Revised Swedish infant feeding guidelines are associated with earlier introduction of allergenic foods.

BACKGROUND: Randomized controlled trials have demonstrated that early introduction of allergenic foods, such as peanut and egg, can reduce food allergy in high-risk children. Many international guidelines recommend introduction of allergenic foods in the first year of life, and accordingly, the Swedish National Food agency released updated guidelines in June 2019. OBJECTIVE: Our aim was to examine whether the age at introduction and consumption frequency of allergenic foods have changed since release of the revised national guidelines on the introduction of solid foods in Sweden. METHODS: Children born between June 2016 and December 2018 (n = 1925) were compared with children born between June 2019 and April 2021 (n = 1761) by using data from the NorthPop Birth Cohort study. Data on food introduction, eczema, and food allergy were prospectively collected until age 18 months by using web-based questionnaires. IgE sensitization was assessed at 18 age months. RESULTS: The proportion of participants who had been introduced to egg, legume, soy products, peanut, almond, and cashew nut during the first year of life increased after implementation of the revised national guidelines. The most significant changes were seen for legume (from 55.2% to 69.8% [adjusted odds ratio = 1.90 (95% CI = 1.62-2.24)]) and peanut (from 29.2% to 43.2% adjusted odds ratio = 1.87 (95% CI = 1.55-2.24)]); consumption frequency had also increased. No differences in the prevalence of eczema, food allergy, or sensitization to the foods of interest were found. CONCLUSION: Since release of the revised guidelines, infants in the general population are introduced to and consume a variety of allergenic foods earlier and more frequently; however, early manifestations of allergic disease have remained unchanged.

Targeting the gut-lung axis by synbiotic feeding to infants in a randomized controlled trial.

BACKGROUND: Formula-fed infants are at increased risk of infections. Due to the cross-talk between the mucosal systems of the gastrointestinal and respiratory tracts, adding synbiotics (prebiotics and probiotics) to infant formula may prevent infections even at distant sites. Infants that were born full term and weaned from breast milk were randomized to prebiotic formula (fructo- and galactooligosaccharides) or the same prebiotic formula with Lactobacillus paracasei ssp. paracasei F19 (synbiotics) from 1 to 6 months of age. The objective was to examine the synbiotic effects on gut microbiota development. RESULTS: Fecal samples collected at ages 1, 4, 6, and 12 months were analyzed using 16S rRNA gene sequencing and a combination of untargeted gas chromatography-mass spectrometry/liquid chromatography-mass spectrometry. These analyses revealed that the synbiotic group had a lower abundance of Klebsiella, a higher abundance of Bifidobacterium breve compared to the prebiotic group, and increases in the anti-microbial metabolite d-3-phenyllactic acid. We also analyzed the fecal metagenome and antibiotic resistome in the 11 infants that had been diagnosed with lower respiratory tract infection (cases) and 11 matched controls using deep metagenomic sequencing. Cases with lower respiratory tract infection had a higher abundance of Klebsiella species and antimicrobial resistance genes related to Klebsiella pneumoniae, compared to controls. The results obtained using 16S rRNA gene amplicon and metagenomic sequencing were confirmed in silico by successful recovery of the metagenome-assembled genomes of the bacteria of interest. CONCLUSIONS: This study demonstrates the additional benefit of feeding specific synbiotics to formula-fed infants over prebiotics only. Synbiotic feeding led to the underrepresentation of Klebsiella, enrichment of bifidobacteria, and increases in microbial degradation metabolites implicated in immune signaling and in the gut-lung and gut-skin axes. Our findings support future clinical evaluation of synbiotic formula in the prevention of infections and associated antibiotic treatment as a primary outcome when breastfeeding is not feasible. TRIAL REGISTRATION: ClinicalTrials.gov NCT01625273 . Retrospectively registered on 21 June 2012.

The breast milk and childhood gastrointestinal microbiotas and disease outcomes: a longitudinal study.

BACKGROUND: We aimed to characterize breast milk microbiota and define associations with saliva and fecal microbiota and selected diseases in preschool children. METHODS: In a longitudinal cohort study, the microbiotas from breast milk, mouth, and fecal samples were characterized by 16S rRNA gene sequencing. Questionnaires and medical records provided information on demographics, medical, and dental data. RESULTS: The phylogeny in breast milk, saliva swabs, and feces differed at all levels (p < 0.0003), though all harbored species in Streptococcus, Veillonella, and Haemophilus. Species richness was highest in breast milk with increasing resemblance with the oral swab microbiota by increasing age. Caries-affected children at age 5 had been fed breast milk with tenfold higher abundance of caries-associated bacteria, e.g., Streptococcus mutans, than caries-free children (p < 0.002). At that age, taxa, e.g., Neisseria sicca were overrepresented in saliva swabs of children with otitis media (LDA score >2, p < 0.05). Gut symbionts, e.g., Bacteroides, were underrepresented in 3-month fecal samples in children later diagnosed with allergic disease (LDA score >2, p < 0.05). CONCLUSIONS: Distinct microbiotas for the three sources were confirmed, though resemblance between milk and oral swab microbiota increased by age. Future studies should evaluate if the observed associations with disease outcomes are causal. IMPACT: Few studies have studied the association between breast milk microbiota and gastrointestinal microbiota beyond early infancy. The present study confirms distinct microbiota profiles in breast milk, saliva swabs, and feces in infancy and indicates increasing resemblance between breast milk and the oral microbiota by increasing age. The fecal microbiota at 3 months was associated with later allergic disease; the saliva microbiota by age 5 differed between children with and without otitis media at the same age; and children with caries by age 5 had been fed breast milk with a higher abundance of caries-associated bacteria.

Associations between pre- and postnatal antibiotic exposures and early allergic outcomes: A population-based birth cohort study.

BACKGROUND: Early life antibiotic treatment is one likely exposure influencing allergy risk. The objective was to investigate associations between pre- and postnatal antibiotic exposures and the development of allergic manifestations until age 18 months. METHODS: We included 1387 mother-child dyads from the prospective, population-based NorthPop birth cohort study. Data on antibiotic exposures in pregnancy and childhood were collected by web-based questionnaires. Until the child turned 18 months old, parents (n = 1219) reported symptoms of wheeze, eczema, and physician-diagnosed asthma; parents (n = 1025) reported physician-diagnosed food allergy. At age 18 months, serum immunoglobulin E levels to inhalant (Phadiatop) and food (Food mix fx5) allergens were determined. Associations were estimated using bivariable and multivariable logistic regressions. RESULTS: Prenatal antibiotic exposure was positively associated with food sensitization in the crude (OR 1.82, 95% CI 1.01-3.26) but not in the adjusted analyses (aOR 1.58, 0.82-3.05). A borderline significant association was found between prenatal exposure and wheeze (aOR 1.56, 0.95-2.57). Postnatal antibiotics were positively associated with wheeze (aOR 2.14, 1.47-3.11), asthma (aOR 2.35, 1.32-4.19), and eczema (aOR 1.49, 1.07-2.06). Postnatal antibiotics were negatively associated with food sensitization (aOR 0.46, 95% CI 0.25-0.83) but not with food allergy nor sensitization to inhalants. CONCLUSION: Pre- and postnatal antibiotic exposure demonstrated positive associations with allergic manifestations and the former also with food sensitization. In contrast, there was a negative association between postnatal antibiotics and food sensitization. Food sensitization is often transient but may precede respiratory allergies. Future studies should investigate the relationship between antibiotic exposure and food sensitization later in childhood.

Physical activity and sedentary time during pregnancy and associations with maternal and fetal health outcomes: an epidemiological study.

BACKGROUND: Physical activity is generally considered safe for the pregnant woman as well as for her fetus. In Sweden, pregnant women without contraindications are recommended to engage in physical activity for at least 30 min per day most days of the week. Physical activity during pregnancy has been associated with decreased risks of adverse health outcomes for the pregnant woman and her offspring. However, there are at present no recommendations regarding sedentary behavior during pregnancy. The aim was to examine the level of physical activity and sedentary time in a representative sample of the pregnant population in Sweden, and to explore potential effects on gestational age, gestational weight gain, birth weight of the child, mode of delivery, blood loss during delivery/postpartum, self-rated health during pregnancy and risk of pregnancy-induced hypertension and preeclampsia. METHODS: This was an epidemiological study using data from the prospective, population-based NorthPop study in Northern Sweden and information on pregnancy outcomes from the national Swedish Pregnancy Register (SPR). A questionnaire regarding physical activity and sedentary time during pregnancy was answered by 2203 pregnant women. Possible differences between categories were analyzed using one-way Analysis of variance and Pearson's Chi-square test. Associations between the level of physical activity/sedentary time and outcome variables were analyzed with univariable and multivariable logistic regression and linear regression. RESULTS: Only 27.3% of the included participants reported that they reached the recommended level of physical activity. A higher level of physical activity was associated with a reduced risk of emergency caesarean section, lower gestational weight gain, more favorable self-rated health during pregnancy, and a decreased risk of exceeding the Institute of Medicine's recommendations regarding gestational weight gain. Higher sedentary time was associated with a non-favorable self-rated health during pregnancy. CONCLUSIONS: Our study showed that only a minority of pregnant women achieved the recommended level of physical activity, and that higher physical activity and lower sedentary time were associated with improved health outcomes. Encouraging pregnant women to increase their physical activity and decrease their sedentary time, may be important factors to improve maternal and fetal/child health outcomes.

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.

Effects of osteopontin-enriched formula on lymphocyte subsets in the first 6 months of life: a randomized controlled trial.

BackgroundHuman milk is rich in osteopontin (OPN), which has immunomodulatory functions.MethodsIn a randomized controlled trial, standard formula (SF) and the same formula with 65 mg of OPN/L (F65) or 130 mg of OPN/L (F130), representing ~50 and 100% of the OPN concentration in human milk, were compared. We examined frequencies and composition of peripheral blood immune cells by four-color immunoflow cytometry of formula-fed infants at ages 1, 4, and 6 months, and compared them with a breastfed (BF) reference group.ResultsThe F130 group had increased T-cell proportions compared with the SF (P=0.036, average effect size 0.51) and F65 groups (P=0.008, average effect size 0.65). Compared with the BF group, the monocyte proportions were increased in the F65 (P=0.001, average effect size 0.59) and F130 (P=0.006, average effect size 0.50) groups, but were comparable among the formula groups.ConclusionOPN in an infant formula at a concentration close to that of human milk increased the proportion of circulating T cells compared with both SF and formula with added OPN at ~50% of the concentration in human milk. This suggests that OPN may favorably influence immune ontogeny in infancy and that the effects appear to be dose-dependent.

Effects of infant formula supplemented with prebiotics compared with synbiotics on growth up to the age of 12 mo: a randomized controlled trial.

BACKGROUND: Growth is an essential outcome measure for evaluating the safety of infant formulas (IF). We investigated the effects of consumption of IF supplemented with prebiotics (fructooligosaccharides, FOS, and galactooligosaccharides, GOS) compared with synbiotics (FOS/GOS and Lactobacillus paracasei ssp. paracasei strain F19) on the growth of healthy infants. METHODS: 182 full-term infants who were weaned completely from breast milk to IF at 28 d of age were randomly assigned to receive prebiotic- or synbiotic-supplemented, otherwise identical, IF until 6 mo of age (intervention period). RESULTS: A total of 146 (80%) infants were included in the intention-to-treat analysis at 6 mo. Anthropometric parameters were similar in the two groups during the intervention and follow-up period until 12 mo of age. Compared with the prebiotic group, a significant reduction in the cumulative incidence of lower respiratory tract infections was found in the synbiotic group; however, the confidence interval of the estimate was wide, resulting in uncertainty. CONCLUSION: The lack of a significant difference between the formula-fed groups in growth, or the occurrence of serious adverse events, supports the safety of using IF supplemented with synbiotics. Further studies are needed to evaluate the effects of such formula on lower-respiratory tract infections.

Bugging allergy; role of pre-, pro- and synbiotics in allergy prevention.

Large-scale biodiversity loss and complex changes in social behaviors are altering human microbial ecology. This is increasingly implicated in the global rise in inflammatory diseases, most notably the "allergy epidemic" in very early life. Colonization of human ecological niches, particularly the gastrointestinal tract, is critical for normal local and systemic immune development and regulation. Disturbances in composition, diversity and timing of microbial colonization have been associated with increased allergy risk, indicating the importance of strategies to restore a dysbiotic gut microbiota in the primary prevention of allergic diseases, including the administration of probiotics, prebiotics and synbiotics. Here, we summarize and discuss findings of randomized clinical trials that have examined the effects of these microbiome-related strategies on short and long-term allergy preventative effects - including new guidelines from the World Allergy Organization which now recommend probiotics and prebiotics for allergy prevention under certain conditions. The relatively low quality evidence, limited comparative studies and large heterogeneity between studies, have collectively hampered recommendations on specific probiotic strains, specific timing and specific conditions for the most effective preventive management. At the same time the risk of using available products is low. While further research is needed before specific practice guidelines on supplement probiotics and prebiotics, it is equally important that the underlying dietary and lifestyle factors of dysbiosis are addressed at both the individual and societal levels.

Dynamics of cytokine mRNA expression and fecal biomarkers in school-children undergoing a double-blind placebo-controlled food challenge series.

BACKGROUND: There is need for prognostic markers for symptomatic food allergy since current diagnostic methods are insufficient and/or time and labor consuming. OBJECTIVE: To estimate the cytokine mRNA profiles in peripheral blood mononuclear cells (PBMC) before and after a double-blind placebo-controlled food challenge series in schoolchildren with suspected allergy to milk, egg or cod and in healthy controls. Analyses of fecal inflammatory biomarkers before and after the challenge were included. METHODS: Twelve-year-old children from a population-based cohort reporting complete avoidance of milk, egg, cod or wheat due to perceived hypersensitivity were clinically examined and those with suspected food allergy were evaluated with a 3-session double-blind placebo-controlled food challenge (n=18). Seven healthy controls participated in a double-blind challenge with egg. Before and after the challenge series, the cytokine mRNA expression was quantified for 13 cytokines discriminating between humoral Th2-, cytotoxic Th1-, regulatory Th3/Tr1- and inflammatory responses. Fecal calprotectin and eosinophil-derived neurotoxin (EDN) were also analyzed in children with suspected food allergy before and after the challenge series. RESULTS: Pre challenge, children with suspected food allergy had higher IL-13andTNF-α expression and lower IFN-γ and IL-15 expression compared to healthy controls (all p<0.05). Children with challenge-proven food allergy had increased IL13andIL-10 expression compared to the levels seen in negative challenges (p<0.05). Post challenge, IL-1ß and IL-6 mRNA levels were elevated in the food allergic children compared to controls (p<0.05). Fecal calprotectin and EDN levels were higher in challenge-proven food allergy compared to a negative challenge although not statistically significantly. CONCLUSION & CLINICAL RELEVANCE: Increased baseline mRNA levels of the Th2-related cytokine IL-13 and the regulatory cytokine IL-10 predicted a positive food challenge outcome. These cytokines in combination with fecal calprotectin and EDN might serve as future prognostic markers for symptomatic, IgE-mediated food allergy but need further validation in a larger patient cohort.

Nutrition, gut microbiota and child health outcomes.

PURPOSE OF REVIEW: Diet is one of the main drivers of the composition and function of the gut microbiota. The scope of this review is to summarize recent studies assessing the role of gut microbiota in clinical pediatric conditions and to review studies using nutritional approaches to favorably modify the gut microbiota to improve health outcomes in children. RECENT FINDINGS: New studies underscore that breastfeeding and infant diet impact the gut microbiome and metagenome. A comprehensive study using metagenomic shotgun sequencing, suggests that the cessation of breastfeeding rather than the introduction of solid foods, drives the functional maturation of the infant gut microbiome toward an adult-like state. There is further support for the view that a disturbed early gut microbiota is implicated in allergic and autoimmune diseases. New studies using prebiotics, probiotics, and synbiotics in various pediatric disorders have yielded promising results, yet the evidence for specific guidelines on their use is still low. SUMMARY: Intestinal dysbiosis is associated with several pediatric disorders but a cause-effect relationship remains to be clearly demonstrated in most conditions. Future studies using new systems biology approaches are anticipated to provide further insight into the functional capacities of the gut microbiome and its establishment in childhood. This may then lay the ground for improved treatment and prevention strategies targeting the gut microbiota.

Milk allergy is a minor cause of milk avoidance due to perceived hypersensitivity among schoolchildren in Northern Sweden.

AIM: We investigated phenotypes of milk hypersensitivity among schoolchildren aged 11-12 in Northern Sweden. METHODS: In a population-based cohort, 1824 (98%) children aged 11-12 participated in a questionnaire survey, skin prick testing, interviews on food hypersensitivity and assessment of body mass index (BMI). Of the 265 children reporting milk hypersensitivity, milk avoidance and no coeliac disease, 236 (89%) participated in a structured interview and blood samples for analyses of milk-specific Immunoglobulin E. The children were then categorised into milk hypersensitivity phenotypes according to preset criteria. RESULTS: In all, 14.5% reported milk hypersensitivity. Of these, 3% were categorised as current milk allergy, 23% as outgrown milk allergy, 40% as probable lactose intolerance and 11% as nondefinable. Furthermore, 23% had discontinued their elimination diet. Milk allergy was associated with other atopic disorders and lower BMI, with an odds ratio of 0.82 and 95% confidence interval of 0.80-0.98. Only 2% had previously undergone an oral challenge. CONCLUSION: The most common symptom phenotypes among Swedish children aged 11-12 with self-reported milk hypersensitivity and milk avoidance were probable intolerance and outgrown milk allergy, while current milk allergy was uncommon. Children with milk allergy had a lower BMI and most lacked a challenge-proven diagnosis.

The gut microbiota and inflammatory noncommunicable diseases: associations and potentials for gut microbiota therapies.

Rapid environmental transition and modern lifestyles are likely driving changes in the biodiversity of the human gut microbiota. With clear effects on physiologic, immunologic, and metabolic processes in human health, aberrations in the gut microbiome and intestinal homeostasis have the capacity for multisystem effects. Changes in microbial composition are implicated in the increasing propensity for a broad range of inflammatory diseases, such as allergic disease, asthma, inflammatory bowel disease (IBD), obesity, and associated noncommunicable diseases (NCDs). There are also suggestive implications for neurodevelopment and mental health. These diverse multisystem influences have sparked interest in strategies that might favorably modulate the gut microbiota to reduce the risk of many NCDs. For example, specific prebiotics promote favorable intestinal colonization, and their fermented products have anti-inflammatory properties. Specific probiotics also have immunomodulatory and metabolic effects. However, when evaluated in clinical trials, the effects are variable, preliminary, or limited in magnitude. Fecal microbiota transplantation is another emerging therapy that regulates inflammation in experimental models. In human subjects it has been successfully used in cases of Clostridium difficile infection and IBD, although controlled trials are lacking for IBD. Here we discuss relationships between gut colonization and inflammatory NCDs and gut microbiota modulation strategies for their treatment and prevention.

Probiotics during weaning: a follow-up study on effects on body composition and metabolic markers at school age.

PURPOSE: An aberrant gut microbiome has been suggested to contribute to the worldwide epidemic of obesity. In animal models, the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) induced upregulation of genes involved in energy homoeostasis, reduced body fat and altered the serum (S) lipoprotein profile. In our previous report, feeding LF19 to infants during weaning impacted the global plasma metabolome. LF19 lowered palmitoleic acid, a monounsaturated fatty acid associated with hypertriglyceridemia and increased visceral adiposity. Therefore, we assessed if feeding LF19 from 4 to 13 months of age would have long-term effects on body composition, growth and metabolic markers. METHODS: Of 179 children included in our baseline study, 120 entered the follow-up at 8-9 years of age, n = 58 in the probiotic and n = 62 in the placebo group. Body composition was measured using dual energy X-ray absorptiometry. Anthropometrics of the child and accompanying parent(s) were assessed. S-lipids, insulin, glucose and transaminases were determined after overnight fasting. RESULTS: LF19 did not affect body mass index z-score, sagittal abdominal diameter, fat-free mass, fat mass index, truncal fat %, android or gynoid fat % and had no long-term impact on any of the assessed metabolic markers (p > 0.05). CONCLUSION: Feeding LF19 during infancy did not modulate body composition, growth or any of the assessed metabolic markers at school age. The steady increase in probiotic products targeting infants and children calls for long-term follow-up of initiated probiotic intervention studies.

Impact of probiotics during weaning on the metabolic and inflammatory profile: follow-up at school age.

We hypothesised that feeding the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) (dep. nr LMG P-17806) during weaning would program the metabolic and inflammatory profile and studied its association with previously assessed body composition. In a double-blind, placebo-controlled trial, 179 infants were randomised to daily feeding of cereals with or without LF19 10(8) CFU from 4 to 13 months of age. At age 8-9 years, 120 children were re-assessed. Using high-sensitivity multiplex immunoassay technology and ELISA, we found that overweight/obese children had increased plasma C-peptide, plasminogen activator inhibitor-1, leptin and serum high-sensitivity C-reactive protein (hsCRP) after overnight fasting compared with normal weight children, independently of LF19. After excluding the obese, leptin and hsCRP were still increased, revealing an aberrant metabolic and inflammatory state already in overweight, pre-pubertal children. Higher body mass index z-score, sagittal abdominal diameter, truncal and total body fat % were associated with an aberrant metabolic and inflammatory profile, emphasising the need for early prevention strategies although no programming effect of LF19 was observed.

Gut microbiota and allergic disease: new findings.

PURPOSE OF REVIEW: Disturbed gut colonization patterns are proposed to be associated with the development of allergic disease. RECENT FINDINGS: Studies using new systems biology methods confirm previous findings that early environmental exposures, for example cesarean delivery, are associated with disturbed gut colonization patterns and reduced microbial diversity. Low microbial diversity in infancy is also observed to precede onset of allergic disease. In a large population-based cohort study, probiotic consumption in pregnancy was associated with reduced risk of eczema and rhinoconjunctivitis in the child, but not asthma. The association between probiotics and rhinoconjunctivitis appeared stronger if both mother and child (from 6 months) consumed probiotics. Follow-up data from primary prevention studies with probiotics do not support a role for probiotics in asthma prevention. In meta-analyses, both prebiotics (high-risk infants only) and probiotics modestly reduce the eczema risk, but no other allergic manifestations. Their use is not generally recommended for prevention, or treatment, of allergic disease. SUMMARY: Gut microbial patterns are associated with susceptibility to allergic disease, but the incomplete understanding of what constitutes a healthy gut microbiota that promotes tolerance, remains a challenge. Further understanding of gut microbial functions may pave the way for more effective allergy prevention and treatment strategies.

Early regular egg exposure in infants with eczema: A randomized controlled trial.

BACKGROUND: Observational studies suggest that early regular ingestion of allergenic foods might reduce the risk of food allergy. OBJECTIVE: We sought to determine whether early regular oral egg exposure will reduce subsequent IgE-mediated egg allergy in infants with moderate-to-severe eczema. METHODS: In a double-blind, randomized controlled trial infants were allocated to 1 teaspoon of pasteurized raw whole egg powder (n = 49) or rice powder (n = 37) daily from 4 to 8 months of age. Cooked egg was introduced to both groups after an observed feed at 8 months. The primary outcome was IgE-mediated egg allergy at 12 months, as defined based on the results of an observed pasteurized raw egg challenge and skin prick tests. RESULTS: A high proportion (31% [15/49]) of infants randomized to receive egg had an allergic reaction to the egg powder and did not continue powder ingestion. At 4 months of age, before any known egg ingestion, 36% (24/67) of infants already had egg-specific IgE levels of greater than 0.35 kilounits of antibody (kUA)/L. At 12 months, a lower (but not significant) proportion of infants in the egg group (33%) were given a diagnosis of IgE-mediated egg allergy compared with the control group (51%; relative risk, 0.65; 95% CI, 0.38-1.11; P = .11). Egg-specific IgG4 levels were significantly (P < .001) greater in the egg group at both 8 and 12 months. CONCLUSION: Induction of immune tolerance pathways and reduction in egg allergy incidence can be achieved by early regular oral egg exposure in infants with eczema. Caution needs to be taken when these high-risk infants are first exposed to egg because many have sensitization already by 4 months of age.

Basophil allergen threshold sensitivity to casein (casein-specific CD-sens) predicts allergic reactions at a milk challenge in most but not all patients.

BACKGROUND: The basophil activation test is an emerging clinical tool in the diagnosis of cow's milk allergy (CMA). The aim was to assess the association between the basophil allergen threshold sensitivity to the major milk protein casein (casein-specific CD-sens), the levels of milk- and casein-specific Immunoglobulin E antibodies (IgE-ab), and the severity of allergic reactions at milk challenges. METHODS: We enrolled 34 patients aged 5-15 (median 9) years who underwent a double-blind placebo-controlled milk-challenge (DBPCMC) as screening before inclusion in an oral immunotherapy study for CMA. The severity of the allergic reaction at the DBPCMC was graded using Sampson's severity score. Venous blood was drawn before the DBPCMC. Milk- and casein-specific IgE-ab were analyzed. Following in vitro stimulation of basophils with casein, casein-specific CD-sens, was determined. RESULTS: Thirty-three patients completed the DBPCMC. There were strong correlations between casein-specific CD-sens and IgE-ab to milk (rs = 0.682, p < .001), and between casein-specific CD-sens and IgE-ab to casein (rs = 0.823, p < .001). There was a correlation between the severity of the allergic reaction and casein-specific CD-sens level (rs = 0.395, p = .041) and an inverse correlation between casein-specific CD-sens level and the cumulative dose of milk protein to which the patient reacted at the DBPCMC (rs = -0.418, p = .027). Among the 30 patients with an allergic reaction at the DBPCMC, 67% had positive casein-specific CD-sens, 23% had negative casein-specific CD-sens, and 10% were declared non-responders. CONCLUSION: Two thirds of those reacting at the DBPMC had positive casein-specific CD-sens, but reactions also occurred despite negative casein-specific CD-sens. The association between casein-specific CD-sens and the severity of the allergic reaction and cumulative dose of milk protein, respectively, was moderate.