A comparative study using gastric ultrasound to evaluate the safety of shortening the fasting time before pediatric echocardiography: a randomized controlled non-inferiority study.

PURPOSE: The objective of this study was to demonstrate that the gastric cross-sectional area (CSA) in the right lateral decubitus position (RLDP) during a 2-h fasting period is not larger than that during a conventional 4-h fasting period prior to pediatric echocardiography. METHODS: 93 patients aged under 3 years scheduled for echocardiography under sedation were enrolled and randomly allocated into two groups; 2-h fasting vs 4-h fasting. For group 4 h (n = 46), the patients were asked to be fasted for all types of liquid for more than 4 h, while group 2 h (n = 47) were asked to be fasted for all types of liquid for 2 h before echocardiography. Gastric ultrasound was performed before echocardiography, and CSARLDP was measured. We compared CSARLDP, incidence of at-risk stomach, fasting duration, and the incidence of major (pulmonary aspiration, aspiration pneumonia) and minor complications (nausea, retching, and vomiting, apnea, and bradycardia) between two groups. RESULTS: The mean difference of CSARLDP (group 2 h-group 4 h) was 0.49 (- 0.18 to 1.17) cm2, and it was within the non-inferiority margin (Δ = 2.1 cm2). There was no difference in the incidence of at-risk stomach (P = 0.514). There was no significant difference in the incidence of major and minor complications between the two groups. CONCLUSION: Two-hour fasting in pediatric patients who need an echocardiography did not increase major and minor complications and CSA significantly.

Cardiac Evaluation before and after Oral Propranolol Treatment for Infantile Hemangiomas.

Background: Most recent clinical practice guidelines addressing the management of infantile hemangiomas (IHs) recommend oral propranolol, a non-selective beta-adrenergic antagonist, as first-line treatment. However, few reports have provided continuous follow-up data regarding cardiac evaluations. Methods: Sixty-four patients diagnosed with IHs and treated with oral propranolol before 2 years of age at the Department of Pediatrics, Kangbuk Samsung Hospital (Seoul, Republic of Korea), with regular examinations between 2017 and 2021, were included. Cardiac evaluations, including electrocardiography, Holter monitoring, chest X-ray, and echocardiography, were performed. Results: Sixty-four patients with IHs successfully underwent continuous follow-up cardiac evaluations. The median age at diagnosis was 2 weeks (1 day to 34.3 weeks). The median age at treatment initiation was 13.6 weeks (2.4-87.9 weeks), the mean longitudinal diameter of hemangioma at diagnosis was 2.8 ± 2.1 cm (0.3-12.0 cm), and the mean percentage of size decrease after 1 year of oral propranolol treatment was 71.8%. None of the 64 patients experienced severe adverse side effects during propranolol treatment. There was no statistically significant differences in echocardiographic function and electrocardiographic data after treatment. Conclusions: Propranolol treatment ≥6 months was effective and safe without significant cardiac toxicity in the treatment of patients with infantile hemangiomas.

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).

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.

Change in Severity and Clinical Manifestation of MIS-C Over SARS-CoV-2 Variant Outbreaks in Korea.

BACKGROUND: There is difference in the incidence of multi-system inflammatory syndrome in children (MIS-C) in patients with different variants of severe acute respiratory syndrome coronavirus 2, however, little is known about the epidemiology in Asian countries. We investigated and compared the epidemiology of the MIS-C during omicron-dominant period with that of previous periods in South Korea. METHODS: We obtained clinical, epidemiological and laboratory data on MIS-C cases from national MIS-C surveillance in South Korea. We defined pre-delta period as January 2020-May 2021; delta period as June 2021-December 2021; and omicron period as January 2022-April 2022. We describe the clinical characteristics and outcomes of MIS-C patients by period. RESULTS: A total of 91 cases were assessed to be MIS-C cases. Number of MIS-C cases have increased from six cases during pre-delta period to 66 cases during omicron period, while the incidence rate (the number of MIS-C cases per 100,000 cases of reported coronavirus disease 2019) has decreased from 38.5 cases per 100,000 (95% confidence interval [CI], 14.1-83.9) during pre-delta period to 1.6 cases per 100,000 (95% CI, 1.2-2.0) during omicron periods. During pre-delta period, 66.7% and 100% had hypotension and gastrointestinal involvement, respectively; while during omicron period, 12.1% and 6.1% had such clinical manifestations. Fifty percent of pre-delta MIS-C patients were taken intensive care unit (ICU) cares, while 10.6% of patients during omicron periods were in ICUs. CONCLUSION: Omicron period were associated with less severe clinical manifestation compared to pre-delta and delta periods. Although incidence rate of MIS-C was lower for the omicron period than pre-delta and delta periods, number of patients reported with MIS-C may pose a substantial clinical burden.

Impact of 6-month triptorelin formulation on predicted adult height and basal gonadotropin levels in patients with central precocious puberty.

Background: Triptorelin, a long-acting gonadotropin-releasing hormone (GnRH) agonist, is available in 1-, 3-, and 6-month formulations to treat central precocious puberty (CPP). The triptorelin pamoate 22.5-mg 6-month formulation recently approved for CPP offers greater convenience to children by reducing the injection frequency. However, worldwide research on using the 6-month formulation to treat CPP is scarce. This study aimed to determine the impact of the 6-month formulation on predicted adult height (PAH), changes in gonadotropin levels, and related variables. Methods: We included 42 patients (33 girls and nine boys) with idiopathic CPP treated with a 6-month triptorelin (6-mo TP) formulation for over 12 months. Auxological parameters, including chronological age, bone age, height (cm and standard deviation score [SDS]), weight (kg and SDS), target height (TH), and Tanner stage, were evaluated at baseline, and after 6, 12, and 18 months of treatment. Hormonal parameters, including serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol for girls or testosterone for boys, were analyzed concurrently. Results: The mean age at treatment initiation was 8.6 ± 0.83 (8.3 ± 0.62 for girls, 9.6 ± 0.68 for boys). The peak LH level following intravenous GnRH stimulation at diagnosis was 15.47 ± 9.94 IU/L. No progression of the modified Tanner stage was observed during treatment. Compared to baseline, LH, FSH, estradiol, and testosterone were significantly reduced. In particular, the basal LH levels were well suppressed to less than l.0 IU/L, and the LH/FSH ratio was less than 0.66. The bone age/chronological age ratio remained stable with a decreasing trend (1.15 at the start of treatment, 1.13 at 12 months, 1.11 at 18 months). PAH SDS increased during treatment (0.77 ± 0.79 at baseline, 0.87 ± 0.84 at the start of treatment, 1.01 ± 0.93 at six months, and 0.91 ± 0.79 at 12 months). No adverse effects were observed during treatment. Conclusion: The 6-mo TP suppressed the pituitary-gonadal axis stably and improved the PAH during treatment. Considering its convenience and effectiveness, a significant shift to long-acting formulations can be expected.

Long-Term Observational Outcomes after Total Correction of Congenital Heart Disease in Korean Patients with Down Syndrome: A National Cohort Study.

Background: In the present study, the population prevalence and postoperative morbidity and mortality in Down syndrome patients who underwent total correction for congenital heart disease were investigated using data from a large national cohort. Methods: Retrospective administrative data from 2,395,966 participants born between 2008 and 2012 were acquired from the National Investigation of Birth Cohort in Korea. Among Down syndrome patients, 58.3% had congenital heart disease and 32.3% underwent total correction. Propensity score matching (maximum 1:1) and stabilized inverse probability treatment weighting (IPTW) were performed for each group (153 Down syndrome patients and 4482 non-Down syndrome patients). Results: T late mortality rate was significantly higher in the Down syndrome group than in the non-Down syndrome group (8.1% vs. 3.8%). No differences were observed in postoperative heart failure and arrhythmias, but pulmonary hypertension was significantly greater in the Down syndrome group than in the non-Down syndrome group (26.9% vs. 7.0%). The length of hospitalization was longer in the Down syndrome group than in the non-Down syndrome group (14 days vs. 11 days; interquartile range (IQR): 10−25 vs. 6−19; p < 0.0001). After total correction, readmission frequency for any reason was minimally but statistically significantly higher in the Down syndrome group compared to the non-Down syndrome group (5 times vs. 5 times; IQR: 3−8 vs. 4−9; p < 0.0001). However, the number of emergency room visits was minimally but significantly lower in the Down syndrome group compared to the non-Down syndrome group (2 visits vs. 2 visits (IQR): 2−7 vs. 1−4; p = 0.016). Conclusions: Down syndrome patients with congenital heart disease undergoing total correction showed pulmonary hypertension after surgery, longer length of hospitalization, frequent hospitalization after surgery, and a higher rate of late mortality.

Association of Familial History of Diabetes, Hypertension, Dyslipidemia, Stroke, or Myocardial Infarction With Risk of Kawasaki Disease.

Background There are few studies on the association with Kawasaki disease in children and the family's history of cardiovascular disease (CVD). The aim of this study was to identify the association of increased risks for Kawasaki disease in children with a family history of CVD. Methods and Results Clinical data of children born in 2008 and 2009 (n=917 707) were obtained from the National Health Insurance Service and the National Health Screening Program for Infants and Children for this study. The cohort consisted of 495 215 participants (53.8%) who completed the family history questionnaire for children 54 to 60 months old. Family history of CVD included 5 medical conditions: hypertension, dyslipidemia, myocardial infarction, stroke, and diabetes. Kawasaki disease was defined using the disease code, intravenous immunoglobulin prescription, and use of antipyretics for more than 25 days. Severe Kawasaki disease was defined as diagnosis of accompanied cardiac/coronary artery complications or intravenous immunoglobulin use ≥2 times. The incidence rate of Kawasaki disease was 124/100 000 person-years (95% CI, 117.5-131.5) for children <2 years old, 95/100 000 person-years (95% CI, 90.5-100.4) in children 2 to 5 years old, and 14/100 000 person-years (95% CI, 12.6-15.6) in children >5 years old. After propensity-score matching, 829 participants with a family history of CVD were diagnosed as having Kawasaki disease (0.68% [95% CI, 0.63-0.72]), and 690 patients with Kawasaki disease (0.56% [95% CI, 0.52-0.61]) had no family history of CVD. The family history of CVD was associated with increased risk for Kawasaki disease (risk ratio, 1.20 [95% CI, 1.08-1.32]) but not for severe Kawasaki disease (risk ratio, 1.23 [95% CI, 0.92-1.65]). Conclusions In this nationwide propensity-score matched study, those with a family history of CVD had a significantly greater risk of Kawasaki disease compared with those who had no family history of CVD.

Association of Antibiotic Use during the First 6 Months of Life with Body Mass of Children.

In this study, our objective was to assess the association of body mass in preschool children with the use of antibiotics within 6 months after birth. National administrative databases were used to examine all children born between 2008 and 2009 in Korea. Exposure was defined as the use of systemic antibiotics during the first 6 months of age. The observed outcomes were stunting (height for age [HFA] z score < −2.0), short stature (HFA z score < −1.64), overweight (body mass index [BMI] for age z score ≥ 1.04), and obesity (BMI for age z score ≥ 1.64), and the children's height and body weight were measured from three to six years of age. To balance characteristics between the antibiotic user and non-user groups, propensity score matching was performed. The outcomes were evaluated using a generalized estimation equation with the logit link function. Analysis of antibiotic use by children during the first 6 months of life indicated there were 203,073 users (54.9%) and 166,505 non-users (45.1%). After PS matching, there were 72,983 antibiotic users and 72,983 non-users. Antibiotic use was significantly associated with stunting (aOR = 1.198, 95% CI = 1.056 to 1.360) and short stature (aOR = 1.043, 95% CI = 1.004 to 1.083), and had significant negative association with HFA z score (weighted ß = −0.023). The use of an antibiotic for 14 days or more had a marked association with stunting. Antibiotic use was also associated with overweight, obesity, and increased BMI for age z score. Antibiotic use during the first 6 months of life increased the risk of stunting, short stature, overweight, and obesity in preschool children.

Association of clinical and social factors with risk of fracture in children with atopic dermatitis.

BACKGROUND: Children with atopic dermatitis (AD) have multiple risk factors for accidental fractures, injuries that can lead to significant morbidity and mortality. However, little is known about the factors that mediate the relationship between AD and fracture in children. OBJECTIVE: Our purpose was to examine the association of AD with fracture and to identify potential mediating factors. METHODS: This retrospective cohort study examined children with and without AD from a longitudinal matched cohort database of 353,040 children registered in the national health insurance service and participated in the national health-screening program of Korea. We defined AD using medical claims and medication prescription records. We investigated accidental fracture events between the index date and the end of follow-up in a propensity score-matched cohort. Pre-specified subgroup analyses considered fractures in four different regions of the body. The mediating effects of 10 possible clinical factors (including the use of antihistamines and systemic corticosteroids) and social factors (including nutritional status and parental safety awareness) were determined. RESULTS: There were 145,704 participating children, 20% with AD and 49% girls. Fractures occurred in 6,652 of the children with AD (23%, mean age: 64.6 ± 29.2 months) and in 24,698 of the control group (21%, mean age 65.0 ± 28.9 months). Children with AD had an 8% greater risk of fracture events overall (adjusted relative risk [aRR]: 1.08, 95% CI: 1.05-1.10). In subgroup analysis, AD was related to increased rates of skull and facial bone fracture (aRR: 1.09, 95% CI: 1.04-1.14), for trunk including vertebrae (aRR: 1.58, 95% CI: 1.22- 2.05), and for distal limbs (aRR: 1.11, 95% CI: 1.07-1.15). However, the relationship with proximal limb fracture was insignificant. Duration of systemic corticosteroid prescription was the largest mediating factor, followed by duration of antihistamine prescription, and infant feeding practices. In particular, the duration of systemic corticosteroid prescription was significantly associated with fracture events (incidence: 20.1% at the 25th percentile and 23.6% at the 75th percentile; difference: 3.4% [95% CI: 2.8-4.0%]). CONCLUSIONS: Children with AD were related to increased fracture events. The key factors with mediating effects were systemic use of corticosteroid and antihistamine. Infant feeding practices had weaker mediating effects.

Surveillance of COVID-19-Associated Multisystem Inflammatory Syndrome in Children, South Korea.

A concerning development during the coronavirus disease pandemic has been multisystem inflammatory syndrome in children. Reports of this condition in East Asia have been limited. In South Korea, 3 cases were reported to the national surveillance system for multisystem inflammatory syndrome in children. All case-patients were hospitalized and survived with no major disease sequelae.

Clinical features, diagnosis, and outcomes of multisystem inflammatory syndrome in children associated with coronavirus disease 2019.

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been spreading worldwide since December 2019. Hundreds of cases of children and adolescents with Kawasaki disease (KD)-like hyperinflammatory illness have been reported in Europe and the United States during the peak of the COVID-19 pandemic with or without shock and cardiac dysfunction. These patients tested positive for the polymerase chain reaction or antibody test for SARS-CoV-2 or had a history of recent exposure to COVID-19. Clinicians managing such patients coined new terms for this new illness, such as COVID-19-associated hyperinflammatory response syndrome, pediatric inflammatory multisystem syndrome temporally associated with COVID-19, or COVID-19-associated multisystem inflammatory syndrome in children (MIS-C). The pathogenesis of MIS-C is unclear; however, it appears similar to that of cytokine storm syndrome. MIS-C shows clinical features similar to KD, but differences between them exist with respect to age, sex, and racial distributions and proportions of patients with shock or cardiac dysfunction. Recommended treatments for MIS-C include intravenous immunoglobulin, corticosteroids, and inotropic or vasopressor support. For refractory patients, monoclonal antibody to interleukin-6 receptor (tocilizumab), interleukin-1 receptor antagonist (anakinra), or monoclonal antibody to tumor necrosis factor (infliximab) may be recommended. Patients with coronary aneurysms require aspirin or anticoagulant therapy. The prognosis of MIS-C seemed favorable without sequelae in most patients despite a reported mortality rate of approximately 1.5%.

Multisystem Inflammatory Syndrome in Children Related to COVID-19: the First Case in Korea.

Since mid-April 2020, cases of multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 that mimics Kawasaki disease (KD) have been reported in Europe and North America. However, no cases have been reported in Korea. We describe an 11-year old boy with fever, abdominal pain, and diarrhea who developed hypotension requiring inotropes in intensive care unit. His blood test revealed elevated inflammatory markers, thrombocytopenia, hypoalbuminemia, and coagulopathy. Afterward, he developed signs of KD such as conjunctival injection, strawberry tongue, cracked lip, and coronary artery dilatation, and parenchymal consolidation without respiratory symptoms. Microbiological tests were all negative including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction. However, serum immunoglobulin G against SARS-CoV-2 was positive in repeated tests using enzyme-linked immunosorbent assay and fluorescent immunoassay. He was recovered well after intravenous immunoglobulin administration and discharged without complication on hospital day 13. We report the first Korean child who met all the criteria of MIS-C with features of incomplete KD or KD shock syndrome.

Trends of Sensitization to Inhalant Allergens in Korean Children Over the Last 10 Years.

PURPOSE: Climate and lifestyle changes increase an individual's susceptibility to various allergens and also the incidence of allergic diseases. We aimed to examine the changes in sensitization rate for aeroallergens over a 10-year period in Korean children. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 4493 children who visited the allergy clinic at a tertiary hospital in Korea for allergic rhinitis or asthma from January 2009 to December 2018. The serum specific immunoglobulin E (IgE) levels were measured to confirm the sensitization against Dermatophagoides farinae (D. farinae), Alternaria, weed and tree pollen mixtures, as well as cat and dog dander through ImmunoCAP test. RESULTS: D. farinae was the most common sensitizing aeroallergen (45.9%) during the 10-year span. The sensitization rate for tree pollen mixture (p for trend <0.001), weed pollen mixtures (p for trend <0.001), dog dander (p for trend=0.025), and cat dander (p for trend=0.003) showed ascending trends during the 10-year study period. Furthermore, the sensitization rate for multiple allergens (≥2) in 2018 increased significantly compared to that in 2009 (p for trend=0.013). Compared with children without sensitization to D. farinae, those with sensitization to D. farinae showed higher sensitization rates to other aeroallergens (p for interaction <0.001). CONCLUSION: Children's sensitization rate to cat and dog dander and weed and tree pollen mixtures significantly increased during the 10-year period in Korea. Children with sensitization to D. farinae are likely to be sensitized to other aeroallergens as well.

Erratum: Significance of Differential Characteristics in Infantile Kawasaki Disease.

This corrects the article on p. 755 in vol. 49, PMID: 31074226.

Significance of Differential Characteristics in Infantile Kawasaki Disease.

BACKGROUND AND OBJECTIVES: Immunological variability in Kawasaki disease (KD) shows age-specific differences; however, specific differences in laboratory values have not been compared between infants and non-infants with KD. We compared age-adjusted Z-values (Z) of white and red blood cells in infants with KD with those in non-infants with KD. METHODS: This study retrospectively investigated 192 infants and 667 non-infants recruited between 2003 and 2015 at the Korea University Hospital. Laboratory values for infants with KD and non-infants with KD were analyzed and age-unadjusted raw values (R) and age-adjusted Z for blood cells counts were determined. RESULTS: Z in infants with KD during pre-intravenous immunoglobulin (IVIG), post-IVIG, and chronic phases showed increased lymphopenia and eosinophilia, low neutrophil:lymphocyte and neutrophil:eosinophil ratios, worse anemia, increased thrombocytosis, and reduced erythrocyte sedimentation rates compared with those in non-infants with KD. The optimal cut-off value for pre-IVIG Z-hemoglobin for prediction of KD in all patients was <-0.01 (area under the curve [AUC], 0.914; sensitivity/specificity, 0.999/0.886; p=0.04). The optimal cut-off value for pre-IVIG C-reactive protein (CRP) for prediction of KD in infants compared to that in febrile control infants was >40 mg/L (AUC, 0.811; sensitivity/specificity, 0.712/0.700; p=0.04). CONCLUSIONS: Laboratory characteristics enable differentiation between infants and non-infants with KD and contribute to a better understanding of changes in blood cell counts. Infants with incomplete KD can be more easily differentiated from infants with simple febrile illness using pre-IVIG Z-hemoglobin and pre-IVIG CRP values.

Increased procalcitonin level is a risk factor for prolonged fever in children with Mycoplasma pneumonia.

PURPOSE: Macrolide-resistant Mycoplasma pneumoniae pneumonia (MPP) is characterized by prolonged fever and radiological progression despite macrolide treatment. Few studies have examined serum procalcitonin (PCT) level in children with MPP. We aimed to investigate the association of acute inflammation markers including PCT with clinical parameters in children with MPP. METHODS: A total of 147 children were recruited. The diagnosis of MPP relied on serial measurement of IgM antibody against mycoplasma and/or polymerase chain reaction. We evaluated the relationships between C-reactive protein (CRP), PCT, and lactate dehydrogenase (LDH) levels and white blood cell (WBC) counts, and clinical severity of the disease. We used multivariate logistic regression analysis to estimate the odds ratio for prolonged fever (>3 days after admission) and hospital stay (> 6 days), comparing quintiles 2-5 of the PCT levels with the lowest quintile. RESULTS: The serum PCT and CRP levels were higher in children with fever and hospital stay than in those with fever lasting ≤ 3 days after admission and hospital stay ≤ 6 days. CRP level was higher in segmental/lobar pneumonia than in bronchopneumonia. The LDH level and WBC counts were higher in children with fever lasting for >3 days before compared to those with fever lasting for ≤ 3 days. The highest quintile of PCT levels was associated with a significantly higher risk of prolonged fever and/or hospital stay than the lowest quintile. CONCLUSION: Serum PCT and CRP levels on admission day were associated with persistent fever and longer hospitalization in children with MPP.