Integrated gut metabolome and microbiome fingerprinting reveals that dysbiosis precedes allergic inflammation in IgE-mediated pediatric cow's milk allergy.

BACKGROUND: IgE-mediated cow's milk allergy (IgE-CMA) is one of the first allergies to arise in early childhood and may result from exposure to various milk allergens, of which ß-lactoglobulin (BLG) and casein are the most important. Understanding the underlying mechanisms behind IgE-CMA is imperative for the discovery of novel biomarkers and the design of innovative treatment and prevention strategies. METHODS: We report a longitudinal in vivo murine model, in which two mice strains (BALB/c and C57Bl/6) were sensitized to BLG using either cholera toxin or an oil emulsion (n = 6 per group). After sensitization, mice were challenged orally, their clinical signs monitored, antibody (IgE and IgG1) and cytokine levels (IL-4 and IFN-γ) measured, and fecal samples subjected to metabolomics. The results of the murine models were further extrapolated to fecal microbiome-metabolome data from our population of IgE-CMA (n = 22) and healthy (n = 23) children (Trial: NCT04249973), on which polar metabolomics, lipidomics and 16S rRNA metasequencing were performed. In vitro gastrointestinal digestions and multi-omics corroborated the microbial origin of proposed metabolic changes. RESULTS: During mice sensitization, we observed multiple microbially derived metabolic alterations, most importantly bile acid, energy and tryptophan metabolites, that preceded allergic inflammation. We confirmed microbial dysbiosis, and its associated effect on metabolic alterations in our patient cohort, through in vitro digestions and multi-omics, which was accompanied by metabolic signatures of low-grade inflammation. CONCLUSION: Our results indicate that gut dysbiosis precedes allergic inflammation and nurtures a chronic low-grade inflammation in children on elimination diets, opening important new opportunities for future prevention and treatment strategies.

Development of an integrated competency framework for postgraduate paediatric training: a Delphi study.

Competency-based education (CBE) has transformed medical training during the last decades. In Flanders (Belgium), multiple competency frameworks are being used concurrently guiding paediatric postgraduate CBE. This study aimed to merge these frameworks into an integrated competency framework for postgraduate paediatric training. In a first phase, these frameworks were scrutinized and merged into one using the Canadian Medical Education Directives for Specialists (CanMEDS) framework as a comprehensive basis. Thereafter, the resulting unified competency framework was validated using a Delphi study with three consecutive rounds. All competencies (n = 95) were scored as relevant in the first round, and twelve competencies were adjusted in the second round. After the third round, all competencies were validated for inclusion. Nevertheless, differences in the setting in which a paediatrician may work make it difficult to apply a general framework, as not all competencies are equally relevant, applicable, or suitable for evaluation in every clinical setting. These challenges call for a clear description of the competencies to guide curriculum planning, and to provide a fitting workplace context and learning opportunities.Conclusion: A competency framework for paediatric post-graduate training was developed by combining three existing frameworks, and was validated through a Delphi study. This competency framework can be used in setting the goals for workplace learning during paediatric training. What is Known: •Benefits of competency-based education and its underlying competency frameworks have been described in the literature. •A single and comprehensive competency framework can facilitate training, assessment, and certification. What is New: •Three existing frameworks were merged into one integrated framework for paediatric postgraduate education, which was then adjusted and approved by an expert panel. •Differences in the working environment might explain how relevant a competency is perceived.

Two cases of DCDC2-related neonatal sclerosing cholangitis with developmental delay and literature review.

Ciliopathies are a group of clinical and molecular heterogeneous conditions with pleiotropic manifestations affecting the central nervous system, renal, liver, skeletal, and ocular systems. Biallelic pathogenic variants in DCDC2 cause a ciliopathy primarily presenting with neonatal sclerosing cholangitis (NSC). Pathogenic variants in DCDC2 have further been reported in the context of nephronophthisis and non-syndromic recessive deafness. Polymorphisms in DCDC2 have also been associated with dyslexia and DCDC2 has a role in neuronal development. We report on two unrelated patients with DCDC2-related NSC with additional central nervous system impairment manifesting as microcephaly, global developmental delay, and axial hypotonia. Histological findings of our patients can mimic biliary atresia or congenital hepatic fibrosis. We further show that transmission electron microscopy in patients with NSC does not always show absence of primary cilia. Hence patients with DCDC2 pathogenic variants should also undergo an evaluation of neuromotor development. Review of all reported patients further reveals a risk for supra-aortic arterial aneurysms.

Autoantibodies and Donor-specific Antibodies are Associated With Graft Dysfunction in Pediatric Liver Transplantation.

OBJECTIVES: Autoantibodies (AAb) and donor-specific HLA antibodies (DSA) are frequently present in pediatric liver transplant (LT) recipients. Their clinical significance remains incompletely understood. We aimed to investigate the prevalence of serum AAb and DSA in pediatric LT recipients and its correlation with patient characteristics and histological and biochemical parameters. METHODS: We retrospectively reviewed the data from 62 pediatric LT patients in follow-up at Ghent University Hospital between January 2007 and February 2018. Blood samples with AAb measurement were taken systematically, liver biopsies (LB) were performed on clinical indication. RESULTS: AAb were detected in 27 (43.3%) patients, with antinuclear antibodies (ANA) being the most frequently (24%) encountered AAb. There was an association between AAb positivity and female gender (P = 0,032) and deceased donor LT (P = 0,006). Patients with positive AAb underwent a higher number of LB during their follow-up (P < 0,001), and an association was found with the presence of nonspecific histologic alterations (P = 0,032) in the absence of de novo autoimmune hepatitis. Positive AAb were also associated with higher alkaline phosphatase (P < 0,001), ALT (P < 0,001), AST (P < 0,001), γ-GT (P = 0,001), IgG (P = 0,011) and lower albumin (P = 0,029). Fourteen out of 50 (28%) patients were DSA-positive, mostly anti-HLA class II. DSA positivity was associated with T-cell-mediated rejection (P = 0,019), higher total (P = 0,033), and direct (P = 0,012) bilirubin and γ-GT (P < 0,001). CONCLUSIONS: The presence of AAb and DSA is associated with histological and biochemical parameters of graft dysfunction. Larger prospective studies are warranted to investigate the causal relationships between AAb and DSA development and outcome parameters post pediatric LT.

Successful liver transplantation in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome: Case report.

BACKGROUND: HHH syndrome is a rare autosomal recessive disorder of the urea cycle, caused by a deficient mitochondrial ornithine transporter. We report the first successful liver transplantation in HHH syndrome performed in a seven-year-old boy. The patient presented at 4 weeks of age with hyperammonemic coma. The plasma amino acid profile was suggestive of HHH syndrome, and the diagnosis was confirmed when sequencing of the SLC25A15 gene identified two mutations p.R275Q and p.A76D. Although immediate intervention resulted in normalization of plasma ammonia levels within 24 hours, he developed cerebral edema, coma, convulsions, and subsequent neurological sequelae. Metabolic control was difficult requiring severe protein restriction and continued treatment with sodium benzoate and L-arginine. Despite substantial developmental delay, he was referred to our center for liver transplantation because of poor metabolic control. Following cadaveric split liver transplantation, there was complete normalization of his plasma ammonia and plasma amino acid levels under a normal protein-containing diet. This excellent metabolic control was associated with a markedly improved general condition, mood and behavior, and small developmental achievements. Twelve years after liver transplantation, the patient has a stable cognitive impairment without progression of spastic diplegia. CONCLUSION: This first case of liver transplantation in HHH syndrome demonstrates that this procedure is a therapeutic option for HHH patients with difficult metabolic control.

Management of Gastrointestinal and Nutritional Problems in Children With Neurological Impairment: A Survey of Practice.

OBJECTIVES: The main aim of this study was to determine the impact on clinical practice of the first European Society of Gastroenterology, Hepatology, and Nutrition (ESPGHAN) position paper on the diagnosis and management of nutritional and gastrointestinal problems in children with neurological impairment (NI). METHODS: In this pilot-study, a web-based questionnaire was distributed between November, 2019 and June, 2020, amongst ESPGHAN members using the ESPGHAN newsletter. Fifteen questions covered the most relevant aspects on nutritional management and gastrointestinal issues of children with NI. A descriptive analysis of responses was performed. RESULTS: A total of 150 health professionals from 23 countries responded to the survey. A considerable variation in clinical practice concerning many aspects of nutritional and gastrointestinal management of children with NI was observed. The most frequently used method for diagnosing oropharyngeal dysfunction was the direct observation of meals with or without the use of standardised scores (n = 103). Anthropometric measurements were the most commonly used tools for assessing nutritional status (n = 111). The best treatment for gastroesophageal reflux disease (GERD) was considered to be proton pump inhibitor therapy by most (n = 116) participants. Regarding tube feeding, nearly all respondents (n = 114) agreed that gastrostomy is the best enteral access to be used for long-term enteral feeding. Fundoplication was indicated at the time of gastrostomy placement especially in case of uncontrolled GERD. CONCLUSIONS: More studies are required to address open questions on adequate management of children with NI. Identifying knowledge gaps paves the way for developing updated recommendations and improving patient care.

The perspectives of parents, general practitioners, and community pharmacists about treating an ill child in primary care: a comparative study.

As children are unable to make health-related decisions themselves, parents play a central role in consultations with healthcare providers. Parents' perspectives are therefore the focus of this study. Our first aim was to determine parents' expectations of a healthcare visit with a general practitioner and a community pharmacist. The second aim was to determine the general practitioners' and community pharmacists' perspectives about consultations with children. An observational cross-sectional study was conducted in April and May 2018. We developed three questionnaires: one for parents, one for general practitioners, and one for community pharmacists. The questionnaire for parents was only available through an online platform. The healthcare providers were questioned face-to-face and through an online platform. The study included 380 respondents. Parents considered prescribing or proposing medication the least important action by a general practitioner or community pharmacist, respectively. As well, parents expect information in most cases from both healthcare providers. The questionnaire for general practitioners and community pharmacists revealed that prescribing or proposing medication was regarded the least important action.Conclusion: Considering parents' expectations for a consultation with a general practitioner or community pharmacist, there is a substantial resemblance with the healthcare providers' perspective.What is Known:• The previous studies focusing on parents' perspectives were carried out in a hospital setting or focused on a specific disorder.• Parents consider reassurance and advice from their general practitioner to be very important; the treatment is considered less important.What is New:• Parents considered for both general practitioners' and community pharmacists' verbal information, answers to their questions, and reassurance as more important than receiving pharmacological treatment, while general practitioners and community pharmacists consider prescribing/proposing medication and providing written information as less important.• The expectations of the different groups (parents in relation to not only the healthcare providers but also the general practitioners and community pharmacists compared to each other) know a great resemblance.

Primum non nocere: lingual frenotomy for breastfeeding problems, not as innocent as generally accepted.

The frenotomy or surgical release of the lingual frenulum is performed with increasing frequency. Restricted tongue mobility, ankyloglossia, is the main indication for this procedure. This clinical diagnosis is often used as synonym for tongue-tie which is blamed for many feeding difficulties resulting in an increase in performed frenotomies. Until recently, little was known about the anatomical structure and normal variation of the tongue-tie. Different grading systems have been developed. Some are exclusively based on appearance of the tongue-tie; others also include functional elements. There is, however, no established relation between the tongue-tie score and the observed feeding problems or outcomes following frenotomy. Therefore, caution is warranted before submitting babies to this procedure.Conclusion: This narrative review aims to give an overview of current knowledge and concerns regarding the tongue-tie, which need to be considered before referral for a frenotomy. What is Known: • The presence of a tongue-tie is associated with a higher frequency of breastfeeding problems. • Hence, frenotomy is advocated and increasingly performed in infants with breastfeeding problems. Current tongue-tie classifications do not allow to predict breastfeeding problems. What is New: • New anatomy insights caution for possible complications resulting from this seemingly innocent practice of frenotomy. • Frenotomy should only be performed after multidisciplinary evaluation of feeding problems, following exclusion and remediation of other causative factors.

A Novel Double-Blind, Placebo-Controlled Food Challenge Matrix for Milk and Raw Egg.

BACKGROUND: The double-blind, placebo-controlled food challenge (DBPCFC) is still considered to be the gold standard in food allergy diagnosis. This test is however not common practice in routine due to several practical limitations, especially for non-IgE-mediated food allergy with its typical delayed food allergic reactions. OBJECTIVE: The aim of this study was to develop and evaluate DBPCFC matrices for the diagnosis of milk and egg allergies which can be applied at home for the diagnosis of delayed food allergic reactions. The main focus was the blinding of milk and raw egg and the development of matrices which can be prepared and consumed conveniently at home with a sufficiently long shelf life (+/- 6 months or longer). METHODS: A sensory test evaluated the blinding of the egg and milk in the matrices. The microbiological analysis confirmed the safety and stability of the developed matrices. To assess the applicability of the matrices, a pilot DBPCFC study for milk including 7 patients was conducted. RESULTS: Sensory tests confirmed that the masking of the allergenic ingredients was sufficient. Microbial safety and stability of the matrices were confirmed up to 6 months of storage at ambient temperatures in the dark. The DBPCFC for milk showed different outcomes and proved its applicability for use at home. CONCLUSION: A novel stable DBPCFC matrix for milk and raw egg has been developed that allows convenient use at the patients' home.

Intra-patient variability in tacrolimus exposure in pediatric liver transplant recipients: Evolution, risk factors, and impact on patient outcomes.

BACKGROUND: This study aims to investigate the evolution and factors associated with TAC IPV and its impact on patient outcomes in pediatric LT recipients. METHODS: This is a retrospective study including 41 children. The TAC IPV was expressed as the coefficient of variation and was calculated for years 1-5 following LT. The number of missed clinic appointments was used as a surrogate marker for therapy adherence. RESULTS: We identified a decrease in the TAC IPV during the first 3 years after LT (P < 0.01). Serum albumin in the first year (P = 0.03), hematocrit (P = 0.02) and total bilirubin (P = 0.04) in the third year, and therapy adherence (P < 0.01) in the fifth year were associated with TAC IPV. High TAC IPV was associated with biopsy-proven acute allograft rejection (P = 0.04) and the need for biopsy during the first year (P = 0.02). There was a borderline association between TAC IPV and donor-specific antibodies (P = 0.08) and CMV viremia (P = 0.07). High TAC IPV was a predictor of need for liver biopsy and AR with an odds ratio of 1.04 (95% CI 1.0-1.1; P = 0.03) and 1.04 (95% CI 1.0-1.1; P = 0.05), respectively. CONCLUSIONS: Our results highlight the impact of biological factors on TAC IPV during the early LT follow-up and later also therapy adherence. High TAC IPV may be associated with adverse patient outcomes.

Accuracy in Diagnosis of Celiac Disease Without Biopsies in Clinical Practice.

BACKGROUND & AIMS: The guidelines of the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition allow for diagnosis of celiac disease without biopsies in children with symptoms and levels of immunoglobulin A against tissue-transglutaminase (TGA-IgA) 10-fold or more the upper limit of normal (ULN), confirmed by detection of endomysium antibodies (EMA) and positivity for HLA-DQ2/DQ8. We performed a large, international prospective study to validate this approach. METHODS: We collected data from consecutive pediatric patients (18 years or younger) on a gluten-containing diet who tested positive for TGA-IgA from November 2011 through May 2014, seen at 33 pediatric gastroenterology units in 21 countries. Local centers recorded symptoms; measurements of total IgA, TGA, and EMA; and histopathology findings from duodenal biopsies. Children were considered to have malabsorption if they had chronic diarrhea, weight loss (or insufficient gain), growth failure, or anemia. We directly compared central findings from 16 antibody tests (8 for TGA-IgA, 1 for TGA-IgG, 6 for IgG against deamidated gliadin peptides, and 1 for EMA, from 5 different manufacturers), 2 HLA-DQ2/DQ8 tests from 2 manufacturers, and histopathology findings from the reference pathologist. Final diagnoses were based on local and central results. If all local and central results were concordant for celiac disease, cases were classified as proven celiac disease. Patients with only a low level of TGA-IgA (threefold or less the ULN) but no other results indicating celiac disease were classified as no celiac disease. Central histo-morphometry analyses were performed on all other biopsies and cases were carefully reviewed in a blinded manner. Inconclusive cases were regarded as not having celiac disease for calculation of diagnostic accuracy. The primary aim was to determine whether the nonbiopsy approach identifies children with celiac disease with a positive predictive value (PPV) above 99% in clinical practice. Secondary aims included comparing performance of different serological tests and to determine whether the suggested criteria can be simplified. RESULTS: Of 803 children recruited for the study, 96 were excluded due to incomplete data, low level of IgA, or poor-quality biopsies. In the remaining 707 children (65.1% girls; median age, 6.2 years), 645 were diagnosed with celiac disease, 46 were found not to have celiac disease, and 16 had inconclusive results. Findings from local laboratories of TGA-IgA 10-fold or more the ULN, a positive result from the test for EMA, and any symptom identified children with celiac disease (n = 399) with a PPV of 99.75 (95% confidence interval [CI], 98.61-99.99); the PPV was 100.00 (95% CI, 98.68-100.00) when only malabsorption symptoms were used instead of any symptom (n = 278). Inclusion of HLA analyses did not increase accuracy. Findings from central laboratories differed greatly for patients with lower levels of antibodies, but when levels of TGA-IgA were 10-fold or more the ULN, PPVs ranged from 99.63 (95% CI, 98.67-99.96) to 100.00 (95% CI, 99.23-100.00). CONCLUSIONS: Children can be accurately diagnosed with celiac disease without biopsy analysis. Diagnosis based on level of TGA-IgA 10-fold or more the ULN, a positive result from the EMA tests in a second blood sample, and the presence of at least 1 symptom could avoid risks and costs of endoscopy for more than half the children with celiac disease worldwide. HLA analysis is not required for accurate diagnosis. Clinical Trial Registration no: DRKS00003555.

Development and validation of a spina bifida-specific pediatric quality of life questionnaire: the Spina Bifida Pediatric Questionnaire, SBPQ.

PURPOSE: Based on existing questionnaires and patient interview, a health-related quality of life (HRQoL) questionnaire in spina bifida (SB) children is created and validated, the Spina Bifida Pediatric Questionnaire (SBPQ). METHODS: SB patients from the SB reference centre Ghent University Hospital, Belgium, with mental ability between 6 and 18 years old and their parents were asked to participate in the study, together with a control group. RESULTS: Thirty-nine patients and parents answered the questionnaire once, 20 patients and their parents the test-retest. Thirty-five controls answered the questionnaire once, 34 controls and their parents the test-retest. The final questionnaire was retained when 3 consecutive patients approved all items. Visual clues were added for children with a mental ability below 10 years of age. The test-retest showed a good to excellent agreement for child self-report in 5 domains (not for social functioning), for parent proxy report in all domains (6), for control self-report in 4 domains (not for domain home) and for control parent proxy report in all domains (5). Internal consistency reliability was good in child self-report and in parent proxy report, except for physical functioning in child self-report. There was parent-child agreement for 4 out of 6 domains. Regarding social and emotional functioning, QoL was rated lower by parents than by children themselves. CONCLUSION: A SB HRQoL questionnaire was developed and validated. Because of visual aid, this questionnaire can be used by both young children and adolescents.

Drug administration via enteral feeding tube in residential care facilities for individuals with intellectual disability: A focus group study on guideline implementation.

People with profound intellectual disabilities often receive medication through enteral feeding tube (EFT). In a previous study, we found that current guidelines concerning medication preparation and administration through EFT are often not followed in residential care facilities (RCFs) for individuals with intellectual disabilities. The present qualitative study aimed to identify barriers and facilitators experienced by RCF staff members to following guidelines on medication administration via EFT, by conducting focus group interviews. Time constraints, lack of knowledge, lack of clear administration instructions, lack of necessary materials, and limited gastric fluid tolerance in certain residents were identified as barriers to following guidelines. Other influencing factors were the number of staff members, residents, and medications; habits; and the residents' comfort and well-being. To optimize care for this vulnerable patient population with EFT, an intervention can be set up focusing on improving staff members' medication-related knowledge and providing clear administration instructions and the necessary materials.

Changes in prescription patterns of acid-suppressant medications by Belgian pediatricians: analysis of the national database, [1997-2009].

OBJECTIVE: The aim of this study was to examine the trend in the prescribing of proton pump inhibitors (PPIs) and histamine 2-receptor antagonists (H2-RAs) for children in Belgium from 1997 to 2009 to encourage discussion regarding appropriate clinical use. METHODS: Monthly claim-based data for PPIs and H2-RAs were obtained from the national health insurance database (Pharmanet 1997-2009). RESULTS: The total monthly volume of all reimbursed antireflux medications, prescribed by Belgian pediatricians, increased 7-fold from 20,782 daily defined doses (DDDs) in January 1997 to 142,912 DDDs in June 2009. During this study period, reimbursed volume of H2-RAs increased from 2575 to 38,996 DDDs and of PPIs from 3472 to 103,926 DDDs per month. CONCLUSIONS: PPI use has increased substantially in children. Its use does not seem to be commensurate with the prevalence of gastroesophageal reflux disease in children. This study encourages clinical discussion regarding well-considered use of these drugs in children.

Prevention of overweight in children younger than 2 years old: a pilot cluster-randomized controlled trial.

OBJECTIVE: The aim of the present study was to evaluate the effects of a 1-year family-based healthy lifestyle intervention implemented through day-care centres on toddlers' BMI Z-scores and reported activity- and dietary-related behaviours. DESIGN: Pilot cluster-randomized controlled trial. SETTING: Seventy child-care centres in three different intervention communities and three paired-matched control communities in Flanders, Belgium. SUBJECTS: A sample of 203 Belgian toddlers aged 9-24 months was included in the study. Objectively assessed weight and height were used to calculate BMI Z-scores. A parental-report questionnaire was used to assess children's lifestyle behaviours. RESULTS: Positive intervention effects were found on BMI Z-score. No intervention effects were found for activity- and dietary-related behaviours targeted by the intervention. In both intervention and control groups, daily consumption of water, soft drinks, sweets and savoury snacks increased while daily consumption of fruit and vegetables decreased over 1 year. Daily physical activity remained stable but screen-time behaviour increased in both groups over time. CONCLUSIONS: The study showed that a family-based healthy lifestyle intervention implemented through day-care centres can lead to healthier weight outcomes in toddlers. In both groups, an unhealthier lifestyle pattern was observed over 1 year which underlines the importance of the early childhood period as the focus of future behavioural interventions.

Microsomal protein per gram of liver (MPPGL) in paediatric biliary atresia patients.

The microsomal protein per gram of liver (MPPGL) is an important scaling factor in the in vitro-in vivo extrapolation of metabolic data obtained in liver microsomes. This study aimed to determine the MPPGL in four biliary atresia patients (0.6-1.6 years old) undergoing liver transplantation, as it is known that the MPPGL is affected by age and possibly by liver disease. Due to the presence of bilirubin in the homogenates and microsomes, the NADPH-cytochrome reductase activity was used to determine the recovery factor, rather than methods using the dithionite difference spectrum. A mean value of 18.73 (± 2.82) mg/g (geometric mean ± SD, n = 4) was observed, which is lower than the expected MPPGL based on the age of the patients (26.60 ± 0.40 mg/g). This suggests a decreased amount of microsomal protein in the livers of biliary atresia patients. Moreover, no differences in MPPGL between different zones of the liver could be detected.

Self-reported prescribing behaviour of vitamin D prophylaxis in healthy children by Belgian paediatricians.

There is currently no consensus on the guidelines for vitamin D prophylaxis in healthy children. The purpose of this study was to investigate the prescribing behaviour of vitamin D prophylaxis among Belgian paediatricians. Between June and September 2022, a questionnaire was distributed by email to all Belgian paediatricians who are a member of at least one of three scientific or professional organisations, as well as to the heads of every Belgian paediatric or neonatal hospital ward. We analysed 426 completed questionnaires. All regions, age categories and subspecialties were represented. Vitamin D prophylaxis is always or frequently recommended by 98% of paediatricians. Fifty-eight per cent of paediatricians advise vitamin D prophylaxis up to the age of six years and 66% of paediatricians advise a daily dose of 400 IU. In nearly every hospital in Belgium (96%), there is a specific protocol for vitamin D prophylaxis for newborns; but not for the paediatric unit (only 30%). Nearly all Belgian paediatricians prescribe vitamin D prophylaxis to infants. Although not recommended by guidelines, 25(OH)D is frequently measured by paediatricians. Practices regarding duration and dosing of vitamin D prophylaxis show large variability. Most neonatal wards do have a protocol, whereas most paediatric wards do not.

The viscosity-enhancing effect of carob bean gum and sodium carboxymethylcellulose when added to infant formula.

Despite limited supporting evidence, the practice of thickening breast milk or infant formula with commercially available thickening agents is prevalent. This study explored the viscosity-enhancing impact of carob bean gum (CBG) and sodium carboxymethylcellulose (NaCMC) when added to infant formula at various concentrations and for different thickening durations. The findings indicate that thickening leads to an exponential increase in milk viscosity, from 25% of the recommended dosage onward. This suggests that minor adjustments in dosage can significantly impact formula thickness, underscoring the importance of accurately dosing and preparing infant milk. The considerable variability in viscosity also emphasizes the need for thoughtful selection of teat size, considering the energy expenditure of the sucking infant. When using 50% of the recommended CBG dose or 25% of NaCMC, the resulting viscosity matches that of a commercially available casein-based formula containing CBG for anti-regurgitation. In the case of CBG, a viscosity plateau is only reached after 30 min. Therefore, educating parents on the correct handling and preparation steps for CBG-thickened infant milk is crucial, including a 30-min waiting period to achieve the intended thickening effect.

In vitro cytochrome p450 activity decreases in children with high pediatric end-stage liver disease scores.

To improve the modeling and simulation of pharmacokinetics in pediatric patients, research into developmental and disease-specific determinants is needed. This article describes the evaluation of the activity of in vitro cytochrome P450 (P450), an important enzyme family in drug metabolism, in children with hepatic dysfunction. The activity of six P450 isoforms (CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A4) was evaluated in 31 patients with different pathologies, predominantly biliary atresia (n = 23). Hypervariable activity was observed for all the isoforms. Compared with average adult activity, low activity levels were seen for CYP1A2, 2C19, 2E1, and 3A4. For CYP2E1 and 3A4, a positive correlation between activity and abundance was observed. Age, comedication, and genotype could not be used as predictors for P450 activity in this patient population. In contrast, the pediatric end-stage liver disease score was negatively correlated with the ln(activity). This finding suggests a decrease in P450 activity with deteriorating hepatic function. Moreover, the activity of all isoforms was correlated, demonstrating a concomitant decrease of all isoforms in young patients with liver disease. To our knowledge, this is the first study to evaluate P450 activity in children with hepatic impairment. The presented data may provide support in the further optimization of a disease-specific model in this patient population.

Validation of the Diet Quality Index for Adolescents by comparison with biomarkers, nutrient and food intakes: the HELENA study.

Food-based dietary guidelines (FBDG) aim to address the nutritional requirements at population level in order to prevent diseases and promote a healthy lifestyle. Diet quality indices can be used to assess the compliance with these FBDG. The present study aimed to investigate whether the newly developed Diet Quality Index for Adolescents (DQI-A) is a good surrogate measure for adherence to FBDG, and whether adherence to these FBDG effectively leads to better nutrient intakes and nutritional biomarkers in adolescents. Participants included 1804 European adolescents who were recruited in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) Study. Dietary intake was assessed by two, non-consecutive 24 h recalls. A DQI-A score, considering the components' dietary quality, diversity and equilibrium, was calculated. Associations between the DQI-A and food and nutrient intakes and blood concentration biomarkers were investigated using multilevel regression analysis corrected for centre, age and sex. DQI-A scores were associated with food intake in the expected direction: positive associations with nutrient-dense food items, such as fruits and vegetables, and inverse associations with energy-dense and low-nutritious foods. On the nutrient level, the DQI-A was positively related to the intake of water, fibre and most minerals and vitamins. No association was found between the DQI-A and total fat intake. Furthermore, a positive association was observed with 25-hydroxyvitamin D, holo-transcobalamin and n-3 fatty acid serum levels. The present study has shown good validity of the DQI-A by confirming the expected associations with food and nutrient intakes and some biomarkers in blood.