Objectives and Study

Antibiotic-associated diarrhea (AAD) is one of important side effects. Some probiotics have some beneficial effects on AAD development when used in combination with antibiotics. The aim of this study was to evaluate the effect of Limosilactobacillus reuteri DSM 17938 on the prevention of AAD in children.

Methods

PEARL study is a prospective (207-2019), multi-center, randomized, placebo controlled clinical trial in Turkey. We enrolled children (6 months-10 years), who have acute otitis media or acute sinusitis, treated with amoxicillin clavulanate for 10-14 days. Group 1 received antibiotic and Limosilactobacillus reuteri DSM 17938 dosed at 10⁸ cfu, twice daily for 10-14 days (Group 1a) during antibiotic treatment or additional 7 days (21 days) after antibiotic cessation (Group 1b). Group 2 received antibiotic and placebo for 10-14 days (Group 2a) or 21 days (Group 2b). Primary end point of this study percentage of children with AAD in first 14 days follow-up. AAD defined as ≥3 loose or watery stools per day for ≥48 hours. Secondary end-points are percentage of children with AAD at 21^st days of antibiotic treatment and also 56^th days of antibiotic treatment and also comparison between the effectiveness of L.reuteri for 10-14 days and 21 days.

Results

We included 330 children (167 boys) in the L.reuteri group and 324 children(156 boys) in the placebo group. The percentage of children with ADD was significantly lower in L.reuteri group compared to placebo at 14^th days, 21^st days and 56^th days (Table 1). The mean duration of diarrhea was longer in placebo group than L.reuteri group (p<0.01). In L.reuteri group there was no difference for AAD between 10-14 days and 21 days use (p>0.05).

Conclusions

This study showed that Limosilactobacillus reuteri DSM 17938 significantly reduced the incidence of AAD in children during the first 14 days of antibiotic use and also 8 weeks follow-up period. (NCT02765217).

Objectives and Study

Diarrhea is the most frequent gastrointestinal symptom of COVID-19. Mechanisms include oxidative stress and chloride secretion mainly triggered by the spike protein acting as an enterotoxin. L. rhamnosus GG (LGG) is included in the ESPGHAN guidelines as an active treatment for acute gastroenteritis. Aim of this study was to evaluate the effects of LGG in an in-vitro model of SARS-CoV-2-induced diarrhea.

Methods

Variations in intensity of short-circuit current (Isc), indicating changes in ion transepithelial fluxes were measured in Caco-2 cells mounted in Ussing chambers after exposure to heat-inactivated SARS-CoV-2 (CoV) or spike protein (Spike). Spectrofluorometry was used to measure reactive oxygen species (ROS). Same experiments were performed with RV and sodium arsenite (ARS), as positive controls in electrical and oxidative studies, respectively, and after pre-treatment of Caco-2 with LGG conditioned medium (mLGG).

Results

CoV and spike induced a rise of Isc consistent with chloride secretion. Pre-treatment of Caco-2 cells with mLGG significantly reduced ion secretion induced by CoV (mLGG+CoV 0.4±0.7 vs CoV 3.3±0.4 µA/cm²; p=0.006) and Spike (mLGG+Spike 0.9±0.32 vs Spike 2.9±0.3 µA/cm²; p=0.002). The preventive effect on ion secretion was similar to that observed with RV-induced secretion. Spike induced a 2-fold increase in ROS production. mLGG pre-treatment significantly reduced ROS (p<0.001) with an antioxidant effect similar to that induced by N-Acetylcysteine (NAC). The anti-oxidant ability of mLGG appeared independent from the oxidative stimuli considering the positive action recorded also against the oxidative agent ARS (p=0.008).

Conclusions

LGG counteracts SARS-CoV-2-induced diarrhea by inhibiting enterotoxic effect and oxidative stress. The action of LGG in form of postbiotic is dependent by the action of moieties secreted in the medium with a direct pharmacological-like action including anti-oxidant proprieties.

Objectives and Study

Acute diarrhea continues to be a leading cause of morbidity, hospitalization, and mortality worldwide. Probiotics have been proposed as a complementary therapy in the treatment of acute diarrhea. The goal of this study is to assess the efficacy and safety of Bifidobacterium animalis subsp. Lactis BLa80, as an adjunct to the treatment of acute watery diarrhea in children with a randomized, double-blinded, placebo-controlled study design.

Methods

Eligible diarrheal children were randomized into intervention group (IG, n=58, conventional treatment for diarrhea in combination with probiotic) and control group (CG, n=53, conventional treatment for diarrhea without probiotic). The primary assessments of this study were duration of diarrhea and the improvement in diarrhea symptoms. Fecal samples were collected from all children before and after intervention to measure levels of sIgA, calprotectin, human beta-defensin 2 (HBD-2), and cathelicidin (LL-37), and to analyze the gut microbiome (GM) composition.

Results

After the intervention, the total duration of diarrhea in the IG (125.2±14.1 h) was significantly shorter than that in the CG (138.7±16.4 h, p <0.001). More children in the IG showed improvements in diarrhea (defined as a decrease in fecal frequency to no more than four times per day and an improved fecal consistency within 72 h after treatment) than those in the CG for both per protocol analysis (84.4% vs 45.3%, p<0.001) and intention-to-treat analysis (81.7% vs. 40.0%, p<0.001). The LL-37 levels in the IG was markedly higher than that in the CG after the intervention (4415.00±1036.93 pg/g vs. 3679.49±871.18 pg/g, p=0.0175) . The intervention led to higher abundance of species Bifidobacterium_breve and Collinsella_aerofaciens and higher alpha-diversity (p<0.05).

Conclusions

Administration of the Bifidobacterium animalis subsp. Lactis BLa80 at a dose of 5×10⁹ CFU/day to children aged 0-3 years resulted in shorter duration of diarrhea, faster improvement in fecal consistency, and beneficial changes in GM composition.

Objectives and Study

Acute diarrhea continues to be a leading cause of morbidity, hospitalization, and mortality worldwide. Probiotics have been proposed as a complementary therapy in the treatment of acute diarrhea. The goal of this study is to assess the efficacy and safety of Bifidobacterium animalis subsp. Lactis XLTG11, as an adjunct to the treatment of acute watery diarrhea in children with a randomized, double-blinded, placebo-controlled study design.

Methods

Eligible diarrheal children were randomized into intervention group (IG, n=35, conventional treatment for diarrhea in combination with probiotic) and control group (CG, n=35, conventional treatment for diarrhea without probiotic). The primary assessments of this study were total duration of diarrhea and the improvement in diarrhea symptoms. Fecal samples were collected from all children before and after intervention to measure levels of sIgA, calprotectin, human beta-defensin 2 (HBD-2), and cathelicidin (LL-37), and to analyze the gut microbiome (GM) composition.

Results

After the intervention, the total duration and hospital stay time of diarrhea in IG [(121.3±11.5 h) and (3.4±1.1d) were significantly shorter than those of children in CG [(133.4±14.1h) and (4.0±1.3 d), p <0.001 and p=0.041, respectively ). More children in the IG showed improvements in diarrhea (defined as a decrease in fecal frequency to no more than four times per day and an improved fecal consistency within 72 h after treatment) than those in the CG for both per protocol analysis (57.1% vs 25.7%, p<0.001) and the same for the intention-to-treat analysis. The calprotectin levels in the IG was markedly lower than that in the CG after the intervention (928.91±158.90 ng/g vs. 1029.86±133.25 ng/g, p=0.028). The intervention led to higher abundance of species Bifidobacterium_longum and Bifidobacterium_breve and higher alpha-diversity of GM (p<0.05).

Conclusions

Administration of the Bifidobacterium animalis subsp. Lactis XLTG11 at a dose of 1×10¹⁰ CFU/day to children aged 0-3 years resulted in shorter duration of diarrhea, faster improvement in fecal consistency, and beneficial changes in GM composition.

Objectives and Study

We report the long-term safety, efficacy, and predictors of response among children with short bowel syndrome-associated intestinal failure (SBS-IF) receiving teduglutide (TED) 0.05 mg/kg/day.

Methods

This was a pooled, post hoc analysis of two open-label, long-term extension studies (NCT02949362, NCT02954458) in children with SBS-IF who received TED or no TED treatment (NTT). Patients were eligible for enrollment if they participated in one of the core phase 3 studies (NCT03571516, NCT01952080, NCT02682381). Endpoints were treatment-emergent adverse events (TEAE), growth parameters, and clinical response (≥20% reduction in parenteral nutrition and/or intravenous fluids [PN/IV] volume from baseline). Multivariable linear regression was used to identify predictors to TED response; the dependent variable was mean change in PN/IV volume at each visit through 144 weeks.

Results

The three patient cohorts were: NTT/NTT=7; TED/TED=69; any TED=78. Among the any TED group, median age at baseline was 4 years and 69.2% were male. Over 144 weeks, the most common TEAE in the any TED group was vomiting (53.8%); growth parameters remained stable. By week 96, 84.1% of the TED/TED group achieved a clinical response, with mean fluid decrease of 50.3 mL/kg/day and calorie decrease of 46.3 kcal/kg/day. Multivariable regression analysis indicated that older age at baseline, absence of stoma, non-White race, longer duration of total TED exposure, and increasing length of remnant small intestine were associated with a significant reduction in mean PN/IV volume requirements while receiving TED (Table 1).

Conclusions

In children with SBS-IF, TED treatment resulted in long-term reductions in PN/IV requirements; TEAEs were consistent with available data. Mean PN/IV volume reductions may depend on longer duration of TED exposure, underlying bowel anatomy, and demographics.

Objectives and Study

Facing with an increasing demand for transition management and guidelines, our intestinal failure team designed a therapeutic educational program specifically intended for adolescents on long-term home parenteral nutrition (HPN). The aim of this study was to report on the first sessions of this program.

Methods

Teenagers on HPN were offered to participate to the program according to their age. To limit the impact on schooling, the adolescent therapeutic educational program (ATEP) was designed in 3 sessions of 5 consecutive days, during school holidays over the year. The ATEP included group sessions on catheter handling, disconnecting and connecting the PN and catheter dressing but also sessions with psychologist, social worker, dance teacher, occupational therapist, fashion specialist, adults (who were once children) on HPN. Six months after the last session 3-day trips to the Futuroscope, Poitiers, France, were organized without any parental presence.

Results

Along the three training courses, a total of 16 adolescents were enrolled in the ATEP. They were aged between 13 and 17 years (median 14 years IQR: 14-16.25). At the time of the course, they received a median of 6 infusions/week (IQR: 5-7). All but three adolescents were receiving Taurolidine lock procedure. All teenagers followed the entire course without dropping out. At the end of the three sessions, 11 adolescents could be considered as fully autonomous, 3 as partially autonomous, at least for disconnection of the central line in the morning and for the CVC dressing, one did not achieve a sufficient autonomy and only one failed to gain any autonomy.

Conclusions

Through the holistic and multi-professional approach of this training and the group cohesion, the adolescents were not only able to handle catheter care and PN connections but were able to understand and accept better their illness and project themselves into their own future.

Objectives and Study

Pediatric feeding disorders (PFDs) are common, and their great phenotypic variability reflects the breadth of the associated nosological profiles. PFDs should be assessed and managed by multidisciplinary teams. Our study aimed to describe clinical signs of feeding difficulties in a group of PFD patients assessed by such a team, and to compare them with children in a control group.

Methods

In this case-control study, case group patients 1 to 6 years old were consecutively recruited through the multidisciplinary unit for the treatment of pediatric feeding difficulties based at Robert Debré Teaching Hospital in Paris, France. Children with an encephalopathy, severe neurometabolic disorder, or genetic syndrome (suspected or confirmed) were excluded. Members of the control group, consisting of children with no feeding difficulties (i.e., Montreal Children’s Hospital Feeding Scale scores below 60) or severe chronic diseases, were recruited from a day care center and 2 kindergartens. Data from medical histories and clinical examination related to mealtime practices, oral motor skills, neurodevelopment, sensory processing, and any functional gastrointestinal disorders (FGIDs) were recorded and compared between groups.

Results

In all, 244 PFD cases were compared with 109 controls (mean ages: cases, 3.42 [± 1.47]; controls, 3.32 [± 1.17]; P = 0.55). Use of distractions during meals was much more among PFD children (cases, 77.46%; controls, 5.5%; P < 0.001), as was conflict during meals. While the groups did not differ in their members’ hand-mouth coordination or ability to grab objects, cases began exploring their environments later; mouthing, especially, was less common in the case group (cases, n = 80 [32.92%]; controls, n = 102 [94.44%]; P < 0.001). FGIDs and signs of visual, olfactory, tactile, and oral hypersensitivity were significantly more frequent among cases.

Conclusions

Initial clinical assessments showed that, in the children with PFDs, normal stages of environmental exploration were altered, and that this was often associated with signs of sensory hypersensitivity and digestive discomfort.

Objectives and Study

In the paediatric population interest is growing in the use of a blended diet for the management of feeding intolerances. It is perceived to be better tolerated compared to commercially available whole protein enteral formulas. The medical nutrition industry have responded to this cultural shift in adopting blended diets and developed an enteral tube feed Compleat ® Paediatric that contain 14% food ingredients, 1g Fibre/ 100ml.

Another perceived factor believed to have an impact on feed tolerance relates to the mode in which nutrition is delivered in relation to intermittent bolus or continuous enteral feeding. This study aimed to evaluate the tolerance of different feeding modes (intermittent bolus/ continuous/ combination) in children who are fed with an 'enteral formula with food derived ingredients'.

Methods

Data was collected by paediatric dietitians from dietetic records over a month period on children who had switched to an enteral formula with food derived ingredients. Data was inputted to a Microsoft form to capture the impact of varying modes of feeding (intermittent bolus/continuous/ combination) on gastrointestinal and anthropometric outcomes.

Results

Forty-three children were recruited between March 2021 to July 2021 across four National Health Service Trusts. Children who were continuously fed saw the greatest reported improvement in retching, abdominal pain and loose stools. Children who were fed intermittent bolus reported the greatest increase in weight (p-value 0.003). Over 90% of dietitians reported nutritional goals were achieved after switching from a standard formula to an enteral formula with food-derived ingredients for both continuous and intermittent bolus feeding; children who were fed continuously reported the highest achievement to meet dietitian’s nutritional goals.

Conclusions

'Enteral formulas with food derived ingredients' are well tolerated and effective in achieving weight gain and meeting dietetic goals whether delivered continuously or as intermittent bolus feed. The clinical situation will determine the most appropriate and effective feeding mode.

Objectives and Study

Hypophosphataemia and refeeding syndrome recently have been reported in preterm babies receiving enhanced nutrition. We aimed to investigate in extremely low birthweight babies (ELBW, <1,000 g) whether serum phosphate and calcium concentrations, and refeeding syndrome (defined as phosphate <1.4 mmol.L^-1 and calcium >2.8 mmol.L^-1) in the first week after birth were associated with neurodevelopment at 2 years’ corrected age (CA).

Methods

Secondary cohort analysis of a subgroup of ELBW babies in the ProVIDe randomised trial of an additional 1 g.d^-1 amino acids in the first five days after birth who had serum biochemistry available. At 2 years’ CA neurodisability was assessed by neurological examination and Bayley III assessment. Associations between neurodisability and serum biochemistry in the first week after birth were tested using t-tests, linear and logistic regression adjusted for sex and smallness-for-gestational-age.

Results

382 babies (47% male) were included. Mean (SD) gestational age was 26.4 (2.3) weeks and birthweight 782 (134) g. 71 babies died before 2 years CA. 181/294 (62%) surviving children assessed were free of neurodisability. Children with neurodisability had lower serum phosphate concentrations than those without neurodisability (mean (SD) 1.2 (0.5) vs. 1.4 (0.4) mmol.L^-1, p<0.01). The combined outcome of death or neurodisability was more common in babies whose serum phosphate was in the lowest (<0.9 mmol.L^-1), compared with the highest (>1.6 mmol.L^-1), quartile (adjusted odds ratio [aOR] 3.5 (95%CI 1.8, 6.8, p<0.001), for those with a serum calcium in the highest (>2.74 mmol.L^-1) compared with the lowest (<2.6 mmol.L^-1) tertile (aOR 2.0 (95%CI 1.1, 3.4, p=0.02) and in babies with refeeding syndrome (aOR, 2.0 95%CI 1.1, 3.5, p=0.02).

Conclusions

Serum phosphate and calcium concentrations, and the presence of refeeding syndrome, in the first week after birth are associated with death and neurodisability. These biochemical disturbances should be preventable with careful nutritional management.

Objectives and Study

The malnutrition rate among infants with congenital heart disease (CHD) is high. An early nutritional evaluation and intervention helps its treatment and improves the prognosis. The objective is to prepare a consensus document for the evaluation and nutritional treatment of infants with CHC.

Methods

A modified Delphi technique was used. Based on the literature and their clinical experience, a scientific committee prepared statements that addressed the referral to Pediatric Nutrition Units (UNP) for the evaluation and nutritional management of infants with CHD. Specialists in pediatric cardiology and pediatric gastroenterology and nutrition evaluated the questionnaire in 2 rounds. Both the members of the scientific committee and the panelists are members of the SEGHNP or SECPCC.

Results

32 specialists participated. After two evaluation rounds, 150 out of 185 proposed items were agreed upon (81%). Cardiac pathologies of low and high nutritional risk and associated cardiac or extracardiac factors that confer high nutritional risk were determined. It is agreed to refer the patient with nutritional risk without having to wait for them to lose weight or have malnutrition. Recommendations for the evaluation and follow-up in nutrition units (NU) and on the calculation of nutritional requirements, the type of nutrition and the route of administration were elaborated. Emphasis is placed on the need for intensive nutritional treatment in the preoperative period and follow-up by the NU in the postoperative period when preoperative intervention has been required. And the need for reassessment by the cardiologist when nutritional goals are not achieved.

Conclusions

Early nutritional assessment and treatment aid better results and improve the long-term prognosis of infants with CHD. These recommendations can be helpful for the early detection and referral of vulnerable populations.

Objectives and Study

We evaluate the association between variations of the FADS/ELOVL gene clusters polymorphisms and children’s body fat mass (FM) at 8.5 years old.

Methods

107 children, 55 born to normal-weight, 25 to overweight and 26 to obese mothers, were included in the present analysis. 32 SNP’s from the FADS 1,2,3 and ELOVL 2,5,6 gene clusters were genotyped. The distributions of the genotypes were compatible with Hardy-Weinberg equilibrium. Linkage disequilibrium, Lewontin’s D′ and pairwise squared correlations r^2 were performed to select the most representative SNP’s. R package SNPassoc: an R package to perform whole genome association studies (type of association=Regression model) was used. ANOVA and Bonferroni post-hoc correction was performed. Children’s body composition was assessed by bioelectrical impedance (BIA) at 8,5 years old.

Results

Children born to obese and overweight mothers showed higher FM%, fat free mass (FFM%) and body water than those born to normal-weight mothers, at 8,5 yrs. The rs174602 SNP from FADS2 was negatively associated with the FM%: major alleles C/C {p=0.013, CI-95% (-3.707, -0.461)} and heterozygosis C/T {p=0.012, CI-95% (-4.114, -0.777)}. FM% resulted lower in children carrying C/T respect to those carrying homozygotic alleles, C/C or T/T {6.76±0.36; 9.34±0.64; 9.85±1.08, respectively; p=0.02; p_adj.=0.033 (adjusted by study group, pre-conceptional BMI, weight gain during pregnancy and maternal cultural level)}.

Conclusions

Major alleles (C/C) of rs174602, and specially C/T, seem to protect against obesity during childhood. Children FADS/ELOVL gene clusters polymorphisms may modulate early programming of obesity. The insight provided here could help to define a personalized nutrition for prevention/treatment of childhood obesity, based on genetic data, PUFAs supplementation, and differentiating by those maternal metabolic conditions favoring childhood obesity. More studies are necessary to confirm the present results.

Funded by Andalusian Economy, Science & Innovation Ministry (PREOBE Excellence Project Ref. P06-CTS-02341), Ministry of Economy & Competitiveness (SAF2015-69265-C2-1-R) and PREciSE (ERA-HDHL-Epigenetics).