive, CD is highly suspected and the child will be referred to hospital for definitive diagnosis according to the Guideline Coeliac Disease of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition guideline. Main outcomes: Incidence rate of new CD diagnoses in the study region in comparison to the one in the same age diagnosed by standard of care in the rest of the Netherlands.Feasibility and cost-effectiveness of active CD case finding at the YHCCs. All costs of active case finding, diagnostics and treatment of CD and the potential short-term and long-term consequences of the disease will be calculated for the setting with and without case finding.Ethical acceptability: by questionnaires on parental and healthcare professionals' satisfaction.A statistical analysis plan was prepared and is published on the GLUTENSCREEN website (Statistical-Analysis-Plan-11-5-2021_def.pdf (glutenscreen.nl) and added as annex 1). Ethics and dissemination: The Medical Ethics Committee Leiden approved this study. If we prove that case finding at the YHCC is feasible, cost-effective and well accepted by the population, implementation is recommended. Trial registration number: NL63291.058.17.

Intestinal Regulatory T Cells as Specialized Tissue-Restricted Immune Cells in Intestinal Immune Homeostasis and Disease.

FOXP3+ regulatory T cells (Treg cells) are a specialized population of CD4+ T cells that restrict immune activation and are essential to prevent systemic autoimmunity. In the intestine, the major function of Treg cells is to regulate inflammation as shown by a wide array of mechanistic studies in mice. While Treg cells originating from the thymus can home to the intestine, the majority of Treg cells residing in the intestine are induced from FOXP3neg conventional CD4+ T cells to elicit tolerogenic responses to microbiota and food antigens. This process largely takes place in the gut draining lymph nodes via interaction with antigen-presenting cells that convert circulating naïve T cells into Treg cells. Notably, dysregulation of Treg cells leads to a number of chronic inflammatory disorders, including inflammatory bowel disease. Thus, understanding intestinal Treg cell biology in settings of inflammation and homeostasis has the potential to improve therapeutic options for patients with inflammatory bowel disease. Here, the induction, maintenance, trafficking, and function of intestinal Treg cells is reviewed in the context of intestinal inflammation and inflammatory bowel disease. In this review we propose intestinal Treg cells do not compose fixed Treg cell subsets, but rather (like T helper cells), are plastic and can adopt different programs depending on microenvironmental cues.

Pharmacological and Parenteral Nutrition-Based Interventions in Microvillus Inclusion Disease.

Microvillus inclusion disease (MVID) is a rare inherited and invariably fatal enteropathy, characterized by severe intractable secretory diarrhea and nutrient malabsorption. No cure exists, and patients typically die during infancy because of treatment-related complications. The need for alternative treatment strategies is evident. Several pharmacological interventions with variable successes have been tried and reported for individual patients as part of their clinical care. Unfortunately, these interventions and their outcomes have remained hidden in case reports and have not been reviewed. Further, recent advances regarding MVID pathogenesis have shed new light on the outcomes of these pharmacological interventions and offer suggestions for future clinical research and trials. Hence, an inventory of reported pharmacological interventions in MVID, their rationales and outcomes, and a discussion of these in the light of current knowledge is opportune. Together with a discussion on MVID-specific pharmacokinetic, -dynamic, and -genetic concerns that pose unique challenges regarding pharmacological strategies, we envision that this paper will aid researchers and clinicians in their efforts to develop pharmacological interventions to combat this devastating disease.

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.

Body Composition Using Air Displacement Plethysmography in Children With Intestinal Failure Receiving Long-Term Home Parenteral Nutrition.

BACKGROUND: Children with intestinal failure (IF) are at risk of growth failure, but little information about body composition is available. Our aim was to assess body composition using air displacement plethysmography (ADP) and relate it to clinical and growth parameters. METHODS: In this prospective descriptive observational 2-center cohort study, children aged 2-18 years receiving home parenteral nutrition (PN) for ≥6 months underwent ADP measurement. Fat mass index (FMI) and fat-free mass index (FFMI) standard deviation scores (SDSs) were calculated to normalize for small body size. RESULTS: Twenty-one out of 22 children, median age 7.4 years, underwent successful ADP measurement after a median PN duration of 5.5 years. They were significantly lighter (median weight for age SDS -0.71, P = 0.004) and shorter (median height for age SDS -1.55, P < 0.001) than the normal population mean; 52% were growing below target height range. They had low FFMI (median SDS -1.53, P < 0.001) and high FMI (median SDS 0.80, P = 0.002). Weight for height and body mass index (BMI) were significantly associated with FFMI and BMI with FMI, but children with the same weight and height showed different body composition. In 13 patients with 1-year follow-up, growth and body composition did not change significantly. CONCLUSION: Children with IF receiving long-term PN show lower FFM and higher FM than healthy children. Additionally, children with similar routine growth parameters showed different body composition. Further studies should evaluate the effect of a patient-tailored approach including physical activity and nutrition advice based on body composition.

Assessment of the Clinical Benefit of Imaging in Children With Unilateral Sensorineural Hearing Loss: A Systematic Review and Meta-analysis.

IMPORTANCE: Imaging used to determine the cause of unilateral sensorineural hearing loss (USNHL) in children is often justified by the high likelihood of detecting abnormalities, which implies that these abnormalities are associated with hearing loss and that imaging has a positive contribution to patient outcome or well-being by providing information on the prognosis, hereditary factors, or cause of hearing loss. OBJECTIVES: To evaluate the diagnostic yield of computed tomography (CT) and magnetic resonance imaging (MRI) in children with isolated unexplained USNHL and investigate the clinical relevance of these findings. EVIDENCE REVIEW: Cochrane Library, Embase, PubMed, and Web of Science databases were searched for articles published from 1978 to 2017 on studies of children with USNHL who underwent CT and/or MRI of the temporal bone. Two authors (F.G.R. and E.N.B.P.) independently extracted information on population characteristics, imaging modality, and the prevalence of abnormalities and assessed the studies for risk of bias. Eligibility criteria included studies with 20 or more patients with USNHL who had CT and/or MRI scans, a population younger than 18 years, and those published in English. MAIN OUTCOMES AND MEASURES: The pooled prevalence with 95% CI of inner ear abnormalities grouped according to finding and imaging modality. FINDINGS: Of 1562 studies, 18 were included with a total of 1504 participants included in the analysis. Fifteen studies were consecutive case studies and 3 were retrospective cohort studies. The pooled diagnostic yield for pathophysiologic relevant findings in patients with unexplained USNHL was 37% for CT (95% CI, 25%-48%) and 35% for MRI (95% CI, 22%-49%). Cochleovestibular abnormalities were found with a pooled frequency of 19% for CT (95% CI, 14%-25%) and 16% for MRI (95% CI, 7%-25%). Cochlear nerve deficiency and associated cochlear aperture stenosis had a pooled frequency of 16% for MRI (95% CI, 3%-29%) and 44% for CT (95% CI, 36%-53%), respectively. Enlarged vestibular aqueduct (EVA) was detected with a pooled frequency of 7% for CT and 12% for MRI in children with USNHL. CONCLUSIONS AND RELEVANCE: Imaging provided insight into the cause of hearing loss in a pooled frequency of about 35% to 37% in children with isolated unexplained USNHL. However, none of these findings had therapeutic consequences, and imaging provided information on prognosis and hereditary factors only in a small proportion of children, namely those with EVA. Thus, there is currently no convincing evidence supporting a strong recommendation for imaging in children who present with USNHL. The advantages of imaging should be carefully balanced against the drawbacks during shared decision making.

The Gut Microbiome in Patients with Intestinal Failure: Current Evidence and Implications for Clinical Practice.

Intestinal failure (IF) is the reduction of gut function or mass below a minimum needed to absorb nutrients and fluids, such that patients are dependent on parenteral nutrition (PN). Patients with IF have an altered gut microbiome. Our aim was to review and evaluate the current evidence on gut microbiome and its metabolic activity, as well as its association with disease characteristics in adults and children with IF. We performed a PubMed literature search for articles published after 2000 using the following terms: intestinal, microbiome, microbiota, short-chain fatty acids, short bowel syndrome, and PN. Literature search was restricted to human studies only. The gut microbiome diversity is remarkably reduced, and community structure is altered with a noticeable overabundance of Proteobacteria, especially the Enterobacteriaceae family. A substantial increase in Lactobacillus level is often reported in patients with IF. Gut microbiome characteristics have been associated with poor growth, liver disease, D-lactic acidosis, and duration of intestinal adaptation. Differences in microbiome characteristics have been found between patients receiving PN and those whose guts have adapted and have been weaned off PN. Future research with prospective sample collection should explore the value of the gut microbiome as a biomarker to guide clinical practice and as a modifiable therapeutic target to optimize outcomes of patients with IF.

Longitudinal Variation of Amino Acid Levels in Human Milk and Their Associations with Infant Gender.

It is discussed that specific amino acids (AAs) have functional roles in early life. Understanding the AA composition in human milk (HM) during lactation assists in specifying these roles. To this end we assessed the levels of free AAs (FAAs), total AAs (free and bound, TAAs) and protein levels in HM in the first 6 months of lactation, and evaluated possible associations with infant gender. HM samples of 25 healthy Dutch mothers participating in the PreventCD study were collected monthly during the first 6 months of lactation. Of the participating mothers, 12 gave birth to a boy and 13 gave birth to a girl. Analyses of the HM samples revealed that levels of free glutamate, glutamine, aspartate, glycine, and serine significantly increased during months 1⁻3 of lactation, both in absolute sense and relative to TAA levels. Evaluation of gender differences by mixed model analyses revealed an association between female infant gender and higher protein content (p = 0.0465) and TAA content (p = 0.0362) in HM during the first 3 months of lactation. Furthermore, there was a tendency for an association of male infant gender with higher levels of free glutamine (p = 0.0948) in HM during the first 3 months of lactation. These results show that FAA, TAA and protein levels in HM display a time-specific occurrence during lactation. Moreover, although confirmation is necessary in view of the small sample size, this study indicates that the AA composition in HM shows differential effects of the infant's sex.

Growth, Body Composition, and Micronutrient Abnormalities During and After Weaning Off Home Parenteral Nutrition.

OBJECTIVES: The aim of the study is to assess growth, body composition, and micronutrient abnormalities in children with intestinal failure (IF) over time, both during and after weaning off parenteral nutrition (PN). METHODS: Retrospective study in children on home PN between 2001 and 2015. Weight-for-age (WFA) and height-for-age (HFA) SD scores (SDS) were calculated, as well as fat mass (FM) and fat-free mass (FFM) SDS obtained by dual energy x-ray absorptiometry. The course of growth parameters and body composition was analyzed with linear-mixed models. All micronutrient measurements during the study period were obtained. RESULTS: Fifty-two patients were included with a median follow-up of 3.4 years. Seventy-one percent weaned off after a median PN duration of 0.9 years. One year after the start of PN, 28 patients were still PN-dependent with median WFA-SDS of -0.66 and median HFA-SDS of -0.96, both significantly lower than zero. Catch-up growth was achieved during PN, but HFA-SDS decreased after weaning (P = 0.0001). At a median age of 6.2 years, median %FM SDS was 0.30 and FFM SDS was -1.21, the latter significantly lower than zero. Frequent micronutrient abnormalities during PN were vitamin A (90%), zinc (87%), and iron (76%) and after weaning vitamin A (94%), E (61%), and 25-OH vitamin D (59%). CONCLUSIONS: Children with IF demonstrate abnormal growth and body composition and frequent micronutrient abnormalities. Longitudinal evaluation showed that catch-up growth occurs during PN, but height SDS decreases after weaning. This underlines the need for close monitoring, also after reaching enteral autonomy.

Bone health of children with intestinal failure measured by dual energy X-ray absorptiometry and digital X-ray radiogrammetry.

BACKGROUND & AIMS: Children with intestinal failure (IF) receiving long-term parenteral nutrition (PN) are at risk of developing low bone mineral density (BMD). Next to the dual energy X-ray absorptiometry (DXA) method, digital X-ray radiogrammetry (DXR) using the BoneXpert software has become available to obtain the Bone Health Index (BHI) in hand radiographs. In this study we 1) evaluated the prevalence of low BMD in children with IF using DXA and DXR, 2) compared DXA and DXR results, and 3) aimed to identify factors associated with low BMD. METHODS: A retrospective study was performed including all children with IF between 2000 and 2015 who underwent a DXA measurement and/or a hand radiograph. Z-scores of BMD total body (BMD TB) and lumbar spine (BMD LS), bone mineral apparent density (BMAD) and bone health index (BHI) were collected. A low BMD and low BHI were defined as a Z-score ≤ -2. DXA and DXR results were compared for cases in which a DXA and hand radiograph were performed within a 6 months' interval. RESULTS: Forty-six children were included. Overall, 24.3% of the children had a low BMD at the first DXA at a median age of 6 years; correction for growth failure (n = 6) reduced this to 16.2%. Fifty percent had a low BHI at the first hand radiograph. Median DXA and BHI Z-scores were significantly lower than reference scores. Age, duration of PN and surgical IF were related to lower Z-scores at the first DXA. Paired DXA and DXR results (n = 18) were compared, resulting in a Cohen's kappa of 0.746 ('substantial') for BMD TB. Spearman's correlation coefficient for BHI and BMD TB Z-scores was 0.856 (p < 0.001). Hand radiography had a sensitivity of 90% and specificity of 86% (BMD TB). CONCLUSIONS: Up to 50% of the children had a low BMD. Children with IF have a significantly poorer bone health than the reference population, also after weaning off PN. Bone health assessment by DXA and DXR showed good agreement, especially for Z-scores ≤ -2. DXR assessment using BoneXpert software seems to be feasible for monitoring of bone health in children with IF.