Early postnatal and concurrent exposure to metals and neurobehavioral outcomes at 5 years: Associations with individual environmental exposures and mixtures.

BACKGROUND: Little is known about the effect of postnatal exposure to heavy metals on children's behavior problems. This study aimed to investigate the association between metal exposure during different stages of postnatal life and neurobehavioral outcomes in preschool children. METHODS: Urinary concentrations of six metals (arsenic, cadmium, chromium, lead, manganese, and vanadium) were measured using inductively coupled plasma mass spectrometry in 220 participants at two time points: before 1 year and at 5 years of age. Mothers completed the Child Behavior Checklist when the children were 5 years old. Multivariable linear and logistic regression analyses were used to evaluate the association between metal concentrations and behavioral outcomes. We employed Bayesian kernel machine regression (BKMR) to assess possible joint effects and potential interactions between metal mixtures and behavioral outcomes. RESULTS: Concentrations of urinary arsenic (As) in infants were associated with higher scores for anxious/shy behavior problems (ß ranging from 0.03 to 0.23). Further analyses showed that As exposure increased the odds of scores falling into the borderline or clinical range on anxious/depressed, affective, and pervasive developmental problems (ORs: 2.45-3.40). Stratification by sex indicated significance in girls but not in boys. BKMR analysis showed that, among the metal mixtures, As displayed a major effect on behavior scores. Concentrations of urinary cadmium in infants were also associated with higher behavioral scores but did not increase the risk of clinical problems. A cross-sectional survey in 5-year-olds did not show a significant association between concurrent metal exposure and behavioral outcome. CONCLUSION: Our results showed that exposure to As and Cd during infancy was associated with emotional problems in children. The effect of arsenic exposure was more pronounced among female infants. We suggest reducing exposure to toxic metals during early postnatal life to prevent behavioral problems in children."

The association between human milk fatty acid composition in mothers with an elevated body mass index and infant growth changes.

BACKGROUND & AIMS: Few studies have investigated alternations in human milk polyunsaturated fatty acid (PUFA) composition in the context of maternal obesity and its effects on infant growth trajectories. This study explored whether maternal weight status and breastfeeding type influence human milk FA composition and infant anthropometry during the first six months of life. METHODS: Mother-infant dyads were enrolled from the Prediction of Allergies in Taiwanese Children birth cohort study. Data concerning maternal pre-pregnancy weight, infants' breastfeeding practices, and anthropometric data were obtained regularly. We identified and compared between the composition of 30 FAs in the colostrum and 2-month milk, respectively, in obese/overweight (OB/OW) and normal-weight (NW) mothers. Multiple linear regression analyses were performed to determine the association between PUFA composition at different lactation stages and infant anthropometric parameter changes and to identify the independent variables for body mass index (BMI) z-scores by six months of age. RESULTS: We included 338 mother-infant dyads (OB/OW mothers, 16.9 %). OB/OW mothers exhibited lower total n-3 PUFAs (P = 0.035), higher ratios of arachidonic acid (C20:4n-6)/eicosapentaenoic acid (C20:5n-3) + docosahexaenoic acid (C22:6n-3), and n-6/n-3 PUFA in colostrum (P = 0.037 and 0.011, respectively), and their offspring had higher body weight and BMI z-scores. Nevertheless, no PUFA composition or n-6/n-3 PUFA ratios in colostrum and 2-month milk were associated with anthropometric parameter changes by age 6 months. Infant birth weight z-scores were independently associated with BMI outcomes at age 6 months (adjusted ß = 0.16, 95 % confidence interval (0.05-0.35), P = 0.010) CONCLUSION: Neither n-3 nor n-6 PUFA profiles nor n-6/n-3 PUFA ratios at different lactation stages were found to be associated with anthropometric changes by age 6 months, suggesting that human milk PUFA composition may not be an important determinant of early infant growth trajectories.

Longitudinal analysis of the impact of smoking exposure on atopic indices and allergies in early childhood.

Background: Exposure to smoking is recognized as a health hazard; however, a longitudinal analysis of the impact of smoking exposure in families on the allergic reactions related to childhood atopic diseases has not been well addressed. Methods: Children who completed a three-year follow-up period from the birth cohort were included in this study. The history of smoking exposure was recorded, and the urine cotinine levels were measured at 1 and 6 months, and 1, 2, and 3 years of age. Specific IgE levels against food and mite allergens were measured at age 6 months, and 1, 2, and 3 years. Their relevance to family smoking exposure and the subsequent development of atopic diseases was also analyzed. This study was approved by the Ethics Committee of Chang Gung Memorial Hospital (No. 102-1842C). Results: A total of 198 infants were enrolled in this study. The prevalence of passive smoking exposure among these children was as high as 45%. The urine cotinine levels were significantly higher in children with history of smoking exposure (P < 0.001). At 6 months of age, the food-specific IgE levels and the prevalence of eczema were significantly higher in children with smoking exposure than in those without smoking exposure (P < 0.05). By contrast, the urine cotinine levels were significantly higher in children with IgE sensitization (>100 kU/L, P < 0.05) at 3 years of age, which was also significantly associated with a higher prevalence of allergic rhinitis and development of asthma (P < 0.01). Conclusion: Family smoking exposure appears to be strongly associated with food sensitization in infancy and with IgE production in later childhood. This could potentially increase the susceptibility of developing infantile eczema and subsequent childhood airway allergies.

Prevalence, associated factors, and impact of adolescent asthma in Taiwan: Global Asthma Network phase I survey.

Background: The prevalence of asthma in Taiwan was increasing in the past 30 years, causing a great impact on adolescent health. This study aimed to investigate the current prevalence, impact, and associated factors of asthma in Taiwanese adolescents. Material and methods: Parents or guardians provided passive consent at home prior to the survey. Adolescents aged 13-14 years completed a questionnaire survey in 2017 in Taipei, Taiwan. The prevalence, impact, and associated factors of asthma were analyzed. We also compared the asthma prevalence with the prevalence in 1995 and 2001. Results: We analyzed 3474 validated questionnaires. The prevalence of physician-diagnosed asthma was 12.4%. The prevalence of current wheezing was 9.2% in 2017, which was 5.2% in 1995 and 7.0% in 2001. 3.3% of 13-14-year-old adolescents had severe asthma symptoms. Asthma significantly impacted the lives of adolescents. Of the students with asthma, 10.9% had school absenteeism, 16.5% urgently needed to see a doctor, 9.5% went to the emergency department, and 3.5% were admitted to hospitals within the preceding 12 months. The associated factors for physician-diagnosed asthma in Taiwanese adolescents were male (prevalence ratio [PR], 1.38; 95% confidence interval [CI], 1.05-1.83; p = 0.02), maternal history of asthma (PR, 2.61; 95% CI, 1.69-4.02; p < 0.01), and recent paracetamol use at least once per month (PR, 2.60; 95% CI, 1.24-5.42; p = 0.01). The associated factors for school absenteeism were nocturnal cough (PR, 1.99; 95% CI, 1.16-3.41; p = 0.01), current wheezing (PR, 7.52; 95% CI, 4.39-12.9; p < 0.01), and recent paracetamol use (at least once per month, PR, 3.16; 95% CI, 1.10-9.06; p = 0.03; at least once per year, PR, 2.19; 95% CI, 1.25-3.83; p < 0.01). Conclusions: The prevalence of physician-diagnosed asthma was 12.4%. Asthma substantially impacted the lives of adolescents. Reducing nocturnal cough, wheezing frequency, and paracetamol usage might help decrease school absenteeism.

Longitudinal assessment of early growth in children with IgE- and non-IgE-mediated food allergy in a healthy infant cohort.

BACKGROUND: There are conflicting associations reported between food allergies (FAs) and poor growth, with some indication that children with multiple FAs are at highest risk. OBJECTIVE: We analyzed longitudinal weight-for-length (WFL) trajectories from our healthy cohort to evaluate growth in children with IgE-mediated FAs and food protein-induced allergic proctocolitis (FPIAP), a non-IgE-mediated FA. METHODS: Our observational cohort of 903 healthy newborn infants was prospectively enrolled to evaluate the development of FAs. Longitudinal mixed effects modeling was used to compare differences in WFL among children with IgE-FA and FPIAP, compared with unaffected children, through age 2. RESULTS: Among the 804 participants who met inclusion criteria, FPIAP cases had significantly lower WFL than unaffected controls during active disease, which resolved by 1 year of age. In contrast, children with IgE-FA had significantly lower WFL than unaffected controls after 1 year. We also found that children with IgE-FA to cow's milk had significantly lower WFL over the first 2 years of age. Children with multiple IgE-FAs had markedly lower WFL over the first 2 years of age. CONCLUSION: Children with FPIAP have impaired growth during active disease in the first year of age which resolves, whereas children with IgE-FA, particularly those with multiple IgE-FA, have impaired growth more prominently after the first year of age. It may be appropriate to focus nutritional assessment and interventions accordingly during these higher risk periods in these patient populations.

Rising prevalence of food allergies in Taiwan: An epidemiological study.

BACKGROUND: Food allergies are becoming more prevalent globally. The purpose of this study was to investigate the epidemiology of food allergies in Taiwan. METHODS: In 2017, a food allergy questionnaire was administered to 6-7-year-old children, 13-14-year-old adolescents, and their parents in Taipei. The results were compared to those from a previous survey conducted in 2004. RESULTS: A total of 16,200 questionnaires were completed, revealing a rise in the prevalence of food allergies from 7.7% to 10.4% in the pediatric group and from 6.4% to 12.5% in the adult group. Peanut allergies also increased to 1.1%. Shrimp and crabs were the most common allergens, with urticaria being the most common symptom. Shortness of breath or wheezing occurred in 10% of individuals, while 2.1% experienced syncope or shock, and 0.1% were admitted to an intensive care unit. Personal history of allergic rhinitis and atopic dermatitis, as well as family histories of food allergies, were risk factors for food allergy in 6-7-year-old children. In the 13-14-year-old group, personal history of asthma, allergic rhinitis, or atopic dermatitis, recent use of acetaminophen, and living with dogs were risk factors. Females, personal histories of asthma, allergic rhinitis, atopic dermatitis, and moist and damp at home were risk factors in adults. Breastfeeding was a protective factor in 6-7-year-old children. CONCLUSION: The increasing prevalence of food allergies, including peanut allergies, in Taiwan warrants attention from physicians to provide appropriate care and education to patients with food allergies. The protective effect of breastfeeding against food allergies shall be emphasized.

Metabolomics Analysis Reveals Molecular Signatures of Metabolic Complexity in Children with Hypercholesterolemia.

Despite the importance of hypercholesterolemia in children, it is overlooked, and there are currently few metabolomics-based approaches available to understand its molecular mechanisms. Children from a birth cohort had their cholesterol levels measured with the aim of identifying the metabolites for the molecular biological pathways of childhood hypercholesterolemia. One hundred and twenty-five children were enrolled and stratified into three groups according to cholesterol levels (acceptable, <170 mg/dL, n = 42; borderline, 170-200 mg/dL, n = 52; and high, >200 mg/dL, n = 31). Plasma metabolomic profiles were obtained by using 1H-nuclear magnetic resonance (NMR) spectroscopy, and partial least squares-discriminant analysis (PLS-DA) was applied using the MetaboAnalyst 5.0 platform. Metabolites significantly associated with different cholesterol statuses were identified, and random forest classifier models were used to rank the importance of these metabolites. Their associations with serum lipid profile and functional metabolic pathways related to hypercholesterolemia were also assessed. Cholesterol level was significantly positively correlated with LDL-C and Apo-B level, as well as HDL-C and Apo-A1 level separately, whereas HDL-C was negatively correlated with triglyceride level (p < 0.01). Eight metabolites including tyrosine, glutamic acid, ornithine, lysine, alanine, creatinine, oxoglutaric acid, and creatine were significantly associated with the different statuses of cholesterol level. Among them, glutamic acid and tyrosine had the highest importance for different cholesterol statuses using random forest regression models. Carbohydrate and amino acid metabolisms were significantly associated with different cholesterol statuses, with glutamic acid being involved in all amino acid metabolic pathways (FDR-adjusted p < 0.01). Hypercholesterolemia is a significant health concern among children, with up to 25% having high cholesterol levels. Glutamic acid and tyrosine are crucial amino acids in lipid metabolism, with glutamic-acid-related amino acid metabolism playing a significant role in regulating cholesterol levels.

Introduction of Egg White and Yolk to Infant Diets and Early Childhood Atopic Dermatitis.

This study investigated whether the introduction of allergenic foods in infancy is associated with atopic dermatitis (AD) in early childhood. Information regarding parental allergic histories, the introduction of six possible allergenic foods (fruits, egg white, egg yolk, fish, shellfish, and peanuts), and physician-diagnosed AD was obtained using age-specific questionnaires (0-2 years). Immunoglobulin E, specific to 20 food allergens, was also quantified at 12 months of age. Logistic regression analyses were used to determine the association between individual food introduction and the outcomes of food sensitization and AD. We found AD development by 2 years of age was significantly related to a parental history of allergy (adjusted odds ratio (aOR) = 1.29) and not being introduced to egg white and yolk during infancy (aORs = 2.27 and 1.97, respectively). Stratified analyses revealed that the introduction of both egg white and yolk was negatively associated with AD by 2 years of age, especially for those children where both parents had allergic diseases (aOR = 0.10). In summary, the introduction of egg white and yolk to an infant's diet may be a modifiable factor in reducing the risk of physician-diagnosed AD by 2 years of age, which may be particularly important for infants where both parents have allergies.

Early infancy dysbiosis in food protein-induced enterocolitis syndrome: A prospective cohort study.

BACKGROUND: The microbiome associations of food protein-induced enterocolitis syndrome (FPIES) are understudied. We sought to prospectively define the clinical features of FPIES in a birth cohort, and investigate for the evidence of gut dysbiosis. METHODS: We identified children diagnosed with FPIES in the Gastrointestinal Microbiome and Allergic Proctocolitis Study, a healthy infant cohort. Children were assessed and stools were collected at each well child visit. The clinical features of the children with FPIES were summarized. Stool microbiome was analyzed using 16S rRNA sequencing comparing children with and without FPIES. RESULTS: Of the 874 children followed up for 3 years, 8 FPIES cases (4 male) were identified, yielding a cumulative incidence of 0.92%. The most common triggers were oat and rice (n = 3, each) followed by milk (n = 2). The children with FPIES were more likely to have family history of food allergy (50% vs. 15.9% among unaffected, p = .03). The average age of disease presentation was 6 months old. During the first 6 months of life, stool from children with FPIES contained significantly less Bifidobacterium adolescentis, but more pathobionts, including Bacteroides spp. (especially Bacteroides fragilis), Holdemania spp., Lachnobacterium spp., and Acinetobacter lwoffii. The short-chain fatty acid (SCFA)-producing Bifidobacterium shunt was expressed significantly less in the stool from FPIES children. CONCLUSIONS: In this cohort, the cumulative incidence over the 3-year study period was 0.92%. During the first 6 months of life, children with FPIES had evidence of dysbiosis and SCFA production pathway was expressed less in their stool, which may play an important role in the pathogenesis of FPIES.

Longitudinal investigation of pathogenic bacterial colonization in early childhood: Emphasis on the determinants of Moraxella catarrhalis colonization.

BACKGROUND: Moraxella catarrhalis is a common, potential pathogen colonizing the respiratory tract in children. However, there is little information regarding the determinants of M. catarrhalis colonization and disease development. METHODS: A population-based cohort study was conducted to collect nasopharyngeal swabs from children aged 1, 2, 4, 6, 12, 18, 24, 36, and 60 months for the detection of four common respiratory tract pathogens, including Staphylococcus aureus, M. catarrhalis, Streptococcus pneumoniae, and Haemophilus influenzae. Questionnaires on breastfeeding status were administered during each visit. RESULTS: A total of 921 children were enrolled between 2012 and 2018. S.aureus was the most common pathogen, although the rates declined during the initial 18 months of life; in contrast, the other three pathogens increased during the first 5 years of life. M. catarrhalis was the second most common colonizing pathogen in all age groups, with prevalence ranging from 0.8% (7/842) at one month to 20.4% (33/162) at 60 months of age. Breastfed children (odds ratio [OR]: 0.56; 95% confidence interval [CI]: 0.35-0.92; P = 0.02) had a lower potential for M. catarrhalis carriage; however, infants with a longer duration of exclusive breastfeeding (OR: 1.12; 95% CI: 1.01-1.25; P = 0.04), especially >12 months of age, had a higher rate of M. catarrhalis carriage. CONCLUSION: Breastfeeding should be promoted because it may be correlated with a lower risk of M. catarrhalis carriage. However, an extended period of exclusive breastfeeding may be positively associated with M. catarrhalis colonization.

Association between Serum Zinc and Toll-like-Receptor- Related Innate Immunity and Infectious Diseases in Well-Nourished Children with a Low Prevalence of Zinc Deficiency: A Prospective Cohort Study.

Existing reports focus on zinc-associated immunity and infection in malnourished children; however, whether zinc also plays an important role in the immune homeostasis of the non-zinc-deficient population remained unknown. This study aimed to investigate the association between zinc status and toll-like receptor (TLR)-related innate immunity and infectious outcome in well-nourished children. A total of 961 blood samples were collected from 1 through 5 years of age. Serum zinc was analyzed, and mononuclear cells isolated to assess TNF-α, IL-6, and IL-10 production by ELISA after stimulation with TLR ligands. Childhood infections were analyzed as binary outcomes with logistic regression. The prevalence of zinc deficiency was 1.4-9.6% throughout the first 5 years. There was significant association between zinc and TLR-stimulated cytokine responses. Higher serum zinc was associated with decreased risk of ever having pneumonia (aOR: 0.94; 95% CI: 0.90, 0.99) at 3 years, and enterocolitis (aOR: 0.96; 95% CI: 0.93, 0.99) at 5 years. Serum zinc was lower in children who have had pneumonia before 3 years of age (72.6 ± 9 vs. 81.9 ± 13 µg/dL), and enterocolitis before 5 years (89.3 ± 12 vs. 95.5 ± 13 µg/dL). We emphasize the importance of maintaining optimal serum zinc in the young population.

Increased fecal human beta-defensin-2 expression in preterm infants is associated with allergic disease development in early childhood.

Background: This study aimed to investigate whether fecal human beta-defensins (HBD)-2 and eosinophil cationic protein (ECP) expression in preterm infants are associated with allergic disease development by age 2 years. Methods: Preterm infants' stool samples were collected at the age of 6 and 12 months postnatally. Information regarding medication exposure histories (antibiotics, antipyretics, probiotics) and physician-diagnosed allergic diseases was obtained using age-specific questionnaires and medical records. We compared the 6-month and 12-month fecal HBD-2 and ECP concentrations between the medication exposure and non-exposure group, respectively, and between children who developed allergic diseases and those who did not by 2 years of age. Univariate and multivariable logistic regression analyses were performed to investigate independent variables related to physician-diagnosed allergic diseases by 2 years of age. Results: Seventy-four preterm infants (gestational age, 31-36 weeks) were included. Fecal HBD-2 levels were significantly increased at 12 months of age among children who developed allergic diseases compared to those who did not (37.18 ± 11.80 ng/g vs. 8.56 ± 4.33 ng/g, P = 0.011). This association was more apparent among allergic children given antibiotics (50.23 ± 16.15 ng/g vs. 9.75 ± 7.16 ng/g, P = 0.008) or antipyretics (46.12 ± 14.22 ng/g vs. 10.82 ± 6.81 ng/g, P = 0.018) during the first year, whereas among allergic children who were previously not exposed to antibiotics or antipyretics, the differences were not significant. Results of the multivariable logistic regression analysis indicated that HBD-2 concentration in 12-month stools was an independent indicator associated with physician-diagnosed allergic diseases by 2 years of age (adjusted odds ratio: 1.03 [95% confidence interval: 1.00-1.05], P = 0.036). Our data revealed a lack of association between fecal ECP and allergic diseases. Conclusions: We found that preterm infants who expressed high fecal HBD-2 at 12 months of age were associated with physician-diagnosed allergic diseases by the age of 2 years. Further studies are needed to determine the role of fecal HBD-2 in the development of allergic diseases.

Metabolomics analysis reveals molecular linkages for the impact of vitamin D on childhood allergic airway diseases.

BACKGROUND: Several studies have reported the relevance between serum vitamin D and allergic immunoglobulin E (IgE) responses and atopic diseases. However, a metabolomics-based approach to the impacts of vitamin D on allergic reactions remains unclear. METHODS: A total of 111 children completed a 3-year follow-up were enrolled and classified based on longitudinal vitamin D status (≥ 30 ng/ml, n = 54; 20-29.9 ng/ml, n = 41; <20 ng/ml, n = 16). Urinary metabolomic profiling was performed using 1 H-Nuclear magnetic resonance (NMR) spectroscopy at age 3. Integrative analyses of their associations related to vitamin D levels, atopic indices, and allergies were performed, and their roles in functional metabolic pathways were also assessed. RESULTS: Six and five metabolites were identified to be significantly associated with vitamin D status and atopic diseases, respectively (FDR-adjusted p-value <.05). A further correlation analysis revealed that vitamin D-associated 3-hydroxyisobutyric acid and glutamine were positively correlated with atopic disease-associated succinic acid and alanine, respectively. Furthermore, hippuric acid was negatively correlated with atopic disease-associated formic acid, which was positively correlated with vitamin D level (p < .01). Absolute eosinophil count (AEC) was positively correlated with serum D. pteronyssinus- and D. farinae-specific IgE level (p < .01) but negatively correlated with vitamin D level (p < .05). Amino acid metabolisms were significantly associated with vitamin D related to childhood allergies. CONCLUSION: Integrative metabolomic analysis provides the link of vitamin D-associated metabolites with the gut microbiome and immunoallergic reactions related to childhood allergies.

Nasopharyngeal microbial profiles associated with the risk of airway allergies in early childhood.

BACKGROUND: Airway microbiota may play an important role in regulating the immune response related to allergic respiratory diseases. A molecular-based approach was used to analyze the association between nasopharyngeal microbiota, serum immunoglobin (Ig)E levels, and childhood respiratory allergies. METHODS: Nasopharyngeal swabs were collected from children aged 36 months with three phenotypes, including allergic respiratory diseases plus atopy, atopy alone, and healthy controls for microbiome analysis using Illumina-based 16S rRNA gene sequencing. RESULTS: In total, 87 children were enrolled, including 36 with allergic respiratory diseases plus atopy, 21 with atopy alone, and 30 healthy controls. Proteobacteria (45.7%), Firmicutes (29.3%), and Actinobacteria (15.3%) were the most prevalent phyla in the study population. Compared with healthy controls, a lower Chao1 index was found in children with allergies (P < 0.035), indicating that bacterial richness was inversely associated with airway allergies. Additionally, in comparison with healthy controls, the genera Acinetobacter, Moraxella, Asaia, and Rhodococcus were more abundant and positively correlated with total serum IgE levels in children with allergies (P < 0.01), whereas the genera Enterococcus and Rickettsia were inversely correlated with total IgE levels, and also appeared to be negatively associated with airway allergies (P < 0.01). CONCLUSIONS: The composition of the nasopharyngeal microbiota alteration may have an influence on childhood respiratory allergies. The inverse association between bacterial richness and allergies postulated that children living in a microbially hygienic environment may increase their risk of developing respiratory allergies.

Longitudinal Metabolomic Analysis Reveals Gut Microbial-Derived Metabolites Related to Formula Feeding and Milk Sensitization Development in Infancy.

Early exposure to formula milk increases the likelihood of cow's milk sensitization and food allergies in the later childhood. However, the underlying mechanisms are multifactorial and unclear. Fifty-five children from a follow-up birth cohort study were grouped into exclusive breastfeeding (EBF, n = 33) and formula feeding (EFF, n = 22) in the first six months of life. Urinary metabolites were longitudinally assessed and analyzed at 6 months, 1, and 2 years of age using 1H-nuclear magnetic resonance (NMR) spectroscopy. Integrated analysis of metabolic profiling associated with formula feeding and milk sensitization related to IgE reactions was also investigated. Twenty-two metabolites were significantly obtained in the EFF set at age 0.5, whereas nine metabolites were predominantly obtained in the milk sensitization set at age 1. A subsequent analysis of metabolic change from 6 months to age 1 identified eight metabolites, including 3-methyl-2-oxovaleric acid, glutarate, lysine, N-phenylacetylglycine, N,N-dimethylglycine, 3-indoxysulfate, 2-oxoglutaric acid, and pantothenate associated with formula feeding and milk sensitization with same trend variation. Among them, 3-indoxysulfate, N-phenylacetylglycine, and N,N-dimethylglycine were gut microbial-derived without IgE association. By contrast, 3-methyl-2-oxovaleric acid, glutarate, and lysine were IgE related associated with formula feeding contributing to milk sensitization (p < 0.05). Longitudinal urinary metabolomic analysis provides molecular insight into the mechanism of formula feeding associated with milk sensitization. Gut microbial-derived metabolites associated with formula feeding and IgE associated metabolites related to branched-chain amino acid metabolism play roles in developing sensitization and allergic symptoms in response to formula feeding.

Kawasaki Shock Syndrome with Initial Presentation as Neck lymphadenitis: A Case Report.

Kawasaki disease (KD) is an acute systemic vasculitis of unknown cause that mainly affects infants and children and can result in coronary artery complications if left untreated. A small subset of KD patients with fever and cervical lymphadenitis has been reported as node-first-presenting KD (NFKD). This type of KD commonly affects the older pediatric population with a more intense inflammatory process. Considering its unusual initial presentation, a delay in diagnosis and treatment increases the risk of coronary artery complications. Herein, we report the case of a 9-year-old female with fever and neck mass that rapidly deteriorated to shock status. A diagnosis of KD was made after the signs and symptoms fulfilled the principal diagnostic criteria. The patient's heart failure and blood pressure improved dramatically after a single dose of intravenous immunoglobulin. This case reminds us that NFKD could be the initial manifestation of KDSS, which is a potentially fatal condition. We review the literature to identify the overlapping characteristics of NFKD and KDSS, and to highlight the importance of early recognition of atypical KD regardless of age. We conclude that unusually high C-reactive protein, neutrophilia, and thrombocytopenia serve as supplemental laboratory indicators for early identification of KDSS in patients with NFKD.

Longitudinal changes in body mass index Z-scores during infancy and risk of childhood allergies.

BACKGROUND: Few studies address the dynamic changes of body mass index (BMI) Z-scores during infancy with breastfeeding and their impact on childhood atopic diseases. METHODS: A total of 183 children from a birth cohort regularly followed-up for 4 years were enrolled in this study. Time series data of BMI Z-scores from 1 month to 2 years of age was clustered using K-means method in R software. Breastfeeding status during the first 6 months of life was recorded and classified. The total serum and specific immunoglobulin E (IgE) levels to food and inhalant allergens were measured at age 0.5, 1, 1.5, and 2 years. RESULTS: Using K-means clustering, the dynamic changes in BMI Z-scores were classified into three clusters (cluster A, increasing, n = 62; cluster B; decreasing, n = 62; cluster C, constant low, n = 59). Despite having no statistical association with atopic diseases, a decreasing trend in infantile BMI Z-scores was significantly associated with a higher prevalence of IgE sensitization at age 1 which increased the risk of rhinitis development at age 4 (P = 0.007). No difference in BMI Z-scores was determined between different breastfeeding patterns. However, exclusive formula feeding ≥6 months was found to be significantly associated with mite sensitization at age 1.5 years which risks asthma development at age 4 (P = 0.001). CONCLUSIONS: A decreasing trend of BMI Z-scores during infancy is determined to be inversely associated with IgE and allergen sensitization, which may potentially increase the risk of allergies in early childhood.

Cord blood soluble Fas ligand linked to allergic rhinitis and lung function in seven-year-old children.

BACKGROUND: Serum or cord blood soluble Fas ligand (FasL) has been related to asthma, allergic rhinitis, and atopic dermatitis in cross-sectional and short-term follow-up studies. However, the association of cord blood soluble FasL with long-term allergic outcomes has seldom been investigated. METHODS: The Prediction of Allergies in Taiwanese Children birth cohort study recruited healthy newborns upon delivery. At birth, blood was collected from the umbilical cords of these children, and the cord blood soluble Fas ligand levels were measured. At the age of seven years, the allergic outcome of each child was diagnosed by pediatric allergists and pulmonologists. Tests were conducted to measure the specific immunoglobulin E, fractional exhaled nitric oxide (FeNO), and pulmonary function levels of each child. RESULTS: Cord blood soluble FasL levels were higher in seven-year-old children with allergic rhinitis (Odds ratio [OR] = 2.41, p = 0.012) and expiratory airway obstruction (the highest forced expiratory volume in 1 second/forced vital capacity < 90%, OR = 2.11, p = 0.022). The FeNO and Dermatophagoides pteronyssinus-specific immunoglobulin E levels of seven-year-old children were positively correlated with cord blood soluble FasL levels (p = 0.006 and 0.02, respectively). CONCLUSION: In this birth cohort, the cord blood soluble FasL levels were associated with allergic rhinitis, obstructive-type lung function, FeNO, and house dust mite sensitization in 7-year-old children. The cord blood soluble FasL level might be used as a predictor for allergic diseases in children who are 7 years old.

Community-Associated Methicillin-Resistant Staphylococcus Aureus Colonization in a Birth Cohort of Early Childhood: The Role of Maternal Carriage.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) colonization in infants may pose a risk for subsequent infection in children. The study aimed to determine S. aureus colonization patterns in infancy, and strain relatedness between maternal and infant colonization. Methods: A prospective cohort study was conducted for nasopharyngeal S. aureus detection in neonates at delivery; in children at 1, 6, 12, 24, 36, and 60 months of age; and from mothers immediately after the delivery of their baby and when their child is 1 month old. A questionnaire for infants and mothers was administered at each planned visit. Results: In total, 521 and 135 infant-mother dyads underwent nasopharyngeal swab collection at 1 month and immediately after delivery, respectively. Among the 521 dyads at 1 month of age, concordant S. aureus colonization was found in 95 dyads, including MRSA in 48.4% (46/95). No concordant MRSA carriage was present among the 135 dyads at delivery. The genetic relatedness of concurrent MRSA-colonized dyads showed that more than two-thirds (32/46 [69.6%]) had identical genotypes, mainly ST 59/PVL-negative/SCCmec IV. Infants aged 1 month had the highest incidence of S. aureus, and the trend declined to a nadir at the age of 12 months. Carrier mothers who smoked cigarettes may increase the risk of infant Staphylococcus colonization (odds ratio, 2.12; 95% confidence interval, 1.23-3.66; p < 0.01). Conclusions: Maternal-infant horizontal transmission may be the primary source of MRSA acquisition in early infancy. The avoidance of passive smoking could be recommended for the prevention of S. aureus carriage.

Levels of 15-HETE and TXB2 in exhaled breath condensates as markers for diagnosis of childhood asthma and its therapeutic outcome.

BACKGROUND: Dysregulation of eicosanoids is associated with asthma and a composite of oxylipins, including exhaled leukotriene B4 (LTB4 ), characterizes childhood asthma. While fractional exhaled nitric oxide (FeNO) has been used as the standard for monitoring steroid responsiveness, the potential utility of eicosanoids in monitoring the therapeutic outcomes remains unclear. We aimed to examine the levels of major eicosanoids representing different metabolic pathways in exhaled breath condensates (EBCs) of children with asthma during exacerbation and after treatment. METHODS: Levels of 6 exhaled eicosanoid species in asthmatic children and healthy subjects were evaluated using ELISA. RESULTS: In addition to those previously reported, including LTB4 , the levels of exhaled 15-hydroxyeicosatetraenoic acid (15-HETE), but not thromboxane B2 (TXB2 ), showed significant difference between asthmatics (N = 318) and healthy controls (N = 97), particularly the severe group showed the lowest levels of exhaled 15-HETE. Receiver operating characteristic (ROC) curve analyses revealed similar distinguishing power for the levels of 15-HETE, FEV1 (forced expiratory volume in the first second), and FeNO, while the 15-HETE/LTB4 ratio was significantly lower in subjects with asthma as compared to that of healthy controls (p < 0.0001). Analysis of asthmatics (N = 75) during exacerbation and convalescence showed significant improvement in lung function (FEV1 , p < .001), but not FeNO, concomitant with significantly increased levels of 15-HETE (p < .001) and reduced levels of TXB2 (p < .05) at convalescence, particularly for those who at the top 30% level during exacerbation. Further, decreased LTB4 and lipoxin A4 (LXA4 ) at convalescence were noted only in those at the top 30 percentile during exacerbation. CONCLUSION: The exhaled 15-HETE was found to discriminate childhood asthma while decreased levels of exhaled TXB2 and increased levels of 15-HETE were prominent at convalescence.