Anna Chmielewska

Randomized Feeding Intervention in Infants at High Risk for Celiac Disease

BACKGROUND A window of opportunity has been suggested for reducing the risk of celiac disease by introducing gluten to infants at 4 to 6 months of age. METHODS We performed a multicenter, randomized, double-blind, placebo-controlled dietary-intervention study involving 944 children who were positive for HLA-DQ2 or HLA-DQ8 and had at least one first-degree relative with celiac disease. From 16 to 24 weeks of age, 475 participants received 100 mg of immunologically active gluten daily, and 469 received placebo. Anti-transglutaminase type 2 and antigliadin antibodies were periodically measured. The primary outcome was the frequency of biopsy-confirmed celiac disease at 3 years of age. RESULTS Celiac disease was confirmed by means of biopsies in 77 children. To avoid underestimation of the frequency of celiac disease, 3 additional children who received a diagnosis of celiac disease according to the 2012 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition diagnostic criteria (without having undergone biopsies) were included in the analyses (80 children; median age, 2.8 years; 59% were girls). The cumulative incidence of celiac disease among patients 3 years of age was 5.2% (95% confidence interval [CI], 3.6 to 6.8), with similar rates in the gluten group and the placebo group (5.9% [95% CI, 3.7 to 8.1] and 4.5% [95% CI, 2.5 to 6.5], respectively; hazard ratio in the gluten group, 1.23; 95% CI, 0.79 to 1.91). Rates of elevated levels of anti-transglutaminase type 2 and antigliadin antibodies were also similar in the two study groups (7.0% [95% CI, 4.7 to 9.4] in the gluten group and 5.7% [95% CI, 3.5 to 7.9] in the placebo group; hazard ratio, 1.14; 95% CI, 0.76 to 1.73). Breast-feeding, regardless of whether it was exclusive or whether it was ongoing during gluten introduction, did not significantly influence the development of celiac disease or the effect of the intervention. CONCLUSIONS As compared with placebo, the introduction of small quantities of gluten at 16 to 24 weeks of age did not reduce the risk of celiac disease by 3 years of age in this group of high-risk children. (Funded by the European Commission and others; PreventCD Current Controlled Trials number, ISRCTN74582487.).

Effects of iron supplementation in nonanemic pregnant women, infants, and young children on the mental performance and psychomotor development of children: a systematic review of randomized controlled trials

BACKGROUND Uncertainty exists regarding the effects of iron supplementation on neurodevelopmental outcomes in the absence of anemia. OBJECTIVE Our objective was to evaluate the effects of iron supplementation in nonanemic pregnant women and in nonanemic healthy children aged <3 y on the mental performance and psychomotor development of children. DESIGN In this systematic review, MEDLINE, EMBASE, and The Cochrane Library were searched through December 2009 for randomized controlled trials (RCTs). RESULTS None of 5 RCTs individually showed a beneficial effect of iron supplementation during early life on the Mental Developmental Index of the Bayley Scales of Infant Development at different ages throughout the first 18 mo. Meta-analysis of 3 RCTs (n = 561) showed that, compared with placebo, supplementation with iron had no significant effect on childrens Mental Developmental Index at approximately 12 mo of age (weighted mean difference: 1.66; 95% CI: -0.14, 3.47). Three of 5 RCTs showed a beneficial effect of iron supplementation on the Psychomotor Development Index at some time points, whereas 2 did not. Meta-analysis of 3 RCTs (n = 561) showed significant improvement on the Psychomotor Development Index at approximately 12 mo of age in the iron-supplemented group compared with the control group (weighted mean difference: 4.21; 95% CI: 2.31, 6.12). Two RCTs showed no effect of iron supplementation on behavior. Neither of the 2 RCTs that addressed the influence of prenatal iron supplementation showed an effect of iron on either the intelligence quotient or behavioral status of the children. CONCLUSION Limited available evidence suggests that iron supplementation in infants may positively influence childrens psychomotor development, whereas it does not seem to alter their mental development or behavior.

Systematic review: early infant feeding and the prevention of coeliac disease

PREVENTCD, Prevent Coeliac Disease, is an international project investigating the hypothesis of possible induction of tolerance to gluten in genetically predisposed children through introducing small quantities of gluten during the period of breastfeeding.

The preventCD study design: towards new strategies for the prevention of coeliac disease

Background PreventCD (www.preventcd.com) is a European multicentre study, which studies the influence of infant nutrition, and that of genetic, immunologic and environmental factors, on the risk of developing coeliac disease (CD). The hypothesis is that it is possible to induce tolerance to gluten by introducing small quantities of gluten to infants, preferably while they are still being breast-fed, and that this might also reduce the risk for related autoimmune disorders. Aim To describe the design of this ongoing European CD research project. Methods PreventCD encompasses two study designs and two study populations: (i) a European multicentre study: a prospective, double-blind, randomized dietary-intervention study among infants from families with high risk of CD, and (ii) a Swedish population-based CD screening study among 12-year-olds from the general population, divided into two birth cohorts that differ with respect to infant feeding practices. Discussion PreventCD is expected to elucidate some of the genetic and immunological mechanisms involved in the process of immune intolerance.

Systematic review with meta-analysis: early infant feeding and coeliac disease – update 2015

New evidence emerged on early feeding practices and the risk of coeliac disease.

Systematic review: racecadotril in the treatment of acute diarrhoea in children.

Racecadotril (acetorphan) is an antisecretory drug that exerts its antidiarrhoeal effects by inhibiting intestinal enkephalinase.

Meta-analysis: Lactobacillus reuteri strain DSM 17938 (and the original strain ATCC 55730) for treating acute gastroenteritis in children

Lactobacillus reuteri ATCC 55730 has been shown to provide a moderate clinical effect in the treatment of acute gastroenteritis (AGE) in children. However, as the L. reuteri ATCC 55730 strain was found to carry potentially transferable resistance traits for tetracycline and lincomycin, it was replaced by a new strain, L. reuteri DSM 17938, without unwanted plasmid-borne antibiotic resistance. Bioequivalence of the two strains has been suggested. We aimed to systematically evaluate data on the effectiveness of L. reuteri DSM 17938 and the original strain, L. reuteri ATCC 55730, in the treatment of AGE in children. The Cochrane Library, MEDLINE, and EMBASE databases, reference lists, and abstract books of major scientific meetings were searched in August 2013, with no language restrictions, for relevant randomised controlled trials (RCTs). Two RCTs (n=196) that evaluated L. reuteri DSM 17938 and three RCTs (n=156) that evaluated L. reuteri ATCC 55730, which involved hospitalised children aged 3 to 60 months, met the inclusion criteria. Compared with placebo or no treatment, DSM 17938 significantly reduced the duration of diarrhoea (mean difference -32 h, 95% confidence interval (CI): -41 to -24) and increased the chance of cure on day 3 (relative risk: 3.5, 95% CI: 1.2 to 10.8, random effects model). Similar results were obtained with the original strain, L. reuteri ATCC 55730. In conclusion, in hospitalised children, use of both strains of L. reuteri reduced the duration of diarrhoea, and more children were cured within 3 days. Data from outpatients and countryspecific cost-effectiveness analyses are needed. Given the limited data and the methodological limitations of the included trials, the evidence should be viewed with caution.

The effect of glucomannan on body weight in overweight or obese children and adults: a systematic review of randomized controlled trials.

OBJECTIVE Glucomannan (GM), a soluble fiber derived from the plant Amorphophallus konjac, is marketed as being helpful in reducing body weight. However, the data supporting this claim are scarce. The aim of this review was to systematically evaluate the effects of GM on body weight (BW) and body mass index (BMI) in otherwise healthy obese or overweight children and adults. METHODS MEDLINE, EMBASE, CENTRAL, and Google Scholar databases were systematically searched up to June 2014 for randomized controlled trials (RCTs) assessing the effectiveness of GM versus placebo. The primary outcome measures were BW and BMI. RESULTS Six eligible RCTs, only one of which performed in children, were included. In adults, three RCTs reported a significant reduction in BW in the GM group compared with the control group at the following different points during the intervention: At week 2 (mean difference [MD], 0.21 kg; 95% confidence interval [CI], 0.13-0.29); at week 4 (MD, 2.04; 95% CI, 0.52-3.56); at week 5 (MD, 1.3; 95% CI, 0.89-1.71); and at week 8 (MD, 3.17; 95% CI, 1.29-5.05). Only one RCT reported a beneficial effect at more than one point. None of the RCTs reported a favorable effect of GM on BMI. CONCLUSIONS In otherwise healthy overweight or obese adults, there is some evidence that in the short term GM may help to reduce BW, but not BMI. Data in children are too limited to draw any conclusions.

The Impact of E-Learning on Adherence to Guidelines for Acute Gastroenteritis: A Single-Arm Intervention Study.

Objective E-learning is a candidate tool for clinical practice guidelines (CPG) implementation due to its versatility, universal access and low costs. We aimed to assess the impact of a five-module e-learning course about CPG for acute gastroenteritis (AGE) on physicians’ knowledge and clinical practice. Study design This work was conceived as a pre/post single-arm intervention study. Physicians from 11 European countries registered for the online course. Personal data, pre- and post-course questionnaires and clinical data about 3 to 5 children with AGE managed by each physician before and after the course were collected. Primary outcome measures included the proportion of participants fully adherent to CPG and number of patients managed with full adherence. Results Among the 149 physicians who signed up for the e-learning course, 59 took the course and reported on their case management of 519 children <5 years of age who were referred to their practice because of AGE (281 and 264 children seen before and after the course, respectively). The course improved knowledge scores (pre-course 8.6 ± 2.7 versus post-course 12.8 ± 2.1, P < 0.001), average adherence (from 87.0 ± 7.7% to 90.6 ± 7.1%, P = 0.001) and the number of patients managed in full adherence with the guidelines (from 33.6 ± 31.7% to 43.9 ± 36.1%, P = 0.037). Conclusions E-learning is effective in increasing knowledge and improving clinical practice in paediatric AGE and is an effective tool for implementing clinical practice guidelines.

Primary Prevention of Celiac Disease: Environmental Factors with a Focus on Early Nutrition.

Celiac disease (CD) is a common autoimmune disorder caused by ingestion of gluten. When diagnosed, it should be treated with a lifelong, strict gluten-free diet. Early infant feeding practices have been suggested as a means of preventing CD. In the last few decades, observational data have suggested that breastfeeding, especially at the time of introducing gluten into the infants diet, as well as the time and mode of gluten first being given to a child could prevent or delay the occurrence of CD. As a result, recommendations advised that it is prudent to avoid both early (<4 months) and late (>7 months) introduction of gluten, and to introduce gluten gradually while the infant is still being breastfed, as this may reduce the risk of celiac disease, type 1 diabetes mellitus, and wheat allergy. Recently, the results of two large randomized trials have shown that breastfeeding in general, breastfeeding during gluten introduction, and early or delayed gluten introduction do not influence the total risk of CD in genetically predisposed individuals. Introducing gluten at 4 versus 6 months in very small amounts, or at 6 versus 12 months, resulted in similar rates of CD in these children. Thus, early feeding practices seem to have no impact on the risk of developing CD during childhood. In children without the genetic predisposition, the age and mode of gluten introduction do not influence the risk anyway.