Differential effects of long- and short-term exposure to PM2.5 on accelerating telomere shortening: from in vitro to epidemiological studies.

Exposure to air pollutants has been associated with DNA damage and increases the risks of respiratory diseases, such as asthma and COPD; however short- and long-term effects of air pollutants on telomere dysfunction remain unclear. We investigated the impact of short- and long-term exposure to fine particulate matter with an aerodynamic diameter below 2.5 µm (PM2.5) on telomere length in human bronchial epithelial BEAS-2B cells, and assessed the potential correlation between PM2.5 exposure and telomere length in the LIGHTS childhood cohort study. We observed that long-term, but not short-term, PM2.5 exposure was significantly associated with telomere shortening, along with the downregulation of human telomerase reverse transcriptase (hTERT) mRNA and protein levels. Moreover, long-term exposure to PM2.5 induced proinflammatory cytokine secretion, notably interleukin 6 (IL-6) and IL-8, triggered subG1 cell cycle arrest, and ultimately caused cell death. Long-term exposure to PM2.5 upregulated the LC3-II/ LC3-I ratio but led to p62 protein accumulation in BEAS-2B cells, suggesting a blockade of autophagic flux. Moreover, consistent with our in vitro findings, our epidemiological study found significant association between annual average exposure to higher PM2.5 and shortening of leukocyte telomere length in children. However, no significant association between 7-day short-term exposure to PM2.5 and leukocyte telomere length was observed in children. By combining in vitro experimental and epidemiological studies, our findings provide supportive evidence linking potential regulatory mechanisms to population level with respect to long-term PM2.5 exposure to telomere shortening in humans.

Clinical features and lymphocyte immunophenotyping analysis in primary immunodeficiency patients with non-transplant lymphoproliferative disorders.

Lymphoproliferative disorders (LPD) comprise a heterogeneous group and are originally classified into the "Disease of immune dysregulation" category. Of 96 Taiwanese patients during 2003-2022, 31 (median 66, range 0.03-675 months) developed LPD, mainly including palpable lymphadenopathy (in 10 patients), intestinal lymphadenopathy associated with refractory inflammatory bowel disease (IBD in 8) and hepatosplenomegaly (in 7) during long-term follow-up (median 144, range 3-252 months). They distributed in the categories of antibody deficiency (2 CVID, 2 TTC37, PIK3CD, PIK3R1 and AICDA each), phagocyte (4 CYBB, 1 STAT1 and 1 IFNRG1), immune dysregulation (2 FOXP3, 2 XIAP and 2 HLH), combined immunodeficiencies (2 IL2RG; CD40L, ZAP70 and unknown each), syndromic features (2 STAT3-LOF, 1 WAS and 1 ATM) and three with anti-IFN-γ autoantibodies. An increased senescent (CD8 + CD57+) and CD21-low, disturbed transitional B (CD38 + IgM++), plasmablast B (CD38++IgM-), memory B (CD19 + CD27+) and TEMRA (CD27-IgD-) components were often observed in cross-sectional immunophenotyping and trended to develop LPD.

Maternal folic acid supplementation during pregnancy in association with childhood overweight or obesity.

OBJECTIVE: This study aimed to examine associations of maternal folic acid supplementation (FAS) during pregnancy with childhood overweight or obesity (OWO) or adiposity. METHODS: In a population-based cohort of 1479 children, maternal FAS during pregnancy was assessed retrospectively by questionnaires. BMI and body fat percentages were measured at a mean age of 6.4 years. Pertinent factors were accounted for in data analyses. RESULTS: Maternal FAS during pregnancy was negatively associated with OWO (adjusted odds ratio: 0.70; 95% CI: 0.50 to 0.99). There were inverse associations of maternal FAS during pregnancy with BMI z score (ß: -0.22; 95% CI: -0.39 to -0.05), whole body fat percentage (ß: -1.28; 95% CI: -2.27 to -0.30), trunk fat percentage (ß: -1.41; 95% CI: -2.78 to -0.04), and limb fat percentage (ß: -1.31; 95% CI: -2.32 to -0.30). Stratified analyses found inverse associations of FAS during pregnancy with OWO, BMI z score, and body fat percentages predominantly among children without breastfeeding and whose parents had a below-tertiary educational level. CONCLUSIONS: This study provides novel evidence that maternal FAS during pregnancy was significantly associated with a decreased risk of childhood OWO and adiposity, particularly among children with no breastfeeding and lower parental educational level.

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.

Physician adherence to anaphylaxis guidelines among different age groups in emergency departments: 20-Year observational study.

BACKGROUND: Anaphylaxis is an acute and serious allergic reaction. Little is known about physician adherence to anaphylaxis guidelines among patients across different age groups. OBJECTIVE: To investigate real-world physician adherence to anaphylaxis guidelines among children, adults, and older adults in emergency departments. METHODS: This study retrospectively analyzed all consecutive patients with anaphylaxis who presented to 2 emergency departments at 2 branches of the largest tertiary hospital in Taiwan, between 2001 and 2020. Patients who met the diagnostic criteria for anaphylaxis were enrolled and grouped by age: children (<18 years), adults (18-64 years), and older adults (≥65 years). RESULTS: We enrolled 771 patients with anaphylaxis (159 children, 498 adults, and 114 older adults). Intramuscular epinephrine was administered in 294 cases (38.1%). There was a significant age-group difference in the rate of intramuscular epinephrine administration (46.5% in children, 37.3% in adults, and 29.8% in older adults; P trend = .004). When stratified by severity, 14.3% of older adults with moderate reactions received intramuscular epinephrine, whereas 35.2% of adults and 55.3% of children received intramuscular epinephrine (P trend < .001), whereas such difference was not found in patients with severe reactions. Upon discharge from emergency departments, 15.3% received allergist referral (52.2% in children, 6.6% in adults, and 1.8% in older adults; P trend < .001); 12.5% received education on avoidance of triggers (18.9%, 11.4%, and 7.9%; P trend = .01), and 16.1% received education on alarm symptoms (21.4%, 15.1%, and 13.2%; P trend = .05). CONCLUSION: The real-world physician adherence to anaphylaxis guidelines remains suboptimal in emergency departments, particularly among older adults. Physician continuing education is needed to improve the gap between anaphylaxis guidelines and clinical practice.

Association between antenatal corticosteroid treatment and severe adverse events in pregnant women.

BACKGROUND: Antenatal corticosteroids are considered the standard of care for pregnant women at risk for preterm birth, but studies examining their potential risks are scarce. We aimed to estimate the associations of antenatal corticosteroids with three severe adverse events: sepsis, heart failure, and gastrointestinal bleeding, in pregnant women. METHODS: Of 2,157,321 pregnant women, 52,119 at 24 weeks 0/7 days to 36 weeks 6/7 days of gestation were included in this self-controlled case series study during the study period of 2009-2018. We estimated incidence rates of three severe adverse events: sepsis, heart failure, and gastrointestinal bleeding. Conditional Poisson regression was used to calculate incidence rate ratios (IRRs) for comparing incidence rates of the adverse events in each post-treatment period compared to those during the baseline period among pregnant women exposed to a single course of antenatal corticosteroid treatment. RESULTS: Among 52,119 eligible participants who received antenatal corticosteroid treatment, the estimated incidence rates per 1000 person-years were 0.76 (95% confidence interval (CI): 0.69-0.83) for sepsis, 0.31 (95% CI: 0.27-0.36) for heart failure, and 11.57 (95% CI: 11.27-11.87) for gastrointestinal bleeding. The IRRs at 5 ~ 60 days after administration of antenatal corticosteroids were 5.91 (95% CI: 3.10-11.30) for sepsis and 4.45 (95% CI: 2.63-7.55) for heart failure, and 1.26 (95% CI: 1.02-1.55) for gastrointestinal bleeding; and the IRRs for days 61 ~ 180 were 2.00 (95% CI: 1.01-3.96) for sepsis, 3.65 (95% CI: 2.14-6.22) for heart failure, and 1.81 (95% CI: 1.56-2.10) for gastrointestinal bleeding. CONCLUSIONS: This nationwide population-based study suggests that a single course of antenatal corticosteroids is significantly associated with a 1.3- to 5.9-fold increased risk of sepsis, heart failure, and gastrointestinal bleeding in pregnant women. Maternal health considerations, including recommendations for adverse event monitoring, should be included in future guidelines for antenatal corticosteroid treatment.

Association of exposure to environmental vanadium and manganese with lung function among young children: A population-based study.

Exposure to environmental metals has been associated with health outcomes including respiratory health. Little is known about the impact of exposure to environmental metals on lung function among young children in general population. This study aimed to investigate the associations of exposure to metals with lung function among young children in a population-based cohort. A total of 1488 children aged 5-8 years attended a follow-up visit as part of the Longitudinal Investigation of Global Health in Taiwanese Schoolchildren (LIGHTS) cohort. We measured urinary samples of vanadium (median: 1.21 ng/mL; interquartile range (IQR): 0.73-1.98), manganese (median: 0.23 ng/mL; IQR: 0.13-0.47), arsenic (median: 40.51 ng/mL; IQR: 21.66-70.49), nickel (median: 1.09 ng/mL; IQR: 0.31-3.60), and cadmium (median: 0.26 ng/mL; IQR: 0.11-0.43) and performed lung function tests. Urinary vanadium concentrations were inversely associated with FVC (ß coefficient for the highest quartile versus the other quartiles: -33.40, p = 0.001), FEV1 (ß: -41.31, p < 0.001), FEV1/FVC ratio (ß: -1.00, p = 0.009), PEF (ß: -92.12, p = 0.004), and FEF25-75 (ß: -82.85, p < 0.001), after adjusting for relevant confounders. Urinary manganese concentrations were inversely associated with FVC (ß: -26.60, p = 0.007), FEV1 (ß: -31.62, p = 0.001), PEF (ß: -84.86, p = 0.009), and FEF25-75 (ß: -69.21, p = 0.002). Stratification analyses found inverse associations of urinary vanadium and manganese concentrations with lung function parameters predominantly among children exposed to environmental tobacco smoke. We did not find significant associations of urinary arsenic, nickel, and cadmium concentrations with lung function parameters. In conclusion, this study adds new evidence showing inverse associations of vanadium and manganese exposure with lung function among young children in the general population. Children with environmental tobacco smoke exposure are particularly vulnerable to adverse impact of vanadium and manganese exposure on lung function.

Prevalence and prescribing patterns of oral corticosteroids in the United States, Taiwan, and Denmark, 2009-2018.

Oral corticosteroids (OCS) are commonly prescribed for acute, self-limited conditions, despite studies demonstrating toxicity. Studies evaluating longitudinal OCS prescribing in the general population are scarce and do not compare use across countries. This study investigated and compared OCS prescription patterns from 2009 to 2018 in the general populations of the United States, Taiwan, and Denmark. This international population-based longitudinal cohort study used nationwide claims databases (United States: Optum Clinformatics Data Mart; de-identified; Taiwan: National Health Insurance Research Database; and Denmark: National Prescription and Patient Registries/Danish National Patient Registry) to evaluate OCS prescribing. We classified annual OCS duration as short-term (1-29 days), medium-term (30-89 days), or long-term (≥90 days). Longitudinal change in annual prevalence of OCS use and physician prescribing patterns were reported. Among 54,630,437 participants, average annual percentage of overall OCS use was 6.8% in the United States, 17.5% in Taiwan, and 2.2% in Denmark during 2009-2018. Prevalence of OCS prescribing increased at an average annual rate of 0.1%-0.17%, mainly driven by short-term prescribing to healthy adults. One-quarter to one-fifth of OCS prescribing was associated with a diagnosis of respiratory infection. Family practice and internal medicine physicians were among the highest OCS prescribers across countries and durations. Age- and sex-stratified trends mirrored unstratified trends. This study provides real-world evidence of an ongoing steady increase in OCS use in the general populations of the United States, Taiwan, and Denmark. This increase is largely driven by short-term OCS prescribing to healthy adults, a practice previously viewed as safe but recently shown to incur substantial population-level risk.

Association between antenatal corticosteroids and risk of serious infection in children: nationwide cohort study.

OBJECTIVE: To investigate the associations between exposure to antenatal corticosteroids and serious infection in children during the first three, six, and 12 months of life. DESIGN: Nationwide cohort study. SETTING: National Health Insurance Research Database, Birth Reporting Database, and Maternal and Child Health Database, 1 January 2008 to 31 December 2019, to identify all pregnant individuals and their offspring in Taiwan. PARTICIPANTS: 1 960 545 pairs of pregnant individuals and their singleton offspring. 45 232 children were exposed and 1 915 313 were not exposed to antenatal corticosteroids. MAIN OUTCOME MEASURES: Incidence rates were estimated for overall serious infection, sepsis, pneumonia, acute gastroenteritis, pyelonephritis, meningitis or encephalitis, cellulitis or soft tissue infection, septic arthritis or osteomyelitis, and endocarditis during the first three, six, and 12 months of life in children exposed versus those not exposed to antenatal corticosteroids. Cox proportional hazards models were performed to quantify adjusted hazard ratios with 95% confidence intervals for each study outcome. RESULTS: The study cohort was 1 960 545 singleton children: 45 232 children were exposed to one course of antenatal corticosteroids and 1 915 313 children were not exposed to antenatal corticosteroids. The adjusted hazard ratios for overall serious infection, sepsis, pneumonia, and acute gastroenteritis among children exposed to antenatal corticosteroids were significantly higher than those not exposed to antenatal corticosteroids during the first six months of life (adjusted hazard ratio 1.32, 95% confidence interval 1.18 to 1.47, P<0.001, for overall serious infection; 1.74, 1.16 to 2.61, P=0.01, for sepsis; 1.39, 1.17 to 1.65, P<0.001, for pneumonia; and 1.35, 1.10 to 1.65, P<0.001, for acute gastroenteritis).Similarly, the adjusted hazard ratios for overall serious infection (P<0.001), sepsis (P=0.02), pneumonia (P<0.001), and acute gastroenteritis (P<0.001) were significantly higher from birth to 12 months of life. In the sibling matched cohort, the results were comparable with those observed in the whole cohort, with a significantly increased risk of sepsis in the first six (P=0.01) and 12 (P=0.04) months of life. CONCLUSIONS: This nationwide cohort study found that children exposed to one course of antenatal corticosteroids were significantly more likely to have an increased risk of serious infection during the first 12 months of life. These findings suggest that before starting treatment, the long term risks of rare but serious infection associated with antenatal corticosteroids should be carefully weighed against the benefits in the perinatal period.

Personal exposure to aldehydes and potential health risks among schoolchildren in the city.

Schoolchildren are sensitive to airborne aldehyde exposures. The knowledge regarding inhalation exposure to aldehydes and the factors influencing exposure in schoolchildren is limited. This study aimed to assess the variability and potential health risks of exposure to aldehydes (including formaldehyde) in schoolchildren. The important factors affecting personal exposure to aldehydes were also explored. Forty schoolchildren were recruited from the urban and suburban areas of Taiwan for aldehyde samplings and questionnaire surveys. Personal and indoor home samples of aldehydes were collected simultaneously during warm and cold seasons. We also identified the potential variables associated with aldehyde exposure based on the participant's responses to the questionnaires using mixed-effects models. The dominant three abundant aldehydes identified in personal exposure samples were formaldehyde (geometric mean, GM = 12.2 µg/m3), acetaldehyde (GM = 5.53 µg/m3), and hexaldehyde (GM = 8.79 µg/m3), accounting for approximately 80% of the total selected aldehydes. Higher personal exposure to aldehydes was observed during the warm season. Moreover, the within-subject variance was predominant, accounting for 66.6 to > 99.9% of the total variance in exposure. Schoolchildren had a high probability of overexposure to formaldehyde and acrolein, which resulted in an incremental lifetime cancer risk of 1.59 × 10-4 (95th percentile = 4.64 × 10-4). Season, location, household refurbishment, and indoor ventilation variables were significantly associated with personal exposure to aldehydes. The results can improve our understanding of aldehyde exposure among schoolchildren to propose mitigation strategies. These findings may be applied to further epidemiological studies.

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.

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.

Use of Leukotriene-Receptor Antagonists During Pregnancy and Risk of Neuropsychiatric Events in Offspring.

This cohort study examines the association of the use of leukotriene-receptor antagonists during pregnancy with the risk of neuropsychiatric events in offspring.

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.

Pimecrolimus for the Treatment of Atopic Dermatitis in Infants: An Asian Perspective.

Atopic dermatitis (AD) is a common chronic, multisystem inflammatory skin disease in pediatric patients. There has been an increase in the incidence of AD in the pediatric population of the Asia-Pacific region. Studies have shown that genetic, epigenetic, environmental and cultural factors may lead to differences in the clinical manifestation and prevalence of AD between races. Early treatment of AD is necessary to prevent the atopic march leading to comorbidities such as asthma and allergic rhinitis. Topical corticosteroids (TCS) are used as first-line therapy for the treatment of AD, but their long-term usage poses a risk to the patient's health. Pimecrolimus (1%) is a topical calcineurin inhibitor (TCI) that is indicated for the treatment of mild to moderate AD. Pimecrolimus has no apparent increase in adverse events compared to TCS, and it causes less of a burning sensation than tacrolimus. The safety and efficacy of pimecrolimus has been established through various clinical trials; yet, in many Asian countries, the use of pimecrolimus in infants is still restricted due to safety concerns. Based on the available evidence, the expert panel recommends pimecrolimus in infants between 3 months and 2 years of age in the Asian population.

Correlation Analysis of Attention and Intelligence of Preterm Infants at Preschool Age: A Premature Cohort Study.

OBJECTIVE: Developmental delay in neurocognitive function has been reported in premature children. This cohort study prospectively followed preterm infants following birth, and herein we present the four-year longitudinal follow-up data of cognitive development at preschool age and analyze correlated factors. METHODS: Term and preterm children received regular clinical evaluations and development assessments after birth, and at age 4 ± 1 years, they received the Wechsler-preschool and primary scale of intelligence, Fourth Edition (WPPSI-IV), excluding those with full-scale intelligence quotient < 70. A total of 150 participants received Conners Kiddie Continuous Performance Test (K-CPT), while 129 participants received ophthalmic evaluation. We adopted Chi-square test, ANOVA, and post hoc analysis to compare group differences. Correlations with K-CPT and WPPSI-IV were analyzed using Pearson's correlation. RESULTS: Group 1 consisted of 25 full-term children, group 2 had 94 preterm children with birth-weight of ≥ 1500 g, and group 3 had 159 preterm children with birth-weight of < 1500 g. Group 1 was the healthiest group and had the best performance in attention and intelligence, while group 3 had the worst physical condition and cognitive performance. The correlation analysis revealed that perinatal factors, including gestational age, birth weight, Apgar scores, and physical conditions, significantly correlated with WPPSI-IV and K-CPT variables. Gender significantly correlated with object assembly of WPSSI-IV and clinical index of K-CPT. Among vision-related variables, best corrected visual acuity correlated most with K-CPT, including clinical index, Omission, and hit reaction time standard error of K-CPT, as well as significantly correlated with information and bug search of WPPSI-IV. CONCLUSIONS: Preterm children at preschool age still had poorer cognitive performance than full-term children, especially those with birth BW less than 1500 g. Gender and vision are correlated with cognitive deficits. Continuous monitoring with comprehensive assessments is recommended.

Contribution of genetic variants associated with primary immunodeficiencies to childhood-onset systemic lupus erythematous.

BACKGROUND: A dysregulated immune response is a hallmark of autoimmune disorders. Evidence suggests that systemic autoimmune diseases and primary immunodeficiency disorders (PIDs) may be similar diseases with different clinical phenotypes. OBJECTIVE: This study aimed to investigate the burden of PID-associated genetic variants in patients with childhood-onset systemic lupus erythematosus (cSLE). METHODS: We enrolled 118 cSLE patients regularly followed at Chang Gung Memorial Hospital. Targeted next-generation sequencing identified PID genetic variants in patients versus 1475 unrelated healthy individuals, which were further filtered by allelic frequency and various functional scores. Customized immune assays tested the functions of the identified variants. RESULTS: On filtration, 36 patients (30.5%) harbored rare variants in PID-associated genes predicted to be damaging. One homozygous TREX1 (c.294dupA) mutation and 4 heterozygous variants with possible dominant PID traits, including BCL11B (c.G1040T), NFKB1 (c.T695G), and NFKB2 (c.G1210A, c.G1651A), were discovered. With recessive traits, variants were found across all PID types; one fifth involved phagocyte number or function defects. Predicted pathogenic PID variants were more predominant in those with a family history of lupus, regardless of infection susceptibility. Moreover, mutation loads were greater among cSLE patients than controls despite sex or age at disease onset. While greater mutation loads were observed among cSLE patients with peripubertal disease onset, no significant differences in sex or phenotype were noted among cSLE patients. CONCLUSION: cSLE is mostly not monogenic. Gene-specific analysis and mutation load investigations suggested that rare and predicted damaging variants in PID-related genes can potentially contribute to cSLE susceptibility.

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.

Pulmonary function in school-age children following intravitreal injection of bevacizumab for retinopathy of prematurity.

The effect of anti-vascular endothelial growth factor on neonatal lung development was inconclusive. To evaluate pulmonary function in school-age children who have received intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP), this study included 118 school-aged children who were grouped into three groups: full-term control children (group 1), preterm children who had not received IVB treatment (group 2) and preterm children with ROP who had received IVB treatment (group 3). Pulmonary function was measured by spirometry and impulse oscillometry. Pulmonary function was significantly better in group 1 than in groups 2 and 3 (all p < 0.05 in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flow between 25 and 75% of FVC (FEF25-75), and respiratory resistance at 5 Hz and difference between respiratory resistance at 5 and 20 Hz (R5-R20). There were no statistically significant differences between group 2 and group 3 in all pulmonary function parameters, including FVC, FEV1, ratio of FEV1 to FVC, FEF25-75, R5, R20, R5-R20, and respiratory reactance at 5 Hz. In conclusion, our study revealed that preterm infants receiving IVB for ROP had comparable pulmonary function at school age to their preterm peers who had not received IVB treatment.