Changes in Microbiota Profile in the Proximal Remnant Intestine in Infants Undergoing Surgery Requiring Enterostomy.

Early-life gut dysbiosis has been associated with an increased risk of inflammatory, metabolic, and immune diseases later in life. Data on gut microbiota changes in infants undergoing intestinal surgery requiring enterostomy are scarce. This prospective cohort study examined the enterostomy effluent of 29 infants who underwent intestinal surgery due to congenital malformations of the gastrointestinal tract, necrotizing enterocolitis, or spontaneous intestinal perforation. Initial effluent samples were collected immediately after surgery and final effluent samples were collected three weeks later. Gut microbiota composition was analysed using real-time PCR and 16S rRNA gene sequencing. Three weeks after surgery, an increase in total bacteria number (+21%, p = 0.026), a decrease in Staphylococcus (-21%, p = 0.002) and Candida spp. (-16%, p = 0.045), and an increase in Lactobacillus (+3%, p = 0.045) and in less abundant genera belonging to the Enterobacteriales family were found. An increase in alpha diversity (Shannon's and Simpson's indexes) and significant alterations in beta diversity were observed. A correlation of necrotizing enterocolitis with higher Staphylococcus abundance and higher alpha diversity was also observed. H2-blockers and/or proton pump inhibitor therapy were positively correlated with a higher total bacteria number. In conclusion, these results suggest that positive changes occur in the gut microbiota profile of infants three weeks after intestinal surgery.

Congenital Glucagon-like Peptide-1 Deficiency in the Pathogenesis of Protracted Diarrhea in Mitchell-Riley Syndrome.

CONTEXT: Mitchell-Riley syndrome due to RFX6 gene mutations is characterized by neonatal diabetes and protracted diarrhea. The RFX6 gene encodes a transcription factor involved in enteroendocrine cell differentiation required for beta-cell maturation. In contrast to the pathway by which RFX6 mutations leads to diabetes, the mechanisms underlying protracted diarrhea are unknown. OBJECTIVE: To assess whether glucagon-like peptide-1 (GLP-1) was involved in the pathogenesis of Mitchell-Riley syndrome protracted diarrhea. METHODS: Two case report descriptions. in a tertiary pediatric hospital. "Off-label" treatment with liraglutide. We describe 2 children diagnosed with Mitchell-Riley syndrome, presenting neonatal diabetes and protracted diarrhea. Both patients had nearly undetectable GLP-1 plasma levels and absence of GLP-1 immunostaining in distal intestine and rectum. The main outcome was to evaluate whether GLP-1 analogue therapy could improve Mitchell-Riley syndrome protracted diarrhea. RESULTS: "Off-label" liraglutide treatment, licensed for type 2 diabetes treatment in children, was started as rescue therapy for protracted intractable diarrhea resulting in rapid improvement during the course of 12 months. CONCLUSION: Congenital GLP-1 deficiency was identified in patients with Mitchell-Riley syndrome. The favorable response to liraglutide further supports GLP-1 involvement in the pathogenesis of protracted diarrhea and its potential therapeutic use.

Evolution of Resting Energy Expenditure, Respiratory Quotient, and Adiposity in Infants Recovering from Corrective Surgery of Major Congenital Gastrointestinal Tract Anomalies: A Cohort Study.

This cohort study describes the evolution of resting energy expenditure (REE), respiratory quotient (RQ), and adiposity in infants recovering from corrective surgery of major congenital gastrointestinal tract anomalies. Energy and macronutrient intakes were assessed. The REE and RQ were assessed by indirect calorimetry, and fat mass index (FMI) was assessed by air displacement plethysmography. Longitudinal variations over time are described. Explanatory models for REE, RQ, and adiposity were obtained by multiple linear regression analysis. Twenty-nine infants were included, 15 born preterm and 14 at term, with median gestational age of 35.3 and 38.1 weeks and birth weight of 2304 g and 2935 g, respectively. In preterm infants, median REE varied between 55.7 and 67.4 Kcal/kg/d and median RQ increased from 0.70 to 0.86-0.92. In term infants, median REE varied between 57.3 and 67.9 Kcal/kg/d and median RQ increased from 0.63 to 0.84-0.88. Weight gain velocity was slower in term than preterm infants. FMI, assessed in a subset of 15 infants, varied between a median of 1.7 and 1.8 kg/m2 at term age. This low adiposity may be related to poor energy balance, low fat intakes, and low RQ¸ that were frequently recorded in several follow-up periods.

Colonisation of the proximal intestinal remnant in newborn infants with enterostomy: a longitudinal study protocol.

INTRODUCTION: The gut microbiota plays a main role in the maintenance of host's health. Exposure to different conditions in early life contributes to distinct 'pioneer' bacterial communities in the intestine, which shape the newborn infant development. Newborn infants with congenital malformations of the gastrointestinal tract (CMGIT), necrotising enterocolitis (NEC) and spontaneous intestinal perforation (SIP) commonly require abdominal surgery and enterostomy. The knowledge about the colonisation of these newborns' intestine by microorganisms is scarce. This protocol is designed to explore the microbial colonisation over time of the proximal intestinal remnant in newborn infants who underwent surgery for CMGIT, NEC or SIP and require enterostomy. METHODS AND ANALYSIS: The literature about microbiota colonisation in newborn infants with enterostomy was reviewed and an observational, longitudinal, prospective study was designed. The infants will be recruited at the Neonatal Intensive Care Unit of the Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central. Samples of the enterostomy effluent will be collected every 3 days, through 21 days after the first collection. The microorganisms colonising the proximal intestinal remnant will be identified using the 16S rRNA sequence analysis and a subset of microorganisms will be quantified using real-time PCR. This protocol may serve as basis for future observational and interventional studies on the modulation of the intestinal microbiota (eg, probiotics) on short and long-term outcomes in this population. ETHICS AND DISSEMINATION: This study protocol was approved by the Ethics Committee of Centro Hospitalar Universitário de Lisboa Central (441/2017) and by the Ethics Committee of NOVA Medical School, Universidade Nova de Lisboa (n°50/2018/CEFCM). The results will be spread through peer-reviewed publications and presentations at international scientific meetings. TRIAL REGISTRATION NUMBER: NCT03340259.

Parenteral nutrition-associated cholestasis and triglyceridemia in surgical term and near-term neonates: A pilot randomized controlled trial of two mixed intravenous lipid emulsions.

BACKGROUND: Cholestasis is a common complication in infants receiving prolonged parenteral nutrition (PN). We studied the effects of two intravenous lipid emulsions composed with either 30% soybean oil, 30% medium-chain triglycerides (MCT), 25% olive oil, and 15% fish oil (SMOF) or with 50% MCT and 50% soybean oil n-6 (MCT/SOY) on the incidence of cholestasis in surgical term and near-term neonates. METHODS: A single-center, double-blinded, randomized controlled trial compared the incidence of cholestasis using either SMOF or MCT/SOY in neonates born at gestational age ≥34 weeks undergoing major surgery. The primary outcome was the incidence of conjugated serum bilirubin >1 mg/dL. Other liver enzymes were assessed as secondary outcomes. A post-hoc analysis assessed serum triglycerides levels. Odds ratios were estimated by mixed-effects regression models. RESULTS: Enrollment was prematurely interrupted because the MCT/SOY became unavailable, thus 49 infants (SMOF 22, MCT/SOY 27) completed the study. The exposure (time on PN, cumulative dose of lipids) was similar in both groups. Similar cumulative incidence rates were found for elevated conjugated bilirubinemia and other liver enzymes. Hypertriglyceridemia >250 mg/dL (12/49) was more frequent in MCT/SOY (37.0%, 95% CI 21.53-55.77) than in SMOF (9.1%, 95% CI 2.53-27.81, p = 0.024). Triglyceridemia at the first assessment (median 8 postnatal days) was significantly higher with MCT/SOY than with SMOF (181 vs. 134 mg/dL, p = 0.006). Over the whole study period, mean triglyceride concentration was 36.5 mg/dL higher with MCT/SOY compared with SMOF (p = 0.013). CONCLUSION: Both emulsions had similar effects on the incidence of cholestasis and markers of liver integrity, but MCT/SOY induced higher serum triglyceride concentrations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02633384.

Fat mass index performs best in monitoring management of obesity in prepubertal children / Índice de massa gorda apresenta melhor desempenho no monitoramento do tratamento da obesidade em crianças pré-púberes

Abstract Objective An early and accurate recognition of success in treating obesity may increase the compliance of obese children and their families to intervention programs. This observational, prospective study aimed to evaluate the ability and the time to detect a significant reduction of adiposity estimated by body mass index (BMI), percentage of fat mass (%FM), and fat mass index (FMI) during weight management in prepubertal obese children. Methods In a cohort of 60 prepubertal obese children aged 3–9 years included in an outpatient weight management program, BMI, %FM, and FMI were monitored monthly; the last two measurements were assessed using air displacement plethysmography. The outcome measures were the reduction of >5% of each indicator and the time to achieve it. Results The rate of detection of the outcome was 33.3% (95% CI: 25.9–41.6) using BMI, significantly lower (p < 0.001) than either 63.3% using %FM (95% CI: 50.6–74.8) or 70.0% (95% CI: 57.5–80.1) using FMI. The median time to detect the outcome was 71 days using FMI, shorter than 88 days using %FM, and similar to 70 days using BMI. The agreement between the outcome detected by FMI and by %FM was high (kappa 0.701), but very low between the success detected by BMI and either FMI (kappa 0.231) or %FM (kappa 0.125). Conclusions FMI achieved the best combination of ability and swiftness to identify reduction of adiposity during monitoring of weight management in prepubertal obese children.

Resumo Objetivo O reconhecimento precoce e preciso do sucesso no tratamento da obesidade pode aumentar a adesão de crianças obesas e suas famílias a programas de intervenção. Este estudo observacional prospectivo visa a avaliar a capacidade e o tempo de detecção de uma redução significativa na adiposidade estimada pelo índice de massa corporal (IMC) no percentual de massa gorda (% MG) e no índice de massa gorda (IMG) durante o controle de peso em crianças obesas pré-púberes. Métodos Em uma coorte de 60 crianças obesas pré-púberes entre três e nove anos, incluídas em um programa ambulatorial de controle de peso, o IMC, o % MG e o IMG foram monitorados mensalmente e as duas últimas medições avaliadas foram feitas com pletismografia por deslocamento de ar. As medições resultantes foram redução de > 5% de cada indicador e atingir o tempo para tanto. Resultados A taxa de detecção do resultado foi de 33,3% (IC de 95% 25,9-41,6) com o uso de IMC, significativamente menor (p < 0,001) do que 63,3% com % MG (IC de 95% 50,6-74,8) ou 70,0% (IC de 95% 57,5-80,1) com IMG. O tempo médio para detectar o resultado foi de 71 dias com o IMG, menos do que 88 dias com %MG e semelhante a 70 dias com o IMC. A concordância entre o resultado detectado pelo IMG e pelo % MG foi elevada (kappa 0,701), porém muito baixa entre o sucesso detectado pelo IMC e pelo IMG (kappa 0,231) ou %MG (kappa 0,125). Conclusões O IMG atingiu a melhor combinação de capacidade e precocidade para identificar redução na adiposidade durante o monitoramento do controle de peso em crianças obesas pré-púberes.

Fat mass index performs best in monitoring management of obesity in prepubertal children.

OBJECTIVE: An early and accurate recognition of success in treating obesity may increase the compliance of obese children and their families to intervention programs. This observational, prospective study aimed to evaluate the ability and the time to detect a significant reduction of adiposity estimated by body mass index (BMI), percentage of fat mass (%FM), and fat mass index (FMI) during weight management in prepubertal obese children. METHODS: In a cohort of 60 prepubertal obese children aged 3-9 years included in an outpatient weight management program, BMI, %FM, and FMI were monitored monthly; the last two measurements were assessed using air displacement plethysmography. The outcome measures were the reduction of >5% of each indicator and the time to achieve it. RESULTS: The rate of detection of the outcome was 33.3% (95% CI: 25.9-41.6) using BMI, significantly lower (p<0.001) than either 63.3% using %FM (95% CI: 50.6-74.8) or 70.0% (95% CI: 57.5-80.1) using FMI. The median time to detect the outcome was 71 days using FMI, shorter than 88 days using %FM, and similar to 70 days using BMI. The agreement between the outcome detected by FMI and by %FM was high (kappa 0.701), but very low between the success detected by BMI and either FMI (kappa 0.231) or %FM (kappa 0.125). CONCLUSIONS: FMI achieved the best combination of ability and swiftness to identify reduction of adiposity during monitoring of weight management in prepubertal obese children.

Mosaic trisomy 18 in a five-month-old infant.

Individuals with mosaic trisomy 18, only approximately 5% of all trisomy 18 cases, carry both a trisomy 18 and an euploid cell line. Their clinical findings are highly variable, from the absence of dysmorphic features to the complete trisomy 18 syndrome. A five-month-old daughter of a 38-year-old mother, with vomiting and feeding problems, was referred to our department. She was undernourished and had axial hypotony and developmental delay, an irregular pattern of hypopigmentation on the right side of the abdomen, and moderate sagittal body asymmetry with left-side muscular hemihypotrophy. Mild craniofacial dysmorphy included dolichocephaly, frontal bossing, prominent occiput, long downslanting palpebral fissures, hypertelorism, and retrognathia. A complex heart defect with atrial and ventricular septal defects, pulmonary artery stenosis, and bicuspid aortic valve was identified. Cytogenetic analysis revealed mosaic trisomy 18 with trisomy in 90% of peripheral lymphocytes and 17% of skin fibroblasts. This case adds to our knowledge of the phenotypic spectrum and the natural history of mosaic trisomy 18 by adding a dysmorphic feature and a cardiac abnormality that, to the best of our knowledge, had not been previously described.

[Echovirus type 13 meningitis: admissions to a paediatric ward at a Lisbon hospital]. / Meningite por echovirus tipo 13.

Infections by echovirus 13 are rare. In our country, it had not been previously reported any infection of this sort until 2000, when eleven echovirus 13 meningitis were observed in the Department of Pediatrics of the Hospital Fernando Fonseca. In England and Spain outbreaks of echovirus 13 meningitis during 2000 was also reported. Based on these facts the authors make an epidemiological analyses of their series.