Prospective evaluation and follow-up of nutritional status of children hospitalized in secondary-care level hospitals: a multicentre study.

Although disease-associated undernutrition is still an important problem in hospitalized children that is often underrecognized, follow-up studies evaluating post-discharge nutritional status of children with undernutrition are lacking. The aim of this multicentre prospective observational cohort study was to assess the rate of acute undernutrition (AU) and/or having a high nutritional risk (HR) in children on admission to seven secondary-care level Dutch hospitals and to evaluate the nutritional course of AU/HR group during admission and post-discharge. STRONGkids was used to indicate HR, and AU was based on anthropometric data (z-score < -2 for weight-for-age (WFA; <1 year) or weight-for-height (WFH; ≥1 year)). In total, 1985 patients were screened for AU/HR over a 12-month period. On admission, AU was present in 9.9% of screened children and 6.2% were classified as HR; 266 (13.4%) children comprised the AU/HR group (median age 2.4 years, median length of stay 3 days). In this group, further nutritional assessment by a dietitian during hospitalization occurred in 44% of children, whereas 38% received nutritional support. At follow-up 4-8 weeks post-discharge, 101 out of orginal 266 children in the AU/HR group (38%) had available paired anthropometric measurements to re-assess nutrition status. Significant improvement of WFA/WFH compared to admission (-2.48 vs. -1.51 SD; p < 0.001) and significant decline in AU rate from admission to outpatient follow-up (69.3% vs. 35.6%; p < 0.001) were shown. In conclusion, post-discharge nutritional status of children with undernutrition and/or high nutritional risk on admission to secondary-care level pediatric wards showed significant improvement, but about one-third remained undernourished. Findings warrant the need for a tailored post-discharge nutritional follow-up.

Association between fat-free mass and survival in critically ill patients with COVID-19: A prospective cohort study.

BACKGROUND: Most critically ill patients with COVID-19 experience malnutrition and weight loss associated with negative clinical outcomes. Our primary aim was to assess body composition during acute and late phase of illness in these patients in relation to clinical outcome and secondary to tailored nutrition support. METHODS: This prospective cohort study included adult critically ill patients with COVID-19. Body composition (fat-free mass [FFM] [exposure of interest], fat mass [FM], skeletal muscle mass [SMM], and phase angle [PA]) was determined with multifrequency bioelectrical impedance analyses in the acute and late phase. Nutrition support data were collected simultaneously. Clinical outcome was defined as intensive care unit (ICU) survival (primary outcome) and 30-90 days thereafter, duration of mechanical ventilation, and length of ICU stay and length of hospital stay (LOS). Nonparametric tests and regression analyses were performed. RESULTS: We included 70 patients (73% male, median age 60 years). Upon admission, median BMI was 30 kg/m2 , 54% had obesity (BMI > 30 kg/m2 ). Median weight change during ICU stay was -3 kg: +3 kg FM and -6 kg FFM (-4 kg SMM). Body composition changed significantly (P < 0.001). Regarding clinical outcome, only low PA was associated with prolonged LOS (odds ratio = 0.83, 95% CI = 0.72-0.96; P = 0.015). Patients with optimal protein intake (>80%) during acute phase maintained significantly more FFM (2.7 kg, P = 0.047) in the late phase compared with patients who received <80%. CONCLUSION: FFM decreased significantly during acute and late phase of illness, but we observed no association with ICU survival. Only low PA was associated with prolonged LOS. FFM wasting likely occurred because of disease severity and immobility.

Effects of correcting metabolic acidosis on muscle mass and functionality in chronic kidney disease: a systematic review and meta-analysis.

Metabolic acidosis unfavourably influences the nutritional status of patients with non-dialysis dependent chronic kidney disease (CKD) including the loss of muscle mass and functionality, but the benefits of correction are uncertain. We investigated the effects of correcting metabolic acidosis on nutritional status in patients with CKD in a systematic review and meta-analysis. A search was conducted in MEDLINE and the Cochrane Library from inception to June 2023. Study selection, bias assessment, and data extraction were independently performed by two reviewers. The Cochrane risk of bias tool was used to assess the quality of individual studies. We applied random effects meta-analysis to obtain pooled standardized mean difference (SMD) and 95% confidence intervals (CIs). We retrieved data from 12 intervention studies including 1995 patients, with a mean age of 63.7 ± 11.7 years, a mean estimated glomerular filtration rate of 29.8 ± 8.8 mL/min per 1.73 m2 , and 58% were male. Eleven studies performed an intervention with oral sodium bicarbonate compared with either placebo or with standard care and one study compared veverimer, an oral HCl-binding polymer, with placebo. The mean change in serum bicarbonate was +3.6 mEq/L in the intervention group and +0.4 mEq/L in the control group. Correcting metabolic acidosis significantly improved muscle mass assessed by mid-arm muscle circumference (SMD 0.35 [95% CI 0.16 to 0.54], P < 0.001) and functionality assessed with the sit-to-stand test (SMD -0.31 [95% CI -0.52 to 0.11], P = 0.003). We found no statistically significant effects on dietary protein intake, handgrip strength, serum albumin and prealbumin concentrations, and blood urea nitrogen. Correcting metabolic acidosis in patients with CKD improves muscle mass and physical function. Correction of metabolic acidosis should be considered as part of the nutritional care for patients with CKD.

Nutritional status of patients with COVID-19 1-y post-ICU stay: A prospective observational study.

OBJECTIVES: Patients discharged from the intensive care unit (ICU) often experience physical complaints and poor nutritional intake, which negatively affect their nutritional status (NS). The aim of this study was to describe the NS of patients with COVID-19 1-y post-ICU stay. METHODS: This was an observational study of adult patients with COVID-19 1-y post-ICU stay. NS assessment (nutrient balance, body composition, and physical status) was performed. We examined nutritional intake and nutrition-related complaints. Nutritional requirements were determined with indirect calorimetry and body composition with bioelectrical impedance. Fat-free mass index (FFMI) and fat mass index (FMI) were calculated. Physical status was determined using handgrip strength, the 6-min walk test, and the 1-min sit-to-stand test. Descriptive statistics and paired sample t tests were used for analysis. RESULTS: We included 48 patients (73% men; median age 60 y [IQR 52;65]). Median weight loss during the ICU stay was 13%. One-y post-ICU stay, 12% of weight was regained. Median body mass index was 26 kg/m2 and 23% of the patients were obese (body mass index >30 kg/m2 and high FMI). Of the patients, 50% had high FMI and 19% had low FFMI. Median reported nutritional intake was 90% of measured resting energy expenditure. Nutrition-related complaints were seen in 16%. Percentages of normal values reached in physical tests were 92% of handgrip strength, 95% of 6-min walking distance, and 79% of 1-min sit-to-stand test. CONCLUSIONS: Despite almost fully regained weight and good physical recovery in adult patients 1-y post-ICU stay, NS remained impaired because of elevated FMI, even though reported nutritional intake was below the estimated requirements.

Clinical applications of body composition and functional status tools for nutrition assessment of hospitalized adults: A systematic review.

BACKGROUND: No global consensus exists on diagnostic criteria for malnutrition. Muscular deficits and functional impairments are major components of available malnutrition diagnostic frameworks because these facets of nutrition status significantly impact outcomes. The purpose of this review is to explore which body composition assessment (BCA) and functional status assessment (FSA) tools are being used for nutrition assessment (NA) and monitoring the response to nutrition interventions (RNIs) in adult inpatients. METHODS: A literature search of Embase, Medline (Ovid), Web of Science, and Cochrane Central was performed to identify studies that used BCA and/or FSA tools for NA (along with an accepted NA diagnostic framework) and/or for monitoring RNI in adult inpatients. RESULTS: The search yielded 3667 articles; 94 were included in the review. The number of studies using BCA and/or FSA tools for NA was 47 and also 47 for monitoring RNI. Seventy-nine percent of studies used bioimpedance for BCA, and 97% that included FSA utilized handgrip strength. When compared against sets of diagnostic criteria, many of the BCA and FSA tools showed promising associations with nutrition status. CONCLUSION: Bioimpedance methods are the most widely used bedside BCA tools, and handgrip strength is the most widely used FSA tool; however, these methods are being used with a variety of protocols, algorithms, and interpretation practices in heterogeneous populations. To create a standardized nutrition status assessment process there is a need for validation studies on bedside methods and the development of globally standardized assessment protocols in clinical inpatient settings.

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.

Comment on Moriconi et al. Very-Low-Calorie Ketogenic Diet as a Safe and Valuable Tool for Long-Term Glycemic Management in Patients with Obesity and Type 2 Diabetes. Nutrients 2021, 13, 758.

With interest, we have read the article of Moriconi et al. [...].

Study Protocol of the Exercise Study: Unraveling Limitations for Physical Activity in Children With Chronic Diseases in Order to Target Them With Tailored Interventions-A Randomized Cross Over Trial.

Introduction: Physical activity is associated with many physiological and psychological health benefits across the lifespan. Children with a chronic disease often have lower levels of daily physical activity, and a decreased exercise capacity compared to healthy peers. In order to learn more about limitations for physical activity, we investigate children with four different chronic diseases: children with a Fontan circulation, children with Broncho Pulmonary Dysplasia (BPD), Pompe disease and inflammatory bowel disease (IBD). Each of these diseases is likely to interfere with physical activity in a different way. Knowing the specific limitations for physical activity would make it possible to target these, and increase physical activity by a personalized intervention. The aim of this study is to first investigate limitations for physical activity in children with various chronic diseases. Secondly, to measure the effects of a tailored exercise intervention, possibly including a personalized dietary advice and/or psychological counseling, on exercise capacity, endurance, quality of life, fatigue, fear for exercise, safety, muscle strength, physical activity levels, energy balance, and body composition. Methods and Analysis: This randomized crossover trial will aim to include 72 children, aged 6-18 years, with one of the following diagnosis: a Fontan circulation, BPD, Pompe disease and IBD. Eligible patients will participate in the 12-week tailored exercise intervention and are either randomized to start with a control period or start with the intervention. The tailored 12-week exercise interventions, possibly including a personalized dietary advice and/or psychological counseling, will be designed based on the found limitations for physical activity in each disease group during baseline measurements by the Rotterdam Exercise Team. Effects of the tailored training interventions will be measured on the following endpoints: exercise capacity (measured by cardiopulmonary exercise test), endurance, physical activity levels, muscle strength, quality of life, fatigue, fear for exercise, disease activity, cardiac function (in children with a Fontan circulation), energy balance, and body composition. Ethics and Dissemination: Conducted according to the Declaration of Helsinki and Good Clinical Practice. Medical-ethical approval was obtained. Trial Registration Number: NL8181, https://www.trialregister.nl/trial/8181.

Effects of Protein and Calorie Restriction on the Metabolism and Toxicity Profile of Irinotecan in Cancer Patients.

Preclinical data suggests that protein and calorie restriction (PCR) might improve treatment tolerability without impairing antitumor efficacy. Therefore, we have studied the influence of PCR on irinotecan pharmacokinetics and toxicity. In this crossover trial, patients with liver metastases of solid tumors were included and randomized to treatment with irinotecan preceded by 5 days of PCR (~ 30% caloric and ~ 70% protein restriction) during the first cycle and a second cycle preceded by a normal diet or vice versa. Pharmacokinetic blood sampling and biopsies of both healthy liver and liver metastases were performed. The primary end point was the relative difference in geometric means for the active metabolite SN-38 concentration in healthy liver analyzed by a linear mixed model. No significant differences were seen in irinotecan (+ 16.8%, P = 0.22) and SN-38 (+ 9.8%, P = 0.48) concentrations between PCR and normal diet in healthy liver, as well as in liver metastases (irinotecan: -38.8%, P = 0.05 and SN-38: -13.8%, P = 0.50). PCR increased irinotecan plasma area under the curve from zero to 24 hours (AUC0-24h ) with 7.1% (P = 0.04) compared with normal diet, whereas the SN-38 plasma AUC0-24h increased with 50.3% (P < 0.001). Grade ≥ 3 toxicity was not increased during PCR vs. normal diet (P = 0.69). No difference was seen in neutropenia grade ≥ 3 (47% vs. 32% P = 0.38), diarrhea grade ≥ 3 (5% vs. 21% P = 0.25), and febrile neutropenia (5% vs. 16% P = 0.50) during PCR vs. normal diet. In conclusion, plasma SN-38 exposure increased dramatically after PCR, whereas toxicity did not change. PCR did not alter the irinotecan and SN-38 exposure in healthy liver and liver metastases. PCR might therefore potentially improve the therapeutic window in patients treated with irinotecan.

Nutritional Feeding Strategies in Pediatric Intestinal Failure.

Intestinal failure is defined as a critical reduction of the gut mass or function, below the minimum needed to absorb nutrients and fluids. The ultimate goal in intestinal failure is to promote bowel adaptation and reach enteral autonomy while a healthy growth and development is maintained. The condition is heterogeneous and complex. Therefore, recommendations for the type and duration of parenteral, enteral, and oral nutrition are variable, with the child's age as an additional key factor. The aim of this review is to provide an overview of nutritional feeding strategies in this heterogeneous population. Different perspectives on nutritional management, nutrition and adaptation, and microbiome and nutrition will be discussed.

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.

Outpatient initiation of the ketogenic diet in children with pharmacoresistant epilepsy: An effectiveness, safety and economic perspective.

BACKGROUND: Children with pharmacoresistant epilepsy usually receive ketogenic diet (KD) as an inpatient, which makes it an expensive treatment. OBJECTIVE: To compare the effectiveness, safety, and costs of outpatient versus inpatient initiated KD. DESIGN: Retrospective observational non-inferiority study. PATIENTS/SETTING: Patients (1-18 years of age) who started KD either inpatient or outpatient. MAIN OUTCOME MEASURES: Effectiveness was defined as ≥50% seizure reduction. Safety was measured by the numbers of emergency visits and complications. Economic impact was analyzed by calculating total costs of treatment. STATISTICAL ANALYSES: Non-inferiority of outpatient initiation was tested using 95% confidence intervals of the differences in effectiveness and safety endpoints between groups with non-inferiority margins of 10%. Nonparametric bootstrap techniques were used to derive a 95% confidence interval for the mean difference in total costs between the groups. RESULTS: Hundred and five patients started KD in the period 2001 to 2017: 43 inpatient and 62 outpatient. At three months, the KD was effective in 61% of outpatients versus 63% of inpatients. The KD was considered safe in 36% of the outpatients, as compared to 29% in the inpatients. Outpatient initiation was shown to be non-inferior to inpatient initiation in terms of safety. Total health care costs of outpatient initiation were € 2901, as compared to € 8195 of inpatient initiation per patient (mean difference € 5294, 95% CI; -€ 7653 to -€ 2935). CONCLUSIONS: Our study suggests that outpatient KD initiation is no worse than inpatient initiation in terms of effectiveness and safety, while carrying lower health care costs.

Ketogenic diet treatment as adjuvant to standard treatment of glioblastoma multiforme: a feasibility and safety study.

BACKGROUND: High-grade glioma cells consume mainly glucose and cannot compensate for glucose restriction. Apoptosis may potentially occur under carbohydrate restriction by a ketogenic diet (KD). We explored the feasibility and safety of KD during standard treatment of chemoradiation in patients with glioblastoma multiforme. METHODS: A full liquid KD induced ketosis within 2 weeks before start of chemoradiation. After 6 weeks, the KD was modified with solid foods and medium-chain-triglyceride emulsions and used for an additional 6 weeks while maintaining ketosis. During the total study period (14 weeks), feasibility, safety, coping (both patient and partner), quality of life (QoL), neurological functioning and impairment were measured. Overall survival was analyzed with actuarial estimates. RESULTS: Eleven patients started the study protocol, nine reached ketosis and six (67%) completed the study. Severe adverse effects did not occur. The majority of coping scores ranged from 3 to 6 on a 10-point scale at all timepoints; QoL, neurological functioning, and impairment did not essentially change over time; overall survival ranged between 9.8 and 19.0 months. CONCLUSION: KD was feasible and safe as an adjuvant to standard chemoradiation treatment of glioblastoma multiforme. A supportive partner and intensive counseling were essential for coping. Future research should identify possible beneficial effects on overall survival. CLINICAL TRIAL REGISTRATION: Netherlands Trial Registry: NTR5167 (registration date 29-01-2015), http://www.trialregister.nl/trialreg/index.asp.

Health-related quality of life, anxiety, depression and distress of mothers and fathers of children on Home parenteral nutrition.

BACKGROUND & AIMS: Parents of children with intestinal failure, dependent on Home Parenteral Nutrition (HPN), may experience psychosocial problems due to the illness and intensive treatment of their child. Literature concerning psychosocial problems is scarce. Therefore, we aimed to investigate Health-Related Quality of Life (HRQOL), levels of anxiety, depression, distress and everyday problems of these mothers and fathers. METHODS: A multicenter study was conducted among 37 mothers and 25 fathers of 37 children on HPN (response-rate 37/49 = 76%, mean age children = 5.1 years, SD = 4.6). Parents completed three questionnaires to measure different outcomes on the KLIK website (www.hetklikt.nu): the TNO-AZL QOL Questionnaire (TAAQOL) to measure HRQOL, the Hospital Anxiety and Depression Scale (HADS) to measure anxiety and depression, and the Distress Thermometer for Parents (DT-P) to measure distress. Scores were compared to Dutch reference mothers and fathers using Mann-Whitney U-tests. RESULTS: No differences were found in HRQOL, measured by the TAAQOL, between HPN parents compared to the reference groups, except for the subscale 'depressive emotions' for mothers (p = .01) and 'daily activities' for fathers (p = .04). HPN mothers reported higher levels of depression compared to reference mothers (p = .001). In addition, HPN mothers and fathers reported higher levels of distress than reference mothers (p = .001) and fathers (p = .03). HPN mothers reported significantly more problems in the practical, emotional, cognitive and parenting domains, fathers in the social, emotional and parenting domains. CONCLUSIONS: On HRQOL, anxiety and depression, HPN parents generally did not show much differences compared to reference parents. However, when asked about parental distress and everyday problems, HPN treatment of their child seems highly stressful for some parents and influences daily functioning. Therefore, structural screening for parental psychosocial problems in clinical practice, e.g. using the DT-P, is necessary in order to improve the well-being of both these parents and their children dependent on HPN.

Ketogenic diet treatment in recurrent diffuse intrinsic pontine glioma in children: A safety and feasibility study.

BACKGROUND: The mean overall survival rate of children with diffuse intrinsic pontine glioma (DIPG) is 9-11 months, with current standard treatment with fractionated radiotherapy and adjuvant chemotherapy. So far, novel therapeutic strategies have not yet resulted in significantly better survival. The main source of energy for glioblastoma cells is glucose. Therefore, metabolic alterations induced by the use of the extremely carbohydrate-restricted ketogenic diet (KD) as adjuvant therapy are subject of interest in cancer research. PROCEDURE: This study explores the safety and feasibility of the KD in children with recurrent DIPG and no remaining treatment options. Safety was defined as the number of adverse effects. Feasibility was defined as the number of patients who were able to use the KD for three months. Coping of patients and parents was measured with questionnaires. RESULTS: Three of 14 children referred to our hospital between 2010 and 2015 were included. Two patients completed the study, and one died before the end of the study. Hospitalizations were needed for placing a nasogastric tube (n = 1) and epileptic seizures (n = 1). Adverse effects related to the diet were mild and transient. Parents were highly motivated during the study. CONCLUSION: Use of KD is safe and feasible, but the effect on survival has to be proven in a larger cohort of children who start the KD earlier after diagnosis, preferably as adjuvant therapy to fractionated radiotherapy.

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.

Congenital Diaphragmatic Hernia and Growth to 12 Years.

OBJECTIVES: Growth problems are reported in patients with congenital diaphragmatic hernia during the first years of life. However, it is unknown if poor growth persists during childhood. We therefore evaluated growth of patients longitudinally until 12 years of age. METHODS: This prospective study included 172 patients (43 treated with extracorporeal membrane oxygenation [ECMO]) born from 1999 to 2014. Z scores of height-for-age (HFA), weight-for-height, and distance-to-target height were calculated at 6 months of age and at 1, 2, 5, 8, and 12 years of age. Data were analyzed by using general linear models. RESULTS: At 1 year of age, the mean weight-for-height z score had declined in ECMO (-1.30, 95% confidence interval: -1.62 to -0.97) and non-ECMO patients (-0.72, 95% confidence interval: -0.91 to -0.54; P < .05). Thereafter in ECMO patients, the mean HFA z score deteriorated between 1 (-0.43, 95% confidence interval: -0.73 to -0.13) and 5 years of age (-1.08, 95% confidence interval: -1.38 to -0.78; P < .01). In non-ECMO patients, the mean HFA z score deteriorated between 2 (-0.35, 95% confidence interval: -0.53 to -0.17) and 5 years of age (-0.56, 95% confidence interval: -0.75 to -0.37; P = .002). At 12 years of age, the mean HFA z score was still less than the norm in both groups: ECMO (-0.67, 95% confidence interval: -1.01 to -0.33) versus non-ECMO (-0.49, 95% confidence interval: -0.77 to -0.20; P < .01). Adjusting for target height improved the mean height z scores but did not bring them to normal range. CONCLUSIONS: Poor linear growth persisted at 12 years of age. The pattern of early deterioration of weight gain followed by a decline in linear growth is suggestive of inadequate nutrition during infancy. Therefore, nutritional assessment and intervention should be started early and should be continued during childhood.

Intestinal rehabilitation for children with intestinal failure is cost-effective: a simulation study.

BACKGROUND: Children with intestinal failure (IF) depend on parenteral nutrition (PN). The goal in the treatment of IF is to wean children off PN through intestinal rehabilitation (IR). Although the healthcare burden of IF is enormous, to our knowledge there has been no previous cost-effectiveness analysis in pediatric IF including IR. OBJECTIVE: We sought to determine the cost-effectiveness of IR in terms of costs and life-years. DESIGN: We simulated the treatment of IF in children in a discrete-event model. Data for this model were derived from patient records, the Dutch Registry of Intestinal Failure and Transplantation, the Intestinal Transplant Registry, and the literature. The time horizon of the model was 40 y. Simulated patients were enrolled at a rate of 40 patients/mo for 10 y. Actual costs were calculated for hospital admissions, surgical interventions, endoscopies, PN, and immunosuppressive medication. We evaluated the cost-effectiveness of IR by comparing 1 scenario with IR with 1 scenario without IR. In the scenario with IR, a proportion of patients who represented those with the ability to wean off PN were assigned to IR. In the scenario without IR, all patients progressed to home PN (HPN). In both scenarios, a proportion of patients receiving HPN were eventually eligible for an intestinal transplantation. RESULTS: IR prolonged survival; the mean number of life-years per patient was 19.4 in the scenario with IR compared with 18.2 in the scenario without IR. Average total costs per patient were €819,292 in the scenario with IR compared with €1,176,830 in the scenario without IR (equivalent to 1,129,230 US$ and 1,622,025 US$, respectively, in January 2014); costs mainly included hospital admissions and PN. CONCLUSIONS: On the basis of our simulations, we concluded that IR improved the survival of children with IF and was associated with cost savings. Therefore, we consider IR to be a cost-effective treatment for children with IF.