Cow’s milk protein allergy (CMPA) is the most common food allergy in infancy. Non-IgE mediated (NIM) forms are little studied and the responsible mechanisms of tolerance acquisition remain obscure. Our aim was to study the intestinal microbiota and related parameters in the fecal samples of infants with NIM-CMPA, to establish potential links between type of formula substitutes, microbiota, and desensitization. Seventeen infants between one and two years old, diagnosed with NIM-CMPA, were recruited. They were all on an exclusion diet for six months, consuming different therapeutic protein hydrolysates. After this period, stool samples were obtained and tolerance development was evaluated by oral challenges. A control group of 10 age-matched healthy infants on an unrestricted diet were included in the study. Microbiota composition, short-chain fatty acids, calprotectin, and transforming growth factor (TGF)-β₁ levels were determined in fecal samples from both groups. Infants with NIM-CMPA that consumed vegetable protein-based formulas presented microbiota colonization patterns different from those fed with an extensively hydrolyzed formula. Differences in microbiota composition and fecal parameters between NIM-CMPA and healthy infants were observed. Non-allergic infants showed a significantly higher proportion of Bacteroides compared to infants with NIM-CMPA. The type of protein hydrolysate was found to determine gut microbiota colonization and influence food allergy resolution in NIM-CMPA cases.

Background: The results of recent studies suggest the usefulness of PCT for early diagnosis of neonatal sepsis, with varying results. The aim of this prospective multicenter study was to determine the behavior of serum PCT concentrations in both uninfected and infected neonates, and to assess the value of this marker for diagnosis of neonatal sepsis of vertical transmission. Methods: PCT was measured in 827 blood samples collected prospectively from 317 neonates admitted to 13 acute-care teaching hospitals in Spain over one year. Serum PCT concentrations were determined by a specific immunoluminometric assay. The diagnostic efficacy of PCT at birth and within 12–24 h and 36–48 h of life was evaluated calculating the sensitivity, specificity, and likelihood ratio of positive and negative results. Results: 169 asymptomatic newborns and 148 symptomatic newborns (confirmed vertical sepsis: 31, vertical clinical sepsis: 38, non-infectious diseases: 79) were studied. In asymptomatic neonates, PCT values at 12–24 h were significantly higher than at birth and at 36–48 h of life. Resuscitation at birth and chorioamnionitis were independently associated to PCT values. Neonates with confirmed vertical sepsis showed significantly higher PCT values than those with clinical sepsis. PCT thresholds for the diagnosis of sepsis were 0.55 ng/mL at birth (sensitivity 75.4%, specificity 72.3%); 4.7 ng/mL within 12–24 h of life (sensitivity 73.8%, specificity 80.8%); and 1.7 ng/mL within 36–48 h of life (sensitivity 77.6%, specificity 79.2%). Conclusion: Serum PCT was moderately useful for the detection of sepsis of vertical transmission, and its reliability as a maker of bacterial infection requires specific cutoff values for each evaluation point over the first 48 h of life.

Background: It has recently been suggested that serum procalcitonin (PCT) is of value in the diagnosis of neonatal sepsis, with varying results. The aim of this prospective multicenter study was to assess the usefulness of PCT as a marker of neonatal sepsis of nosocomial origin. Methods: One hundred infants aged between 4 and 28 days of life admitted to the Neonatology Services of 13 acute-care teaching hospitals in Spain over 1-year with clinical suspicion of neonatal sepsis of nosocomial origin were included in the study. Serum PCT concentrations were determined by a specific immunoluminometric assay. The reliability of PCT for the diagnosis of nosocomial neonatal sepsis at the time of suspicion of infection and at 12–24 h and 36–48 h after the onset of symptoms was calculated by receiver-operating characteristics (ROC) curves. The Youden's index (sensitivity + specificity - 1) was used for determination of optimal cutoff values of the diagnostic tests in the different postnatal periods. Sensitivity, specificity, and the likelihood ratio of a positive and negative result with the 95% confidence interval (CI) were calculated. Results: The diagnosis of nosocomial sepsis was confirmed in 61 neonates. Serum PCT concentrations were significantly higher at initial suspicion and at 12–24 h and 36–48 h after the onset of symptoms in neonates with confirmed sepsis than in neonates with clinically suspected but not confirmed sepsis. Optimal PCT thresholds according to ROC curves were 0.59 ng/mL at the time of suspicion of sepsis (sensitivity 81.4%, specificity 80.6%); 1.34 ng/mL within 12–24 h of birth (sensitivity 73.7%, specificity 80.6%), and 0.69 ng/mL within 36–48 h of birth (sensitivity 86.5%, specificity 72.7%). Conclusion: Serum PCT concentrations showed a moderate diagnostic reliability for the detection of nosocomial neonatal sepsis from the time of suspicion of infection. PCT is not sufficiently reliable to be the sole marker of sepsis, but would be useful as part of a full sepsis evaluation.

Aim: to evaluate validity and concordance of Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP) and Screening Tool for Risk On Nutritional status and Growth (STRONGkids) screening tools for assessment of nutritional risk in pediatric inpatients. Methods: Prospective longitudinal observational multicenter study in children aged 1 month or older admitted as inpatients. Weight, height, cause of admission, demographic data, length of stay, and nutritional interventions were recorded. STAMP and STRONGkids were applied within the first 72 h of admission. Anthropometric measurements were recorded again 12–18 months after admission. Results: Eighty-one patients with median age of 4.1 years completed the study. Agreement between tools was moderate (κ = 0.47). STAMP had a greater tendency to classify patients as high risk (12.3% vs. 2.5%). Both tools showed very weak correlation with height for age. All undernourished patients at the beginning and the end of the study were classified as medium or high risk by STAMP and STRONGkids (100% sensitivity), although specificity was below 50% in all cases. There were no differences in length of stay based on nutritional risk with any of the tools. Conclusions: STAMP and STRONGkids demonstrated moderate agreement, with high sensitivity but low specificity for the diagnosis of undernutrition. Further studies are required to analyze cost-effectiveness of these tools and nutritional interventions derived from them.

Cow's milk protein allergy (CMPA) is the most common allergy in the first year of life. Non-IgE mediated CMPA is characterized by digestive symptoms and tolerance development before the age of three. Gut microbiota composition in early life has been associated with food allergy. The ingestion of different foods/nutrients may mark different shifts in the microbial colonization of the infant intestine as well as the consumption of probiotics. Aim: To analyze changes in microbiota composition and metabolic and cytokine profiles in fecal samples from infants with non-IgE mediated CMPA after successful milk challenges, tolerance acquisition, and increasing dairy introduction in their diet. Methods: Twelve children with CMPA, aged between 1 and 2 years old, were recruited for the study. Participants were initially consuming hypoallergenic hydrolyzed formulas (four of them supplemented with the probiotic Lactobacillus rhamnosus GG), before being exposed to a standardized oral challenge (SOC) with cow's milk. Fecal samples were collected before, 1 week, and 1 month after performing the SOC. Changes in gut microbiota were determined by high-throughput amplicon sequencing of the 16S rRNA gene. Levels of lactobacilli were also determined by quantitative PCR (qPCR). Microbial metabolites were analyzed by chromatographic methods and fecal cytokines related to the Th1/Th2 balance were determined by immunoassay. Results: Lactic acid bacteria significantly increased in infants who outgrew non-IgE CMPA, after the introduction of milk. Microbial metabolites derived from the fermentation of proteins, such as branched chain fatty acids, and p-cresol, diminished. After the SOC, some cytokines related to inflammation (TNF-α, IFN-γ) increased. Accompanying the introduction of an unrestricted diet, we found significant differences in fecal microbial composition, metabolites, and cytokines between infants who did not consume the probiotic L. rhamnosus GG and those that did. Conclusions: These findings indicate that the introduction of intact milk proteins is followed by modifications in the infant gut environment through changes in immune mediators, microbiota, and its metabolic end-products. Consumption of probiotics during CMPA may contribute to gut homeostasis by fine-tuning these profiles.