Laura A. Czerkies

Effects of Prebiotic-Containing Infant Formula on Gastrointestinal Tolerance and Fecal Microbiota in a Randomized Controlled Trial

BACKGROUND Prebiotic-containing infant formula may beneficially affect gastrointestinal tolerance and commensal microbiota composition. OBJECTIVE Assess gastrointestinal tolerance and fecal microbiota, pH, and short-chain fatty acid (SCFA) concentrations of infants consuming formula with or without prebiotics. DESIGN Full-term formula-fed infants were studied to a breastfed comparison group (BF). Formula-fed infants (FF) were randomized to consume a partially hydrolyzed whey formula with (PRE) or without (CON) 4 g/L of galacto-oligosaccharides and fructo-oligosaccharides (9:1). Fecal bacteria, pH, and SCFA were assessed at baseline, 3 weeks, and 6 weeks. Caregivers of patients recorded stool characteristics and behavior for 2 days before the 3- and 6-week visits. RESULTS Feces from infants fed PRE had a higher absolute number (P = .0083) and proportion (P = .0219) of bifidobacteria than CON-fed infants and did not differ from BF. BF had a higher proportion of bifidobacteria than CON (P = .0219) and lower number of Clostridium difficile than FF (P = .0087). Feces from formula-fed infants had higher concentrations of acetate (P < .001), butyrate (P < .001), propionate (P < .001), and total SCFAs (P = .0230) than BF; however, fecal pH was lower (P = .0161) in PRE and BF than CON. Prebiotic supplementation did not alter stool patterns, tolerance, or growth. BF had more frequent stools that were yellow (P < .0001) and more often liquid than FF (P < .0001). CONCLUSIONS Infant formula containing the studied oligosaccharides was well tolerated, increased abundance and proportion of bifidobacteria, and reduced fecal pH in healthy infants.

Bifidobacterium lactis Bb12 enhances intestinal antibody response in formula-fed infants: A randomized, double-blind, controlled trial

BACKGROUND Addition of probiotics to infant formula may positively affect immune function in nonexclusively breastfed infants. This study aimed to investigate the effect of infant starter formula containing the probiotic Bifidobacterium animalis subspecies lactis (Bb12) on intestinal immunity and inflammation. METHODS Six-week-old healthy, full-term infants (n = 172) were enrolled in a prospective, randomized, double-blind, controlled clinical trial with 2 groups studied in parallel to a breastfed comparison group. Formula-fed (FF) infants were randomized to partially hydrolyzed whey formula (CON) or the same formula containing 10(6) colony-forming units (CFU) Bb12/g (PRO) for 6 weeks. Fecal secretory IgA (sIgA), calprotectin, lactate, and stool pH were assessed at baseline, 2 weeks, and 6 weeks. Anti-poliovirus-specific IgA and anti-rotavirus-specific IgA were assessed at 2 and 6 weeks. RESULTS Among vaginally delivered FF infants, PRO consumption increased (P < .05) fecal sIgA compared to CON. Anti-poliovirus-specific IgA concentration increased (P < .05) in all infants consuming PRO, whereas anti-rotavirus-specific IgA tended to increase (P = .056) with PRO consumption in cesarean-delivered infants. Anthropometrics and tolerance did not differ significantly between FF infants. CONCLUSIONS Infants consuming formula with Bb12 produced feces with detectable presence of Bb12 and augmented sIgA concentration. Furthermore, cesarean-delivered infants consuming Bb12 had heightened immune response, as evidenced by increased anti-rotavirus- and anti-poliovirus-specific IgA following immunization. These results demonstrate that negative immune-related effects of not breastfeeding and cesarean delivery can be mitigated by including Bb12 in infant formula, thereby providing infants a safe, dietary, immune-modulating bacterial introduction.

Patterns of Clinical Management of Atopic Dermatitis in Infants and Toddlers: A Survey of Three Physician Specialties in the United States

OBJECTIVE To describe atopic dermatitis (AD) management patterns in children ≤36 months old as reported by pediatricians, dermatologists, and allergists in the US. STUDY DESIGN A nationally-representative survey was administered to pediatricians (n = 101), dermatologists (n = 26), and allergists (n = 26). Main outcomes included referrals to health care professionals, suggested/ordered laboratory tests, management approach (dietary, pharmacologic, or combination of both) by age, AD location, and severity. RESULTS Significant differences were observed in referrals to healthcare professionals (P < .001). Pediatricians more frequently referred to dermatologists than allergists in mild (52.4% vs 32.0%) and moderate/severe (60.6% vs 38.1%) cases. Dermatologists referred to allergists less frequently for mild (9.1%) than moderate/severe (40.7%) AD cases. Pediatricians (59%), allergists (61.5%), and dermatologists (26.9%) reported treating at least some of their patients with AD with dietary management (infant formula change) alone (with or without emollients). Soy-based formulas were often used. For mild AD, the most commonly reported first-line pharmacologic treatments included topical emollients, topical corticosteroids, and barrier repair topical therapy/medical devices. Over 80% of physicians used a dietary and pharmacologic combination approach. Dermatologists were most likely to manage AD symptoms with a pharmacologic-only approach. AD lesion location influenced pharmacologic treatment in >80% of physicians. CONCLUSIONS Significant and distinct differences in AD treatment approach exist among physicians surveyed. Most pediatricians and allergists use formula change as a management strategy in some patients, whereas dermatologists favor a pharmacologic approach. This diversity may result from inadequate evidence for a standard approach. Consistent methods for managing AD are needed.

Evaluation of Hypoallergenicity of a New, Amino Acid–Based Formula

The American Academy of Pediatrics (AAP) defined a formula as hypoallergenic if it ensures with 95% confidence that 90% of infants with confirmed cow’s milk allergy (CMA) will not react with defined symptoms under double-blind, placebo-controlled conditions. This study’s objective was to determine whether a new amino acid–based formula (AAF) meets the AAP hypoallergenicity criteria. Methods. Children with CMA were randomized to double-blind placebo-controlled food challenges (DBPCFC) with a new AAF and a commercial AAF in crossover fashion followed by an at-home open challenge with the new AAF. Allergic reactions were assessed using a scoring system. Results. Thirty-three subjects completed DBPCFCs with both formulas without acute allergic reactions. The lower bound 95% confidence interval for hypoallergenicity was 91.3%. No unusual stool patterns, allergic symptoms, or signs of intolerance were reported during the open challenge. Conclusion. The new AAF meets AAP hypoallergenicity criteria and can be recommended for the management of CMA.

Growth and Tolerance of Term Infants Fed Formula With Probiotic Lactobacillus reuteri

Background. Lactobacillus reuteri has been studied for its safety and beneficial effects in infants. This study assessed growth of infants fed a partially hydrolyzed whey formula with L reuteri. Methods. Healthy term infants were randomized to 1 of 2 formulas (partially hydrolyzed whey formula with (PRO) or without (CON) L reuteri from 14 to 112 days of age. Anthropometric measures were assessed at 14, 28, 56, 84, and 112 days of age. Tolerance records were completed 2 days prior to each visit. Results. A total of 122 subjects completed study per protocol (60 PRO, 62 CON). No differences were seen in daily weight gain, length, or head circumference. Overall, between groups, there were no significant differences in formula intake, stool frequency, color, consistency, flatulence, frequency of spit-up/vomiting, mood, sleep, or incidence of adverse events. Conclusion. Infants fed probiotic formula had similar growth to infants fed control formula. Both formulas were well tolerated.

A Randomized Controlled Trial Assessing Growth of Infants Fed a 100% Whey Extensively Hydrolyzed Formula Compared With a Casein-Based Extensively Hydrolyzed Formula

This study compared the growth of healthy infants fed a hypoallergenic 100% whey-based extensively hydrolyzed formula (EHF) with Bifidobacterium lactis (test) with that of infants fed an extensively hydrolyzed casein formula (control). Formula-fed infants (14 ± 3 days) were randomized to test or control groups until 112 days of age. Anthropometrics were assessed at 14, 28, 56, 84, and 112 days, and daily records were kept for 2 days prior to study visits. Serum albumin and plasma amino acids at 84 days were assessed in a subset. A total of 282 infants were randomized (124 test, 158 control). Significantly more infants dropped out of the control (56%) as compared with the test (41%) group. Mean daily weight gain was significantly higher in the test group compared with the control group (27.95 ± 5.91 vs 25.93 ± 6.12 g/d; P = .027) with the test group reporting significantly fewer stools (2.2 vs 3.6 stools/d; P < .0001). The control group reported significantly more days with >3 loose stools/d and a higher incidence of vomiting as compared with the test group. There were no differences in gas, mood, sleep, or serum albumin. Plasma arginine and valine were significantly lower in the test group, whereas leucine and lysine were higher; all values were within normal limits. Significantly more adverse events attributed to the study formula were reported in the control group. The 100% whey-based hypoallergenic EHF containing Bifidobacterium lactis and medium chain triglycerides supported growth of healthy infants. Future studies on the application of this formula in clinically indicated populations are warranted.

Assessment of Growth of Infants Fed an Amino Acid-Based Formula

Objective This studys primary aim was to compare the growth (daily weight gain) of infants consuming a new (Test) amino acid-based formula (AAF) or a commercially available AAF (Control). Methods Healthy infants were randomized to Test or Control from 14 to 112 days of age. Anthropometric measurements were taken at 14,28, 56, 84, and 112 days of age. Tolerance records were completed prior to each visit. Serum albumin and plasma amino acids were ascertained in a subset of infants at 84 days of age. Results A total of 119 subjects completed the study per protocol. Mean daily weight gains were 27.26 ± 4.92 g/day for Control and 27.42 ± 6.37 g/day for Test (P = 0.8812). There were no significant differences between groups in formula intake, adverse events, flatulence, spit-up/vomiting, mood, or sleep. Albumin and plasma amino acids were within normal limits for both groups. Conclusions Infants fed the new AAF had similar daily weight gains as infants fed a commercially available AAF.

Early Nutrition and its Effect on the Development of Allergic Diseases

The prevalence of allergic conditions (atopic conditions) has been increasing and affects up to a third of the global population. The effects of early nutrition on the development of allergic conditions and its role in their dietary management is well-recognized. The purpose of this chapter is to review the role of early nutrition on specific allergic conditions, focused on atopic dermatitis, the most common allergic disease in infancy, and on emerging evidence related to the role of nutrition in food protein induced enterocolitis syndrome and eosinophilic esophagitis. Implications of nutrition during this early period of growth and development has the potential to impact the quality of life of children and their long-term health.

Hypoallergenicity of a New Extensively Hydrolyzed 100% Whey-based FormulaContaining Probiotics

Objective: The American Academy of Pediatrics (AAP) defined an infant formula as hypoallergenic if it ensures with 95% confidence that 90% of infants/children with confirmed cow’s milk protein allergy (CMA) do not react under double-blind, placebo-controlled conditions. The aim of this study was to determine whether a new 100% whey protein extensively hydrolyzed formula containing B. lactis CNCM I-3446, meets AAP hypoallergenicity criteria. Methods: Children with CMPA were randomized to double-blind placebo-controlled food challenges (DBPCFC) with a new extensively hydrolyzed formula (Test) and a commercial extensively hydrolyzed formula (Control) in a cross-over fashion. CMPA was confirmed by elevated serum cow’s milk (CM)-IgE levels, positive skin prick test to CM extract, or positive CM oral challenge within 6 months prior to enrollment. Allergic reactions in the DBPCFC’s were assessed using a comprehensive scoring system. If both challenges were tolerated, subjects participated in an at-home week-long Test open challenge. Results: Seventy-seven children (3.30 ± 2.98 years old) with recently confirmed CMPA were enrolled. Of the 68 subjects participating in the Test DBPCFC, one had an allergic reaction (lower bound 95% confidence interval of 0.921 for Test), while 4 out of 75 subjects participating in the DBPCFC with Control had an allergic reaction. The Test formula met the AAP hypoallergenicity criteria. Average formula intake during the Test open challenge was 250ml/ day. One 6-year old subject reported angioedema, atopic dermatitis, rash around the eyes, and red swollen eyes on open challenge Day 6. This subject did not report any symptoms during the Test DBPCFC, was not exclusively formula-fed during the open challenge, and did not discontinue formula during the open challenge. Conclusion: The new Test EHF meets the AAP criteria for hypoallergenicity and can be recommended for the management of CMPA.