Evaluation of ImpENSA technology-enabled behaviour change module delivered to healthcare professionals in South Africa to improve micronutrient nutrition during the first 1000 days.

Healthcare professionals (HCPs) have vital roles in providing evidence-based care to promote healthy micronutrient nutrition in early life. Providing such care requires scalable training to strengthen knowledge and confident application of effective behaviour change skills. Among 33 public and private HCPs (primarily dietitians) in South Africa, we evaluated the behaviour change aspects of a technology-enabled National Qualification Sub-Framework level 6 programme, Improving Early Nutrition and Health in South Africa ('ImpENSA'). This programme comprises two self-directed micronutrient and behaviour change knowledge-based eLearning and one facilitated online practical skills modules to improve maternal and infant micronutrient nutrition. Using assessments, questionnaires and interviews, we collected data at baseline, after module completion and at 3-month follow-up after programme completion. Questionnaire and interview data showed major improvements in understanding of and attitudes towards person-centred behaviour change support immediately following the eLearning module on behaviour change. The assessment pass rate increased from 38% at baseline to 88% postmodule, demonstrating significant knowledge gain in behaviour change support. Intention to change practice towards a person-centred approach was high and many had already started implementing changes. Three months postprogramme, support was centred around patients' needs. Open relationships with patients, improved patient outcomes and increased job satisfaction were among reported outcomes. Many reported becoming better change facilitators and reflective practitioners. Additional improvements in understanding and attitudes to behaviour change support were evident, reinforced by making changes and experiencing positive outcomes. The findings suggest that technology-enabled learning can equip HCPs with knowledge and skills to effectively support behaviour change for healthy micronutrient nutrition during pregnancy and infancy.

Strain-Specificity of Probiotics in Pediatrics: A Rapid Review of the Clinical Evidence.

OBJECTIVE: The dogma of probiotic strain-specificity is widely accepted. However, only the genus- and species-specific effects of probiotics are supported by evidence from clinical trials. The aim of this rapid review was to assess clinical evidence supporting the claim that the efficacy of probiotics in the pediatric population is strain-specific. METHODS: The Cochrane Library, MEDLINE, and EMBASE databases were searched (up to August 2022) for randomized controlled trials (RCTs) conducted in children aged 0-18 years evaluating the effects of prophylactic or therapeutic administration of probiotics (well-characterized at the strain level) for conditions such as antibiotic-associated diarrhea, acute diarrhea, necrotizing enterocolitis, respiratory tract infections, Helicobacter pylori infection, and atopic dermatitis. To allow evaluation of strain-specificity, a trial could only be included in the review if at least one additional RCT assessed the effect of a different strain of the same species against the same comparator. RCTs without proper strain-level data were excluded. In the absence of identifying head-to-head strain versus strain RCTs, indirect comparisons were made between interventions. RESULTS: Twenty-three RCTs were eligible for inclusion. Out of the 11 performed comparisons, with 1 exception (two Lacticaseibacillus paracasei strains in reducing atopic dermatitis symptoms), no significant differences between the clinical effects of different strains of the same probiotic species were found. CONCLUSIONS: Head-to-head comparison is an optimal study design to compare probiotic strains, but such comparisons are lacking. Based on indirect comparisons, this rapid review demonstrates insufficient clinical evidence to support or refute the claim that probiotic effects in children are strain-specific.

Gluten- and casein-free diet and autism spectrum disorders in children: a systematic review.

PURPOSE: Effective treatments for core symptoms of autism spectrum disorders (ASD) are lacking. We systematically updated evidence on the effectiveness of a gluten-free and casein-free (GFCF) diet as a treatment for ASD in children. METHODS: The Cochrane Library, MEDLINE, and EMBASE databases were searched up until August 2016, for randomized controlled trials (RCTs); additional references were obtained from reviewed articles. RESULTS: Six RCTs (214 participants) were included. With few exceptions, there were no statistically significant differences in autism spectrum disorder core symptoms between groups, as measured by standardized scales. One trial found that compared with the control group, in the GFCF diet group there were significant improvements in the scores for the 'communication' subdomain of the Autism Diagnostic Observation Schedule and for the 'social interaction' subdomain of the Gilliam Autism Rating Scale. Another trial found significant differences between groups in the post-intervention scores for the 'autistic traits', 'communication', and 'social contact' subdomains of a standardized Danish scheme. The remaining differences, if present, referred to parent-based assessment tools or other developmental/ASD-related features. No adverse events associated with a GFCF diet were reported. CONCLUSIONS: Overall, there is little evidence that a GFCF diet is beneficial for the symptoms of ASD in children.

ω-3 Fatty Acid Supplementation Does Not Affect Autism Spectrum Disorder in Children: A Systematic Review and Meta-Analysis.

Background: Effective treatments for the core symptoms of autism spectrum disorder (ASD) are still lacking.Objective: We aimed to update the data on the effectiveness of ω-3 (n-3) fatty acid (FA) supplementation as a treatment for ASD.Methods: The Cochrane Library, MEDLINE, and EMBASE databases were systematically searched up until August 2016 with no language restrictions for randomized controlled trials (RCTs) comparing ω-3 FA supplementation with placebo or with no supplementation. Participants were children diagnosed with ASD. All functional outcome measures reported were considered. For dichotomous outcomes, the results for individual studies and pooled statistics were reported as RRs. Mean differences (MDs) were calculated for continuous outcomes.Results: Five RCTs (183 participants) were included. With 4 exceptions, there were no statistically significant differences in ASD symptoms between groups measured by validated scales. Among studies that used the Aberrant Behavior Checklist, parents' ratings indicated significant improvement in lethargy symptoms in the ω-3 FA group compared with the placebo group (2 RCTs) (pooled MD: 1.98; 95% CI: 0.32, 3.63). Among studies that used the Behavioral Assessment System for Children, parents' ratings indicated significant worsening of both externalizing behavior (2 RCTs) (pooled MD: -6.22; 95% CI: -10.9, -1.59) and social skills (1 RCT) (MD: -7; 95% CI: -13.62, -0.38) in the ω-3 FA group compared with the placebo group. One RCT reported a significant improvement in the ω-3 FA group for the daily-living component of the Vineland Adaptive Behavior Scale (MD: 6.2; 95% CI: 0.37, 12.03). Adverse effects were similar in both groups.Conclusions: Because of the limited number of included studies and small sample sizes, no firm conclusions can be drawn. However, the limited data currently available suggest that ω-3 FA supplementation does not enhance the performance of children with ASD.

Mean corpuscular volume of control red blood cells determines the interpretation of eosin-5'-maleimide (EMA) test result in infants aged less than 6 months.

Eosin-5'-maleimide (EMA) binding test is a flow cytometric test used to detect hereditary spherocytosis (HS). To perform the test sample from patients, 5-6 reference samples of red blood are needed. Our aim was to investigate how the mean corpuscular volume (MCV) of red blood cells influences on the value of fluorescence of bounded EMA dye and how the choice of reference samples affects the test result. EMA test was performed in peripheral blood from 404 individuals, including 31 children suffering from HS. Mean fluorescence channel of EMA-RBCs was measured with Cytomics FC500 flow cytometer. Mean corpuscular volume of RBCs was assessed with LH750 Beckman Coulter. Statistical analysis was performed using Graph Pad Prism. The correlation Spearman coefficient between mean channel of fluorescence of EMA-RBCs and MCV was r = 0.39, p < 0.0001. Interpretation of EMA test depends on MCV of the reference samples. If reference blood samples have lower MCV than the patients MCV, EMA test result might be negative. Due to different MCV values of RBCs in infancy and ca. Three months later, EMA test in neonates might be interpreted falsely negative. Samples from children younger than 3 months old had EMA test result 86.1 ± 11.7 %, whereas same samples that analyzed 4.1 ± 2.1 later had results of 75.4 ± 4.5 %, p < 0.05. Mean fluorescence of EMA-bound RBC depends on RBC's volume. MCV of reference samples affects EMA test results; thus, we recommend selection of reference samples with MCV in range of ±2 fL compared to MCV of patient RBC's.

Point-of-care ultrasound to assess degree of dehydration in children: a systematic review with meta-analysis.

BACKGROUND: There is no perfect method to assess level of dehydration in children. There are studies with conflicting results, where point-of-care ultrasound (POCUS) measurement of diameter ratio of the inferior vena cava to the aorta (IVC/Ao) was used to predict degree of dehydration. OBJECTIVE: To systematically review the diagnostic accuracy of POCUS measurement of IVC/Ao ratio in predicting dehydration in children. METHODS: MEDLINE, EMBASE and Cochrane databases were searched. The primary outcome was the diagnostic accuracy of IVC/Ao ratio. The pooled sensitivity and specificity were calculated. Quality analysis was conducted using Quality Assessment of Diagnostic Accuracy Studies-2. RESULTS: Eleven studies (2679 patients) were included. The most numerous group (five studies) used percentage weight change as a reference standard; the pooled sensitivity, specificity of POCUS in this group were: 0.7 (95% CI: 0.67 to 0.73), I2: 82%; 0.53 (95% CI: 0.5 to 0.53), I2: 84%. In the remaining studies, different comparator tests were used: Clinical Dehydration Scale (two studies, 0.8 (95% CI: 0.72 to 0.86), I2: 0%; 0.56 (95% CI: 0.48 to 0.65), I2: 0%; clinical judgement (three studies, 0.78 (95% CI: 0.73 to 0.83), I2: 95%; 0.82 (95% CI: 0.77 to 0.86), I2: 93% and one study used the Dehydration: Assessing Kids Accurately score model. CONCLUSION: This systematic review and meta-analysis showed that POCUS has a moderate sensitivity and specificity for identifying dehydration in children. Its use as a complementary diagnostic tool could be promising but needs to be validated in randomised controlled trials. PROSPERO REGISTRATION NUMBER: CRD42022346166.

Probiotics and Antibiotic-Induced Microbial Aberrations in Children: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Probiotics are often considered in children to prevent antibiotic-associated diarrhea. However, the underlying mechanistic effects and impact of probiotics on antibiotic-induced microbiota changes are not well understood. Objective: To investigate the effects of a multispecies probiotic on the gut microbiota composition in children receiving antibiotics. Design, Setting, and Participants: This is a secondary analysis of a randomized, quadruple-blind, placebo-controlled clinical trial from February 1, 2018, to May 31, 2021, including 350 children receiving broad-spectrum antibiotics in the inpatient and outpatient settings. Patients were followed up until 1 month after the intervention period. Fecal samples and data were analyzed between September 1, 2022, and February 28, 2023. Eligibility criteria included 3 months to 18 years of age and recruitment within 24 hours following initiation of broad-spectrum systemic antibiotics. In total, 646 eligible patients were approached and 350 participated in the trial. Intervention: Participants were randomly assigned to receive daily placebo or a multispecies probiotic formulation consisting of 8 strains from 5 different genera during antibiotic treatment and for 7 days afterward. Main Outcomes and Measures: Fecal stool samples were collected at 4 predefined times: (1) inclusion, (2) last day of antibiotic use, (3) last day of the study intervention, and (4) 1 month after intervention. Microbiota analysis was performed by 16S ribosomal RNA gene sequencing. Results: A total of 350 children were randomized and collected stool samples from 88 were eligible for the microbiota analysis (54 boys and 34 girls; mean [SD] age, 47.09 [55.64] months). Alpha diversity did not significantly differ between groups at the first 3 times. Shannon diversity (mean [SD], 3.56 [0.75] vs 3.09 [1.00]; P = .02) and inverse Simpson diversity (mean [SD], 3.75 [95% CI, 1.66-5.82] vs -1.31 [95% CI, -3.17 to 0.53]; P = 1 × 10-4) indices were higher in the placebo group compared with the probiotic group 1 month after intervention. Beta diversity was not significantly different at any of the times. Three of 5 supplemented genera had higher relative abundance during probiotic supplementation, but this difference had disappeared after 1 month. Conclusions and Relevance: The studied probiotic mixture had minor and transient effects on the microbiota composition during and after antibiotic treatment. Further research is needed to understand their working mechanisms in manipulating the microbiome and preventing antibiotic-associated dysbiosis and adverse effects such as antibiotic-associated diarrhea. Trial Registration: ClinicalTrials.gov Identifier: NCT03334604.

Multispecies Probiotic for the Prevention of Antibiotic-Associated Diarrhea in Children: A Randomized Clinical Trial.

Importance: The efficacy of multispecies probiotic formulations in the prevention of antibiotic-associated diarrhea (AAD) remains unclear. Objective: To assess the effect of a multispecies probiotic on the risk of AAD in children. Design, Setting, and Participants: This randomized, quadruple-blind, placebo-controlled trial was conducted from February 2018 to May 2021 in a multicenter, mixed setting (inpatients and outpatients). Patients were followed up throughout the intervention period. Eligibility criteria included age 3 months to 18 years, recruitment within 24 hours following initiation of broad-spectrum systemic antibiotics, and signed informed consent. In total, 646 eligible patients were approached and 350 patients took part in the trial. Interventions: A multispecies probiotic consisting of Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Lactobacillus acidophilus W37, L acidophilus W55, Lacticaseibacillus paracasei W20, Lactiplantibacillus plantarum W62, Lacticaseibacillus rhamnosus W71, and Ligilactobacillus salivarius W24, for a total dose of 10 billion colony-forming units daily, for the duration of antibiotic treatment and for 7 days after. Main Outcomes and Measures: The primary outcome was AAD, defined as 3 or more loose or watery stools per day in a 24-hour period, caused either by Clostridioides difficile or of otherwise unexplained etiology, after testing for common diarrheal pathogens. The secondary outcomes included diarrhea regardless of the etiology, diarrhea duration, and predefined diarrhea complications. Results: A total of 350 children (192 boys and 158 girls; mean [range] age, 50 [3-212] months) were randomized and 313 were included in the intention-to-treat analysis. Compared with placebo (n = 155), the probiotic (n = 158) had no effect on risk of AAD (relative risk [RR], 0.81; 95% CI, 0.49-1.33). However, children in the probiotic group had a lower risk of diarrhea regardless of the etiology (RR, 0.65; 95% CI, 0.44-0.94). No differences were observed between the groups for most of the secondary outcomes, including adverse events. Conclusions and Relevance: A multispecies probiotic did not reduce the risk of AAD in children when analyzed according to the most stringent definition. However, it reduced the overall risk of diarrhea during and for 7 days after antibiotic treatment. Our study also shows that the AAD definition has a significant effect on clinical trial results and their interpretation. Trial Registration: ClinicalTrials.gov Identifier: NCT03334604.

Probiotics for the prevention of antibiotic-associated adverse events in children-A scoping review to inform development of a core outcome set.

INTRODUCTION: Routine use of probiotics during antibiotic therapy in children remains a subject of discussion. To facilitate synthesis of individual study results and guideline formulation, it is important to assess predefined, similar, and clinically important outcomes. Core outcome sets are a proposed solution for this issue. The aim of this review was to document choice, design, and heterogeneity of outcomes in studies that assessed the effects of probiotics used for the prevention of antibiotic-associated adverse events in children. METHODS: A scoping literature search covering three major databases was performed. Studies that evaluated oral probiotics' use concomitant with antibiotic therapy in children were included. Data on outcome definitions, measurement instruments, and follow-up were extracted. The outcomes were assigned to predefined core areas and domains. Data were analyzed descriptively. RESULTS: Thirty-seven studies were included in this review. Diarrhea, the most commonly reported outcome, had diagnostic criteria clearly defined only in 21 studies. In total, 16 different definitions of diarrhea were identified. Diarrhea duration, severity, and etiology were reported in 9, 4, and 7 studies, respectively. Twenty studies assessed gastrointestinal symptoms other than diarrhea. Seven studies reported outcomes related to resource use or the economic impact of the intervention. Only 2 studies assessed outcomes related to life impact. None of the studies predefined adverse events of probiotic use. CONCLUSIONS: Identified outcomes were characterized by substantial heterogeneity. The majority of outcomes were not designed to evaluate endpoints of real-life relevance. Results from this review suggest the need for a new core outcome set consisting of outcomes important for decision-making.

Early Life Exposure to Antibiotics and Autism Spectrum Disorders: A Systematic Review.

We systematically reviewed evidence from observational studies on the associations between autism spectrum disorders (ASD) and early-life antibiotic exposure. Eleven articles were included in the review. Prenatal antibiotic exposure was associated with a slightly increased risk of ASD in two cohort studies on overlapping populations and in one case-control study; in three other case-control studies, no significant association was found. One cohort study found a slightly reduced risk of ASD after postnatal antibiotic exposure, while two other cohort studies on overlapping populations and three case-control studies reported an increased risk. Meta-analysis of the eligible studies showed no significant associations. Current data are conflicting and do not conclusively support the hypothesis that early-life antibiotic exposure is associated with subsequent ASD development.

Effect of a multispecies probiotic on reducing the incidence of antibiotic-associated diarrhoea in children: a protocol for a randomised controlled trial.

INTRODUCTION: Certain individual probiotic strains have been proven to be effective in reducing the risk of antibiotic-associated diarrhoea (AAD). However, the effects of using multispecies probiotics (MPs) remain unclear. We aim to assess the effectiveness of a specific MP preparation (Winclove 612) in reducing the incidence of AAD in children. METHODS AND ANALYSIS: A total of 350 children aged 6 months to 18 years, undergoing antibiotic treatment, will be randomly allocated to receive either a MP consisting of two strains of Bifidobacterium (B. bifidum W23 and B. lactis W51) and six strains of Lactobacillus (L. acidophilus W37, L. acidophilus W55, L. paracasei W20, L. plantarum W62, L. rhamnosus W71 and L. salivarius W24) at a total dose of 1010 colony-forming units daily, or a placebo, from the first day of antibiotic treatment until 7 days after antibiotic cessation, up to a maximum of 17 days. The primary outcome will be the incidence of AAD, defined as ≥3 loose or watery stools (a score of A on the Amsterdam Infant Stool Scale or a score of 5-7 on the Bristol Stool Form scale) in 24 hours, caused either by Clostridium difficile or of otherwise unexplained aetiology, occurring during the intervention period. The secondary outcomes will include the incidence of AAD according to alternative definitions; the incidence of any kind of diarrhoea; the duration of diarrhoea; the need for hospitalisation; intravenous rehydration or discontinuation of antibiotic treatment due to diarrhoea; adverse events; and the intestinal microbiota composition. ETHICS AND DISSEMINATION: The study protocol is approved by the Ethics Committee of the Medical University of Warsaw. The findings will be published in a peer-reviewed journal and submitted to relevant conferences. DATE AND PROTOCOL VERSION IDENTIFIER: 14/10/2017. TRIAL REGISTRATION NUMBER: NCT03334604; Pre-results.