BACKGROUND:Isoflavone (ISO) consumption during pregnancy may affect food allergy (FA) in offspring through estrogen-like and other biological effects; however, this ISO-FA association in mother-child pairs remains elusive. Herein, the maternal ISO-childhood FA association was investigated using the Japanese birth cohort data. METHODS:The data from the Japan Environment and Children's Study, including 86,012 and 75,307 mother-child pairs, with FA in children aged ≤1 year and 1-3 years, respectively, were analyzed. Maternal ISO consumption (total daidzein and genistein) was assessed using a food frequency questionnaire. Physician-diagnosed FA data were obtained using questionnaires completed by caregivers. ISO consumption data was categorized into quartiles (Q1: reference), and the ISO-FA association was assessed through multivariable logistic regression analysis after adjusting for maternal age, educational level, smoking status, pre-pregnancy body mass index, history of allergies, blood folic acid concentration, total energy intake, and infant feeding method up to 4 months of age. RESULTS:Overall, FA cases in children aged ≤1 and 1-3 years were 6.6% and 12.1%, respectively. Maternal ISO consumption was negatively associated with FA in all children aged ≤1 year (Q3, adjusted odds ratio [aOR]: 0.91, 95% confidence interval [CI]: 0.84-0.99; Q4, aOR: 0.86, 95% CI: 0.79-0.93) and in those aged 1-3 years (Q3, aOR: 0.93, 95% CI: 0.88-0.99; Q4, aOR: 0.88, 95% CI: 0.83-0.95). Furthermore, in sex-stratified analysis, a negative association was observed between maternal ISO consumption and FA in female children of all ages, whereas this inverse association was observed only in 1-3-year-old male children. CONCLUSIONS:Overall, the findings show that maternal ISO consumption during pregnancy may reduce the risk of childhood FA, exhibiting sex-difference effects on offspring development.

BACKGROUND:Vitamin D influences immune development, but its role in childhood asthma remains unclear. Findings from studies examining vitamin D exposure from pregnancy into early childhood in relation to childhood asthma have been inconsistent, and few have assessed exposure longitudinally. We examined vitamin D status from pregnancy through early childhood to identify the critical window for physician-diagnosed asthma. METHODS:Among 205 children from the Chiba High-Risk Birth Cohort for Allergy, we analyzed serum 25-hydroxyvitamin D (25(OH)D) measured at five time points: maternal blood at 36 weeks' gestation, cord blood at birth, and child blood at 1, 2, and 5 years. Asthma was diagnosed at age 5 years using national guideline criteria and classified as no asthma, suspected asthma, or asthma. Multinomial logistic regression models assessed associations adjusted for maternal asthma, prenatal smoking exposure, and birth season. RESULTS:Maternal and cord blood 25(OH)D concentrations were low (median: 12.0 ng/mL in maternal blood and 6.0 ng/mL in cord blood), whereas postnatal concentrations ranged from 21.0 to 23.4 ng/mL in ages 1-5 years. Cord blood 25(OH)D levels showed a marginal inverse association with asthma (adjusted odds ratio per 1 ng/mL, 0.801; 95% confidence interval: 0.635-1.010). Maternal and postnatal 25(OH)D concentrations showed no clear associations with asthma risk, although estimates showed a similar inverse trend. CONCLUSION:Among measurements from late pregnancy through early childhood, cord blood 25(OH)D showed the strongest association with asthma risk at age 5 years, suggesting that fetal vitamin D exposure is a particularly relevant window for asthma development.

BACKGROUND:Severe Th2 inflammatory diseases, including food allergy, are known to be associated with osteoporosis. However, while IL-4 inhibits osteoclast differentiation, detailed mechanisms of osteoporosis caused under IL-4-excessive environments remain unclear. METHODS:OVA23-3 mice are transgenic mice expressing OVA-specific T-cell receptors and develop significant IL-4-producing T-cell responses resulting in food-allergic enteropathy associated with osteoporosis when fed an egg white (EW) diet. This enteropathy is characterized by phases of inflammation and desensitization; bone loss develops during the inflammatory phase with the onset of allergic enteropathy and is maintained during the desensitization phase when the enteropathy is alleviated by immunological tolerance induction by continuous EW-feeding. We used this model to elucidate the mechanism of food antigen-induced osteoporosis, particularly in an IL-4-dominant environment. RESULTS:During the inflammatory phase, EW-feeding promoted osteoclastogenesis with increased mast cells, suppressed by administering anti-IL-4 antibody to the model. This finding suggests a critical role for IL-4 in the induction of osteoclastogenesis, which may be associated with mast cells and eosinophils over-differentiation and lead to osteoporosis. However, during the desensitization phase, the bone loss mechanism switched to high metabolic bone turnover, maintaining osteoclast activity despite amelioration of the enteropathy by continuous EW feeding. The increased number of IL-10-producing Tregs from mesenteric lymph nodes may reduce osteoclastogenesis during the desensitization phase, but did not suppress osteoporosis. CONCLUSIONS:The present study provides a new perspective on a poorly understood mechanism of osteoporosis in severe allergies, suggesting the importance of maintaining bone health in allergic patients, including food allergies.

OBJECTIVES:This study aimed to evaluate clinical and serological factors influencing systemic disease activity in primary Sjögren's disease (SjD) using the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) and to identify distinct patient subgroups in a Japanese cohort. METHODS:Data from 7444 patients with ESSDAI ≥5 registered in Japan's National Database of Designated Intractable Diseases were analysed. Univariate and multivariate regression analyses evaluated the impact of demographic and serological factors on ESSDAI scores. K-means clustering identified subgroups based on significant variables. RESULTS:Male patients exhibited higher ESSDAI scores (coefficient: 0.76, P = .0007), whereas Hashimoto's disease was associated with lower scores (coefficient: -0.53, P = .009). Anti-SS-B/La (coefficient: 1.08, P = .0002) and high titre of antinuclear antibody (ANA) (coefficient: 0.64, P = .02) were associated with increased ESSDAI. Clustering identified three subgroups: a 'classic' SjD group with balanced systemic involvement, a male-specific group with severe manifestations, and a Hashimoto's disease group with milder activity. CONCLUSIONS:Primary SjD in Japan exhibits significant heterogeneity influenced by demographic and serological factors. Male sex and specific autoantibodies correlate with higher systemic activity, whereas Hashimoto's disease is associated with reduced severity. These findings elucidate the need for personalised management and longitudinal studies.

Background: CCL25, CCL28, and IL-7 are present in breast milk and are known to contribute to the infant's thymus function and mucosal immune system. However, little is known about the relationship between the concentration of these cytokines/chemokines in breast milk and the development of atopic dermatitis (AD) in infancy. Objective: The purpose of this study was to investigate whether the concentration of these cytokines/chemokines in breast milk is related to the development of AD in infants. Methods: In this study, we measured the concentrations of cytokines/chemokines in colostrum collected within 5 days of birth and in breast milk collected at 1-month of birth in 281 infants belonging to a birth cohort using sandwich ELISA, and analyzed the relationship with the development of AD in infants at 9 months of age. Results: There was no association between CCL25 and CCL28 levels in breast milk and 9-month AD. On the other hand, IL-7 levels in colostrum ingested by AD infants were significantly higher than those ingested by non-AD infants (median, ng/mL: 0.186 vs 0.119, Mann-Whitney U test, P < 0.01). In addition, IL-7 showed a significant dose-dependent relationship with AD. This relationship was only observed in mothers with allergies. Conclusion: The results of this study show that IL-7 levels in breast milk may offer insights into the pathophysiological mechanisms of infantile AD.

Background Vitamin D is associated with fetal growth and development. It also plays an essential role in the body's immune system and placental regulation of the mother. This study investigated the correlation between vitamin D intake and 25-hydroxyvitamin D, interleukin-6, and ferritin levels in the maternal and umbilical cord. Materials and methods A cross-sectional study was conducted from June to December 2022 in Hermina Hospital, General Hospital Bunda Padang, and Army Hospital Dr. Reksodiwiryo. A total of 40 pregnant persons were observed in this study. The participants approved and signed the informed consent. The data were collected using a food frequency questionnaire. Maternal and umbilical cord serum were analyzed using enzyme-linked immunosorbent assay. All data were normally distributed, and the Pearson correlation test was performed. Results Mean vitamin D intake was 16,54 ± 2,92 mcg, maternal and umbilical cord serum 25(OH)D levels were 14,74 ± 4,93 ng/mL and 17,02 ± 5,94 ng/mL, maternal and umbilical cord serum IL-6 levels were 81,04 ± 12,23 and 98,75 ± 16,58 ng/L, maternal and umbilical cord serum ferritin levels were 41 ± 50,97 and 122,97 ± 71,23 ng/mL. There was a moderate correlation between vitamin D intake and serum 25(OH)D maternal (r = 0,379 and p = 0,016) and umbilical cord (r = 0,490 and p = 0,001). Vitamin D intake showed weak, non-significant correlations with maternal IL-6 (r = 0,292, p = 0,068) and umbilical cord IL-6 (r=-0,243, p = 0,131), and negligible correlation with maternal (r = 0,006, p = 0,971) and umbilical cord ferritin (r=-0,205, p = 0,204). Conclusions This study found a moderate correlation between maternal vitamin D intake and serum 25(OH)D, but weak correlations with IL-6 and ferritin.

Introduction:Biomarkers for the early detection of severe neonatal conditions, such as necrotizing enterocolitis and sepsis, remain inadequate. Reactive oxygen species (ROS) produced during neutrophil activation are emerging as potential biomarkers of these diseases. This study aimed to evaluate the feasibility of bedside ROS measurement and establish baseline levels in neonates. Methods:Using the FLP-H4200 fluorescence-based system, OCl- were measured from 3 μl of whole blood. Twenty neonates (13 preterm and seven full-term) were included. On postpartum day 4, OCl- levels were measured using residual blood samples. Results:Baseline OCl- levels averaged 31,340 ± 10,674 and 26,022 ± 11,363 in full-term and preterm neonates, respectively (p = 0.35). No significant correlations were observed between OCl- levels and gestational age, birth weight, maternal milk intake, bilirubin, and C-reactive protein levels. Discussion:The FLP-H4200 system is feasible for rapid and minimally invasive ROS measurement in neonates. Although no significant associations with clinical factors were identified, elevated ROS levels compared with those in adults suggest neonatal adaptation to oxidative stress. Further research is required to evaluate ROS dynamics progressively and their clinical use in neonatal disease prediction.

Background The early identification of developmental concerns requires understanding individual differences that may represent early signs of neurodevelopmental conditions. However, few studies have longitudinally examined how child and maternal factors interact to shape these early developmental characteristics. Objective We aim to identify factors from the perinatal to infant periods associated with early developmental characteristics that may precede formal diagnoses and propose a method for evaluating individual differences in neurodevelopmental trajectories. Methods A prospective longitudinal observational study of 147 mother-child pairs was conducted from gestation to 12 months post partum. Assessments included prenatal questionnaires and blood collection, cord blood at delivery, and postpartum questionnaires at 1, 6, and 12 months. The Modified Checklist for Autism in Toddlers (M-CHAT) was used to evaluate developmental characteristics that might indicate early signs of atypical neurodevelopment. Polychoric or polyserial correlation coefficients assessed relationships between M-CHAT scores and longitudinal variables. L2-regularized logistic regression and Shapley Additive Explanations predicted M-CHAT scores and determined feature contributions. Results Twenty-one factors (4 prenatal, 3 at birth, and 14 postnatal) showed significant associations with M-CHAT scores (adjusted P values<.05). The predictive accuracy for M-CHAT scores demonstrated reasonable predictive accuracy (area under the receiver operating characteristic curve=0.79). Key predictors included infant sleep status after 6 months (nighttime sleep duration, bedtime, and difficulties falling asleep), maternal Kessler Psychological Distress Scale scores, and Mother-to-Infant Bonding Scale scores after late gestation. Conclusion Maternal psychological distress, mother-infant bonding, and infant sleep patterns were identified as significant predictors of early developmental characteristics that may indicate emerging developmental concerns. This study advances our understanding of early developmental assessment by providing a novel approach to identifying and evaluating early indicators of atypical neurodevelopment.

BACKGROUND:Food sensitization (FS) develops in early infancy and is a risk factor for subsequent food allergy (FA). Recent evidence suggests relationships of gut microbiota with FS and FA. However, little is known about the role of neonatal gut microbiota in the pathobiology of these manifestations. OBJECTIVES:We sought to characterize gut microbiota in children using an enterotyping approach and determine the association of gut microbiota and the enterotypes with the development of FS and FA. METHODS:We combined gut microbiome and fecal short-chain fatty acid data from 2 longitudinal birth-cohort studies in Japan, clustered the microbiome data from children who were 1 week to 7 years old and their mothers and identified enterotypes. We also determined the associations of gut microbiota and enterotypes with risks of developing FS and FA across the 2 studies using multivariable regression models. RESULTS:Data from the 2563 microbiomes identified 6 enterotypes. More gut bacteria (eg, Bifidobacterium) in 1-month-old children showed significant relationships with the development of FS and FA than in 1-week-old children. Enterotypes at 1 month old consisted of Bacteroides-dominant, Klebsiella-dominant, and Bifidobacterium-dominant enterotypes. Bifidobacterium-dominant enterotypes with the highest fecal propionate concentration had the lowest risks of developing FS and FA, especially of hen egg white sensitization. Bifidobacterium-dominant enterotypes had lower risks at 2 years old in one study (vs Bacteroides-dominant enterotype, adjusted odds ratio [adjOR]: 0.10, 95% CI: 0.01-0.78; vs Klebsiella-dominant enterotype, adjOR: 0.10, 95% CI: 0.01-0.77) and at 9 months old in the other study (vs Bacteroides-dominant enterotype, adjOR: 0.33, 95% CI: 0.11-0.91). CONCLUSIONS:In these birth-cohort studies, gut microbiome clustering identified distinct neonatal enterotypes with differential risks of developing FS and FA.

Background/Objectives: Stunting and weight faltering (WF) remain pressing public health challenges in low- and middle-income countries, with long-term consequences for child growth, development, and survival. While the role of gut health in early growth is increasingly recognized, evidence on how the gut microbiome and metabolome respond to nutritional interventions in WF infants is scarce. This study explored gut microbiome and metabolome changes in Indonesian infants aged 6-12 months who overcame WF following a one-month intervention. Methods: Infants were assigned to either a Nutritional Advice (NA) group or a Nutritional Advice plus Oral Nutritional Supplements (NAONS) group. Stool samples were collected before and after the intervention for microbiome (16S rRNA sequencing) and metabolome (LC-MS) analysis. Results: Significant shifts in gut microbial composition (beta diversity) and species richness (Chao1 index) were observed in both groups, suggesting enhanced microbial diversity and gut resilience. Within-group analysis revealed increases in beneficial genera such as Faecalibacterium and Peptostreptococcus, and a reduction in pro-inflammatory Fusobacterium in the NA group. The NAONS group showed a notable decrease in Proteus, a potentially pathogenic genus. Between-group comparisons indicated higher abundances of Lactococcus and Leuconostoc in the NAONS group, likely reflecting the influence of milk protein-rich supplements on microbial colonization, favoring lactic acid bacteria over SCFA-producing taxa, leading to better gut health. Metabolome analysis revealed significant changes in the NA group, increases in metabolites like Threonine, Tryptophan, and Xylose pointed to improved energy metabolism and gut health, while a decrease in Oxalic Acid suggested better metabolic efficiency. In contrast, the NAONS group, while benefiting from rapid weight gain, displayed a distinct metabolic profile influenced by high milk protein intake. No significant correlations were found between microbiome and metabolome changes, highlighting the complexity of gut-host interactions, suggesting that the interventions led to independent shifts in the aforementioned profiles. Conclusions: Overall, the findings suggest that nutritional interventions may enhance gut health and support recovery from weight faltering, providing insights into strategies that may contribute to restoring healthy growth trajectories and preventing stunting by modulating gut health.

Garlic allergy is rare and is infrequently reported as a food allergy. This report details the case of a 13-month-old girl who developed an allergy to garlic. The consumption of a stew containing undercooked garlic triggered her allergic reaction. Blood tests revealed a garlic-specific IgE level of 10.3 kUA/L. In addition, in the skin prick test, a 4 × 4 mm, 2 × 2 mm, and 1 × 1 mm wheal was induced by raw garlic, garlic heated for 5 min, and garlic heated for 10 min, respectively. She had a known history of egg allergy. The foods consumed at the time did not contain eggs and included all other foods she had previously tolerated, except garlic. Therefore, we diagnosed her with a garlic allergy. We performed western blotting and mass spectrometric analysis and identified alliin lyase 1 and alliin lyase 2 as the major allergens. We further confirmed that the patient’s sera reacted with recombinant alliin lyase 1 and 2. To our knowledge, this is the first report to accurately demonstrate the involvement of alliin lyase 1 and alliin lyase 2 in a patient with garlic allergy. Moreover, it highlights the differences in reactivity to garlic heated for different durations. In patients with garlic allergy, reactivity to heating time should be examined with skin prick tests.

OBJECTIVES:We aimed to assess the unmet medical needs of young adult patients with juvenile idiopathic arthritis (JIA) by evaluating real-world treatment data. METHODS:We analysed data on JIA in the age group of 20-29 years from the National Database of Designated Incurable Diseases of Japan, which records severe cases or those requiring high-cost medical care registered between April 2018 and March 2020. RESULTS:Overall, 322 patients with JIA transitioning to adulthood were included. A high frequency of methotrexate use was observed among all JIA subtypes. The frequency of methotrexate use at registration was significantly higher in patients with rheumatoid factor-positive polyarthritis and those with oligoarthritis or polyarthritis than in those with systemic arthritis. The historical use percentage of any biological disease-modifying antirheumatic drug was ≥85% for all JIA subtypes. The proportion of patients with ≥2 biological disease-modifying antirheumatic drug prescriptions was significantly higher in patients with rheumatoid factor-positive polyarthritis than in those with systemic arthritis. CONCLUSIONS:High-cost drugs were necessary for many patients with JIA transitioning to young adulthood and registered in the database. Further studies on the medical interventions and support for these patients are needed.

Background The early identification of developmental concerns requires understanding individual differences that may represent early signs of neurodevelopmental conditions. However, few studies have longitudinally examined how child and maternal factors interact to shape these early developmental characteristics. Objective We aim to identify factors from the perinatal to infant periods associated with early developmental characteristics that may precede formal diagnoses and propose a method for evaluating individual differences in neurodevelopmental trajectories. Methods A prospective longitudinal observational study of 147 mother-child pairs was conducted from gestation to 12 months post partum. Assessments included prenatal questionnaires and blood collection, cord blood at delivery, and postpartum questionnaires at 1, 6, and 12 months. The Modified Checklist for Autism in Toddlers (M-CHAT) was used to evaluate developmental characteristics that might indicate early signs of atypical neurodevelopment. Polychoric or polyserial correlation coefficients assessed relationships between M-CHAT scores and longitudinal variables. L2-regularized logistic regression and Shapley Additive Explanations predicted M-CHAT scores and determined feature contributions. Results Twenty-one factors (4 prenatal, 3 at birth, and 14 postnatal) showed significant associations with M-CHAT scores (adjusted P values<.05). The predictive accuracy for M-CHAT scores demonstrated reasonable predictive accuracy (area under the receiver operating characteristic curve=0.79). Key predictors included infant sleep status after 6 months (nighttime sleep duration, bedtime, and difficulties falling asleep), maternal Kessler Psychological Distress Scale scores, and Mother-to-Infant Bonding Scale scores after late gestation. Conclusion Maternal psychological distress, mother-infant bonding, and infant sleep patterns were identified as significant predictors of early developmental characteristics that may indicate emerging developmental concerns. This study advances our understanding of early developmental assessment by providing a novel approach to identifying and evaluating early indicators of atypical neurodevelopment.

ANALYSIS:with peptide microarrays containing linear epitopes of allergenic proteins is expected to provide information on the clinical status of the patient, but peptide arrays are still limited to research use. We thus aimed at developing a simple and sensitive peptide array that operates with more cost-effective ECL detection, so that it can be routinely used in clinical practice. For this purpose, instead of directly immobilizing the peptides onto the microarray surface as in the previous reports, we developed a two-step immobilization technique using microbeads. Peptides biotinylated at the N-terminal are first bound to microbeads with streptavidin (sAV) on the surface, followed by immobilization of the peptide-bound beads onto the microarray substrate using the photoreactive crosslinker. In this way, we were able to overcome the limitations of direct immobilization in increasing the amount and accessibility of peptides and greatly enhance the sensitivity so that ECL detection became possible. In the present study, we analyzed sera from cow's milk allergy (CMA) patients with our peptide array containing 20 peptides from αS1-casein. The results showed that IgE epitope patterns of patients could be visualized individually, and confirmed that the pattern is unique to each patient.

Environmental changes are considered to be a major cause of the recent rapid increase in allergic diseases including food allergy (FA). The disturbance of gut microbiota (dysbiosis) is considered to be pivotal in the causation of FA, among several environmental factors. The formation of normal intestinal microbiota and improvement of dysbiosis with probiotics and/or prebiotics may prevent FA. Hitherto, there is no strong evidence that probiotics or prebiotics prevent FA. Currently, the administration of probiotics and prebiotics only during pregnancy and after birth is considered to prevent FA. However, the WAO guideline does not recommend probiotic and/or prebiotic supplementation during pregnancy or breastfeeding for the prevention of FA because of the low certainty of the evidence. There are many unresolved concerns, like the selection of target subjects, the selection and combination of bacterial species to be used, etc. Nevertheless, probiotics and prebiotics could be promising therapeutic interventions for the prevention of FA. However, further research needs to be conducted in the future to explore the role of prebiotics and probiotics in preventing FA. A collaborative effort between researchers and clinicians to explore this topic should be encouraged.

A worldwide issue, vitamin D deficiency affects pregnant mothers and babies everywhere, including Indonesia. It involves the adaptive immune system by controlling the production of pro-and anti-inflammatory cytokines and the balance between humoral (Th2) and cell-mediated (Th1) immunity. The aim of this study was to investigate the relationship between vitamin D and the cytokines IL-6 and IL-10 in infants. It also examined the relationship between ferritin and IL-6/IL-10 in newborns. The study collected 114 umbilical cord blood samples from term-born mothers without clinical symptoms. IL-6 and IL-10 were among the cytokine profiles measured by the enzyme-linked immunosorbent assay (ELISA). SPSS was used for statistical analysis, and an in -silico investigation was carried out to examine the molecular relationships between vitamin D and IL-6/IL-10. Using the 20 ng/mL as the cut-off for vitamin D insufficiency suggested the insignificant association of vitamin D with IL-6 (p=0.42), IL-10 (p=0.76), and ferritin (p=0.47). When the umbilical cord vitamin D level was categorized into four quartiles, the association with the highest statistical significance (quartile 4 versus quartile was observed for IL-6 (p<0.001), IL-10 (p<0.001), and ferritin (p<0.001). However, the linear regression did not suggest the significant correlations of vitamin D with IL-6 (p=0.40) and IL-10 (p=0.45). A significant correlation based on the linear regression was found between ferritin and IL-10 (p=0.03). Molecular docking studies demonstrated binding affinities of -8.04 kcal/mol for IL-6-vitamin D and -8.53 kcal/mol for IL-10 -vitamin D complexes, with stable root mean square deviation throughout the simulations. This study contributes valuable insights into the clinical and computational analysis of the relationship of vitamin D with IL-6 or IL-10.

Background: Preterm infants discharged from the neonatal intensive care unit (NICU) have a risk of severe viral respiratory tract infections (RTIs). Researchers have recently reported the potential use of postbiotics to decrease RTIs in young children. However, the safety and efficacy of postbiotics for preventing RTIs in preterm infants is not yet established. Methods: We conducted a pilot double-blind, randomized, placebo-controlled study of the heat-killed lactic acid bacterium Pediococcus acidilactici K15 in 41 preterm infants born at <36 weeks of gestation and discharged from the NICU at Chiba University Hospital. Results: Following once-daily K15 or placebo treatment for one year, no significant differences were found in the mean number of febrile days (4.5 [1.5-7.4] days vs. 6.6 [2.6-10.5] days). The subgroup analysis showed that the effect of treatment on the number of febrile days was more prominent in the K15 group than in the placebo group, among children with older siblings. The 16S rRNA gene sequencing of fecal samples illustrated that the genus Faecalimonas was enriched in the K15 group, potentially promoting butyrate production by butyrate-producing bacteria. No adverse events were found to be associated with K15 intake. Conclusion: There were no clear data to show the effectiveness of K15 in preventing fever and RTIs in preterm babies during infancy. A larger clinical trial is warranted.

BACKGROUND:This study aimed to clarify the diagnostic and predictive factors for perennial allergic rhinitis (PAR) onset in children by analyzing the results of the Chiba High-risk Birth Cohort for Allergy study, which examined newborns with a family history of allergies.METHODS:Overall, 306 pregnant women were recruited. Their newborns were examined by otolaryngologists and pediatric allergists at 1, 2, and 5 years of age. Participants with clinical and laboratory data available at all consultation points were considered eligible.RESULTS:Among 187 eligible participants, the prevalence rates of PAR were 2.1%, 4.3%, and 24.1% at 1, 2, and 5 years of age, respectively. AR-specific nasal local findings and eosinophils in nasal smear were observed in a substantial number of patients with PAR at 1 and 2 years of age. Factors present up to 2 years of age that were associated with PAR onset at 5 years of age, in descending order, were as follows: sensitization to house dust mites (HDM), nasal eosinophilia, and sensitization to cat dander. In 44 cases with HDM sensitization, nasal eosinophilia up to 2 years of age achieved a sensitivity of 76.0% and a specificity of 73.7% for predicting PAR onset at 5 years.CONCLUSIONS:Rhinitis findings and nasal eosinophilia are useful auxiliary diagnostic items for pediatric PAR. Sensitization to HDM and nasal eosinophilia were the most influential factors associated with future PAR onset. A combination of these factors may facilitate the prediction of PAR onset.