Age-related effects of Mycoplasma pneumoniae infection and subsequent asthma exacerbation in children.

BACKGROUND: Mycoplasma pneumoniae causes community-acquired pneumonia in children and increases asthma risk, but large studies are lacking. OBJECTIVE: To assess the link between M. pneumoniae infection and to asthma exacerbation, in children with allergies, and age of infection impact. METHODS: This retrospective cohort study analyzed medical records of South Korean children between January 2002 and December 2017. The study's exposure was hospitalization with an M. pneumoniae-related diagnosis, and the outcome was defined as asthma exacerbation, confirmed by hospitalization at least 6 months after M. pneumoniae infection, with alternative validation using asthma diagnosis and systemic steroid prescription records. Hazard ratios (HRs) for asthma exacerbation risk were estimated for the matched cohort using a Cox proportional hazards model stratified by allergic comorbidities. Time-dependent covariates and age-stratified exposure groups were used to calculate odds ratios. RESULTS: The study included 84,074 children with M. pneumoniae infection and 336,296 unexposed children. Follow-up for 12.2 ± 2.3 years found the exposed group had a significant risk of asthma exacerbation (HR 2.86, 95% confidence interval [CI] 2.67-3.06) regardless of allergic comorbidities. The risk was highest (over threefold) in children infected between 24 and 71 months. Sensitivity analysis using an alternative definition of the outcome showed an HR of 1.38 (95% CI 1.35-1.42), further supporting the association between M. pneumoniae infection and asthma exacerbation. CONCLUSION: M. pneumoniae infection was significantly associated with an increased risk of subsequent asthma exacerbation regardless of allergic comorbidities. Further research needed for understanding and confirmation.

Population-based retrospective cohort study on community-acquired pneumonia hospitalization in children with a ventricular septal defect.

The cohort consisted of 9400 exposed children diagnosed with ventricular septal defect (VSD). The risk of community-acquired pneumonia (CAP) or asthma with VSD was assessed using the Cox proportional hazard model with an inverse probability of treatment weighting. During a mean follow-up of 6.67 years (starting from 12 months after birth), there were 2100 CAP admission cases among exposed patients (incidence rate: 33.2 per 1000 person-years) and 20,109 CAP admission cases among unexposed children (incidence rate: 29.6 per 1000 person-years), with hazard ration of 1.09 (95% CI 1.04-1.14).

Rotavirus hospitalization in early childhood: fine motor skills and cognition at six years old-Population-based cohort study.

Rotavirus is linked to severe childhood gastroenteritis and neurological complications, but its impact on neurodevelopment remains uncertain. We examined data from 1,420,941 Korean children born between 2009 and 2011, using the Korean National Health Insurance System. At age 6, we assessed neurodevelopmental outcomes using the validated Korean Developmental Test, covering six major domains. Utilizing propensity score-based Inverse Probability Weighting to ensure covariates including considering covariates including sex, birth weight, changes in body weight from birth to 4-6 months of age, head circumference at 4-6 months of age, residence at birth, economic status, infant feeding types, and birth year. The main analysis that encompassed 5,451 children with rotavirus hospitalization and 310,874 unexposed individuals reveled heightened odds of suspected delays in fine motor skills and cognition among exposed children. Our results suggest an association between rotavirus-related hospitalization in infancy and suspected delays in fine motor function and cognition in 6-year-olds.

Trends in Incidence and Drug Prescriptions for Croup in Children Under 5 Years of Age: A 2002-2019 Population-Based Study.

BACKGROUND: Tracking national croup trends can provide important insights for childhood health management. This study aimed to analyze the incidence and drug prescription trends in Korean children over a two-decade period. METHODS: This population-based study encompassed 479,783 children aged < 5 years from 2002-2019, utilizing the National Health Insurance Service-National Sample Cohort. We identified participants with a primary croup diagnosis who were admitted to or visited the emergency room. Age-specific and age-adjusted incidence rates/10,000 person-years were calculated. We assessed using orthogonal polynomial contrasts and stratified by various factors (sex, age, residential area, economic status, comorbidities, and healthcare facility types). We observed changes in the use of five medications: inhaled steroids, systemic steroids, inhaled epinephrine, antibiotics, and short-acting bronchodilators. Generalized binomial logistic regression was used to analyze factors influencing prescription strategies. RESULTS: In 2002, the croup-related visits were 16.1/10,000 person-years, increasing to 98.3 in 2019 (P for trend < 0.001). This trend persisted, regardless of age, sex, region, and economic status. Children with comorbid atopic dermatitis or asthma maintained consistent croup rates, while those without comorbidities increased. Treatment trends showed decreasing antibiotic (73-47%) and oxygen use (21.3-3.4%), with increasing nebulized epinephrine (9.3-41.5%) and multiple drug prescriptions (67.8-80.3%). Primary care centers exhibited a greater increase in prescription usage and hospitalization duration than did tertiary healthcare institutions. CONCLUSION: Over the past two decades, croup incidence has risen, accompanied by increased epinephrine use and decreased antibiotic prescriptions. Longer hospitalization and higher medication use were mainly observed in primary care facilities.

Unraveling the link between atopic dermatitis and autoimmune diseases in children: Insights from a large-scale cohort study with 15-year follow-up and shared gene ontology analysis.

BACKGROUND: Atopic dermatitis and autoimmune diseases are highly heritable conditions that may co-occur from an early age. METHODS: The primary study is a national administrative cohort study involving 499,428 children born in 2002, tracked until 2017. Atopic dermatitis was defined as five or more principal diagnoses of atopic dermatitis and two or more topical steroid prescriptions. We estimated the risks for the occurrence of 41 autoimmune diseases, controlling for risk factors. In addition, we sourced a gene library from the National Library of Medicine to conduct a comprehensive gene ontology. We used Gene Weaver to identify gene set similarity and clustering, and used GeneMania to generate a network for shared genes. RESULTS: Exposed and unexposed groups included 39,832 and 159,328 children, respectively. During a mean follow-up of 12 years, the exposed group had an increased risk of autoimmune disease (hazard ratio, 1.27 [95 % confidence interval, 1.23-1.32]) compared to the unexposed group. The hazard ratios of autoimmune illnesses consistently increased with two- and five years lag times and alternative atopic dermatitis definitions. Shared genes between atopic dermatitis and autoimmune diseases were associated with comorbidities such as asthma, bronchiolitis, and specific infections. Genetic interactions of these shared genes revealed clustering in Th1, Th2, Th17, and non-classifiable pathways. CONCLUSIONS: Atopic dermatitis was significantly associated with an increased risk of subsequent autoimmune disease. we identified the genetically associated disease in atopic dermatitis patients comorbid with autoimmune disease and demonstrated a genetic network between atopic dermatitis and autoimmune diseases.

Neurodevelopment in Term Infants with Normal Birthweight following Postnatal Systemic Steroid Exposure.

BACKGROUND: Studies investigating the potential impact of systemic steroid exposure during early infancy on neurological development in full-term infants with normal birth weight are lacking. METHODS: This population-based administrative cohort study used data of national health insurance and a health-screening program for infants and children and included full-term infants who were born in Korea between 2008 and 2012 with normal birth weight and did not have any specific perinatal or neurodevelopmental diseases. The prescription of systemic steroids within the first 3 months of age was mainly considered. The neurological development of children was assessed using the Korean Development Screening Test (K-DST) at 6 years of age. To balance the baseline characteristics of the control and exposed groups, stabilized Inverse Probability of Treatment Weighting with trimming was performed in the main cohort. Ordinal logistic regression was used to assess the association between systemic steroid exposure and unfavorable results in the K-DST. RESULTS: The control and exposure groups had 246,168 and 5,083 children, respectively. The K-DST suggested unfavorable results in 8.1% and 8.6% children in the control and exposure groups, respectively (weighted odds ratio [OR], 95% confidence interval [CI], 1.03, 0.93 - 1.14). When each domain of the K-DST was considered separately, the risk of unfavorable results in the exposed group was not significantly different from that in the control group. CONCLUSIONS: No significant association was observed between exposure to systemic steroids during early infancy and neurodevelopmental impairment at 6 years of age.

The association between phthalate exposure and pubertal development.

Antiandrogenic effect of phthalates have been reported; however, results regarding the effect of phthalate exposure in pubertal children have been inconsistent. We aimed to investigate the relationship between phthalate exposure and pubertal development, especially whether high molecular weight phthalates (HMWP) and low molecular weight phthalates (LMWP) are differently associated in boys and girls. Urinary phthalate metabolites (4 HMWPs and 3 LMWPs) in Korean children (236 boys and 202 girls, aged 10 to 12 years) were measured. The association between phthalate levels and pubertal development (pubertal stages self-reported by parents and sex steroid levels) was analyzed by generalized linear regression after adjusting for age, body mass index z score, and premature birth and/or low birth weight. Both the highest quartile of HMWP (Q4 vs Q1, adjusted odds ratio [OR], 0.238; 95% confidence interval [CI], 0.090-0.627; p = 0.004) and LMWP (Q4 vs Q1, adjusted OR, 0.373; 95% CI, 0.151-0.918; p = 0.032) were inversely associated with pubertal stages in boys, whereas the highest quartile of LMWP (Q4 vs Q1, adjusted OR, 2.431; 95% CI, 1.024-5.768; p = 0.044) was significantly related to advanced pubertal stages in girls. Testosterone levels in boys were significantly lower at the highest quartile of HMWP (adjusted ß = - 0.251; 95% CI, - 0.476 to - 0.027; p = 0.028). However, in girls, we could not find any significant relationship between HMWP or LMWP and estradiol levels. CONCLUSIONS: Our results suggest that phthalate exposure, especially exposure to the HMWP, may have inverse association with male pubertal development. Further investigation is required to verify the relationship of phthalate exposure and pubertal development in girls. WHAT IS KNOWN: • Exposure to phthalates may have antiandrogenic effects. • Studies on the association between phthalates and pubertal development have yielded inconsistent results. WHAT IS NEW: • Phthalate levels were inversely associated with self-reported pubertal stages in boys. • Exposure to phthalates might have a negative influence on male pubertal development.

Associations of personal urinary volatile organic compounds and lung function in children.

BACKGROUND: We investigated the correlation between urine VOC metabolites and airway function in children exposed to anthropogenic volatile organic compounds (VOCs), notable pollutants impacting respiratory health. METHODS: Out of 157 respondents, 141 completed skin prick tests, spirometry, IOS, and provided urine samples following the International Study of Asthma and Allergies in Childhood (ISAAC)-related questions. Allergic sensitization was assessed through skin prick tests, and airway functions were evaluated using spirometry and impulse oscillometry (IOS). Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) was recorded and FEV1/FVC ratio was calculated. Airway mechanics parameters including respiratory resistance at 5 Hz (Rrs5) mean respiratory resistance between 5 Hz and 20 Hz (Rrs5-20), were also recorded. Urine concentrations of metabolites of benzene, ethylbenzene, toluene, xylene, styrene, formaldehyde, carbon-disulfide were analyzed by gas chromatography/tandem mass spectroscopy. RESULTS: The median age at study participation was 7.1 (SD 0.3) years. Muconic acid (benzene metabolites) and o-methyl-hippuric acid (xylene metabolites) above medians were associated with a significant increase in Rrs5 (muconic acid: aß = 0.150, p = .002; o-methyl-hippuric acid: aß = 0.143, p = .023) and a decrease in FEV1/FVC (o-methyl-hippuric acid: aß = 0.054, p = .028) compared to those below median. No associations were observed for Rrs5-20 and FEV1 between the groups categorized as above and below the median (all parameter p values > .05). CONCLUSIONS: Elevated levels of benzene and xylene metabolites were associated with a significant increase in Rrs5 and a decrease in FEV1/FVC, related to increased resistance and restrictive lung conditions compared to individuals with concentrations below the median.

The KAAACI Guidelines for Sublingual Immunotherapy.

Allergen immunotherapy is regarded as the only disease-modifying treatment option for various allergic conditions, including allergic rhinitis and asthma. Among the routes of administration of allergens, sublingual immunotherapy (SLIT) has gained clinical interest recently, and the prescription of SLIT is increasing among patients with allergies. After 30 years of SLIT use, numerous pieces of evidence supporting its efficacy, safety, and mechanism allows SLIT to be considered as an alternative option to subcutaneous immunotherapy. Based on the progressive development of SLIT, the current guideline from the Korean Academy of Asthma, Allergy, and Clinical Immunology aims to provide an expert opinion by allergy, pediatrics, and otorhinolaryngology specialists with an extensive literature review. This guideline addresses the use of SLIT, including 1) mechanisms of action, 2) appropriate patient selection for SLIT, 3) the currently available SLIT products in Korea, and 4) updated information on its efficacy and safety. This guideline will facilitate a better understanding of practical considerations for SLIT.

Cascade of atopic dermatitis comorbidities in children after birth for 15 years.

BACKGROUND: Individuals with atopic dermatitis often develop other conditions. OBJECTIVE: This study aimed to determine how atopic dermatitis comorbidities develop in children over time. METHODS: This population-based administrative cohort study used national health insurance data. We traced individuals born in Korea between 2002 and 2003 to 2018. The date of initial atopic dermatitis diagnosis was set as the index date. Fifty-three childhood comorbidities of atopic dermatitis were identified as outcomes of interest by performing a comprehensive literature search and comparing the prevalence of diagnostic codes in children with and without atopic dermatitis. Four control children per individual in the atopic dermatitis group were randomly matched based on sex and index date. The association between atopic dermatitis and the development of each specified disease was assessed using proportional hazard assumption, followed by mapping of the temporal sequences of interconnected comorbidities. RESULTS: The atopic dermatitis and control groups contained 67,632 and 270,528 individuals, respectively. The median age at the index date was 10 months, whereas the median follow-up period was 15 years. Twenty diseases that were associated with a higher risk of atopic dermatitis were identified and a chain of interconnected conditions created. The progression began in childhood with febrile seizures, constipation, and asthma, and was later associated with the emergence of food allergy, allergic rhinitis, psychiatric disorders, and autoimmune diseases. CONCLUSION: Our study highlights the temporal nature of atopic dermatitis comorbidities in children, and indicates that an understanding of the comorbidities may inform its clinical management and treatment.

Investigating the occurrence of autoimmune diseases among children and adolescents hospitalized for Mycoplasma pneumoniae infections.

Background: Mycoplasma pneumoniae infection is common in the general population and may be followed by immune dysfunction, but links with subsequent autoimmune disease remain inconclusive. Objective: To estimate the association of M. pneumoniae infection with the risk of subsequent autoimmune disease. Methods: This retrospective cohort study examined the medical records of South Korean children from 01/01/2002 to 31/12/2017. The exposed cohort was identified as patients hospitalized for M. pneumoniae infection. Each exposed patient was matched with unexposed controls based on birth year and sex at a 1:10 ratio using incidence density sampling calculations. The outcome was subsequent diagnosis of autoimmune disease, and hazard ratios (HRs) were estimated with control for confounders. Further estimation was performed using hospital-based databases which were converted to a common data model (CDM) to allow comparisons of the different databases. Results: The exposed cohort consisted of 49,937 children and the matched unexposed of 499,370 children. The median age at diagnosis of M. pneumoniae infection was 4 years (interquartile range, 2.5-6.5 years). During a mean follow-up time of 9.0 ± 3.8 years, the incidence rate of autoimmune diseases was 66.5 per 10,000 person-years (95% CI: 64.3-68.8) in the exposed cohort and 52.3 per 10,000 person-years (95% CI: 51.7-52.9) in the unexposed cohort, corresponding to an absolute rate of difference of 14.3 per 10,000 person-years (95% CI: 11.9-16.6). Children in the exposed cohort had an increased risk of autoimmune disease (HR: 1.26; 95% CI: 1.21-1.31), and this association was similar in the separate analysis of hospital databases (HR: 1.25; 95% CI 1.06-1.49). Conclusion: M. pneumoniae infection requiring hospitalization may be associated with an increase in subsequent diagnoses of autoimmune diseases.

KAAACI Guidelines for Allergen Immunotherapy.

Allergen immunotherapy (AIT) is a causative treatment for various allergic diseases such as allergic rhinitis, allergic asthma, and bee venom allergy that induces tolerance to offending allergens. The need for uniform practice guidelines in AIT is continuously growing because of the increasing discovery of potential candidates for AIT and evolving interest in new therapeutic approaches. This guideline is an updated version of the Korean Academy of Asthma Allergy and Clinical Immunology recommendations for AIT published in 2010. This updated guideline proposes an expert opinion by allergy, pediatrics, and otorhinolaryngology specialists with an extensive literature review. The guideline deals with basic knowledge and methodological aspects of AIT, including mechanisms, clinical efficacy, patient selection, allergens extract selection, schedule and doses, management of adverse reactions, efficacy measurements, and special consideration in pediatrics. The guidelines for sublingual immunotherapy will be covered in detail in a separate article.

Association between First-Generation Antihistamine Use in Children and Cardiac Arrhythmia and Ischemic Heart Disease: A Case-Crossover Study.

Cardiotoxicity from first-generation H1-antihistamines has been debated since the 1990s. However, large-scale studies on this topic in a general pediatric population are lacking. This study aimed to assess the association between first-generation H1-antihistamine use and cardiovascular events in a nationwide pediatric population. In this case-crossover study, the main cohort included children with cardiovascular events from the National Health Insurance Service database (2008-2012 births in Korea) until 2018. The second cohort excluded children with specific birth histories or underlying cardiovascular diseases from the main cohort. Cardiovascular events of interest included cardiac arrhythmia and ischemic heart disease. Odds ratios (ORs) of cardiovascular events were estimated using conditional logistic regression models, comparing first-generation H1-antihistamine use during 0-15 days before cardiovascular events (hazard period) with use during 45-60 and 75-90 days before events (control periods). Among the participants, 1194 (59.9%) were aged 24 months to 6 years, and 1010 (50.7%) were male. Cardiovascular event risk was increased among users of first-generation H1-antihistamines (adjusted OR [aOR], 1.201; 95% confidence interval, 1.13-1.27). Significant odds of cardiovascular events persisted within 10 and 5 days (aOR, 1.25 and 1.25). In the second cohort, the association was comparable with that in the main cohort. Our findings indicate that cardiovascular event risk is increased in children who are administered first-generation H1-antihistamines.

Associations between Delayed Introduction of Complementary Foods and Childhood Health Consequences in Exclusively Breastfed Children.

The timing of complementary food (CF) introduction is closely related to childhood health, and it may vary depending on the region, culture, feeding type, or health condition. Despite numerous studies on the benefits of breastfeeding and the optimal timing of CF introduction, there have been limited investigations regarding delayed CF introduction in exclusively breastfed children. We compared an exposed group (CF introduction ≥7 months) with a reference group (CF introduction at 4 -< 7 months) regarding hospital admission, disease burden, and growth until age 10. Data from a nationwide population-based cohort study involving children born between 2008 and 2012 in the South Korea were analyzed. The final cohort comprised 206,248 children (165,925 in the exposed group and 40,323 in the reference group). Inverse probability of treatment weighting with propensity score matching was used to balance baseline health characteristics in the comparison groups. We estimated the incident risk ratios (IRR) for outcomes using modified Poisson regression and weighted odds ratios (weighted ORs) and their 95% confidence intervals (CIs) using multinomial logistic regression. The exposed group was associated with low height-for-age z-score (HAZ) (IRR (95% CI) for -1.64 < HAZ ≤ -1.03: 1.11 (1.08 to 1.14); HAZ ≤ -1.64: 1.21 (1.14 to 1.27)) and frequent (≥6 events) hospitalizations (weighted OR 1.18 (1.09 to 1.29). The rates of hospital admission, death, and specific medical conditions did not differ between groups. However, delaying the introduction of CF until seven months in exclusively breastfed infants was associated with frequent hospitalization events and lower heights.

Association between atopic dermatitis and school readiness in preschool children.

BACKGROUND: Although atopic dermatitis (AD) in children affects diverse stages of life, no studies have reported on the association between school readiness and AD. METHODS: This study used Korean National Health Insurance data and the Health Screening Program for Infants and Children. Among all children born between 2008 and 2012 in Korea, those who were assessed for school readiness through questionnaires in a health screening program performed at 54 and 60 months old were enrolled. AD was defined based on the International Classification of Diseases codes, with two or more prescriptions of topical corticosteroids during the first 54-60 months of life. The primary outcome was the association between school readiness and AD. The questionnaire relating to school readiness comprised six items - cognitive skills, social development, activeness, concentration, emotional development, and language skills. Logistic regression analysis was used to identify the associations between school readiness and AD. RESULTS: This study included 239,673 children without AD and 38,229 children with AD. The average age at which school readiness was assessed was 4.8 years. AD was associated with vulnerability in activeness (adjusted odds ratio: 1.127; 95% confidence interval: 1.071-1.186) and concentrations (1.170; 1.093-1.254). The impact of AD on concentrations showed consistent results regardless of sex, exposure to systemic corticosteroids and antihistamines, and age at the diagnosis of AD. CONCLUSIONS: Children with AD have vulnerability in school readiness in the aspects of activeness and concentration.

Rotavirus-Associated Hospitalization in Children With Subsequent Autoimmune Disease.

Importance: Rotavirus infection is a common cause of gastroenteritis in children that can trigger autoimmune processes, but the nature of this interaction remains poorly understood. Objective: To estimate the association of rotavirus infection with the risk of subsequent autoimmune disease. Design, Setting, and Participants: This population-matched cohort study used data from children and adolescents (aged younger than 18 years) in South Korea (national registers from January 1, 2002, to December 31, 2017). The cohort consisted of 86 157 patients in the exposure group who had experienced rotavirus-associated hospitalization and the same number of matched patients in the unexposed group. Data analyses were from May 1, 2020, through October 20, 2022. Exposures: Hospitalization for rotavirus infection. Main Outcomes and Measures: The main outcome was childhood autoimmune diseases during the study defined by diagnoses according to the National Health Insurance Database. Hazard ratios (HRs) with 95% CIs for autoimmune diseases were estimated using a Cox model, with multiple confounding factors controlled. Results: This cohort study consisted of 1 914 461 individuals born in South Korea from 2002 to 2005 who were potentially eligible. After exclusions, there were 86 517 individuals in the exposed group and 86 517 in the unexposed group after 1:1 incidence density sampling. The study included 49 072 (57.0%) male patients. The median (IQR) age at diagnosis of rotavirus-associated hospitalization was 1.5 (0.9-2.7) years, and the HR for autoimmune disease in the exposed group was 1.24 (95% CI, 1.19-1.28) for a mean (SD) follow-up time of 12.1 (3.2) years. The use of more stringent definitions for exposure and outcomes in a multivariable stratified analysis also indicated that rotavirus-associated hospitalization was associated with an increased risk of subsequent autoimmune disease (HR, 1.22 [95% CI, 1.16-1.28]). Sensitivity analysis showed that individuals with rotavirus-associated hospitalization was related to multiple autoimmune syndromes (2 or more: HR, 1. 51 [95% CI, 1. 31-1. 73]; 3 or more: HR, 1. 79 [95% CI, 1.18-2.72]) and that the number of rotavirus-associated hospitalization were associated with higher risks for autoimmune disease in a dose-dependent manner (single hospitalization event: HR, 1.20 [95% CI, 1.16-1.24]; multiple events HR, 1.60 [95% CI, 1.49-1.72]). Conclusions and Relevance: Our results indicate that rotavirus-associated hospitalization is significantly associated with subsequent autoimmune disease during childhood. Clinicians should be aware of the heightened susceptibility to autoimmune disease in individuals with prior rotavirus-associated hospitalization.

Infant Feeding Pattern Clusters Are Associated with Childhood Health Outcomes.

(1) Background: Feeding behavior habits have a pattern with a certain tendency during infancy. We aimed to identify the associations between feeding patterns in infancy and the subsequent 10-year childhood disease burden. (2) Methods: Data from 236,372 infants were obtained from the national health insurance and screening program records in South Korea. Parent-administered questionnaires during infancy provided details on the feeding type and types/frequency of complementary food for analyzing feeding patterns. The outcomes were all-cause hospitalization and the development of 15 representative childhood diseases until the age of 10 years. Anthropometric measurements obtained at 6 years of age were analyzed. To estimate outcome risks while considering multiple risk factors, we employed a Cox proportional hazard and modified Poisson regression. (3) Results: Three clusters were identified: high prevalence of breastfeeding with regular exposure to a variety of solid foods (n = 116,372, cluster 1), similar prevalence of breastfeeding and formula feeding with less exposure to solid foods (n = 108,189, cluster 2), and similar prevalence of breastfeeding and formula feeding with the least exposure to solid foods in infancy (n = 11,811, cluster 3). Compared with cluster 1, children in clusters 2 and 3 had increased risks of all-cause hospitalization (hazard ratio (HR), (95% confidence interval (CI)), 1.04 (1.03-1.06) and 1.08 (1.05-1.11), respectively). Children in clusters 2 and 3 had an increased risk of upper respiratory infection, pneumonia, and gastroenteritis, as well as neurobehavioral diseases. Overweight/obesity at the age of 6 years was associated with clusters 2 and 3. (4) Conclusions: Feeding patterns in infancy were associated with an increased risk of childhood disease burden.

Assessment of Neurodevelopment and Growth in Congenital Hypothyroidism: Serial 6-Year Follow-up Study of 408 Patients.

CONTEXT: The link between congenital hypothyroidism (CH) and neurodevelopment is suggested, yet studies applying quantifiable measures are lacking. Moreover, socioeconomic disparities and subtle variation in timing of approach make the relationship difficult to detect. OBJECTIVE: To evaluate associations between CH and abnormalities in neurodevelopment and growth and determine the critical period for intervention. METHODS: We utilized a nationwide database to conduct a longitudinal analysis of 919 707 children. Exposure to CH was identified using claims-based data. The primary outcome of interest was suspected neurodevelopmental disorder, as measured using the Korean Ages & Stages Questionnaires (K-ASQ) administered annually from 9 to 72 months of age. Secondary outcomes were height and BMI z-scores. After randomly matching cases and controls at a 1:10 ratio, we employed inverse probability of treatment weighting and generalized estimating equation models for our analyses. We conducted subgroup analysis based on the age of treatment initiation. RESULTS: The prevalence of CH in our population was 0.05% (n = 408). Relative to the control group, the CH group had higher risk of suspected neurodevelopmental disorders (propensity score-weighted odds ratio: 4.52; 95% CI: 2.91, 7.02), and significantly increased risk in each of the 5 K-ASQ domains. No time interactions were noted at any rounds for the outcomes according to when the neurodevelopmental assessment was conducted (all P for interaction >.05). The CH group also had higher risk for low height-for-age z-score, but not for elevated BMI-for-age z-score. In subgroup analysis, delayed medication for CH correlated with worse neurodevelopmental outcomes. CONCLUSION: The CH group had worse neurodevelopmental outcomes and reduced height-for-age z-score. Outcomes were worse when onset of treatment was increasingly delayed.

Long COVID in children and adolescents: prevalence, clinical manifestations, and management strategies.

Long coronavirus disease (COVID), also known as postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection, has been defined as signs and symptoms which persist for 4 weeks or even lasting for 6 months after the initial infection. Although the prevalence of long COVID in children is currently unknown, epidemiological investigations have reported cases in pediatric populations. Clinical manifestations of long COVID in children include respiratory symptoms, such as cough and dyspnea, as well as neuropsychiatric and general conditions, including fatigue, headache, and muscle weakness. The pathophysiology of long COVID in children is still being investigated, but potential mechanisms include viral persistence, autoimmunity, and neuroinflammation. Risk factors for long COVID in children are not yet well understood, but studies have suggested that children with a history of severe acute COVID-19 infection or comorbidities may be at increased risk. Evaluation for respiratory symptoms of long COVID in children is essential, including spirometry and imaging studies to assess lung function and any potential damage. Furthermore, long COVID in children has been associated with a higher prevalence of mental health problems than in adults, emphasizing the importance of monitoring and addressing these aspects in pediatric patients. Although our understanding of long COVID in children and adolescents is still evolving, it is clear that the condition can have significant impacts on their health and well-being. The aim of this review is to synthesize the current knowledge on the prevalence, risk factors, and pathophysiology of long COVID in children and adolescents, and to discuss potential management strategies based on existing evidence.