Cow's Milk-related Symptom Score (CoMiSS) values in presumed healthy European infants aged 6-12 months: a cross-sectional study.

The Cow's Milk-related Symptom Score (CoMiSS) is an awareness tool for evaluating cow's milk-related symptoms. Previous studies have focused on providing CoMiSS values for healthy and symptomatic infants aged 0-6 months. However, there is a notable gap in the literature concerning CoMiSS values for infants older than 6 months. This cross-sectional study aimed to determine CoMiSS values in presumed healthy infants who have completed 6 months and are up to 12 months old, hereafter referred to as 6 to 12 months old. Physicians from six European countries prospectively determined CoMiSS values in infants attending well-child clinics. Exclusion criteria included preterm delivery, acute or chronic disease, and the consumption of a therapeutic formula, dietary supplements (except vitamins), or medication. The following information was collected: gestational age, gender, age, type of feed (breast milk or infant formula), and complementary feeding. Descriptive statistics were summarized with mean and standard deviation for normally distributed continuous variables, median and IQR for non-normally distributed variables, and differences in CoMiSS values were analyzed with appropriate tests. Data from 609 infants were obtained. The overall median (Q1-Q3) CoMiSS values were 3 (1-5). Significant differences were found across age groups (p < 0.001), but not across groups based on gender (p = 0.551) or feeding type (p = 0.880).   Conclusions: This study provided CoMiSS values in presumed healthy infants aged 6-12 months. Additional studies should be conducted to establish the use of CoMiSS to assess cow's milk-related symptoms in infants 6 months and older. What is Known: • The Cow's Milk-related Symptom Score (CoMiSS) is an awareness tool for evaluating symptoms related to cow's milk. • CoMiSS values for presumed healthy infants aged 0-6 months infants are already available. What is New: • CoMiSS values in European infants aged 6-12 months are provided. • These CoMiSS values differed across various age groups but not across groups based on gender or feeding type.

Early-life environment and the risk of eczema at 2 years-Meta-analyses of six Finnish birth cohorts.

BACKGROUND: Urban-related nature exposures are suggested to contribute to the rising prevalence of allergic diseases despite little supporting evidence. Our aim was to evaluate the impact of 12 land cover classes and two greenness indices around homes at birth on the development of doctor-diagnosed eczema by the age of 2 years, and the influence of birth season. METHODS: Data from 5085 children were obtained from six Finnish birth cohorts. Exposures were provided by the Coordination of Information on the Environment in three predefined grid sizes. Adjusted logistic regression was run in each cohort, and pooled effects across cohorts were estimated using fixed or random effect meta-analyses. RESULTS: In meta-analyses, neither greenness indices (NDVI or VCDI, 250 m × 250 m grid size) nor residential or industrial/commercial areas were associated with eczema by age of 2 years. Coniferous forest (adjusted odds ratio 1.19; 95% confidence interval 1.01-1.39 for the middle and 1.16; 0.98-1.28 for the highest vs. lowest tertile) and mixed forest (1.21; 1.02-1.42 middle vs. lowest tertile) were associated with elevated eczema risk. Higher coverage with agricultural areas tended to associate with elevated eczema risk (1.20; 0.98-1.48 vs. none). In contrast, transport infrastructure was inversely associated with eczema (0.77; 0.65-0.91 highest vs. lowest tertile). CONCLUSION: Greenness around the home during early childhood does not seem to protect from eczema. In contrast, nearby coniferous and mixed forests may increase eczema risk, as well as being born in spring close to forest or high-green areas.

Cow's Milk-Related Symptom Score (CoMiSS): From Bristol to Brussels Stool Scale.

OBJECTIVES: The Cow's Milk-related Symptom Score (CoMISS) is an awareness tool for evaluating cow's milk-related symptoms in otherwise healthy infants <1 year of age. This study assessed whether replacing the Bristol Stool Form Scale (BSFS) with the Brussels Infants and Toddlers Stool Scale (BITSS) in non-toilet-trained infants would modify the overall CoMiSS and change the clinical approach regarding potential cow's milk allergy. METHODS: Non-toilet-trained infants aged <13 months were assessed by CoMiSS using the 7 images from the BSFS (CoMiSS-BSFS) compared to the 4 images of stools from BITSS (CoMiSS-BITSS). The Wilcoxon signed-rank test and Pearson correlation coefficient were calculated. A post hoc analysis using identical tests was performed in subsets of CoMiSS-BSFS scores ≥10, ≥12, ≤5, and ≥6. RESULTS: Eight hundred forty-four pairwise scores were collected. Applying the Wilcoxon test over the complete dataset, the difference between CoMiSS-BSFS and CoMiSS-BITSS was statistically significant ( P < 0.001). However, there was no significant difference in the subsets with CoMiSS-BSFS ≥10, ≥12, and ≥6 ( P = 0.84, P = 0.48, and P = 0.81, respectively). The significant difference remained restricted to the group with CoMiSS-BSFS ≤5, considered at low risk for CM-related symptoms ( P < 0.001). CONCLUSION: Replacing BSFS with BITSS does not change the cutoff for awareness of possible CM-related symptoms and will not impact the use of CoMiSS in clinical practice. Changes in CoMiSS remained limited to the subgroup with a low risk for CM-related symptoms.

Decrease in paediatric emergency room visits during the COVID-19 pandemic restrictions: A population-based study.

AIM: To investigate paediatric emergency room (ER) visits to evaluate the immediate health effects of COVID-19 pandemic restrictions on children. METHODS: We retrospectively examined paediatric ER visits in the Helsinki University Hospital (HUH) district during the first wave of the pandemic (1 March to 31 May 2020), and a 2-month period immediately before and after. These periods were compared to the corresponding time periods in 2015-2019 ('reference period'). RESULTS: The total number of ER visits decreased by 23.4% (mean 6474 during the reference period, 4960 during the pandemic period (incidence rate ratio [IRR] 0.75, 95% confidence interval 0.72-0.77; p < 0.001). This was due to a decrease in visits related to infectious diseases; visits due to surgical reasons did not decrease. The amount or proportion of patients triaged to the most urgent class (Emergency Severity Index 1) did not increase. Paediatric ER visits returned to baseline after lifting of restrictions. CONCLUSIONS: Although paediatric ER visits substantially decreased during the pandemic restrictions, children seen at the ER were not more severely ill. Our results do not indicate immediate detrimental health effects of pandemic control measures on children.

Perinatal Probiotic Mixture and Development of Allergic Sensitization up to 13 Years of Age.

BACKGROUND: Probiotics have shown promising results in primary prevention of allergies in early years, but the long-term effects on allergic sensitization need more evaluation. OBJECTIVES: We conducted a randomized double-blind placebo-controlled study to determine whether the use of a mixture of pre- and probiotics perinatally affects the prevalence of immunoglobulin E (IgE) sensitization up to 13 years in high-risk children. METHODS: One thousand two hundred twenty-three pregnant women were randomized to receiving probiotics or placebo from 36 gestational weeks until delivery, and their infants received pre- and probiotics or placebo from birth until 6 months. At 2, 5, and 13 years, blood samples were taken to determine specific IgE levels against common foods, pollen, and animal antigens. RESULTS: The prevalence of IgE sensitization to any allergen was high and increased with age. No significant difference in the prevalence of IgE sensitization to any particular one of the tested allergens was found between the groups. At 2, 5, and 13 years these prevalence rates of IgE sensitization to any allergen were 31.1 and 34.1%, 50.1 and 45.6%, and 61.4 and 56.8% in the probiotic and placebo groups, respectively. At 13 years, IgE sensitization to cat/dog dander was more frequent in the probiotic group compared to the placebo group (40.2 vs. 31.0%, p = 0.03). CONCLUSIONS: In high-risk children, perinatal use of a mixture of probiotics did not affect the prevalence of sensitization to any one of the tested allergens, but it was associated with more frequent IgE sensitization to cat/dog dander at 13 years.

Perinatal probiotic intervention prevented allergic disease in a Caesarean-delivered subgroup at 13-year follow-up.

BACKGROUND: The long-term effects of probiotic intervention for primary prevention of allergic diseases are not well known. We previously reported less eczema until 10 years in our probiotic intervention trial. OBJECTIVE: To investigate the effect of early probiotic intervention on the prevalence of allergic diseases up to 13 years of age. METHODS: Pregnant women (n = 1223) carrying a child at a high risk of allergy (at least one parent with allergic disease) were randomized to receive a mixture of probiotics (Lactobacillus rhamnosusGG and LC705, Bifidobacterium breve Bb99 and Propionibacterium freudenreichii) or placebo in a double-blind manner from 36 weeks of gestation until birth. Their infants received the same product for the first six months (registration number NCT00298337). At 13-year follow-up, the participants were requested to return a questionnaire and to provide a blood sample. RESULTS: A questionnaire was returned by 642 participants (63.1% of intention-to-treat infants), and 459 provided a blood sample. In the whole cohort, there were no statistically significant differences in doctor-diagnosed allergic disease (55.2% and 59.0%, probiotic and placebo group, respectively) or allergic disease (47.9% and 51.6%) based on the ISAAC questionnaire data. Inhalant-specific IgE sensitization (>0.7 kU/L) was 59.3% in the probiotic group and 49.8% in the placebo group (P = 0.040). In a post hoc analysis made in Caesarean-delivered subgroup, allergy was reported in 41.5% of the probiotic group and 67.9% of the placebo group (P = 0.006), and eczema in 18.9% and 37.5%, respectively (P = 0.031). In the whole cohort, 8.5% of the probiotic group had suffered from wheezing attacks during the previous 12 months vs 14.7% in the placebo group (P = 0.013). There were no statistically significant differences discovered between the characteristics of the participating group and the dropout group. CONCLUSIONS: Probiotic intervention protected Caesarean-delivered subgroup from allergic disease and eczema, but not the total cohort.

Outcome of oral immunotherapy for persistent cow's milk allergy from 11 years of experience in Finland.

BACKGROUND: The safety and efficacy of long-term milk oral immunotherapy (OIT) in Finnish children with persistent cow's milk allergy (CMA) were evaluated in an open-label, non-randomized study. METHODS: During the 11-year study, 296 children aged 5 years or older with immunoglobulin E (IgE)-mediated CMA started milk OIT. Follow-up data were collected at three time points: the post-buildup phase, 1 year thereafter, and at the cross-sectional long-term follow-up between January 2016 and December 2017. Patients were divided according to baseline milk-specific IgE (sIgE) level and by the amount of milk consumption at the long-term follow-up. The high-dose group consumed ≥2 dL of milk daily, while the failure group consumed <2 dL of milk or were on a milk-avoidance diet. RESULTS: Out of the initial study group, 244/296 (83%) patients participated in the long-term follow-up. Among these patients, 136/244 (56%) consumed ≥2 dL of milk daily. The median follow-up time was 6.5 years. Of the recorded markers and clinical factors, the baseline milk sIgE level was most associated with maintaining milk OIT (P < 0.001). Respiratory symptoms in the post-buildup phase increased the risk of treatment failure (OR 3.5, 95% CI: 1.5-8.1, P = 0.003) and anaphylaxis (OR 14.3, 95% CI: 1.8-114, P = 0.01). CONCLUSION: More than half of the patients were able to maintain the targeted milk dose in their daily diet. Baseline milk sIgE level and reactivity during the early treatment stage strongly predicted the long-term outcome and safety of milk OIT.

Celiac Disease by the Age of 13 Years Is Not Associated With Probiotics Administration in Infancy.

Probiotics are theoretically promising in primary prevention of celiac disease (CD), but research evidence on the topic is scarce. We used the data and material of a clinical double-blind randomized placebo-controlled trial on primary allergy prevention (n = 1223) to investigate in an exploratory study whether administration of a mix of pro- and prebiotics during late pregnancy and first 6 months of life was associated with prevalence of CD during 13-year follow-up. Children who fulfilled diagnostic criteria for CD (n = 11) and subjects with a serum sample available for analyzing CD antibodies (n = 867) were included. CD or elevated tissue transglutaminase IgA antibodies were not associated with probiotics or placebo. Nor were there any associations with the mode of delivery, the duration of exclusive or total breast-feeding, or respiratory infections during the first 2 years of life. Allergic diseases or sensitization by the age of 2 or 5 years were not clearly associated with the development of CD.

Wheat oral immunotherapy was moderately successful but was associated with very frequent adverse events in children aged 6-18 years.

AIM: This study investigated oral immunotherapy (OIT) for children aged 6-18 years with wheat allergies. METHODS: Well-cooked wheat spaghetti was given to 100 children with wheat allergies every day for 17 weeks, increasing from 0.3 to 2000 mg of wheat protein, followed by three- and nine-month maintenance phases. Blood samples were taken before therapy and at follow-up visits. The study was carried out in 2009-2015 in four Finnish paediatric allergology units. RESULTS: The children (67% male) had a mean age of 11.6 years (range 6.1-18.6), and 57 were using wheat daily 16 months after the initiation of therapy. Allergic symptoms occurred in 94/100 children: mild in 34, moderate in 36 and severe in 24. Specific immunoglobulin E (IgE) for ω-5-gliadin was significantly higher in patients who did not reach the target dose and were related to the intensity of reactions. CONCLUSION: The majority (57%) of children with wheat allergies could use wheat in their daily diet 16 months after the initiation of OIT, but 94/100 had adverse reactions and 60 were moderate or severe. Specific IgE to ω-5-gliadin may provide a biomarker for how much wheat can be tolerated and the intensity of the reactions to immunotherapy.

FUT2-dependent breast milk oligosaccharides and allergy at 2 and 5 years of age in infants with high hereditary allergy risk.

PURPOSE: Manifestation of allergic disease depends on genetic predisposition, diet and commensal microbiota. Genetic polymorphism of mothers determines their breast milk glycan composition. One major determinant is the fucosyltransferase 2 (FUT2, secretor gene) that was shown to be linked to commensal microbiota establishment. We studied whether FUT2-dependent breast milk oligosaccharides are associated with allergic disease in breast-fed infants later in life. METHODS: We analyzed FUT2-dependent oligosaccharides in breast milk samples of mothers (n = 266) from the placebo group of a randomized placebo-controlled trial of prebiotics and probiotics as preventive against allergic disease in infants with high allergy risk (trial registry number: NCT00298337). Using logistic regression models, we studied associations between FUT2-dependent breast milk oligosaccharides and incidence of allergic disease at 2 and 5 years of age. RESULTS: At 2 years, but not at 5 years of age, we observed a presumed lower incidence (p < 0.1) for IgE-associated eczema manifestation in C-section-born infants who were fed breast milk containing FUT2-dependent oligosaccharides. By logistic regression, we observed a similar relation (p < 0.1) between presence of FUT2-dependent breast milk oligosaccharides and IgE-associated disease and IgE-associated eczema in C-section-born infants only. When testing with the levels of breast milk oligosaccharide 2'-fucosyllactose as proxy for FUT2 activity, we observed significant (p < 0.05) associations in the C-section-born infants with 'any allergic disease,' IgE-associated disease, eczema and IgE-associated eczema. CONCLUSION: The data indicate that infants born by C-section and having a high hereditary risk for allergies might have a lower risk to manifest IgE-associated eczema at 2 years, but not 5 years of age, when fed breast milk with FUT2-dependent milk oligosaccharides. Further studies with larger cohorts and especially randomized controlled intervention trials are required to build on these preliminary observations.

Serum 25-Hydroxyvitamin D in Early Childhood Is Nonlinearly Associated with Allergy.

BACKGROUND: Vitamin D has several immunological functions. Data on the relation of vitamin D status and allergy are controversial. METHODS: We investigated the association between serum concentrations of 25-hydroxyvitamin D (25-OHD) and allergy in childhood. The study population (n = 819) was part of a randomized, double-blind, placebo-controlled trial where the mothers of offspring with a high risk for allergy received a mixture of probiotics (or placebo) for the last 4 weeks of pregnancy, and the child received this from birth to 6 months. Study subjects were followed for the emergence of sensitization and allergic symptoms for a period of 5 years, with medical examinations at the ages of 3 and 6 months, 2 and 5 years and also in the event of allergic symptoms. Levels of 25-OHD were measured in umbilical cord blood (UCB) samples (n = 724) and serum samples drawn at the age of 2 years (n = 369); the data were categorized into tertiles (T1-T3) and quartiles (Q1-Q4). The relation between 25-OHD levels and sensitization and allergy was analyzed with multivariable logistic regression analysis. RESULTS: 25-OHD levels in T2 in UCB were associated with a higher risk for sensitization by the age of 2 years and allergic disorders by the age of 5 years. In the serum samples, at the age of 2 years, 25-OHD levels in Q3 were associated with a higher risk of sensitization and IgE-mediated allergies by the age of 5 years. CONCLUSIONS: The 25-OHD levels in early childhood are associated with the emergence of allergy, but the association appears to be nonlinear.

A workshop report on the development of the Cow's Milk-related Symptom Score awareness tool for young children.

UNLABELLED: Clinicians with expertise in managing children with gastrointestinal problems and/or atopic diseases attended a workshop in Brussels in September 2014 to review the literature and determine whether a clinical score derived from symptoms associated with the ingestion of cow's milk proteins could help primary healthcare providers. The Cow's Milk-related Symptom Score (CoMiSS), which considers general manifestations, dermatological, gastrointestinal and respiratory symptoms, was developed as an awareness tool for cow's milk-related symptoms. It can also be used to evaluate and quantify the evolution of symptoms during therapeutic interventions, but does not diagnose cow's milk protein allergy and does not replace a food challenge. Its usefulness needs to be evaluated by a prospective randomised study. CONCLUSION: The CoMiSS provides primary healthcare clinicians with a simple, fast and easy-to-use awareness tool for cow's milk-related symptoms.

Specific antibodies in oral immunotherapy for cow's milk allergy: kinetics and prediction of clinical outcome.

BACKGROUND: METHODS for predicting the clinical outcome of specific oral immunotherapy (OIT) would improve the safety of the therapy. METHODS: We investigated 40 children aged 6-17 years with IgE-mediated cow's milk allergy (CMA) who either successfully completed OIT (n = 32) or discontinued the therapy due to adverse reactions (n = 8). From sera drawn before and after OIT, we analyzed specific IgA, IgG, IgG1 and IgG4 to cow's milk (CM), casein, ß-lactoglobulin and ovalbumin (with enzyme-linked immunosorbent assay) and IgE to CM and hen's egg white [with enzymatic fluoroimmunoassay (Phadia ThermoFisher Scientific CAP system)]. As a reference, we also analyzed serum samples from 8- to 9-year-old children who either had no history of CMA (n = 76) or who had spontaneously recovered from IgE-mediated CMA (n = 56). RESULTS: Levels of specific IgA, IgG, IgG1 and IgG4 to CM and casein, and CM-specific IgE prior to OIT were higher in children who discontinued the therapy than in those who achieved desensitization (p < 0.05). Adverse reactions in the entire population were associated with low IgG and IgG4, but high IgG1 levels to ovalbumin (p < 0.05). Specific IgA, IgG, IgG1 and IgG4 to CM proteins significantly increased and IgE to CM decreased during OIT in children who achieved desensitization (p < 0.01). In those who discontinued OIT, only IgG, IgG1 and IgG4 to CM increased significantly (p < 0.03) and CM IgE remained unchanged. CONCLUSIONS: High specific IgE, IgA and IgG-class antibodies to CM proteins appear to predict failure to achieve desensitization in CM OIT. Specific IgA and IgG-class antibodies to CM increase and CM IgE decreases during desensitization.

Use of IgE and IgG4 epitope binding to predict the outcome of oral immunotherapy in cow's milk allergy.

BACKGROUND: Oral immunotherapy (OIT) with cow's milk (CM) has been reported to induce a number of specific antibody responses, but these remain to be fully characterized. Our objective was to explore whether IgE and IgG4 epitope binding profiles could predict the risk of side effects during CM OIT. METHODS: The study population consisted of 32 children (6-17 yr of age) with CM allergy: 26 children who successfully completed OIT and six children who discontinued therapy due to adverse reactions. We investigated sera drawn before and after OIT. We analyzed specific IgE and IgG4 binding to CM protein-derived peptides with a microarray-based immunoassay. Antibody binding affinity was analyzed with a competition assay where CM proteins in solution competed with peptides printed on the microarray. RESULTS: IgE binding to CM peptides decreased and IgG4 binding increased following the OIT in children who attained desensitization. Compared with children who successfully completed OIT, those who discontinued OIT due to adverse reactions developed increased quantities and affinity of epitope-specific IgE antibodies and a broader diversity of IgE and IgG4 binding, but less overlap in IgE and IgG4 binding to CM peptides. CONCLUSIONS: Detailed analysis of IgE and IgG4 binding to CM peptides may help in predicting whether CM OIT will be tolerated successfully. It may thus improve the safety of the therapy.

How mothers perceive infants with unspecific gastrointestinal symptoms suggestive of cow's milk allergy?

AIM: To determine whether specific infant behavioural characteristics are present in children suspected of cow's milk allergy because of gastrointestinal symptoms. METHODS: We prospectively recruited 57 children (median age 8.7 months) with a suspicion of gastrointestinally manifested cow's milk protein allergy (GI-CMPA). None had detectable cow's milk-specific IgE. Mothers were asked to complete the Parenting Stress Index (PSI) Child Domain, and those with children below 18 months of age (n = 49) also the Infant Temperament Questionnaire (ITQ). GI-CMPA was diagnosed with the double-blind, placebo-controlled food challenge. Control group (n = 22) consisted of patients (age range 4-26 months), attending the Pediatric Allergy Unit, who did not have diagnosed or suspected food allergies. RESULTS: The scores were significantly higher for the PSI (n = 48) Child Domain (p < 0.0001) and for the ITQ (n = 44) subscale Difficultness (p = 0.0045) compared with the control patients without suspected/diagnosed food allergy. The difference between the challenge positive (n = 18) and negative (n = 39) patients remained statistically insignificant. After 6 months, in both groups, the scores (PSI Child Domain p = 0.0004, ITQ Difficultness p = 0.0393) were lower, but the ITQ Difficultness score still remained higher than in the controls (p = 0.0453). CONCLUSION: The mothers often perceive infants with unspecific symptoms suggestive of GI-CMPA as demanding and temperamentally difficult.

Dairy consumption and vitamin D concentration in adolescents with challenge-confirmed cow's milk allergy during infancy.

BACKGROUND/OBJECTIVES: Milk is an important source of dietary calcium and, if fortified, vitamin D. Cow's milk allergy (CMA) is treated with a milk elimination diet. Although most children become tolerant by age 3 years, some continue dairy avoidance. It remains unclear whether adolescents with a history of CMA adopt similar milk consumption as their peers. We assessed dairy consumption and concentration of serum 25-hydroxyvitamin D (25(OH)D) in adolescents with either confirmed CMA or a negative CMA challenge in infancy (CMA-refuted group) and age-matched controls. SUBJECTS/METHODS: This study is based on a previously reported randomized controlled trial from 1999 to 2002 on the treatment effect of probiotics on atopic eczema in participants aged <12 months (n = 230) with data on CMA status. We followed up these participants, aged 15-18 years, in 2017 (n = 104). A 20-item food frequency questionnaire assessed dairy consumption. An automated immunoassay measured 25(OH)D concentration. RESULTS: Median dairy product consumption did not differ between adolescents with CMA (449 g/d, n = 40), the CMA-refuted group (566 g/d, n = 36), and controls (235 g/d, n = 51) (P = 0.117). Median 25(OH)D concentrations were 76.0, 79.3, and 80.8 nmol/l, respectively (P = 0.844). Among participants, 93% were vitamin D sufficient (25(OH)D ≥ 50 nmol/l), with no differences between groups (P = 0.914). CONCLUSION: Among adolescents with a history of CMA during infancy, our study found no reintroduction failure of milk and no difference in vitamin D insufficiency rate compared with peers. Current management of CMA seems to adequately minimize later nutritional disadvantages associated with a cow's milk elimination diet.

Early-life gut microbiota associates with allergic rhinitis during 13-year follow-up in a Finnish probiotic intervention cohort.

Perinatal and early-life factors reported to affect risk of allergic diseases may be mediated by changes in the gut microbiota. Here, we explored the associations between the infant gut microbiota and allergic morbidity in childhood until 13 years of age in a subgroup of the FLORA probiotic intervention cohort. A mixture of four probiotic strains with galacto-oligosaccharides was administrated to the mothers from the 36th week of the pregnancy and later to their infants until 6 months of age. The infants were monitored for the manifestations of atopic eczema, food allergy, allergic rhinitis, and asthma by a pediatrician at 2 and 5 years of age; the allergic status was subsequently verified by a questionnaire at 10 and 13 years of age. The fecal microbiota at 3 months was profiled by 16S rRNA amplicon sequencing targeting the V3-V4 region, with and without adjusting for potentially important early-life factors. Overall, the positive diagnosis for allergic rhinitis between 2 and 13 years was associated with microbiota composition both in non-adjusted and adjusted models. This association was more pronounced in children born to one parent with confirmed atopic diseases compared to those who had two atopic parents and was characterized by a lower relative abundance of Bifidobacterium and Escherichia/Shigella spp. and a higher proportion of Bacteroides. While the probiotic and galacto-oligosaccharides intervention in the entire cohort was previously shown to reduce the prevalence of eczema to a certain extent, no associations were found between the 3-month gut microbiota and childhood eczema in the studied sub-cohort.IMPORTANCEAllergic diseases have increased in prevalence during the past decades globally. Although probiotics have been considered a promising strategy for preventing certain allergy related symptoms, studies connecting the infant gut microbiota and later life allergic morbidity in various populations remain limited. The present study supports an association between the infant microbiota and allergic morbidity after first years of life, which has been rarely examined.CLINICAL TRIALSRegistered at ClinicalTrials.gov (NCT00298337).

Human milk antibodies to global pathogens reveal geographic and interindividual variations in IgA and IgG.

BACKGROUNDThe use of high-throughput technologies has enabled rapid advancement in the knowledge of host immune responses to pathogens. Our objective was to compare the repertoire, protection, and maternal factors associated with human milk antibodies to infectious pathogens in different economic and geographic locations.METHODSUsing multipathogen protein microarrays, 878 milk and 94 paired serum samples collected from 695 women in 5 high and low-to-middle income countries (Bangladesh, Finland, Peru, Pakistan, and the United States) were assessed for specific IgA and IgG antibodies to 1,607 proteins from 30 enteric, respiratory, and bloodborne pathogens.RESULTSThe antibody coverage across enteric and respiratory pathogens was highest in Bangladeshi and Pakistani cohorts and lowest in the U.S. and Finland. While some pathogens induced a dominant IgA response (Campylobacter, Klebsiella, Acinetobacter, Cryptosporidium, and pertussis), others elicited both IgA and IgG antibodies in milk and serum, possibly related to the invasiveness of the infection (Shigella, enteropathogenic E. coli "EPEC", Streptococcus pneumoniae, Staphylococcus aureus, and Group B Streptococcus). Besides the differences between economic regions and decreases in concentrations over time, human milk IgA and IgG antibody concentrations were lower in mothers with high BMI and higher parity, respectively. In Bangladeshi infants, a higher specific IgA concentration in human milk was associated with delayed time to rotavirus infection, implying protective properties of antirotavirus antibodies, whereas a higher IgA antibody concentration was associated with greater incidence of Campylobacter infection.CONCLUSIONThis comprehensive assessment of human milk antibody profiles may be used to guide the development of passive protection strategies against infant morbidity and mortality.FUNDINGBill and Melinda Gates Foundation grant OPP1172222 (to KMJ); Bill and Melinda Gates Foundation grant OPP1066764 funded the MDIG trial (to DER); University of Rochester CTSI and Environmental Health Sciences Center funded the Rochester Lifestyle study (to RJL); and R01 AI043596 funded PROVIDE (to WAP).