Efficacy and safety of a new low-volume PEG with citrate and simethicone bowel preparation for pediatric elective colonoscopy: Phase 3 RCT.

Background and study aims Currently available polyethylene glycol (PEG)-based preparations continue to represent a challenge in children. The aim of this study was to compare the efficacy and safety of a new low-volume PEG preparation with a conventional PEG-electrolyte solution (PEG-ES) in children and adolescents. Patients and methods This was a multicenter, randomized, observer-blind, parallel-group, phase 3 clinical trial, where patients were randomized between PMF104 (Clensia) and a conventional PEG-ES (Klean-Prep), and stratified by age stratum (2 to <6; 6 to < 12;12 to <18 years). The primary endpoint was to test the non-inferiority of PMF104 versus PEG-ES, in terms of colon cleansing. Safety, tolerability, acceptability, palatability, and compliance were also assessed. Efficacy endpoints were analyzed in the per protocol set (PPS) and full analysis set (FAS) and safety and tolerability endpoints in the safety set (SAF). Results Of the 356 patients enrolled, 258 were included in the PPS, 346 in the FAS, and 351 in the SAF. Non-inferiority of PMF104 was confirmed for children aged > 6 years and for all age groups in PPS and FAS, respectively. Optimal compliance was reported more frequently in the PMF104 than in the PEG-ES group, in both PPS (86.1% vs. 68.4%) and FAS (82.9% vs. 65.3%). Both preparations were equally safe and tolerable. Palatability and acceptability were considered better in the PMF104 group than in the PEG-ES group (27.1% vs. 15.3% and 15.3% vs. 3.5%, respectively). Conclusions In children aged 6 to 17 years, the new low-volume product PMF104 is non-inferior to the reference PEG-ES in terms of bowel cleansing, safety, and tolerability, with slightly better results in compliance, palatability, and acceptability.

Treatment of pediatric heterozygous familial hypercholesterolemia 7 years after the EAS recommendations: Real-world results from a large French cohort.

BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) predisposes to premature cardiovascular diseases. Since 2015, the European Atherosclerosis Society has advocated initiation of statins at 8-10 years of age and a low-density lipoprotein cholesterol (LDL-C) target of <135 mg/dL. Longitudinal data from large databases on pharmacological management of pediatric HeFH are lacking. OBJECTIVE: Here, we describe treatment patterns and LDL-C goal attainment in pediatric HeFH using longitudinal real-world data. METHODS: This was a retrospective and prospective multicenter cohort study (2015-2021) of children with HeFH, diagnosed genetically or clinically, aged <18 years, and followed up in the National French Registry of FH (REFERCHOL). Data on the study population as well as treatment patterns and outcomes are summarized as mean±SD. RESULTS: We analyzed the data of 674 HeFH children (age at last visit: 13.1 ± 3.6 years; 82.0 % ≥10 years; 52.5 % females) who were followed up for a mean of 2.8 ± 3.5 years. Initiation of lipid-lowering therapy was on average at 11.8 ± 3.0 years of age for a duration of 2.5 ± 2.8 years. At the last visit, among patients eligible for treatment (573), 36 % were not treated, 57.1 % received statins alone, 6.4 % statins with ezetimibe, and 0.2 % ezetimibe alone. LDL-C was 266±51 mg/dL before treatment and 147±54 mg/dL at the last visit (-44.7 %) in treated patients. Regarding statins, 3.3 %, 65.1 %, and 31.6 % of patients received high-, moderate-, and low-intensity statins, respectively. Overall, 59 % of children on statin therapy alone and 35.1 % on bitherapy did not achieve the LDL-C goal; fewer patients in the older age group did not reach the treatment goal. CONCLUSION: Pediatric patients with FH followed up in specialist lipid clinics in France receive late treatment, undertreatment, or suboptimal treatment and half of them do not reach the therapeutic LDL-C goal. Finding a more efficient framework for linking scientific evidence to clinical practice is needed.

Recurrent "outsider" intronic variation in the SLC5A6 gene causes severe mixed axonal and demyelinating neuropathy, cyclic vomiting and optic atrophy in 3 families from Maghreb.

Sodium dependent multivitamin transporter (SMVT) deficiency is a very rare autosomal recessive disorder characterized by multisystemic clinical manifestations due to combined biotin, panthotenic acid and lipoic acid deficiency. About 10 families have been described so far. Accurate diagnosis is crucial because of the possibility of a supplementation treatment with proven efficacy. Here we describe 4 new patients (3 additional families) originating from the same world region (Algeria, Maghreb). All patients, born form consanguineous parents, were homozygous carriers of the same intronic variation, outside of canonical sites, in the SLC5A6 gene encoding SMVT. RNA study in one family allowed confirming the pathogenic effect of the variation and re-classifying this variant of uncertain significance as pathogenic, opening the possibility of genetic counseling and treatment. The identification of the same variation in three distinct and apparently unrelated families is suggestive of a founder effect. The phenotype of all patients was very similar, with systematic optic atrophy (initially considered as a very rare sign), severe cyclic vomiting, and rapidly progressive mixed axonal and demyelinating sensory motor neuropathy.

Medical management of vegetarian and vegan children in France: Medical practices and parents' perceptions.

OBJECTIVES: Despite a significant increase in the prevalence of vegetarianism and veganism in children in France, data on the care pathway of these children are scarce. This study aimed to describe the characteristics of the medical follow-up of vegan/vegetarian children, to evaluate the medical practices, and to analyze the perceptions of parents. MATERIALS AND METHODS: This was a double cross-sectional survey. One questionnaire was sent to parents of vegetarian/vegan children, and the other to French doctors (pediatricians or general practitioners). RESULTS: A total of 241 vegetarian families responded to the study and nearly one quarter (n = 67, 28 %) were unsatisfied with the medical follow-up of their child. Parents considered that their child's diet was responsible for refusing a medical consultation in 11 % (n = 27) of cases. In almost one third of cases (n = 70, 29 %), participants declared that the doctor was unaware of their child's diet. Vitamin B12 supplementation was commonly used (n = 195, 81 %), mainly by self-medication, and laboratory testing was performed for 30 % (n = 72) of children. Regarding the questionnaire for doctors, most of the participants (n = 318/501, 63 %) reported having vegetarian/vegan children in their cohort. A few of them (n = 70, 14 %) declared they did not systematically screen for meat and fish consumption during consultations. Doctors caring for vegetarian/vegan children had 27 % correct answers to questions regarding the nutrition guidelines. Overall, 36 % of them (n = 117) systematically referred the child to a specialist. CONCLUSION: The medical follow-up of vegetarian/vegan children in France is very heterogeneous. Parents and doctors alike stressed the need to develop reliable sources of knowledge. A systematic screening of the diet and a referral to a specialist could help to improve the management of vegetarian/vegan children.

Prevalence and Etiologies of Renal and Urinary Manifestations in a Large Cohort of Children With Inflammatory Bowel Disease.

BACKGROUND AND OBJECTIVES: Renal and/or urinary manifestations (RUM) have been reported in pediatric patients with inflammatory bowel disease (IBD) but their incidence is unknown. The aims of this study were to assess the prevalence and causes of these manifestations in children with IBD and determine the causal link with 5-aminosalicylic acid (5-ASA) treatment. METHODS: A retrospective observational study was performed with children with diagnosis of IBD. All children with RUM during follow-up and/or impaired renal function [estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m 2 ] were identified. RESULTS: Of 228 included patients, 9 (3.9%) had a RUM during follow-up [follow-up: 5 years (1-12 years)] at a median age of 16 years (8-17 years). It concerned 7 of 171 patients with Crohn disease and 2 of 57 with ulcerative colitis. Seven patients were taking 5-ASA at the time of the RUM. Only 1 of them had an iatrogenic renal complication related to this treatment. Patients with RUM had a more severe disease with increased anti-tumor necrosis factor-α use ( P = 0.031), more abscesses ( P = 0.003), and a higher rate of digestive surgery ( P = 0.04). For the whole cohort, a significant decrease in eGFR was found during follow-up (121 vs 107 mL/min/1.73 m 2 , P < 0.001). At the end of follow-up, 38 of 202 (19%) patients had an eGFR < 90 mL/min/1.73 m 2 . CONCLUSION: In children with IBD, RUM can occur, independently of treatment with 5-ASA. During follow-up, a significant decrease in eGFR was observed. We suggest monitoring renal function in all patients with IBD.

Impact of diet on sensory processing in early childhood: summary of an interactive webconference / expert roundtable discussion.

Pediatric feeding disorders can be seen in up to 45% of normally developing children aged under 5 years old, mainly during the first three years of life when the child has inadequate food intake and/or difficulty maintaining adequate growth, and/or lack of age-appropriate eating habit. This article describes the opinion of a group of experts on children eating patterns and how to manage pediatric feeding disorders, with the aim to improve the quality of life of children and their caregivers.

Factors Predicting Statin Initiation During Childhood in Familial Hypercholesterolemia: Importance of Genetic Diagnosis.

OBJECTIVE: To identify childhood and parental factors associated with initiation of statin therapy in children with heterozygous familial hypercholesterolemia (HeFH), including underlying genetic diagnosis or parental premature atherosclerotic cardiovascular disease (ASCVD). STUDY DESIGN: This multicenter cohort study included 245 HeFH child-parent pairs from the REFERCHOL national register (2014-2020). Demographic and clinical characteristics at the last visit were collected. Vascular disease in parents was defined as a history of ASCVD, and/or a coronary artery calcium score >100, and/or stenosis of >50% in at least carotid artery. Statistical analyses included descriptive analysis, logistic regression for univariate and multivariate effects of statins, and a sensitivity analysis combining the characteristics of children and parents. RESULTS: Among the 245 children in the study cohort, 135 (58%), with a mean age of 14 ± 3 years, were treated with a statin. In multivariable analysis, the predictive childhood factors associated with statin treatment were genetic diagnosis (OR, 2.5; 95% CI, 1.3 to 4.9; P = .01), older age (OR, 4.4; 95% CI, 1.8-10.6; P = .01), more than 2 visits (OR, 2.36; 95% CI, 1.18-4.73; P = .015), and longer duration of follow-up (OR, 1.3; 95% CI, 1.1-1.6; P < .001). The predictive parental factor associated with childhood treatment was the presence of vascular disease (OR, 2.4; 95% CI, 1.0-5.7; P = .04). CONCLUSIONS: HeFH confirmed by DNA testing during childhood and a history of vascular disease in parents were independently associated with statin treatment in children with HeFH. Genetic diagnosis may be useful for cardiovascular prevention in children.

Managing Cow's Milk Protein Allergy with an Extensively Hydrolyzed Formula: Results from a Prospective, Non-Interventional Study in France (EVA Study).

Symptoms related cow's milk proteins allergy (CMPA) usually improve between two to four weeks following an elimination diet, firstly with extensively hydrolyzed formulas (eHF). The aim of the EVA study was to observe the evolution of CMPA-related symptoms in real life after initiation of a whey-based extensively hydrolyzed formula (w-eHF, Althéra®, Nestlé Health Science, Switzerland). This cross-sectional prospective non-interventional study was carried out alongside paediatricians in private practice in France between June 2019 and June 2020. Infants aged 0−3 years presenting with confirmed diagnosis or clinical symptoms suggesting CMPA were enrolled. Data were collected at enrolment (baseline visit) and three to five weeks later (follow-up visit). Symptoms were assessed using the Cow's Milk-related Symptom Score (CoMiSS®). The per protocol population included 135 infants. The average number of symptoms per infant significantly decreased under the study formula (from 2.81 to 1.36, p < 0.001) and the proportions of infants with any CMPA related symptoms decreased. Daily crying and regurgitation showed the largest decline, respectively −44.4% and −31.85% (p < 0.001). These results describe the early management of symptoms suspected to be related to CMPA in routine practice that was rarely described in the literature. The number and severity of symptoms decreased most of the cases after commencing the study formula.

[Gluten intolerance in infants and children: diagnosis and what recommendations?] / Intolérance au gluten en pédiatrie : diagnostic et recommandations.

Gluten intolerance in infants and children: what diagnosis and what recommendations? Gluten intolerance or celiac disease is a relatively common pathology that is still underdiagnosed in pediatrics due to its heterogeneous presentation. Apart from the classic form of malabsorption with diarrhea and growth retardation, pathology should be sought in the event of a family history of celiac disease, autoimmunity and in the context of certain syndromes. Other clinical or laboratory signs should also suggest the diagnosis. Any suspicion should lead to assays for total IgA and anti- transglutaminase IgA. If the child is symptomatic or not, the absence of upper gastrointestinal endoscopy with biopsies is possible to make the diagnosis after agreement of the family, if the levels of anti-transglutaminase IgA are greater than 10 times the upper limit of normal, and if the anti-endomysium IgA, assayed on a second sample, are also positive. Management is based on a strict gluten-free diet.

Intolérance au gluten en pédiatrie : diagnostic et recommandations. L'intolérance au gluten, ou maladie coeliaque, est relativement fréquente mais reste sous-diagnostiquée en pédiatrie du fait de sa présentation hétérogène. En dehors du tableau classique de malabsorption, avec diarrhée et retard de croissance, elle doit être recherchée en cas d'antécédents familiaux de maladie coeliaque, d'auto-immunité et dans le cadre de certains syndromes. D'autres signes cliniques ou biologiques doivent également évoquer ce diagnostic. Toute suspicion impose le dosage des IgA totales et des IgA antitransglutaminase. Que l'enfant soit symptomatique ou non, si les taux d'IgA antitransglutaminase sont supérieurs à 10 fois la limite supérieure à la normale, et si les IgA anti-endomysium, dosées sur un deuxième prélèvement, sont également positives, le diagnostic peut être posé sans endoscopie digestive haute avec biopsies, après accord de la famille. La prise en charge repose sur un régime d'éviction strict du gluten à vie.

[Chronic aqueous diarrhea in children: An unusual etiology]. / Diarrhée aqueuse chronique chez l'enfant : une étiologie à ne pas méconnaître.

Peripheral neuroblastic tumors are the most common extracranial solid tumors in children. On the other hand, diarrheal neuroblastic tumors are quite rare and not easy to diagnose in the early stage. We report a case of neuroblastic tumor in a 2-year old girl presenting with aqueous diarrhea caused by paraneoplasic secretion of VIP.

Feasibility of open abdomen surgery treatment for near fatal necrotizing enterocolitis in preterm infants.

INTRODUCTION: Necrotizing Enterocolitis (NEC) remained a dramatic complication leading to death or neonatal morbidities in preterms. For some, Intra-Abdominal Hypertension (IAH) and Abdominal Compartment Syndrome worsened the multi-organ failure. An open abdomen surgery could be an alternative to conventional surgical treatment to move beyond this stage. OBJECTIVES: To retrospectively describe the clinical course, pre- and post-operative features of preterms suffering from severe NEC with IAH treated by open abdomen surgery and referred to our center from October 2007 to September 2019. Our secondary objective is to identify various risk factors for mortality in this population. METHODS: Data on neonatal, clinical, biological, pre and post-operative features and outcome were collected. Univariate analyses were performed to compare their pre and post-operative features stratifying on outcome. RESULTS: Among 29 included patients, 14 (48%) survived to discharge without short bowel syndrome. Death was associated with an earlier postnatal age at NEC (16.3 ± 9.1 versus 31.3 ± 25.9 days; p = 0.004) and followed a withdrawal of treatment in 60% of cases. Surgery was associated with a significant improvement of respiratory and hemodynamic features (decrease of mean ventilator pressure from 13.1 ± 5.4 to 11.3 ± 4.0 cmH2O, p < 0.001), oxygen requirement (mean FiO2 decreased from 65.0% ± 31.2 to 49.0% ± 24.6, p < 0.001) and inotropic score (from 38.6 ± 70.1 to 29.9 ± 64.3, p < 0.001). In the survival group, pre and post-operative findings exhibited a significant increase of serum lactate concentrations from 2.7 ± 1.6 to 11.0 ± 20.3 mmol/L (p = 0.02) but a similar pH. CONCLUSION: Open abdomen surgery could be considered to rescue preterms with near fatal NEC. IAH and Abdominal Compartment Syndrome in these preterms should be investigated through further studies. LEVEL OF EVIDENCE: Level III.

Feeding disorders in children with oesophageal atresia: a cross-sectional study.

INTRODUCTION: With advances in surgical and neonatal care, the survival of patients with oesophageal atresia (OA) has improved over time. Whereas a number of OA-related conditions (delayed primary anastomosis, anastomotic stricture and oesophageal dysmotility) may have an impact on feeding development and although children with OA experience several oral aversive events, paediatric feeding disorders (PFD) remain poorly described in this population. The primary aim of our study was to describe PFD in children born with OA, using a standardised scale. The secondary aim was to determine conditions associated with PFD. METHODS: The Feeding Disorders in Children with Oesophageal Atresia Study is a national cohort study based on the OA registry from the French National Network. Parents of children born with OA between 2013 and 2016 in one of the 22 participating centres were asked to complete the French version of the Montreal Children's Hospital Feeding Scale. RESULTS: Of the 248 eligible children, 145 children, with a median age of 2.3 years (Q1-Q3 1.8-2.9, min-max 1.1-4.0 years), were included. Sixty-one children (42%) developed PFD; 13% were tube-fed (n=19). Almost 40% of children with PFD failed to thrive (n=23). The presence of chronic respiratory symptoms was associated with the development of PFD. Ten children with PFD (16%) had no other condition or OA-related complication. CONCLUSION: PFD are common in children with OA, and there is no typical profile of patients at risk of PFD. Therefore, all children with OA require a systematic screening for PFD that could improve the care and outcomes of patients, especially in terms of growth.

Implication of Heterozygous Variants in Genes of the Leptin-Melanocortin Pathway in Severe Obesity.

CONTEXT: Unlike homozygous variants, the implication of heterozygous variants on the leptin-melanocortin pathway in severe obesity has not been established. OBJECTIVE: To describe the frequency, the phenotype, and the genotype-phenotype relationship for heterozygous variants in LEP, LEPR, POMC, and PCSK1 in severe obesity. METHODS: In this retrospective study, genotyping was performed on at least 1 of the LEP, LEPR, POMC, and PCSK1 genes in 1486 probands with severe obesity (600 children, 886 adults). The phenotype was collected in 60 subjects with heterozygous variants and 16 with homozygous variants. We analyzed variant frequency, body mass index (BMI), age of obesity onset, food impulsivity, and endocrine abnormalities. RESULTS: The frequency of subjects with homozygous variants was 1.7% (n = 26), and 6.7% (n = 100) with heterozygous variants. Adults with homozygous variants had a higher BMI (66 vs 53 kg/m2, P = .015), an earlier onset of obesity (0.4 vs 5.4 years, P < .001), more often food impulsivity (83% vs 42%, P = .04), and endocrine abnormalities (75% vs 26%, P < .01). The BMI was higher for subjects with high-impact heterozygous variants (61 vs 50 kg/m², P = .045) and those with a second heterozygous variant on the pathway (65 vs 49 kg/m², P < .01). In children, no significant differences were found for the age of obesity onset and BMI. CONCLUSION: Heterozygous variants in LEP, LEPR, POMC, and PCSK1 are frequent in severe obesity and sometimes associated with a phenotype close to that of homozygotes. These data suggest a systematic search for variants in severe early-onset obesity, to discuss therapy that targets this key pathway.

A European Survey on Digestive Perianastomotic Ulcerations, a Rare Crohn-like Disorder Occurring in Children and Young Adults.

OBJECTIVES: Digestive perianastomotic ulcerations (DPAU) resembling Crohn disease lesions are long-term complications of intestinal resections, occurring in children and young adults. They are known to be uncommon, severe and difficult to treat. METHODS: In the absence of recommendations, we performed a large European survey among the members of the ESPGHAN working group on inflammatory bowel disease (IBD) in order to collect the experience of expert pediatric gastroenterologists on DPAU. RESULTS: Fifty-one patients (29 boys and 22 girls) were identified from 19 centers in 8 countries. Most patients were followed after necrotizing enterocolitis (n = 20) or Hirschsprung disease (n = 11). The anastomosis was performed at a median age (interquartile range) of 6 [1-23] months, and first symptoms occurred 39 [22-106] months after surgery. Anemia was the most prevalent symptom followed by diarrhea, abdominal pain, bloating, and failure to thrive. Hypoalbuminemia, elevated CRP, and fecal calprotectin were common. Deep ulcerations were found in 59% of patients usually proximally to the anastomosis (68%). During a median follow-up of 40 [19-67] months, treatments reported to be the most effective included exclusive enteral nutrition (31/35, 88%), redo anastomosis (18/22, 82%), and alternate antibiotic treatment (37/64, 58%). CONCLUSIONS: Unfortunately, persistence of symptoms, failure to thrive, and abnormal laboratory tests at last follow-up in most of patients show the burden of DPAU lacking optimal therapy and incomplete understanding of the pathophysiology.

Comparison of Symptom Control in Pediatric Gastroparesis Using Endoscopic Pyloric Botulinum Toxin Injection and Dilatation.

OBJECTIVES: The objective of this study was to assess the tolerance and efficacy of endoscopic intrapyloric botulinum toxin injection compared with pyloric dilatation in children with gastroparesis. METHODS: This was a retrospective descriptive multicentre study that included pediatric patients treated between 2010 and 2018 at 4 tertiary hospitals. RESULTS: Data were collected for 24 patients. The median age at diagnosis was 2.5 years (range 0.5-4.7). A total of 46 endoscopic procedures were performed. The endoscopic procedure was multiple in 63% of patients. Among the interventions, 76% were successful and 15% were unsuccessful. The recurrence rate was 57% and the median time to recurrence was 3.7 months (0.1-73). The efficacy did not differ significantly between the 2 methods at the first intervention and as a second-line treatment. The recurrence rate also did not differ significantly between the 2 methods. No complications were reported. The median follow-up was 19.8 months (1.7-61.7). CONCLUSIONS: In this retrospective multicentre study, endoscopic management of gastroparesis by balloon dilatation or botulinum toxin was safe in children and seemed to be partially efficient within the first months. Symptoms recurred frequently and required repetition of the interventions.

[Inadequate infant diets and false food allergies]. / Régimes alimentaires inadaptés du nourrisson et fausses allergies alimentaires.

INADEQUATE INFANT DIETS AND FALSE FOOD allergiesthe administration, by families, of more or less extensive avoidance diets of food to their infants has been a growing problem in recent years. Regardless of certain parental beliefs, these diets are also often set up to treat mild digestive disorders or suspected food allergies. In young children, these diets, without cow's milk protein, vegetarians or even vegans or eliminating foods on unsuitable allergological tests, not supervised by health professionals, can lead to nutritional complications which are sometimes serious and life-threatening. It is therefore important to detect possible nutritional deficiencies, to treat them and to resume, after explanations to the family, a diet as little restricted as possible.

RÉGIMES ALIMENTAIRES INADAPTÉS DU NOURRISSON ET FAUSSES ALLERGIES alimentairesla mise en place, par les familles, de régimes d'évictions, plus ou moins larges, de certains aliments pour leurs nourrissons est un problème croissant depuis quelques années. Indépendamment de certaines croyances parentales, ces régimes sont également souvent destinés à traiter des troubles digestifs bénins ou des allergies alimentaires supposées. Chez le jeune enfant, ces régimes qu'ils soient végétariens, végétaliens ou reposant sur des tests allergologiques inadaptés et non encadrés par des professionnels de santé, peuvent conduire à des complications nutritionnelles parfois graves, engageant le pronostic vital. Il est donc important de dépister d'éventuelles carences, de les traiter et de reprendre, idéalement après explications à la famille, un régime le moins restreint possible.