Amino Acid Formula Containing Synbiotics in Infants with Cow’s Milk Protein Allergy: A Systematic Review and Meta-Analysis

Abstract

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.

The Use of an Amino Acid Formula Containing Synbiotics in Infants with Cow’s Milk Protein Allergy—Effect on Clinical Outcomes

“…The findings of this study are consistent with clinical trials of the only AAF-Syn currently available on prescription in the UK, which have shown significant reductions in infections, medications and hospital admissions when compared to AAF in infants with CMPA [20][21][22][23][24]. It is possible that the benefits seen are related to the clinical ef-fect of the specific synbiotic, which may have modified the dysbiotic gut microbiome of infants with CMPA, bringing it closer to that observed in studies of healthy breastfed infants [20][21][22][23]40,41]. The precise mechanism of the synbiotic effect remains unknown; however, the improvement of the gut microbiota profile through synbiotics may inhibit the growth of pathogenic organisms, thereby helping to reduce the incidence of infections [42] and associated healthcare usage in turn.…”

“…The findings of this study are consistent with clinical trials of the only AAF-Syn currently available on prescription in the UK, which have shown significant reductions in infections, medications and hospital admissions when compared to AAF in infants with CMPA [ 20 , 21 , 22 , 23 , 24 ]. It is possible that the benefits seen are related to the clinical effect of the specific synbiotic, which may have modified the dysbiotic gut microbiome of infants with CMPA, bringing it closer to that observed in studies of healthy breastfed infants [ 20 , 21 , 22 , 23 , 40 , 41 ].…”

“…Whilst this retrospective analysis of case records from the THIN database offers novel findings from clinical practice in real-world settings, to add to the growing evidence base of a specific AAF-Syn from RCTs [ 20 , 21 , 22 , 23 , 24 ], the applicability of the findings to eHF containing synbiotics (eHF-Syn) is unknown. Evidence from RCTs suggests that eHF supplemented with the same synbiotic blend may be associated with lower usage of medications in infants with atopic dermatitis and with greater improvement in skin symptoms among infants with an IgE-mediated response [ 43 , 44 ].…”

“…Studies have demonstrated clinical benefits of modulating the infant gut microbiota with pre- or probiotics when given within HAF or as a supplement to formulae, including a reduction in atopic dermatitis (AD) and an earlier resolution of CMPA [ 16 , 17 , 18 , 19 ]. In particular, randomised controlled trials (RCTs) have shown that infections, hospital admissions and the use of antibiotics and concurrent medications occurred in fewer infants who were fed a specific AAF containing both pre- and probiotics (synbiotics) compared to those who received an AAF without synbiotics [ 20 , 21 , 22 , 23 , 24 ]. However, real-world evidence (data collected by clinicians as part of the routine care of patients) investigating these effects in the clinical setting is lacking.…”

Effect of Probiotic, Prebiotic, or Synbiotic Supplement on Children, Adolescents, or Infants: A Protocol of an Umbrella Review

“…However, their included literature are major low-quality evidence, reducing credibility with their results. Sorensen K [21] believed that compared with the amino acid formula alone, the hospitalization rate and overall drug use (including antimicrobial agents and antibiotics) of infants allergic to milk protein were lower in the amino acid formula containing synbiotics. However, there are some controversies between different researchers.…”