A specific synbiotic-containing amino acid-based formula restores gut microbiota in non-IgE mediated cow's milk allergic infants: a randomized controlled trial.

BACKGROUND: Altered gut microbiota is implicated in cow's milk allergy (CMA) and differs markedly from healthy, breastfed infants. Infants who suffer from severe CMA often rely on cow's milk protein avoidance and, when breastfeeding is not possible, on specialised infant formulas such as amino-acid based formulas (AAF). Herein, we report the effects of an AAF including specific synbiotics on oral and gastrointestinal microbiota of infants with non-IgE mediated CMA with reference to healthy, breastfed infants. METHODS: In this prospective, randomized, double-blind controlled study, infants with suspected non-IgE mediated CMA received test or control formula. Test formula was AAF with synbiotics (prebiotic fructo-oligosaccharides and probiotic Bifidobacterium breve M-16V). Control formula was AAF without synbiotics. Healthy, breastfed infants were used as a separate reference group (HBR). Bacterial compositions of faecal and salivary samples were analysed by 16S rRNA-gene sequencing. Faecal analysis was complemented with the analysis of pH, short-chain fatty acids (SCFAs) and lactic acids. RESULTS: The trial included 35 test subjects, 36 controls, and 51 HBR. The 16S rRNA-gene sequencing revealed moderate effects of test formula on oral microbiota. In contrast, the gut microbiota was substantially affected across time comparing test with control. In both groups bacterial diversity increased over time but was characterised by a more gradual increment in test compared to control. Compositionally this reflected an enhancement of Bifidobacterium spp. and Veillonella sp. in the test group. In contrast, the control-fed infants showed increased abundance of adult-like species, mainly within the Lachnospiraceae family, as well as within the Ruminococcus and Alistipes genus. The effects on Bifidobacterium spp. and Lachnospiraceae spp. were previously confirmed through enumeration by fluorescent in situ hybridization and were shown for test to approximate the proportions observed in the HBR. Additionally, microbial activity was affected as evidenced by an increase of l-lactate, a decrease of valerate, and reduced concentrations of branched-chain SCFAs in test versus control. CONCLUSIONS: The AAF including specific synbiotics effectively modulates the gut microbiota and its metabolic activity in non-IgE mediated CMA infants bringing it close to a healthy breastfed profile.Trial registration Registered on 1 May 2013 with Netherlands Trial Register Number NTR3979.

A specific synbiotic-containing amino acid-based formula in dietary management of cow's milk allergy: a randomized controlled trial.

BACKGROUND: Here we report follow-up data from a double-blind, randomized, controlled multicenter trial, which investigated fecal microbiota changes with a new amino acid-based formula (AAF) including synbiotics in infants with non-immunoglobulin E (IgE)-mediated cow's milk allergy (CMA). METHODS: Subjects were randomized to receive test product (AAF including fructo-oligosaccharides and Bifidobacterium breve M-16V) or control product (AAF) for 8 weeks, after which infants could continue study product until 26 weeks. Fecal percentages of bifidobacteria and Eubacterium rectale/Clostridium coccoides group (ER/CC) were assessed at 0, 8, 12, and 26 weeks. Additional endpoints included stool markers of gut immune status, clinical symptoms, and safety assessments including adverse events and medication use. RESULTS: The trial included 35 test subjects, 36 controls, and 51 in the healthy reference group. Study product was continued by 86% and 92% of test and control subjects between week 8-12, and by 71% and 80%, respectively until week 26. At week 26 median percentages of bifidobacteria were significantly higher in test than control [47.0% vs. 11.8% (p < 0.001)], whereas percentages of ER/CC were significantly lower [(13.7% vs. 23.6% (p = 0.003)]. Safety parameters were similar between groups. Interestingly use of dermatological medication and reported ear infections were lower in test versus control, p = 0.019 and 0.011, respectively. Baseline clinical symptoms and stool markers were mild (but persistent) and low, respectively. Symptoms reduced towards lowest score in both groups. CONCLUSION: Beneficial effects of this AAF including specific synbiotics on microbiota composition were observed over 26 weeks, and shown suitable for dietary management of infants with non-IgE-mediated CMA.Trial Registration NTR3979.

A synbiotic-containing amino-acid-based formula improves gut microbiota in non-IgE-mediated allergic infants.

BackgroundPrebiotics and probiotics (synbiotics) can modify gut microbiota and have potential in allergy management when combined with amino-acid-based formula (AAF) for infants with cow's milk allergy (CMA).MethodsThis multicenter, double-blind, randomized controlled trial investigated the effects of an AAF-including synbiotic blend on percentages of bifidobacteria and Eubacterium rectale/Clostridium coccoides group (ER/CC) in feces from infants with suspected non-IgE-mediated CMA. Feces from age-matched healthy breastfed infants were used as reference (healthy breastfed reference (HBR)) for primary outcomes. The CMA subjects were randomized and received test or control formula for 8 weeks. Test formula was a hypoallergenic, nutritionally complete AAF including a prebiotic blend of fructo-oligosaccharides and the probiotic strain Bifidobacterium breve M-16V. Control formula was AAF without synbiotics.ResultsA total of 35 (test) and 36 (control) subjects were randomized; HBR included 51 infants. At week 8, the median percentage of bifidobacteria was higher in the test group than in the control group (35.4% vs. 9.7%, respectively; P<0.001), whereas ER/CC was lower (9.5% vs. 24.2%, respectively; P<0.001). HBR levels of bifidobacteria and ER/CC were 55% and 6.5%, respectively.ConclusionAAF including specific synbiotics, which results in levels of bifidobacteria and ER/CC approximating levels in the HBR group, improves the fecal microbiota of infants with suspected non-IgE-mediated CMA.

Clinical update: recurrent abdominal pain in children.

Recurrent abdominal pain (RAP) is common in children and most cases have a non-organic cause. Diagnosis is made by excluding other serious causes, and early referral and intervention help ensure a better outcome. RAP can cause significant anxiety in parents and carers, who can become overwhelmed by fear of serious disease and feel helpless by being unable to relieve their child's pain. Parents and children (especially adolescents) need explanation that there is nothing seriously wrong with their 'tummy' and provide reassurance and support. Although there is limited evidence, pharmacological therapies are used in severe cases. The main crux of therapy is non-pharmacological and includes symptom control through lifestyle changes, dietary interventions and behavioural therapies with an aim to return to normal activity.

Clinical update: vomiting in infants.

Vomiting is very common in infants and is mostly caused by non-serious conditions. However, community practitioners may come across infants with serious causes of vomiting, requiring prompt referral. Bilious vomiting should always raise suspicion of a surgical cause and needs urgent assessment by the paediatric/surgical team. The role of community practitioners in the assessment of vomiting infants for 'red flag' symptoms and early interventions are discussed.

Challenges in management of irritable bowel syndrome in children.

Irritable bowel syndrome (IBS) is a common cause of recurrent abdominal pain (RAP) in children and can be a debilitating experience for both child and family. Organic causes of RAP symptoms such as celiac and inflammatory bowel diseases should be excluded before a diagnosis of IBS is made. Treatment consists of dietary manipulation, drugs, and stress management. Newer therapies may offer better control of symptoms with minimal side-effects. This article discusses the challenges faced by pediatricians in managing IBS and reviews management in the context of children from the Indian subcontinent.

Assessment of childhood obesity in secondary care: OSCA consensus statement.

This expert opinion provides detailed guidance on assessing obesity in secondary paediatric practice. This guidance builds on existing recommendations from National Institute of Health and Clinical Excellence in the UK, and is evidence based where possible. Guidance is provided on which obese children and young people are appropriate to be seen in secondary care and relevant history and investigations, and guidance on when further investigation of causes and obesity-related comorbidity is appropriate.

Clinical and economic impact of using macrogol 3350 plus electrolytes in an outpatient setting compared to enemas and suppositories and manual evacuation to treat paediatric faecal impaction based on actual clinical practice in England and Wales.

OBJECTIVE: To estimate the clinical and economic impact of using macrogol 3350 plus electrolytes (macrogol 3350; Movicol; Movicol Paediatric Plain) in an outpatient setting compared to enemas and suppositories and manual evacuation to treat paediatric faecal impaction. METHODS: A chart review was undertaken to extract clinical outcomes and resource use from the case notes of a cohort of children aged 2-11 years with faecal impaction who initially received either macrogol 3350 (in an outpatient setting) or enemas and suppositories or manual evacuation for initial disimpaction. Five centres across England and Wales participated in the study. These data were used to inform a decision model which depicted the management of children during the disimpaction phase and for a period of 12 weeks following initial disimpaction. Unit resource costs at 2005/2006 prices were applied to the resource utilisation estimates within the model, enabling the incremental costs and consequences of using macrogol 3350 in an outpatient setting, compared to the other treatments, to be estimated. RESULTS: 112 patients treated with macrogol 3350, 101 who received enemas and suppositories and 11 who underwent a manual evacuation were eligible for analysis. Ninety-seven per cent of children treated with macrogol 3350 were successfully disimpacted within 5 days, compared to 73% of those who received enemas and suppositories and 89% of those who underwent a manual evacuation (p < 0.001). There were no significant differences in reported adverse events between the different treatments for disimpaction, with the exception of vomiting which was significantly higher among those who underwent a manual evacuation (18% versus 2% with the other treatments; p < 0.01). There were no significant differences in the number of clinician outpatient visits between treatments. However, macrogol 3350-treated patients had significantly fewer hospital admissions than those who received the other interventions (0.1 versus 1.4 and 1.0 for enemas and suppositories and manual evacuation respectively; p < 0.05) and occupied fewer bed days. The total NHS cost of disimpaction and subsequent maintenance of children initially treated with macrogol 3350 was estimated to be 694 pounds sterling (95% CI: 496 pounds sterling; 892 pounds sterling). This compared with 2759 pounds sterling (95% CI: 1266 pounds sterling; 4252 pounds sterling) and 2333 pounds sterling (95% CI: 1609 pounds sterling; 3058 pounds sterling) for those who initially received enemas and suppositories or underwent a manual evacuation, respectively. Hence, using macrogol 3350 instead of enemas and suppositories and manual evacuation to disimpact the whole annual cohort of faecally impacted children aged 2-11 years in England could potentially reduce annual NHS expenditure on this condition by 59% (5 million pounds sterling) and reduce the annual number of paediatric hospital admissions for this condition by 92% (4330). CONCLUSION: Within the limitations of our model, macrogol 3350 affords the NHS a clinically effective and cost-effective treatment for the disimpaction of children suffering from faecal impaction compared to enemas and suppositories or a manual evacuation, and has the potential to release healthcare resources for alternative use within the system.

Treatment of faecal impaction with polyethelene glycol plus electrolytes (PGE + E) followed by a double-blind comparison of PEG + E versus lactulose as maintenance therapy.

OBJECTIVES: To assess the efficacy of polyethylene glycol 3350 plus electrolytes (PEG + E; Movicol) as oral monotherapy in the treatment of faecal impaction in children, and to compare PEG + E with lactulose as maintenance therapy in a randomised trial. PATIENTS AND METHODS: An initial open-label study of PEG + E in the inpatient treatment of faecal impaction (phase 1), followed by a randomised, double-blind comparison between PEG + E and lactulose for maintenance treatment of constipation over a 3-month period (phase 2) in children aged 2 to 11 years with a clinical diagnosis of faecal impaction. RESULTS: Disimpaction on PEG + E was achieved in 58 (92%) of 63 of children (89% of 2-4 year olds and 94% of 5-11 year olds) without additional interventions. A maximum dose of 4 sachets (for 2-4 year olds) or 6 sachets (for 5-11 year olds) was required; median time to disimpaction was 6 days (range, 3-7 days). Seven children (23%) reimpacted whilst taking lactulose, whereas no children reimpacted while taking PEG + E (P = 0.011). The total incidence rate of adverse events seen was higher in the lactulose group (83%) than in the PEG + E group (64%). CONCLUSIONS: PEG + E is safe and highly effective in the management of childhood constipation. It allows a single orally administered laxative to be used for disimpaction without recourse to invasive interventions. It is significantly more effective than lactulose as maintenance therapy, both in efficacy in treating constipation and efficacy in preventing the recurrence of faecal impaction.