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Since gestational age (GA) is an important factor influencing the presence of specific microbiomes, we aimed to characterize the core microbiomes of preterm infants compared to full-term (FT) infants. This study investigated the differences in microbiota composition between very preterm (VP), moderate-to-late preterm (MLP), and FT neonates by examining the core microbiomes of a large cohort of Korean neonates. Meconium samples from 310 neonates with a GA range of 22–40 weeks were collected, and 16S rRNA analyses were performed; 97 samples were obtained from the FT, 59 from the VP, and 154 from the MLP group. Firmicutes, Bacteroidetes, and Proteobacteria were the phylum-level core microbiomes. Infants born before 37 weeks showed a disruption in the core microbiomes. At the phylum level, the relative abundance of Bacteroidetes was positively (r = 0.177, p = 0.002) correlated with GA, while that of Proteobacteria was negatively (r = −0.116, p = 0.040) correlated with GA. At the genus level, the relative abundances of Bacteroides and Prevotella were positively correlated with GA (r = 0.157, p = 0.006; r = 0.160, p = 0.005). The meconium of preterm infants exhibited significantly lower α-diversities than that of FT infants. β-diversities did not appear to differ between the groups. Overall, these findings underscore the importance of GA in shaping the early gut microbiome. [ABSTRACT FROM AUTHOR]

Background/Objectives: Extrauterine growth restriction (EUGR) is associated with high mortality and an increased incidence of poor neurodevelopmental outcomes in preterm infants. In this study, we aimed to compare the Intergrowth-21ST (IG-21ST) and Fenton charts in predicting long-term neurodevelopmental and anthropometric outcomes of very low birth weight (VLBW) infants. Methods: Data were collected from 2649 VLBW infants registered in the Korean Neonatal Network born between 240/7 and 316/7 weeks of gestational age from January 2013 to December 2017. Follow-up assessments were conducted at 18–24 months of age, corrected for prematurity. Multiple logistic regression analysis was performed to evaluate the association between EUGR and long-term outcomes. Results: Among the 2649 VLBW infants, 60.0% (1606/2649) and 36.9% (977/2649) were diagnosed as having EUGR defined by the Fenton chart (EUGRF) and by the IG-21ST chart (EUGRIG), respectively. The EUGRIG group exhibited a higher proportion of infants with cerebral palsy, neurodevelopmental impairment (NDI), and growth failure. In multiple logistic regression analysis, adjusted for risk factors for long-term outcome, the EUGRIG group showed higher risk of cerebral palsy (adjusted odds ratio [aOR], 1.66; 95% confidence interval [CI], 1.04–2.65), NDI (aOR, 2.09; 95% CI, 1.71–2.55), and growth failure (aOR, 1.57; 95% CI, 1.16–2.13). Infants with EUGRF tended to develop NDI (aOR, 1.29; 95%CI, 1.03–1.63) and experience growth failure (aOR, 2.44; 95% CI, 1.77–3.40). Conclusions: The IG-21ST chart demonstrated a more effective prediction of long-term neurodevelopmental outcomes, whereas the Fenton chart may be more suitable for predicting growth failure at 18–24 months. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of direct swallowing training (DST) alone and combined with oral sensorimotor stimulation (OSMS) on oral feeding ability in very preterm infants.Design: Blinded, parallel group, randomised controlled trial (1:1:1).Setting: Neonatal intensive care unit of a South Korean tertiary hospital.Participants: Preterm infants born at <32 weeks of gestation who achieved full tube feeding.Interventions: Two sessions per day were provided according to the randomly assigned groups (control: two times per day sham intervention; DST: DST and sham interventions, each once a day; DST+OSMS: DST and OSMS interventions, each once a day).Primary Outcome: Time from start to independent oral feeding (IOF).Results: Analyses were conducted in 186 participants based on modified intention-to-treat (63 control; 63 DST; 60 DST+OSMS). The mean time from start to IOF differed significantly between the control, DST and DST+OSMS groups (21.1, 17.2 and 14.8 days, respectively, p=0.02). Compared with non-intervention, DST+OSMS significantly shortened the time from start to IOF (effect size: -0.49; 95% CI: -0.86 to -0.14; p=0.02), whereas DST did not. The proportion of feeding volume taken during the initial 5 min, an index of infants' actual feeding ability when fatigue is minimal, increased earlier in the DST+OSMS than in the DST.Conclusions: In very preterm infants, DST+OSMS led to the accelerated attainment of IOF compared with non-intervention, whereas DST alone did not. The effect of DST+OSMS on oral feeding ability appeared earlier than that of DST alone.Trial Registration Number: ClinicalTrials.gov Registry (NCT02508571). [ABSTRACT FROM AUTHOR]

The Warburg effect is important for cancer cell proliferation. This phenomenon can be flexible by interaction between glycolysis and mitochondrial oxidation for energy production. We aimed to investigate the anticancer effects of the pyruvate dehydrogenase kinase inhibitor, dichloroacetate (DCA) and the mitochondrial respiratory complex I inhibitor metformin in liver cancer cells. The anticancer effect of DCA and/or metformin on HepG2, PLC/PRF5 human liver cancer cell lines, MH-134 murine hepatoma cell lines, and primary normal hepatocytes using MTT assay. Inhibition of lactate/ATP production and intracellular reactive oxygen species generation by DCA and metformin was investigated. Inhibition of PI3K/Akt/mTOR complex I was evaluated to see whether it occurred through AMPK signaling. Anticancer effects of a combination treatment of DCA and metformin were evaluated in HCC murine model. The results showed that metformin and DCA effectively induced apoptosis in liver cancer cells. A combination treatment of metformin and DCA did not affect viability of primary normal hepatocytes. Metformin upregulated glycolysis in liver cancer cells, thereby increasing sensitivity to the DCA treatment. Metformin and DCA inhibited mTOR complex I signaling through upregulated AMPK-independent REDD1. In addition, metformin and DCA increased reactive oxygen species levels in liver cancer cells, which induced apoptosis. A combination treatment of metformin and DCA significantly suppressed the tumor growth of liver cancer cells using in vivo xenograft model. Taken together, the combined treatment of metformin and DCA suppressed the growth of liver cancer cells. This strategy may be effective for patients with advanced liver cancer. [ABSTRACT FROM AUTHOR]

The objective of this systematic review and meta-analysis was to summarize the effects of early initiation and achievement of a high dose of parenteral lipids (≥1.5 g/kg/day reached within the first 24 h of birth) on growth and adverse outcomes in preterm infants. PubMed, EMBASE, and Cochrane databases were utilized to search for publications for this meta-analysis. Randomized controlled trials were eligible if data on growth or clinical outcome was available. The search returned nine studies. The mean proportion of postnatal weight loss (%) was lower (mean difference [MD]: −2.73; 95% confidence interval [CI]: −3.69, −1.78), and the mean head circumference near the term equivalent age (cm) was higher in the early high lipid treatment group (MD: 0.67; 95% CI: 0.25, 1.09). There was a favorable association of early high lipid administration with the incidence of extrauterine growth restriction (relative risk [RR]: 0.27; 95% CI: 0.15, 0.48). Generally, there were no differences in morbidities or adverse outcomes with early high lipid administration. Early initiation of parenteral lipids and high dose achieved within the first 24 h of life appear to be safe and endurable and offer benefits in terms of growth. [ABSTRACT FROM AUTHOR]

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.)

Objective: To evaluate the effects of direct swallowing training (DST) alone and combined with oral sensorimotor stimulation (OSMS) on oral feeding ability in very preterm infants., Design: Blinded, parallel group, randomised controlled trial (1:1:1)., Setting: Neonatal intensive care unit of a South Korean tertiary hospital., Participants: Preterm infants born at <32 weeks of gestation who achieved full tube feeding., Interventions: Two sessions per day were provided according to the randomly assigned groups (control: two times per day sham intervention; DST: DST and sham interventions, each once a day; DST+OSMS: DST and OSMS interventions, each once a day)., Primary Outcome: Time from start to independent oral feeding (IOF)., Results: Analyses were conducted in 186 participants based on modified intention-to-treat (63 control; 63 DST; 60 DST+OSMS). The mean time from start to IOF differed significantly between the control, DST and DST+OSMS groups (21.1, 17.2 and 14.8 days, respectively, p=0.02). Compared with non-intervention, DST+OSMS significantly shortened the time from start to IOF (effect size: -0.49; 95% CI: -0.86 to -0.14; p=0.02), whereas DST did not. The proportion of feeding volume taken during the initial 5 min, an index of infants' actual feeding ability when fatigue is minimal, increased earlier in the DST+OSMS than in the DST., Conclusions: In very preterm infants, DST+OSMS led to the accelerated attainment of IOF compared with non-intervention, whereas DST alone did not. The effect of DST+OSMS on oral feeding ability appeared earlier than that of DST alone., Trial Registration Number: ClinicalTrials.gov Registry (NCT02508571)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: With the coronavirus disease 2019 (COVID-19) pandemic lasting for more than a year, it is imperative to identify the associated changes in the use of emergency medical care for efficient operation of the pediatric emergency department (PED). This study was conducted to determine the long-term impact of the COVID-19 pandemic on patterns of PED visits., Methods: This is a retrospective observational study of visits to the PED of six hospitals, between January 1, 2017, and December 31, 2020. We compared changes in the characteristics of patients before and during the COVID-19 pandemic., Results: A total of 245 022 visits were included in this analysis. After the first case of COVID-19 was reported in Korea, we observed a significant decrease (54.2%) in PED visits compared with the annual average number of visits in the previous 3 years. Since then, the weekly number of PED visits decreased by 11.9 person/week (95% CI: -15.3--8.4, P < 0.001), which included an increase of 0.21% (95% CI: 0.15%-0.26%, P < 0.001) per week in high acuity patients. From 2017 to 2020, the proportion of infectious respiratory diseases by year was 25.9%, 27.0%, 28.6%, and 16.3%, respectively, demonstrating a significant decrease in 2020 (P < 0.001)., Conclusions: During the COVID-19 pandemic, the number of patient visits to PEDs continues to decline, especially among those with infectious diseases. However, the disease severity of patients has gradually increased. There has been a change in the characteristics of visits to PEDs after COVID-19 which will require an appropriate response from a long-term perspective., (© 2021 Japan Pediatric Society.)

Background: School-aged children born very preterm have been suggested to have worse cognitive and behavioral outcomes than children born full-term. Executive function (EF) is a higher level of cognitive function related to academic achievement. The present study aimed to evaluate the cognitive (including EF) and behavioral outcomes of Korean children born extremely preterm (EP) and to analyze any biological or socioeconomic risk factors for poor cognitive outcomes in this population., Methods: A total of 71 infants weighing < 1,000 g at birth or born before 30 weeks of gestation (EP group) who were admitted to the neonatal intensive care unit from 2008 to 2009 were included in this study and compared with 40 term-birth controls. The Korean Wechsler Intelligence Scale for Children-Fourth Edition, Advanced Test of Attention (ATA), Stroop test, Children's Color Trails Test (CCTT), and Wisconsin Card Sorting Test (WCST) were used. Additionally, the Korean Child Behavior Checklist (K-CBCL) and Korean ADHD Rating Scale (K-ARS) were completed. Perinatal and demographic data were collected and analyzed., Results: The mean full-scale intelligence quotient (FSIQ) score in the EP group was significantly lower than that of the term control group (89.1 ± 18.3 vs. 107.1 ± 12.7; P < 0.001). In the EP group, 26 (37%) children had an FSIQ score below 85, compared to only one child (3%) in the control group. Furthermore, the EP group showed significantly worse EF test results (ATA, Stroop test, CCTT, WCST). Except for the higher social immaturity subscore in the EP group, the K-CBCL and K-ARS scores were not different between the two groups. EP children who received laser treatment for retinopathy of prematurity (ROP) had an 8.8-fold increased risk of a low FSIQ score, and a 1-point increase in the discharge weight Z-score decreased the risk of a low FSIQ score by approximately half in this EP cohort., Conclusion: This is the first Korean study to investigate the cognitive and behavioral outcomes of school-aged children born EP. In the study cohort, EP children exhibited significantly lower FSIQ scores and EF than their full-term peers, and 37% of them had cognitive problems. Nonetheless, except for social immaturity, the behavioral problems were not different in EP children. Severe ROP and low discharge weight Z-score were identified as independent risk factors for low FSIQ score after adjusting for birth weight., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

The government of South Korea implemented social distancing measures to control the coronavirus disease 2019 (COVID-19) outbreak. This study aimed to compare the composite preterm (PT) or low birth weight (LBW) birth rates during the COVID-19 pandemic period in South Korea to those during the prior decade, and to find out the associations of childbirth during the pandemic period with PT or LBW births. Over a ten-year period, this retrospective cohort study was performed in a single hospital in the Seoul metropolitan city. The COVID-19 period was defined as running from 22 March 2020, to 31 October 2020, and the pre-COVID-19 period as the sum of parallel periods from 2011 to 2019. Trends in composite birth rates were investigated, and logistic regression analysis was conducted to investigate independent factors associated with composite births. There were 246 and 2765 singleton deliveries during the COVID-19 period and the pre-COVID-19 period, respectively. The composite birth rate decreased from 16.5% to 9.8%. Childbirth during the pandemic was independently associated with a decreased composite birth rate (adjusted odds ratio, 0.563; 95% confidence interval, 0.355-0.844, p = 0.015). These findings suggested that the COVID-19 pandemic might provide an opportunity to find out preventive factors for PT or LBW births.