Effect of Low-Dose Iron Supplementation on Early Development in Breastfed Infants: A Randomized Clinical Trial.

Importance: Breastfed infants are at risk of iron deficiency, which is associated with suboptimal development. There is a paucity of evidence on the effects of iron supplementation on child development, and current guidelines are divergent. Objective: To assess whether daily iron supplementation, 1 mg/kg, between 4 and 9 months in exclusively or predominantly breastfed infants improves psychomotor development at 12 months. Design, Setting, and Participants: This was a randomized, double-blind, placebo-controlled trial conducted between December 2015 and May 2020 with follow-up through May 2023 in an outpatient setting in Poland and Sweden. Participants were healthy singleton infants born at term with birth weight greater than 2500 g who were exclusively or predominantly breastfed (>50%) and did not have anemia (hemoglobin >10.5 g/dL) at age 4 months. Exclusion criteria included major illness, congenital anomaly, food allergy, and difficulty communicating with caregivers. Interventions: Iron (micronized microencapsulated ferric pyrophosphate), 1 mg/kg, or placebo (maltodextrin) once daily from age 4 to 9 months. Main Outcomes and Measures: The primary outcome was psychomotor development assessed by motor score of Bayley Scales of Infant and Toddler Development III at 12 months, adjusted for gestational age, sex, and maternal education. Secondary outcomes included cognitive and language scores at 12 months; motor, cognitive, and language scores at 24 and 36 months; iron deficiency (serum ferritin <12 ng/mL), and iron deficiency anemia (iron deficiency and hemoglobin <10.5 g/dL) at 12 months. Results: Of 221 randomized infants (111 female), 200 (90%) were included in the intention-to-treat analysis (mean [SD] age, 12.4 [0.8] months). Iron supplementation (n = 104) compared to placebo (n = 96) had no effect on psychomotor development (mean difference [MD] for motor score, -1.07 points; 95% CI, -4.69 to 2.55), cognitive score (MD, -1.14; 95% CI, -4.26 to 1.99), or language score (MD, 0.75; 95% CI, -2.31 to 3.82) at 12 months. There were no significant differences at 24 and 36 months. The intervention did not reduce the risk for iron deficiency (relative risk [RR], 0.46; 95% CI, 0.16 to 1.30) or iron deficiency anemia (RR, 0.78; 95% CI, 0.05 to 12.46) at 12 months. Conclusion and Relevance: No benefit was found with daily low-dose iron supplementation between 4 and 9 months with respect to psychomotor development, risk of iron deficiency, or iron deficiency anemia among breastfed infants in a setting of low risk of anemia. Trial Registration: ClinicalTrials.gov Identifier: NCT02242188.

Gelatine tannate in the management of acute gastroenteritis in children: a randomised controlled trial.

OBJECTIVE: To assess the efficacy of gelatine tannate (a complex of tannic acid with astringent and anti-inflammatory properties, and a protective gelatine) for the treatment of acute gastroenteritis (AGE) in children. DESIGN: Randomised, double-blind, placebo-controlled trial. Intention-to-treat analysis. SETTING: Two paediatric hospitals in Warsaw. PARTICIPANTS: Children younger than 5 years of age with AGE, defined as a change in stool consistency to a loose or liquid form (according to the Bristol Stool Form Scale or Amsterdam Stool Form Scale) and/or an increase in the frequency of evacuations (≥3 in 24 hours), lasting for no longer than 5 days. INTERVENTIONS: Seventy-two children were assigned to receive gelatine tannate (n=36) or placebo (n=36) in addition to standard rehydration therapy. The gelatine tannate was administered at an age-dependent dose (250-500 mg), and both study products were taken four times per day for 5 days. PRIMARY AND SECONDARY OUTCOME MEASURES: The main outcome measure was duration of diarrhoea. Secondary outcomes included the need for intravenous rehydration, need for hospitalisation of outpatients, number of watery stools per day, vomiting, weight gain, adverse events, recurrence of diarrhoea, severity of diarrhoea according to the Vesikari Scale and use of concomitant medications. RESULTS: Sixty-four children (89%) completed the intervention and were included in the analysis. The duration of diarrhoea after randomisation was similar in the gelatine tannate and placebo groups (75.6±27.8 vs 75.5±29.0 hours, respectively, mean difference 0.1 hours, 95% CI -14.1 to 14.3 hours). There was no significant difference between groups in the number of watery stools per day throughout the study period. There were also no differences in any other secondary outcome measures between groups. CONCLUSION: In children with AGE younger than 5 years of age, gelatine tannate was ineffective as an adjunct to rehydration therapy. TRIAL REGISTRATION NUMBER: NCT02280759.

Probiotic Bacterial and Fungal Strains: Claims with Evidence.

BACKGROUND: Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit for the host. This review summarizes current (i.e. published in the last 5 years) key evidence on probiotic efficacy and its safety in adults and children. To identify relevant data, searches of MEDLINE and the Cochrane Library databases were performed in August 2015 to locate randomized controlled trials (RCTs) or their meta-analyses. The focus was on commonly used, well-specified, bacterial and yeast probiotics for the treatment of gastrointestinal disorders. The MEDLINE database was also searched for evidence-based clinical practice guidelines, developed by scientific societies in the same timeframe. Data on safety of probiotics were obtained from a document developed by the US Agency for Healthcare Research and Quality. KEY MESSAGES: A number of relevant RCTs and meta-analyses are available. Saccharomyces boulardii is the most studied yeast probiotic, and Lactobacillus rhamnosus GG is the most studied bacterial probiotic. For both, the best documented fact is their efficacy for the treatment of acute gastroenteritis, especially in children, and for the prevention of antibiotic-associated diarrhea, both in adults and children. There is some evidence to support the use of probiotics to prevent or treat other diseases, such as necrotizing enterocolitis, infantile colic, Helicobacter pylori infection, and irritable bowel syndrome, but further studies are needed to identify which strain(s) is/are the most effective. Data on safety, particularly long-term safety, are limited. The risk of side effects is greater in people who have severe underlying health conditions. CONCLUSIONS: The evidence on bacterial and yeast probiotics has considerably expanded during recent years. Accumulated data allow one to make informed decisions about the effectiveness of probiotics and about how to reduce the use of those without proven efficacy.

Efficacy and safety of gelatine tannate for the treatment of acute gastroenteritis in children: protocol of a randomised controlled trial.

INTRODUCTION: Worldwide, acute gastroenteritis in children, usually caused by viruses, leads to considerable morbidity and mortality. The treatment is aimed at preventing and treating dehydration, promoting weight gain after rehydration, and reducing the duration and severity of diarrhoea. Effective and inexpensive interventions that could add to the effect of oral rehydration therapy are of interest. Recently, in many European countries, gelatine tannate is being widely marketed for treating acute gastroenteritis. Gelatine tannate is a complex of tannic acid, which possesses astringent and anti-inflammatory properties, and a protective gelatine. Currently, there is no evidence to support the use of gelatine tannate for treating acute gastroenteritis in children and only scant evidence to support the use of gelatine tannate in adults. We aim to assess the efficacy of gelatine tannate for the treatment of acute gastroenteritis in children. METHODS AND ANALYSIS: This will be a blind, placebo-controlled, randomised trial. Children younger than 5 years of age with acute gastroenteritis defined as a change in stool consistency to loose or liquid form (according to the Bristol Stool Form scale or Amsterdam Stool Form scale) and/or an increase in the frequency of evacuations (typically ≥ 3 in 24 h), lasting for no longer than 5 days, will be recruited. A total of 72 children will be randomised to receive either gelatine tannate (children younger than 3 years of age will receive 250 mg, 4 times/day, and those older than 3 years of age will receive 500 mg, 4 times/day) or matching placebo for 5 days. The primary outcome measure is the duration of diarrhoea. ETHICS AND DISSEMINATION: The Bioethics Committee approved the study protocol. The findings of this trial will be submitted to a peer-reviewed paediatric journal. Abstracts will be submitted to relevant national and international conferences. TRIAL REGISTRATION NUMBER: NCT02280759; Pre-results.

No effect of proton pump inhibitors on crying and irritability in infants: systematic review of randomized controlled trials.

Proton pump inhibitors are increasingly being used to treat infants with crying and/or irritability based on the assumption that these symptoms are attributable to gastroesophageal reflux. However, the data from a systematic review of randomized controlled trials do not support the use of proton pump inhibitors to decrease infant crying and irritability.