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Background: Though Aspirin and intravenous immunoglobulin (IVIG) remain the standard treatments for Kawasaki Disease (KD) to minimize coronary artery damage, the duration and dosage of aspirin are inconsistent across hospitals. However, the lack of multi-center randomized trials prevents definitive answers to the impact of high-dose aspirin., Methods: This clinical trial was structured as a prospective, evaluator-blinded, multi-center randomized controlled trial with two parallel arms, aiming to assess the effectiveness of IVIG as a standalone primary therapy of KD in comparison to the combination of IVIG with high-dose aspirin therapy. KD patients were enrolled between September, 2016 and August, 2019. A final cohort of 134 patients were randomly assigned to the standard and test groups with 69 and 65 patients, respectively. The Standard group received IVIG (2 g/kg) along with aspirin (80-100 mg/kg/day) until fever subsided for 48 hours. The test group received IVIG (2 g/kg) alone. Following the initial treatment, both groups received a daily aspirin dose (3-5 mg/kg) for six weeks. The primary outcome measure was the occurrence of coronary artery lesions (CAL) at the 6-8 weeks mark. The secondary outcome is IVIG resistance., Results: The overall rate of CAL in test group decreased from 10.8% at diagnosis to 1.5% and 3.1% at 6 weeks and 6 months, respectively. The CAL rate of standard group declined from 13.0% to 2.9% and 1.4%, with no statistically significant difference (P>0.1) in the frequency of CAL between the two groups. Furthermore, no statistically significant differences were found for treatment (P>0.1) and prevention (P>0.1) effect between the two groups., Conclusions: This marks the first prospective multi-center randomized controlled trial comparing the standard treatment of KD using IVIG plus high-dose aspirin against IVIG alone. Our analysis indicates that addition of high-dose aspirin during initial IVIG treatment is neither statistically significant nor clinically meaningful for CAL reduction., Registration: URL: http://www.clinicaltrials.gov ; identifier: NCT02951234., What Is New?: This study represents the first multi-center randomized controlled trial investigating the efficacy of high-dose aspirin or intravenous immunoglobulin (IVIG) during the acute stage of KD. This study assessed the impact of discontinuing high-dose aspirin (80-100 mg/kg/day) on the occurrence of CAL during the acute phase treatment of Kawasaki Disease.No significant differences were observed between high-dose aspirin plus IVIG treatment and IVIG alone treatment in terms of the frequency of abnormal coronary artery abnormalities. Additionally, our analysis revealed no statistically significant differences in either the treatment effect (the number of cases successfully treated) or prevention effect (the prevention of new cases) between these two treatments., What Are the Clinical Implications?: Comparison analysis indicated the non-inferiority between two groups with or without high-dose aspirin.Administering the standard 2 g/kg/day IVIG without high-dose aspirin (80-100 mg/kg/day) during the acute phase therapy for KD does not increase the risk of coronary artery lesions, which are a primary cause of morbidity and mortality in KD patients.Addition of high-dose aspirin during initial IVIG treatment is not statistically significant or clinically meaningful.

Background: Gestational diabetes mellitus has been linked to inflammation, immune dysregulation in offspring, and changes in the microbiota. It may have long-term implications for the health of children. The aim of this study was to determine if gestational diabetes mellitus increases the risk of allergic diseases in offspring., Methods: The data source was the National Health Insurance Research Database (NHIRD) of Taiwan. The pairing of mothers and children was established by connecting the NHIRD with the Taiwan Maternal and Child Health Database. First-time pregnant mothers between 2004 and 2019 were enrolled. The GDM group consisted of 22,741 cases. The control group was selected from individuals without GDM matched by maternal age, neonatal gender, and neonatal birthdate at a ratio of 1-4. The primary endpoint was the incidence of childhood allergic diseases, such as asthma, allergic rhinitis, atopic dermatitis, and urticaria. The secondary endpoint was the risk associated with the development of allergic diseases in offspring, considering the presence or absence of insulin therapy., Results: The development of allergic rhinitis, atopic dermatitis, and urticaria were found to be significantly associated with GDM. However, no significant association was observed between GDM and asthma. GDM control without insulin was associated with an increased risk of developing allergic rhinitis, urticaria, and atopic dermatitis. However, in the group receiving insulin treatment, there was no significant elevation in the risk of any allergic diseases., Conclusion: GDM may elevate the risk of certain atopic diseases in offspring, such as allergic rhinitis, atopic dermatitis, and urticaria., Competing Interests: Declaration of competing interest The authors declare there are no conflicts of interest to disclose., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Background: In 2020, Taiwan experienced a dramatic disruption of daily life due to measures aimed at limiting the spread of coronavirus disease 2019 (COVID-19), although domestic COVID-19 cases were extremely rare. This provided a chance to investigate the change of incidence and possible triggers of Kawasaki disease (KD) without the interference of multisystem inflammatory syndrome in children., Methods: This population-based study used Taiwan's National Health Insurance Research Database. To detect the change in KD incidence in children less than 6 years old during the period of social distancing policy in 2020, the autoregressive integrated moving average model was used based on seasonal variation and the increasing trend of KD incidence over the past 10 years. The trends in population mobility and common infectious diseases were also analyzed to observe their effects on KD incidence., Results: The predicted monthly incidence [95% confidence interval (CI)] of KD in April, May and June 2020 were 5.26 (3.58-6.94), 5.45 (3.70-7.20) and 5.41 (3.61-7.21) per 100,000 person-months. The actual observed incidences were 2.41, 2.67 and 2.60 per 100,000 person-months, respectively, representing a 51.2%, 51.0% and 51.9% reduction in incident rates in the 3-month period of stringent COVID-19 mitigation measures. The trend was not proportionate to the profound decline of common infectious cases., Conclusions: KD incidence decreased by approximately 50% during the period of stringent COVID-19 mitigation measures in 2020 in Taiwan. Human-to-human contact may be a potential KD trigger, but there are likely other contributing factors aside from infection., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To compare the neurodevelopmental outcomes of preterm infants before and during the COVID-19 pandemic., Design: Premature infants born in 2018 were assigned to the pre-pandemic group, while those born in 2019 were assigned to the during-pandemic group., Setting: Nationwide cohort study., Patients: Very low birthweight premature infants registered in the Taiwan Premature Infant Follow-up Network database., Interventions: Anti-epidemic measures, including quarantine and isolation protocols, social distancing, the closure of public spaces and restrictions on travel and gatherings during COVID-19 pandemic., Main Outcome Measures: Outcomes were measured by Bayley Scales of Infant and Toddler Development Third Edition at corrected ages of 6, 12 and 24 months old. Generalised estimating equation (GEE) was applied to incorporate all measurements into a single model., Results: Among the 1939 premature infants who were enrolled, 985 developed before the pandemic, while 954 developed during the pandemic. Premature infants whose development occurred during the pandemic exhibited better cognitive composite at the corrected age of 6 months (beta=2.358; 95% CI, 1.07 to 3.65; p<0.001), and motor composite at corrected ages of 12 months (beta=1.680; 95% CI, 0.34 to 3.02; p=0.014). GEE analysis showed that infants who had grown during the pandemic achieved higher scores in cognitive composite (beta=1.416; 95% CI, 0.36 to 2.48; p=0.009)., Conclusion: Premature infants in Taiwan who developed during the pandemic showed better neurodevelopment compared with those born before the pandemic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A challenge in accurately identifying and classifying left ventricular hypertrophy (LVH) is distinguishing it from hypertrophic cardiomyopathy (HCM) and Fabry disease. The reliance on imaging techniques often requires the expertise of multiple specialists, including cardiologists, radiologists, and geneticists. This variability in the interpretation and classification of LVH leads to inconsistent diagnoses. LVH, HCM, and Fabry cardiomyopathy can be differentiated using T1 mapping on cardiac magnetic resonance imaging (MRI). However, differentiation between HCM and Fabry cardiomyopathy using echocardiography or MRI cine images is challenging for cardiologists. Our proposed system named the MRI short-axis view left ventricular hypertrophy classifier (MSLVHC) is a high-accuracy standardized imaging classification model developed using AI and trained on MRI short-axis (SAX) view cine images to distinguish between HCM and Fabry disease. The model achieved impressive performance, with an F 1-score of 0.846, an accuracy of 0.909, and an AUC of 0.914 when tested on the Taipei Veterans General Hospital (TVGH) dataset. Additionally, a single-blinding study and external testing using data from the Taichung Veterans General Hospital (TCVGH) demonstrated the reliability and effectiveness of the model, achieving an F 1-score of 0.727, an accuracy of 0.806, and an AUC of 0.918, demonstrating the model's reliability and usefulness. This AI model holds promise as a valuable tool for assisting specialists in diagnosing LVH diseases., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Wei-Wen Chen et al.)

Purpose: The prevalence of atopic diseases has increased in recent decades. A possible link between antibiotic use during pregnancy and childhood atopic disease has been proposed. The aim of this study is to explore the association of antibiotic exposure during pregnancy with childhood atopic diseases from a nationwide, population-based perspective., Methods: This was a nationwide population-based cohort study. Taiwan's National Health Insurance Research Database was the main source of data. The pairing of mothers and children was achieved by linking the NHIRD with the Taiwan Maternal and Child Health Database. This study enrolled the first-time pregnancies from 2004 to 2010. Infants of multiple delivery, preterm delivery, and death before 5 years old were excluded. All participants were followed up at least for 5 years. Antenatal antibiotics prescribed to mothers during the pregnancy period were reviewed. Children with more than two outpatient visits, or one admission, with a main diagnosis of asthma, allergic rhinitis, or atopic dermatitis were regarded as having an atopic disease., Results: A total of 900,584 children were enrolled in this study. The adjusted hazard ratios of antibiotic exposure during pregnancy to childhood atopic diseases were 1.12 for atopic dermatitis, 1.06 for asthma, and 1.08 for allergic rhinitis, all of which reached statistical significance. The trimester effect was not significant. There was a trend showing the higher the number of times a child was prenatally exposed to antibiotics, the higher the hazard ratio was for childhood atopic diseases., Conclusions: Prenatal antibiotic exposure might increase the risk of childhood atopic diseases in a dose-dependent manner., (© 2024. The Author(s).)

Objectives: The management of patent ductus arteriosus (PDA) is a critical concern in premature infants, and different hospitals may have varying treatment policies, fluid management strategies, and incubator humidity. The Asian Neonatal Network Collaboration (AsianNeo) collected data on prematurity care details from hospitals across Asian countries. The aim of this study was to provide a survey of the current practices in the management of PDA in premature infants in Asian countries., Methods: AsianNeo performed a cross-sectional international questionnaire survey in 2022 to assess the human and physical resources of hospitals and clinical management of very preterm infants. The survey covered various aspects of hospitals resources and clinical management, and data were collected from 337 hospitals across Asia. The data collected were used to compare hospitals resources and clinical management of preterm infants between areas and economic status., Results: The policy of PDA management for preterm infants varied across Asian countries in AsianNeo. Hospitals in Northeast Asia were more likely to perform PDA ligation ( p  < 0.001) than hospitals in Southeast Asia. Hospitals in Northeast Asia had stricter fluid restrictions in the first 24 h after birth for infants born at <29 weeks gestation ( p  < 0.001) and on day 14 after birth for infants born at <29 weeks gestation ( p  < 0.001) compared to hospitals in Southeast Asia. Hospitals in Northeast Asia also had a more humidified environment for infants born between 24 weeks gestation and 25 weeks gestation in the first 72 h after birth ( p  < 0.001). A logistic regression model predicted that hospitals were more likely to perform PDA ligation for PDA when the hospitals had a stricter fluid planning on day 14 after birth [Odds ratio (OR) of 1.70, p  = 0.048], more incubator humidity settings (<80% vs. 80%-89%, OR of 3.35, p  = 0.012 and <80% vs. 90%-100%, OR of 5.31, p  < 0.001)., Conclusions: In advanced economies and Northeast Asia, neonatologists tend to adopt a more conservative approach towards fluid management, maintain higher incubator humidity settings and inclined to perform surgical ligation for PDA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Hsieh, Jeng, Lin, Lin, Rohsiswatmo, Dewi, Chee, Neoh, Velasco, Imperial, Nuntnarumit, Ngerncham, Chang, Kim, Quek, Amin, Kusuda, Miyake and Isayama.)

This study compared gut (fecal) microbiota profiles between pre-term and full-term infants, assuming that pre-term infants without feeding intolerance would have gut microbiota similar to those of full-term infants. A total of 13 pre-term infants (gestational age < 37 weeks, birthweight ≤ 2500 g) and 10 full-term infants were included. The pre-term infants were assigned to the feeding tolerance (FT) group (n = 7) if their daily intake exceeded 100 mL/kg/day at two weeks after birth, or the feeding intolerance (FI) group (n = 6). Microbial DNA from weekly fecal samples was analyzed. The microbiota profiles of the pre-term infants and full-term infants were significantly different ( p = 0.0001), as well as the FT and FI groups ( p = 0.0009). The full-term group had more diversity, with higher concentrations of facultative anaerobes such as Bifidobacteriaceae and Lactobacteriaceae. The FT group's gut microbiota matured over four weeks, with higher levels of digestion-related bacteria, while the FI group had more pathogens. In the FI group, a significant difference was observed between the first and second weeks, with no significant differences noted between the first week and the third or fourth weeks. The delay in the development of the pre-term infants' gut microbiota may be associated with the FI.

Background: The rate of preterm birth is increasing globally. It causes significant short-term and long-term health care burdens. A comprehensive recognition of the risk factors related to preterm births is important in the prevention of preterm birth. Our study is to investigate the incidence and maternal risk factors of preterm birth from a nationwide population-based perspective., Methods: This is a retrospective cohort study. All live births from 2004 to 2014 in Taiwan enrolled. The main data source was Taiwan's Birth Certificate Application (BCA) database. The BCA database was linked with the National Health Insurance Research Database (NHIRD) to establish any links between information on newborns and maternal underlying disease., Results: A total of 1,385,979 births were included in the analysis. The incidence of preterm birth increased gradually in Taiwan from 8.85% in 2004 to 10.73% in 2014. Maternal age, socioeconomic status, maternal allergy and autoimmune diseases, gynecological diseases, and pregnancy-related complications were significant risk factors for preterm birth., Conclusion: The overall incidence of preterm births has gradually increased in Taiwan. Maternal age, socioeconomic status, certain underlying diseases, and pregnancy-related complications were risk factors for preterm birth., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2023 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Introduction: Gestational hypertension can lead to complications, such as preeclampsia. Preeclampsia is one of leading causes of perinatal morbidity and mortality. Abnormal placentation, immune dysregulation, and maternal inflammatory response are possible etiologies. The burden of atopic diseases is increasing worldwide. Prenatal exposure might play a role in the pathogenesis of these two diseases. The aim of this study was to evaluate the association between gestational hypertension and atopic diseases from a nationwide perspective., Material and Methods: The primary data were retrieved from Taiwan's National Health Insurance Research Database. The Maternal and Child Health Database was used to generate links between mothers and children. From 2004 to 2019, mothers with a diagnosis of gestational hypertension were identified as cases. The control groups were matched to the cases by maternal age, neonatal gender, date of birth, at a control-to-case ratio of 4:1. Each child was reviewed to confirm the diagnosis of atopic disease. Covariates including both maternal and neonatal factors were also collected., Results: A total of 1,935,874 primiparas were enrolled in this study. After excluding 16,851 mothers with a history of hypertension, a total of 1,919,023 offspring were included in the study for the period 2004-2019. Gestational hypertension was associated with asthma (HR, 1.12, 95% CI, 1.02-1.23) and atopic dermatitis (HR, 1.10, 95% CI, 1.00-1.21) in offspring after controlling for cofactors. Nevertheless, gestational hypertension did not play an independent factor for allergic rhinitis (HR, 1.02, 95% CI, 0.95-1.10) or urticaria (HR, 1.02, 95% CI, 0.91-1.15)., Conclusion: Maternal gestational hypertension increases the cumulative risk for asthma and atopic dermatitis in offspring., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2023 Yang, Lin and Lin.)

Introduction: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders which cause long term social and behavior impairment, and its prevalence is on the rise. Studies about the association between maternal autoimmune diseases and offspring ASD have controversial results. The aim of this study was to investigate whether maternal autoimmune diseases increase the risk of ASD in offspring from a population-based perspective., Methods: The data sources were Taiwan's National Health Insurance Research Database (NHIRD) and Taiwan's Maternal and Child Health Database (MCHD), which were integrated and used to identify newborns whose mothers were diagnosed with autoimmune disease. Newborns were matched by maternal age, neonatal gender, and date of birth with controls whose mothers were without autoimmune disease using a ratio of 1:4 between 2004 and 2019. Data on diagnoses of autoimmune disease and autism spectrum disorders were retrieved from NHIRD. Patients who had at least 3 outpatient visits or at least 1 admission with a diagnosis of autoimmune disease and autism spectrum disorders were defined as incidence cases. The risks of ASD in offspring were compared between mothers with or without autoimmune disorders., Results: We identified 20,865 newborns whose mothers had been diagnosed with autoimmune disease before pregnancy and matched them at a ratio of 1:4 with a total of 83,460 newborn whose mothers were without autoimmune disease, by maternal age, neonatal gender, and date of birth. They were randomly selected as the control group. The cumulative incidence rates of autism spectrum disorders (ASD) were significantly higher among the offspring of mothers with autoimmune diseases. After adjusting for cofactors, the risk of ASD remained significantly higher in children whose mother had autoimmune diseases. Regarding to specific maternal autoimmune disease, Sjögren's syndrome and rheumatoid arthritis were both associated with elevated risks of ASD in offspring., Conclusion: Mother with autoimmune disease might be associated with increasing the risk of autism spectrum disorder in offspring., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Lin and Lin.)

Kawasaki Disease (KD) is the most common acquired pediatric heart disease in the developed world. Rapid infusion of high-dose intravenous immunoglobulin is the standard therapy. Different manufacturing processes of IVIG may influence their efficacy. This study aims to conduct a head to head comparison of two IVIGs, TBSF and Privigen, from a nationwide perspective. The main data source was the National Health Insurance Research Database (NHIRD) of Taiwan. A total of 3368 KD cases involving children under 2 years of age were enrolled from January 2015 to November 2020. The primary endpoint was IVIG resistance, which we defined as the total amount exceeding 26 g in one admission. The secondary endpoints encompassed two distinct criteria: coronary involvement, which was defined as the prolonged use of aspirin or anti-coagulation agents between 180 and 360 days after the index date, and recurrence, which was defined as readmission for IVIG therapy occurring more than 30 days after previous KD index day and continuing until the end of the follow-up period. Privigen demonstrated a lower IVIG resistance rate at 9.4% in comparison to TBSF, which exhibited a rate of 9.7% (odds ratio 0.72, 95% CI 0.52-0.99). Privigen had a lower odds of coronary involvement (odds ratio 0.38, 95% CI 0.18-0.82). There is no difference in recurrence rate (odds ratio 0.60, 95% CI 0.22-1.68). Privigen might have a lower rate of IVIG resistance and reduced coronary artery involvement. The discrepancy may be due to the concentration, the stabilizers, or the source of plasma. Further investigation is needed to compare the effectiveness of different IVIGs in the large randomized controlled clinical trial., (© 2023. The Author(s).)

The healthcare industry has made significant progress in the diagnosis of heart conditions due to the use of intelligent detection systems such as electrocardiograms, cardiac ultrasounds, and abnormal sound diagnostics that use artificial intelligence (AI) technology, such as convolutional neural networks (CNNs). Over the past few decades, methods for automated segmentation and classification of heart sounds have been widely studied. In many cases, both experimental and clinical data require electrocardiography (ECG)-labeled phonocardiograms (PCGs) or several feature extraction techniques from the mel-scale frequency cepstral coefficient (MFCC) spectrum of heart sounds to achieve better identification results with AI methods. Without good feature extraction techniques, the CNN may face challenges in classifying the MFCC spectrum of heart sounds. To overcome these limitations, we propose a capsule neural network (CapsNet), which can utilize iterative dynamic routing methods to obtain good combinations for layers in the translational equivariance of MFCC spectrum features, thereby improving the prediction accuracy of heart murmur classification. The 2016 PhysioNet heart sound database was used for training and validating the prediction performance of CapsNet and other CNNs. Then, we collected our own dataset of clinical auscultation scenarios for fine-tuning hyperparameters and testing results. CapsNet demonstrated its feasibility by achieving validation accuracies of 90.29% and 91.67% on the test dataset.

(1) Background: Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are common cognitive and behavioral disorders. Antibiotics are widely used in pregnant women and their newborns. The objective of this study was to examine the potential association between prenatal exposure to antibiotics and the risk of ADHD and ASD in childhood from a nationwide perspective. (2) Methods: The Taiwan National Health Insurance Research Database (NHIRD) was used as the primary data source. This nationwide cohort study included only first-time pregnancies. A total of 906,942 infants were enrolled. All infants were followed up for at least 6 years. The Cox regression model was applied for covariate control. (3) Results: Prenatal exposure to antibiotics was found to significantly increase the cumulative incidence of ADHD while having only a borderline effect on the cumulative incidence of ASD. Exposure to antibiotics during any of the three different gestational age ranges significantly increased the cumulative risk. However, only exposure after 34 weeks of gestation had a significant impact on the occurrence of ASD. The study also revealed a dose-dependent effect on the occurrence of ADHD but no effect on the occurrence of ASD. (4) Conclusions: This study suggests that prenatal exposure to antibiotics may increase the risk of developing ADHD and ASD later in life.

Objective: Transcatheter closure of atrial septal defect (ASD) has become an alternative treatment to surgical repair. One of the challenges is the prolapse of the left atrial disc during the procedure. Many techniques have been developed to prevent the prolapse but not reduce it. In this study, we present a novel technique, termed push back technique, that help reduce the prolapsed device., Methods: We enrolled 24 patients (8 males, 16 females) between May 2008 and January 2023 who underwent the push back technique during transcatheter closure of ASD in Taichung Veterans General Hospital. We recorded the hemodynamic data, success rate and complications including device embolization/migration, valvular regurgitation, pericardial effusion, and residual shunt., Results: The median age was 6.3 years (1.2-70.5 years) and the median weight was 19.1 kg (7.8-90 kg). Fifteen (62.5%) patients had mild pulmonary hypertension. The median Qp/Qs was 2.54 (1.5-8.8). The median ASD stretched size was 21.2 mm (7.7-35.3 mm). The median device size was 22 mm (8-40 mm). The median fluoroscopy time was 14 min (5-23 min) and median procedure time was 47 min (25-78 min). The push back technique successfully reduced the prolapsed device in 21 (87.5%) patients. There was no complication in all patients., Conclusion: We present a novel push back technique that can successfully reduce the prolapsed device in 87.5% (21/24) patients without complications. It is feasible, safe and effective., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Liao, Jan, Lin, Lee and Fu.)

Introduction: Inguinal hernia repair is one of the most common surgeries worldwide. However, there is limited information on its underlying genetic mechanism. Studies on the genetic factors related to inguinal hernia in Han Chinese are lacking. Therefore, we aimed to conduct a hospital-based study to assess the genetic factors and comorbidities underlying inguinal hernia in Taiwan. Materials and Methods: This was a retrospective case-control study. Utilizing data from the Taiwan Precision Medicine Initiative, we identified 1000 patients with inguinal hernia and 10,021 matched controls without inguinal hernia between June 2019 and June 2020. Four susceptibility loci (rs2009262, rs13091322, rs6991952, and rs3809060) associated with inguinal hernia were genotyped by the Taiwan Biobank version 2 (TWBv2) array. Inguinal hernia, surgery types, and comorbidities were obtained from the electronic health records of Taichung Veterans General Hospital. Results: Adult-onset inguinal hernia was associated with WT1 rs3809060 GT/TT genotype in males and EFEMP1 rs2009262 TC/CC genotype in females. In addition, we identified sex-specific risk factors associated with inguinal hernia; benign prostatic hyperplasia in males (OR: 3.19, 95% CI: 2.73 - 3.73, p < 0.001), chronic obstructive pulmonary disease in females (OR: 2.34, 95% CI: 1.33 - 4.11, p = 0.003) and overweight, defined by body mass index ≧24 kg/m 2 (OR: 0.75, 95% CI: 0.65 - 0.86, p <0.001 in males, and OR: 0.60, 95% CI:0.37 - 0.98, p = 0.042 in females), were inversely associated with inguinal hernia. After stratifying BMI, overweight males with EFEMP1 rs2009262 TC/CC genotype exhibited a higher risk of inguinal hernia (OR: 1.31, 95% CI: 1.07 - 1.61, p = 0.01). Additionally, rs3809060 was specifically associated with male patients with direct-type inguinal hernia (OR: 1.62, 95% CI: 1.19 - 2.22, p = 0.002). Conclusion: Genetic susceptibility appears to participate in the pathogenesis of inguinal hernia in the Taiwanese population in a sex-specific manner. Future studies are needed to illuminate the complex interplay between heredity and comorbidities., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objectives: To study the association between antenatal corticosteroids treatment and childhood mental disorders in infants born at different gestational ages, and to investigate the effect of different administration timing., Study Design: This population-based cohort study used data from the Taiwan National Health Insurance Research Database. All singleton live births born between 2004 and 2010 were enrolled and followed up for at least 6 years. The primary outcome was any childhood mental disorder. Secondary outcomes included 7 specific subgroups of mental disorders., Results: A total of 1 163 443 singleton infants were included in the analysis, and 16 847 (1.45%) infants were exposed to antenatal corticosteroid treatment. Children exposed to antenatal corticosteroids were found to have a higher risk of developing childhood mental disorders in the entire cohort (hazard ratio [HR], 1.13; 95% CI, 1.08-1.18), the term group (HR, 1.11; 95% CI, 1.05-1.16), and the late-preterm group (HR, 1.15; 95% CI, 1.06-1.25). The administration of corticosteroids in the early stage of pregnancy (<28 weeks of gestation) significantly increased the risk of childhood mental disorders (HR, 1.22; 95% CI, 1.14-1.31)., Conclusions: Exposure to antenatal corticosteroid treatment increases the cumulative risk of childhood mental disorders and attention deficit hyperactivity disorders, both in term and late preterm infants. The administration of corticosteroids in the early stage of pregnancy tends to increase the risk of mental disorders., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Electromyographic (EMG) endotracheal tubes with surface electrodes are used during neck surgery to prevent recurrent laryngeal nerve (RLN) injury. Proper positioning of the EMG tube is of paramount importance. In this study, we aimed to compare the use of video laryngoscopy with other methods for achieving the optimal depth of the EMG tube., Methods: We retrospectively enrolled 489 adult patients (with 675 nerves at risk [NAR]) undergoing surgery using the EMG endotracheal tube. Patients were categorized into three groups with: rigid laryngoscope (n = 140, NAR = 187), conventional laryngoscope (n = 262, NAR = 370), and video laryngoscope (n = 87, NAR = 118). A formula for predicting optimal depths of the EMG tube was obtained from data of the standard group with rigid laryngoscope. Depths of the EMG endotracheal tube were measured and postoperative RLN injuries were analyzed., Results: Based on linear regression, the formula was derived for predicting the optimal depth of EMG endotracheal tube (cm) = 11.028 + 0.635 * gender (female = 0; male = 1) + 0.069 * height (cm). Compared to conventional laryngoscope, intubation of EMG tube with video laryngoscope resulted in less discrepancy between its actual value and optimal value, and the tube depth was more correct (OR = 2.888, 95% CI = 1.753-4.757, p < 0.001). All five postoperative permanent RLN injuries were found in the group with conventional laryngoscope., Conclusion: EMG endotracheal tube insertion with video laryngoscopy is superior to conventional laryngoscopy, as well as an alternative to rigid laryngoscopy. The video laryngoscopy is a novel approach to get optimal depth of EMG endotracheal tube during neck surgery., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

Background: Cryptogenic strokes related to a patent foramen ovale (PFO) in young patients have been reported. Percutaneous transcatheter occlusion is considered a safe and effective method for achieving PFO closure. Here, we present our experience of PFO closure in a series of young patients diagnosed with cryptogenic stroke., Methods: This was a retrospective study of 62 patients who were younger than 60 years of age and previously diagnosed with cryptogenic stroke. They underwent cardiac catheterization for the diagnosis of PFO and/or device closure. Bubble and echocardiography studies, the patients' characteristics, complications, and recurrence of stroke were recorded. The Risk of Paradoxical Embolism (RoPE) score index was also calculated., Results: Patients with a bubble study grade greater than grade I were likely to have PFO (odds ratio: 22.2 [95% confidence interval: 1.2-412.3]). The mean RoPE score in the PFO closure group was 7.18. Two patients (3.9%) developed atrial fibrillation during the procedure. Ischemic stroke recurred in two patients (3.3%)., Conclusions: Combining a bubble study with transcranial Doppler ultrasound or transthoracic echocardiography may increase the validity of PFO diagnosis. Because of the low recurrence rate of stroke and low complication rate, it is important to identify PFO patients with a bubble study grade greater than grade I. Closure of PFO may be a good strategy for preventing recurrent stroke among such patients.

The condition of partial anomalous origin of a branch pulmonary artery from the descending aorta could be found in several diseases and should be carefully differentiated. We report an unusual case of anomalous systemic arterial supply to normal basal segments of the left lower lung and another case of intralobar pulmonary sequestration. These two cases were treated successfully by transarterial embolisation using the Amplatzer Vascular Plug. We also set up a diagnostic algorithm to differentiate these diseases from anomalous systemic arterial supply to the pulmonary region. It is possible to make the correct diagnosis using the step-by-step diagnostic algorithm and careful interpretation of chest computed tomography angiography.

Introduction: Immune thrombocytopenia (ITP) is one of the most common hematologic disorders in children. However, its etiology is still unclear. Epidemiological studies have shown that air pollution is a plausible risk factor in stimulation of oxidative stress, induction of inflammation, and onset of autoimmune diseases. The objective of this article is to examine the effects of prenatal exposure to air pollution on the occurrence of immune thrombocytopenia (ITP) in children., Materials and Methods: This is a nationwide, population-based, matched case-control study. Using data from Taiwan's Maternal and Child Health Database (MCHD), we identified 427 children with ITP less than 6 years of age and age-matched controls without ITP between 2004 and 2016. Levels of prenatal exposure to air pollutants were obtained from 71 Environmental Protection Administration monitoring stations across Taiwan according to the maternal residence during pregnancy. Patients who had outpatient visits or admission with diagnosis of ITP and subsequently received first-line treatment of intravenous immunoglobulin or oral glucocorticoids were defined as incidence cases., Results: Prenatal exposure to particulate matter <10 μm (PM10) in diameter and the pollutant standard index (PSI) increased the risk of childhood ITP. Conversely, carbon monoxide (CO) exposure during pregnancy was negatively associated with the development of ITP., Conclusion: Certain prenatal air pollutant exposure may increase the incidence of ITP in children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yen, Lin, Lin, Hsu and Lin.)

Kawasaki disease (KD) is the most common form of acquired pediatric cardiac disease in the developed world. However, its etiology is still unclear. Epidemiological studies have shown that air pollution is a plausible risk factor in stimulating oxidative stress, inducing inflammation and causing autoimmune diseases. This study aims to assess the connections between prenatal and early life air pollution exposure to the incidence of KD. The main data source of this nationwide longitudinal study was the National Health Insurance Research Database (NHIRD) of Taiwan. NHIRD was linked with Taiwan Maternal and Child Health Database to establish the link between mothers and children. In total, 4192 KD cases involving children under 6 years of age were identified between January 2004 and December 2010. Children in the control group were randomly selected at a 1:4 ratio and matched using their age and index year. Integrated data for the air pollutants were obtained from 71 Environmental Protection Agency monitoring stations across Taiwan. Patients who had main admission diagnosis of KD and subsequently received intravenous immunoglobulin treatment were defined as incidence cases. Ambient exposure, including pollutant standards index (PSI), carbon monoxide (CO), nitric oxide (NO), nitric dioxide (NO 2 ), and nitrogen oxide (NOx) during pregnancy were all positively associated with KD incidence. Conversely, ozone (O 3 ) exposure had a negative correlation. Exposure to CO, NO, NO 2, and NOx after childbirth remained consistent with regards to having a positive association with KD incidence. Exposure to PSI and O 3 after delivery displayed no significant association with KD. Both prenatal and postnatal cumulative CO, NO, NO 2 , and NOx exposure had a dose dependent effect towards increasing KD incidence. Certain prenatal and early life air pollutant exposure may increase the incidence of KD., (© 2022. The Author(s).)

Background: Premature births account for around 11% of the world's live births. With the improvements in survival that have been achieved in recent years, the neurological outcomes of these infants have attracted greater attention. The aim of this study was to evaluate the association between postnatal weight loss and neurodevelopment outcomes of very low birth weight premature infants., Methods: This was a prospective cohort study that was conducted in a tertiary referral center. Premature infants of birth weight less than 1500 g born between October 2015 and January 2017 were enrolled. Perinatal-demographic characteristics, medical interventions, and nutrition records were collected. The Bayley III tests performed by licensed child psychiatrists at corrected ages 6, 12, and 24 months old were adopted as outcome measurements., Results: In total, 52 infants were enrolled. The mean birth weight was 1071 g and the mean gestational age was 29.0 weeks. According to the univariate analysis, the duration of postnatal weight loss had a significantly negative impact on motor outcomes at 12 and 24 months old. The negative impact remained robust after adjusting for confounding factors by multiple linear regression models. The effect of repeated measurement was further considered by generalized estimating equation (GEE) models. GEE models also demonstrated a negative association between the duration of body weight loss and motor scores., Conclusion: The duration of postnatal weight loss might have a negative influence on long-term motor development in premature infants. Further studies of nutrition status and motor development are needed to elucidate the precise underlying mechanism., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021. Published by Elsevier B.V.)

Background: Cannulation in low birth weight (LBW) neonates using larger sheaths could increase the risk of vascular injury. This study investigated the relationship between body weight (BW) and diameter of femoral vessels in LBW neonates and whether BW can be used to predict femoral vessel diameter., Methods: The cohort included 100 neonates weighing < 2.5 kg (.57-2.42 kg) with a gestational age of 24-39 weeks. Vascular ultrasonography was used to measure diameters of the bilateral femoral arteries (FA) and veins (FV). The cohort was divided into four groups according to weight: group-A, 2-2.49 kg (n = 28); group-B, 1.5-1.99 kg (n = 38); group-C, 1-1.49 kg (n = 21); and group-D, < 1 kg (n = 13); or according to BSA: group-A, BSA > .16 m 2 (n = 25); group-B, .13-.16 m 2 (n = 40); group-C, .1-.13 m 2 (n = 22); and group-D, < .1 m 2 (n = 13)., Results: The median vessel diameters (mm) in groups A-D according to weight were FA, 1.96, 1.86, 1.78, and 1.53, and FV, 2.30, 2.28, 2.13, and 1.87, respectively. The median vessel diameters (mm) in groups A-D according to BSA were FA, 1.96, 1.86, 1.76, and 1.53, and FV, 2.30, 2.28, 2.05, and 1.87, respectively. There were positive correlations between BW and femoral vessel diameter (correlation coefficient: .56 and .55 between BW and FA and FV, respectively) (p < 0.001), and between BSA and femoral vessel diameter (correlation coefficient: .56 and .55 between BSA and FA and FV, respectively) (p < 0.001)., Conclusions: BW is a predictor of femoral vessel diameter in LBW newborns. This finding may help to avoid using larger sheath in smaller vessels., (© 2021 Wiley Periodicals LLC.)

Background: In extremely low birth weight (ELBW) infants, the patent ductus arteriosus (PDA) with left-to-right shunt and an increase in systemic artery resistance may cause increasing preload and afterload of the left ventricle. The immature myocardium in ELBW infants has a limited ability to respond to the change, which leads to hemorrhagic complications. In this study, we detected the hemodynamic change of cardiac performance and applied a clinical strategy to prevent PDA-associated hemorrhagic complications in ELBW infants. Methods: We enrolled ELBW infants at a single medical center in Taiwan. The customized circulatory management was performed by echocardiography after birth until the PDA closed. Inotropic agents were administrated according to the requirements of hemodynamic parameters or clinical conditions. The primary outcomes were hemorrhagic complications including pulmonary hemorrhage and intraventricular hemorrhage (IVH) greater than grade II. The secondary outcomes were the rate of surgical ligation of PDA, mortality, necrotizing enterocolitis, and bronchopulmonary dysplasia. Results: A total of 20 ELBW infants were evaluated by customized circulatory management from 2019 to 2020. We reviewed 35 ELBW infants born between 2017 and 2018 in our hospital, who served as the non-management group. The management group had a significantly lower incidence rate of IVH greater than grade 2 ( p = 0.02). Other outcomes showed no significant differences. Dobutamine was prescribed in 8 cases in the management group, and end-systolic wall stress (ESWS) was significantly decreased after Dobutamine administration ( p = 0.017). Conclusion: The incidence rate of IVH greater than grade II in ELBW infants decreased after use of customized circulatory management in our study. The strategy of customized circulatory management might be an effective "early target therapy" for hemodynamically significant PDA in high-risk ELBW infants. Inotropic therapy with Dobutamine could be a useful medical choice for improving cardiac function to prevent hemorrhagic complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Li, Hsu, Lin, Hsu, Wang and Lin.)

Background: Acute heart failure (AHF) is the major cause of death in children with severe enterovirus 71 (EV71) infection. This study aimed to report our clinical experience with EV71-related AHF, as well as to discuss its pathogenesis and relationship to Takotsubo syndrome (TTS). Methods: A total 27 children with EV71-related AHF between 1998 and 2018 were studied. The TTS diagnosis was based on the International Takotsubo Diagnostic Criteria. Results: Acute heart failure-related early death occurred in 10 (37%) of the patients. Sinus tachycardia, systemic hypertension, and pulmonary edema in 100, 85, and 81% of the patients, respectively, preceded AHF. Cardiac biomarkers were significantly increased in most patients. The main echocardiographic findings included transient and reversible left ventricular (LV) regional wall motion abnormality (RWMA) with apical ballooning. High concentrations of catecholamines either preceded or coexisted with AHF. Myocardial pathology revealed no evidence of myocarditis, which was consistent with catecholamine-induced cardiotoxic damage. Patients with EV71-related AHF who had received close monitoring of their cardiac function, along with early intervention involving extracorporeal life support (ECLS), had a higher survival rate (82 vs. 30%, p = 0.013) and better neurological outcomes (59 vs. 0%, p = 0.003). Conclusion: EV 71-related AHF was preceded by brain stem encephalitis-related hypercatecholaminemia, which resulted in a high mortality rate. Careful monitoring is merited so that any life-threatening cardiogenic shock may be appropriately treated. In view of the similarities in their clinical manifestations, natural course direction, pathological findings, and possible mechanisms, TTS and EV71-related AHF may represent the same syndrome. Therefore, we suggest that EV71-related AHF could constitute a direct causal link to catecholamine-induced secondary TTS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jan, Fu, Chi, Lee, Huang, Wang, Wei, Lin, Chen and Hwang.)

Post-procedural right ventricular pseudoaneurysm is a rare but life-threatening complication of interventional catheterisation. We describe a 3-day-old newborn who underwent transcatheter intervention for pulmonary atresia with a complication of right ventricular pseudoaneurysms, and transcatheter embolisation of the pseudoaneurysms was performed at 3-week-old. It is the first described case that receives transcatheter closure of right ventricular pseudoaneurysms in a newborn with a favourable outcome.

Introduction: Genetic susceptibility and immune dysregulation play important roles in the pathogenesis of Kawasaki disease (KD). However, it is still unclear whether KD causes immune disorder later in life or whether inherited susceptibility to immune disorders causes KD. The aim of this study was to elucidate whether inherited immune disease properties from mothers increase the risk of KD from a population-based perspective. Method: Taiwan's National Health Insurance Research Database was the main data source in this study. Parents and children were linked using the Taiwan Maternal and Child Health Database. Patients diagnosed with KD and younger than 18 years from 2004 to 2015 were enrolled as the study population. The control group was randomly selected from individuals without the diagnosis of KD matched by age, index year, sex, and urbanization level at a ratio of 1 to 10. The prevalence of maternal autoimmune and allergic diseases was compared between groups. Results: In total, 7,178 children were found to have been diagnosed with Kawasaki disease. Then 71,780 children matched by index year, gender, and urbanization were randomly selected to serve as the control group. Children born from mothers with asthma and allergic rhinitis had a higher risk of developing KD. Children of mothers with an autoimmune disorder had a significantly increased tendency to develop KD. Maternal numbers of autoimmune disorders showed a dose-dependent relationship with KD incidence. Conclusion: This is the first population-based study to investigate maternal immune diseases and the risk of KD in their children. Children of mothers with immune disorders tend to have a higher risk of KD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chu, Lin, Lin and Hsu.)

Background: Prospective registry studies of congenital heart disease (CHD)-associated pulmonary artery hypertension (PAH) are rare. We established a multicenter registry of CHD-PAH: the TACHYON (TAiwan Congenital Heart disease associated with pulmonarY arterial hypertension) registry., Methods: The prospective TACHYON registry was initiated in January 2016. Nine pediatric cardiology centers with 99 patients were included. Using this database, we evaluated clinical characteristics and outcomes., Results: Twelve patients with incomplete data were excluded. For the remaining 87 patients, mean age of enrollment was 37.4(SD 18.2) years, and the male to female ratio was 60:27. PAH after defect closure accounted for 46 (52.9%) and Eisenmenger syndrome for 30 (34.5%) cases. Atrial septal defect was the most common (48.3%) disease, followed by ventricular septal defect. Mean pulmonary artery pressure was 56.7 (SD 19.4) mmHg. PAH-targeted therapy was used in 95.4% of patients. Sildenafil and bosentan were the most common drugs. After mean 23.9 months of follow-up, the 2-year Kaplan-Meier survival rate was 93.2%. According to univariate Cox regression analysis, significant risk factors included right heart failure signs, symptom progression, high-risk baseline N-terminal pro-brain natriuretic peptide (BNP)/BNP, high-risk baseline 6-min walking distance (6MWD), and high baseline hemoglobin/hematocrit level. Using the three noninvasive parameters (functional class, 6MWD, NT-pro BNP/BNP) proposed by the European Society of Cardiology, the total number of high-risk criteria predicted survival rate reliably., Conclusions: Using the TACHYON registry is feasible, but the physicians' adherences to guidelines are unsatisfactory. Midterm outcomes of PAH-target therapy are favorable and predictable using noninvasive parameters., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: The major burden of diseases in childhood has shifted from infectious diseases to chronic health conditions in recent decades. Although the rates of infectious diseases have decreased, the incidence of chronic diseases stemming from infectious agents continues to grow. Enterovirus is a major infectious disease of childhood and has been linked to numerous chronic diseases. We analyzed population-based data from Taiwan's National Health Insurance Research Database (NHIRD) to investigate the correlations between enterovirus infection and major chronic health conditions in children. Method: Children diagnosed with enterovirus (EV) infection during 1999-2003 were identified from the Longitudinal Health Insurance Database 2000 (LHID 2000), a subdataset of Taiwan's National Health Insurance Research Database (NHIRD). A total of 14,168 patients were selected after excluding patients with existing chronic diseases and missing data. Another 14,168 children matched by age and sex were selected as the control group. Five primary outcomes, including attention deficit and hyperactivity disorder (ADHD), epilepsy, asthma, allergic rhinitis, and atopic dermatitis, were recorded. Results: The risks of ADHD, asthma, allergic rhinitis, and epilepsy were significantly increased in the EV group compared with the control group. The risk of atopic dermatitis was significantly increased in the crude model. However, there were no significant differences in the adjusted model. The risks of ADHD, asthma, allergic rhinitis, and epilepsy were also significantly increased in patients with severe EV infection compared with patients with non-severe EV infection. Conclusion: Chronic diseases, such as ADHD, epilepsy, asthma, allergic rhinitis, and atopic dermatitis were shown to be associated with enterovirus infection during childhood. EV infection during early childhood might have long-term public health implications and thus prevention strategies should be implemented., (Copyright © 2020 Tseng, Lin and Lin.)

Background: Breast milk is the optimal choice for feeding premature babies. However, the prevalence rate of extrauterine growth restriction in preterm infants remains high., Objectives: The purpose of this study was to analyze the macronutrients present in human milk and the correlation with the growth of in-hospital preterm infants., Methods: This prospective study is based on data from 99 in-hospital preterm infants younger than 37 weeks of gestational age on an exclusively human milk diet. Infants who had previously received parenteral nutrition were eligible, but they had to have reached full enteral feeding at the time that the samples were taken. A total of 3282 samples of raw human milk or donor pasteurized milk were collected. The levels of lactose, protein, fat, and energy in the samples were measured using a Miris human milk analyzer. The primary outcome was weight growth velocity (g/kg/day) which was obtained using two-point approach., Results: The mean (±standard deviation) macronutrient composition per 100 mL of milk was 7.2 (±0.3) g of lactose, 1.1 (±0.2) g of true protein, 3.5 (±0.9) g of fat, and 66.9 (±6.5) kcal of energy. The protein concentration in human milk had a positive, significant correlation with body weight gain, with a coefficient of 0.41 (p < 0.001). After adjusting for gestational age, postmenstrual age, small-for-gestational age, intraventricular hemorrhage, patent ductus arteriosus or congestive heart failure, duration of total parenteral nutrition support, bottle feeding or use of orogastric tube, and ventilator support, total daily protein intake was associated with body weight growth (p < 0.001)., Conclusion: Both the protein concentration in human milk and the daily total protein intake had a positive correlation with the body weight gain of premature infants. Routine analysis of breast milk and individualized fortification might be indicated to optimize the growth of preterm infants., Competing Interests: The authors have declared that no competing interests exist.

Background: Very-low-birth-weight (VLBW) infants have a high risk of postdischarge growth retardation (GR). Continued GR might exert negative long-term effects on their health. This study examined the prevalence and the risk factors for postdischarge GR among VLBW infants in Taiwan., Methods: Nationwide data from the Taiwan Premature Infant Follow-up Network between 2007 and 2011 were analyzed. Infants with a gestational age (GA) < 37 weeks and birth body weight (BBW) < 1500 g were enrolled. They were followed up after discharge at the corrected ages of 6, 12, and 24 months. Associations between postdischarge GR at the follow-ups and possible risk factors were analyzed., Results: The prevalence of postdischarge GR among 2124 VLBW infants was 17.3%, 19.4%, and 13.8% at the corrected age (CA) of 6, 12, and 24 months, respectively. The significant perinatal factors of postdischarge GR were being small for gestational age (SGA) and extremely low birth weight (ELBW). ELBW infant with extra-uterine growth retardation (EUGR) at discharge or longer length of hospital stay (LOS) had poorer growth outcomes. Among non-ELBW infants, EUGR at discharge and surgical necrotizing enterocolitis (NEC) were the main influencing factors of unfavorable growth outcomes. RDS with surfactant therapy had a positive effect of postdischarge growth outcomes in ELBW infants., Conclusion: Postdischarge GR is still a serious problem in Taiwan. Being SGA and ELBW and EUGR were significant risk factors for postdischarge GR throughout the first two years of life in VLBW infants. An integrated and organized team for postdischarge care as well as scheduled follow-ups, detailed nutritional education, and thorough inspection are necessary., (Copyright © 2019. Published by Elsevier B.V.)

Background: The location of the accessory pathway (AP) can be precisely identified on surface electrocardiography (ECG) in adults with Wolff-Parkinson-White (WPW) syndrome. However, current algorithms to locate the AP in pediatric patients with WPW syndrome are limited., Objective: To propose an optimal algorithm that localizes the AP in pediatric patients with WPW syndrome., Methods: From 1992 to 2016, 180 consecutive patients aged below 18 years with symptomatic WPW syndrome were included. After the exclusion of patients with non-descriptive electrocardiography (ECG), multiple APs, congenital heart diseases, non-inducible tachycardia, and those who received a second ablation, 104 patients were analyzed retrospectively. Surface ECG was obtained before ablation and evaluated by using previously documented algorithms, from which a new pediatric algorithm was developed., Results: Previous algorithms were not highly accurate when used in pediatric patients with WPW syndrome. In the new algorithm, the R/S ratio of V1 and the polarity of the delta wave in lead I could distinguish right from the left side AP with 100% accuracy. The polarity of the delta wave of lead V1 could distinguish free wall AP from septal AP with an accuracy of 100% in left-side AP, compared to 88.6% in leads III and V1 for right-side AP. The overall accuracy was 92.3%., Conclusions: This simple, novel algorithm could differentiate left from right AP and septal from free wall AP in pediatric patients with WPW syndrome.

Purpose: Hypercatecholaminemia-related heart failure has been proposed as the main cause of enterovirus A71-related (EV-A71) early mortality. The purpose of this study was to measure urine catecholamine concentrations in severe EV-A71-infected children. Methods: A total of 35 children, aged 2.5 ± 2.1 years, were divided into three groups. Group I: 15 septic shock patients, group II: 17 EV-A71-stage-2 patients, and group III: 3 EV-A71-stage-4 patients. The laboratory results, cardiac biomarkers and urine catecholamine concentrations were statistically analysed. Results: Group I had the highest C-reactive protein (CRP) levels and group II had the lowest B-type natriuretic peptide (BNP) and its N-terminal prohormone among the groups ( p  = 0.039, <0.01 and <0.01, respectively). Group III patients had significantly higher urine catecholamine and troponin-I values among the groups. If urine epinephrine (Epi) >134 ug/gCr, norepinephrine (NE) >176 ug/gCr and vanillylmandelic acid (VMA) >11.7 mg/gCr were used as the cutoff points to differentiate groups II and III, the sensitivities and specificity were all 100%. Conclusions: The significantly elevated urine catecholamine concentrations in EV-A71-stage-4 patients support the hypothesis that hypercatecholaminemia-related heart failure is involved in severe EV-A71 infection. Urine catecholamines could be used as reliable biomarkers for differentiation of severe EV-A71 infection with or without heart failure and septic shock.

Background: The practices promoted by the Baby-friendly Hospital Initiative have become a part of current mainstream postpartum infant care. Rooming-in to facilitate skin-to-skin contact and breastfeeding is a major component of this initiative. However, whether rooming-in is associated with admission for neonatal hyperbilirubinemia has seldom been reported. The aim of this study was to evaluate the association between rooming-in and neonatal hyperbilirubinemia., Methods: This was a retrospective cohort study. Term neonates were consecutively enrolled from the nursery of a medical center from January 2011 to December 2013. During the study period, rooming-in care was strongly encouraged according to the World Health Organization guidelines, if the parents agreed. The endpoint was defined as admission for phototherapy. Risk of neonatal hyperbilirubinemia in rooming-in neonates was calculated. Potential confounding factors, including exclusive breastfeeding, potential ABO incompatibility, Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency, and body weight loss (BWL), were adjusted by multiple logistic regression models., Results: Totally, 3341 infants were enrolled in this study after excluding 40 infants admitted for other reasons. The rooming-in rate increased yearly during the study period. However, the rate of neonatal hyperbilirubinemia also increased simultaneously. The odds ratio (OR) of neonatal hyperbilirubinemia in the rooming-in group was 7.04 (95% CI, 4.41∼11.24). The rooming-in group demonstrated a higher percentage of exclusive breastfeeding and BWL >10% at 3 days of age. After adjusting for potential confounding factors, rooming-in was still a significant risk factor for neonatal hyperbilirubinemia (OR: 8.48; 95% CI: 5.04∼14.25)., Conclusions: The practice of rooming-in is now part of the mainstream postpartum newborn care. However, the increased incidence of neonatal hyperbilirubinemia is a potential side effect of which healthcare providers should be aware. Further research is needed to confirm the role of rooming-in in neonatal hyperbilirubinemia., (Copyright © 2018. Published by Elsevier B.V.)

Background: Aberrant right subclavian artery is the most common congenital aortic arch anomaly. There are a few reports concerning the clinical manifestations and follow-up of this CHD detected by echocardiographic screening., Methods: A total of 1737 full-term neonates, with a male-to-female ratio of 900:837, received echocardiographic screening. Neonates with or without isolated aberrant right subclavian artery were studied during infancy., Results: Among the 1737 cases, a total of 15 (0.86%) female-predominant neonates, with a male-to-female ratio of 6:9, had isolated aberrant right subclavian artery. They were compared with 20 age- and gender-matched normal neonates. There were no significant differences in maternal age, gestational age, or para gravity between the two groups, except for birth size (birth length- and weight-for-age percentiles, p = 0.006 and 0.045, respectively), which was smaller in the aberrant right subclavian artery group. Although there were no significant differences in developmental history, gastrointestinal, or respiratory symptoms, neonates with aberrant right subclavian artery had a higher incidence of mild developmental delay and feeding difficulty than normal infants (21 versus 0%, p = 0.061; 36 versus 20%, p = 0.264, respectively). The growth rates of body length and weight during infancy were not significantly different between the two groups., Conclusions: Echocardiography can be applied as a first-line investigation in the diagnostic work-up for aberrant right subclavian artery. Neonates with aberrant right subclavian artery had a smaller size at birth, although growth rates were not significantly different from those of normal infants. This study does not support an active surgical policy for asymptomatic infants with isolated aberrant right subclavian artery. A larger study and longer follow-up of affected infants is recommended.

[This corrects the article DOI: 10.1371/journal.pone.0192574.].

Background: For infants with very low birth weights (VLBW), their neurodevelopmental outcomes are thought to be associated with extra-uterine growth retardation (EUGR). In this study, based on a single institute, we analyzed the association between different levels or severity of EUGR of VLBW infants and their neurodevelopmental outcomes later at a corrected age of 24 months., Methods: This is a hospital-based retrospective cohort study. The severity of EUGR was classified into three categories according to the z-score of discharge weight: z < -2.0, <-2.5, and <-3.0. The outcomes were assessed using the Bayley Scales of Infant Development-II (BSID-II) at a corrected age of 24 months. We then estimated the association of EUGR with low mental developmental index (MDI) or low psychomotor developmental index (PDI). Multiple logistic regression and stratified analyses were used to adjust for the possible confounding factors., Results: In total, 224 VLBW infants were enrolled in this study from 1997 to 2006. In the univariate analysis, EUGR for weight at discharge from hospital was associated with MDI <85 at the corrected age of 24 months, and this association was related to the severity of EUGR (z < -2.5, OR: 1.92 (1.04-3.53); z < -3.0, OR: 2.83 (1.26-6.36)). In addition, the relationship was not confounded by gender nor small for gestational age. The stratified analysis against hemodynamic significant patent ductus arteriosus also revealed that EUGR was an independent predictor for neurodevelopmental outcomes., Conclusion: In VLBW preterm infants, EUGR was significantly associated with low MDI scores assessed at a corrected age of 24 months. Early evaluation and recognition of EUGR should be emphasized when caring for preterm infants., (Copyright © 2017. Published by Elsevier B.V.)

Background: Premature infants are at high risk for developmental delay and cognitive dysfunction. Besides medical conditions, growth restriction is regarded as an important risk factor for cognitive and neurodevelopmental dysfunction throughout childhood and adolescence and even into adulthood. In this study, we analyzed the relationship between post-discharge body weight and psychomotor development using a nationwide dataset., Materials and Methods: This was a nationwide cohort study conducted in Taiwan. Total of 1791 premature infants born between 2007 and 2011 with a birth weight of less than 1500 g were enrolled into this multi-center study. The data were obtained from the Taiwan Premature Infant Developmental Collaborative Study Group. The growth and neurodevelopmental evaluations were performed at corrected ages of 6, 12 and 24 months. Post-discharge failure to thrive was defined as a body weight below the 3rd percentile of the standard growth curve for Taiwanese children by the corrected age., Results: The prevalence of failure to thrive was 15.8%, 16.9%, and 12.0% at corrected ages of 6, 12, and 24 months, respectively. At corrected ages of 24 months, 12.9% had low Mental Developmental Index (MDI) scores (MDI<70), 17.8% had low Psychomotor Developmental Index (PDI) scores (PDI<70), 12.7% had cerebral palsy, and 29.5% had neurodevelopmental impairment. Post-discharge failure to thrive was significantly associated with poor neurodevelopmental outcomes. After controlling for potential confounding factors (small for gestational age, extra-uterine growth retardation at discharge, cerebral palsy, gender, mild intraventricular hemorrhage, persistent pulmonary hypertension of newborn, respiratory distress syndrome, chronic lung disease, hemodynamic significant patent ductus arteriosus, necrotizing enterocolitis, surfactant use and indomethacin use), post-discharge failure to thrive remained a risk factor., Conclusion: This observational study observed the association between lower body weight at corrected age of 6, 12, and 24 months and poor neurodevelopmental outcomes among VLBW premature infants. There are many adverse factors which can influence the neurodevelopment in NICU care. More studies are needed to elucidate the causal relationship.

Background: The traditional treatment of subarterial ventricular septal defect (VSD) is open heart surgery. This study aimed to evaluate the feasibility, safety and outcome of transcatheter closure with the Amplatzer duct occluder (ADO)., Methods: Between March 2012 and June 2015, a total of 16 patients (8 male and 8 female) with subarterial VSD who underwent transcatheter closure with the ADO were enrolled retrospectively. Their age ranged from 3.0 to 65.6 years, with the median of 35.6 years; their body weights ranged from 14 to 92 kg with the median of 60 kg. All patients had prolapse of the right coronary cusp without subaortic rim. Mild aortic regurgitation was noted in 11 (69%) patients., Results: Left ventriculogram showed VSD size ranged from 1.3 to 9.3 mm with the median of 3.5 mm. The device was successfully implanted in 88% (14/16) of the patients. Although one patient had mild skin allergy to contrast medium, no other complication was noted. Complete closure rate was 64%, 86%, 86% and 86% at 1-day, 1-month, 6-month and 12-month follow-up, respectively. Two patients developed new or worsening aortic regurgitation during follow-up., Conclusion: Transcatheter closure of subarterial VSD with ADO is technically feasible and safe in patients older than 7 years of age. However, development or worsening of aortic regurgitation requires long-term follow-up., (Copyright © 2017. Published by Elsevier Taiwan LLC.)

Background: Transcatheter device closure of postmyocardial infarction ventricular septal defect (PMIVSD) is less invasive than surgical repair. However, its feasibility, timing, outcome, and prognostic factors remain unclear., Methods: This was a multicenter, retrospective cohort study. Between February 2012 and July 2015, a total of 10 (8 male and 2 female) patients with PMIVSD undergoing attempted device closure were enrolled retrospectively. The procedures were performed under general anesthesia with fluoroscopic and transesophageal echocardiographic guidance., Results: The patients enrolled in the study were in the age range 50-85 years (median age of 76.5 years). The interval from infarction to device closure ranged from 6-147 days, with the median of 12 days. A total of 13 devices were implanted in 10 patients. There were five Amplatzer muscular ventricular septal defect occluders, four Amplatzer septal occluders, three Amplatzer PMIVSD occluders and one Amplatzer vascular plug II. Complications included transient ventricular tachycardia in three patients, device embolization in one patient, and tracheal bleeding in one patient. No procedure-related death, stroke, or cardiac tamponade was noted. During follow-up, two patients died of heart failure and two patients died of sepsis. Overall, subjects with age ≥ 80 years, systolic blood pressure ≤ 90 mmHg, and procedure time ≥180 minutes were significant predictor factors for mortality. All patients with the interval of infarction to device closure >12 days survived., Conclusion: Our findings indicate that transcatheter device closure of PMIVSD is technically feasible, safe, and effective to reduce the shunt. The crucial prognostic factors were ascertained to be age ≥ 80 years, systolic blood pressure ≤ 90 mmHg, and procedure time ≥180 minutes., (Copyright © 2016. Published by Elsevier Taiwan LLC.)