Overall, there is little evidence that a GFCF diet is beneficial for the symptoms of ASD in children.
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. Electronic supplementary material The online version of this article (10.1007/s10803-019-04093-y) contains supplementary material, which is available to authorized users.
IMPORTANCEThe 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 PARTICIPANTSThis 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 MEASURESThe 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
Our main finding was that probiotics and fermented formulas did not cause d-lactic acidosis in healthy children.
IntroductionCertain 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 analysisA 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 disseminationThe 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 identifier14/10/2017.Trial registration numberNCT03334604; Pre-results.
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.
IntroductionRoutine 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. MethodsA 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. ResultsThirty-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.
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