Cow’s milk protein allergy (CMPA) is associated with dysbiosis of the infant gut microbiome, with allergic and immune development implications. Studies show benefits of combining synbiotics with hypoallergenic formulae, although evidence has never been systematically examined. This review identified seven publications of four randomised controlled trials comparing an amino acid formula (AAF) with an AAF containing synbiotics (AAF-Syn) in infants with CMPA (mean age 8.6 months; 68% male, mean intervention 27.3 weeks, n = 410). AAF and AAF-Syn were equally effective in managing allergic symptoms and promoting normal growth. Compared to AAF, significantly fewer infants fed AAF-Syn had infections (OR 0.35 (95% CI 0.19–0.67), p = 0.001). Overall medication use, including antibacterials and antifectives, was lower among infants fed AAF-Syn. Significantly fewer infants had hospital admissions with AAF-Syn compared to AAF (8.8% vs. 20.2%, p = 0.036; 56% reduction), leading to potential cost savings per infant of £164.05–£338.77. AAF-Syn was associated with increased bifidobacteria (difference in means 31.75, 95% CI 26.04–37.45, p < 0.0001); reduced Eubacterium rectale and Clostridium coccoides (difference in means −19.06, 95% CI −23.15 to −14.97, p < 0.0001); and reduced microbial diversity (p < 0.05), similar to that described in healthy breastfed infants, and may be associated with the improved clinical outcomes described. This review provides evidence that suggests combining synbiotics with AAF produces clinical benefits with potential economic implications.

Children with or at risk of faltering growth require nutritional support and are often prescribed oral nutritional supplements (ONS). This randomised controlled trial investigated the effects of energy-dense paediatric ONS (2.4 kcal/ml, 125 ml: cONS) versus 1.5 kcal/ml, 200 ml ONS (sONS) in community-based paediatric patients requiring oral nutritional support. Fifty-one patients (mean age 5.8 years (SD 3)) with faltering growth and/or requiring ONS to meet their nutritional requirements were randomised to cONS (n = 27) or sONS (n = 24) for 28 days. Nutrient intake, growth, ONS compliance and acceptability, appetite and gastro-intestinal tolerance were assessed. Use of the cONS resulted in significantly greater mean total daily energy (+ 531 kcal/day), protein (+ 10.1 g/day) and key micronutrient intakes compared with the sONS group at day 28 and over time, due to high ONS compliance (81% of patients ≥ 75%), maintained intake from diet alone and improved appetite in the cONS group, compared with the sONS group. Although growth increased in both intervention groups, results were significant in the cONS group (weight (p = 0.007), height (p < 0.001) and height z-score (p = 0.006)).Conclusions: This study shows that use of energy-dense (2.4 kcal/ml) low-volume paediatric-specific ONS leads to improved nutrient intakes, growth and appetite in paediatric patients requiring oral nutrition support compared with standard energy density ONS.Trial registration: The trial is registered at clinicaltrials.gov, identification number NCT02419599. What is Known:• Faltering growth is the failure of children to achieve adequate growth at a normal rate for their age and requires nutritional support, including the use of oral nutritional supplements (ONS).• Energy-dense, low-volume ONS have benefits over standard ONS in adults. What is New:• This is the first RCT to investigate the effects of energy-dense, low-volume ONS (2.4 kcal/ml, 125 ml) in children with faltering growth, showing significant improvements in total nutrient intake and increased growth.• Energy-dense, low-volume ONS can play a key role in the management of faltering growth.

Cow’s milk protein allergy (CMPA) is common and costly. Clinical trials of infants with CMPA have shown that the use of an amino acid formula containing pre- and probiotics (synbiotics) (AAF-Syn) may lead to significant reductions in infections, medication prescriptions and hospital admissions, compared to AAF without synbiotics. These effects have not yet been confirmed in real-world practice. This retrospective matched cohort study examined clinical and healthcare data from The Health Improvement Network database, from 148 infants with CMPA (54% male, mean age at diagnosis 4.69 months), prescribed either AAF-Syn (probiotic Bifidobacterium breve M16-V and prebiotics, including chicory-derived oligo-fructose and long-chain inulin) or AAF. AAF-Syn was associated with fewer symptoms (−37%, p < 0.001), infections (−35%, p < 0.001), medication prescriptions (−19%, p < 0.001) and healthcare contacts (−18%, p = 0.15) vs. AAF. Infants prescribed AAF-Syn had a significantly higher probability of achieving asymptomatic management without hypoallergenic formula (HAF) (adjusted HR 3.70, 95% CI 1.97–6.95, p < 0.001), with a shorter clinical course of symptoms (median time to asymptomatic management without HAF 1.35 years vs. 1.95 years). AAF-Syn was associated with potential cost-savings of £452.18 per infant over the clinical course of symptoms. These findings may be attributable to the effect of the specific synbiotic on the gut microbiome. Further research is warranted to explore this. This real-world study provides evidence consistent with clinical trials that AAF-Syn may produce clinical and healthcare benefits with potential economic impact.

This pilot study evaluated a high-energy, high-protein, peptide-based, (medium-chain triglycerides) MCT-containing enteral tube feed (Nutrison Peptisorb Plus HEHP^®, Nutricia Ltd., Trowbridge, BA14 0XQ, UK.) containing 1.5 kcal/mL and 7.5 g protein/100 mL. Fifteen community-based, enterally tube-fed adults (42 (SD 16.3) years) received the intervention feed daily for 28 days, with gastrointestinal tolerance, compliance and nutrient intake assessed at baseline and after the intervention period. Incidence and intensity of constipation (p = 0.496), nausea (p = 1.000), abdominal pain (p = 0.366) and bloating (p = 0.250) remained statistically unchanged, yet the incidence and intensity of diarrhoea improved significantly after receiving the intervention feed (Z = −2.271, p = 0.023). Compliance with the intervention feed was significantly greater compared to the patient’s baseline regimens (99% vs. 87%, p = 0.038). Compared to baseline, use of the intervention feed enabled patients to significantly increase total energy (1676 kcal/day (SD 449) to 1884 kcal/day (SD 537), p = 0.039) and protein intake (73 g/day (SD 17) to 89 g/day (SD 23), p = 0.001), allowing patients to better achieve energy (from 88% to 99%, p = 0.038) and protein (from 101% to 121%, p < 0.001) requirements. This pilot study demonstrates that a high-energy, high-protein, peptide-based, MCT-containing enteral tube feed maintains gastrointestinal tolerance and improves compliance, energy and protein intake in complex, enterally tube-fed, community-based adult patients, though more work is recommended to confirm this.