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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: Patent ductus arteriosus (PDA) is commonly encountered morbidity which often occurs as up to 60% of extremely preterm infants born at < 29 weeks gestational age (GA). Purpose: This study aims to assess the clinical risk factors associated with PDA ligation among very low birth weight infants (VLBWI) and evaluate the neurodevelopmental outcomes of those who underwent PDA ligation. Methods: A total of 540 VLBWI were initially diagnosed with PDA in our 50-bed level IV NICU at Seoul St. Mary's Hospital, The Catholic University of Korea, between January 2015 and June 2023. Among these 540 VLBWI with PDA, only 221 had consistent hemodynamically significant (hs) PDA which required intervention including fluid restriction, medical treatment, or surgical ligation. In this study, only those 221 VLBWI with hsPDA who underwent neurodevelopmental assessment at corrected 18–24 months of age were included in this study analysis. Results: Out of 221 VLBWI diagnosed with hemodynamically significant (hs) PDA, 133 (60.2%) underwent PDA ligation, while the remaining 88 (39.8%) had their hs PDAs closed either medically or with fluid restriction. The mean gestational age and birth weight were significantly lower in PDA ligation group compared to no PDA ligation group (27.02 ± 2.17 vs. 27.98 ± 2.36, 907.31 ± 258.36 vs. 1006.07 ± 283.65, p = 0.001, 0.008). Resuscitation including intubation at delivery and intraventricular hemorrhage (IVH) (grade ≥ 3) were significantly higher in PDA ligation group. The clinical outcomes in the PDA ligation group revealed significantly worse oucomes compared to the no PDA ligation group. Both resuscitation, including intubation at delivery, and IVH (grade ≥ 3), consistently exhibited an increased risk for PDA ligation in a multivariable logistic regression analysis. Concerning neurodevelopmental outcomes, infants who underwent PDA ligation demonstrated significantly lower cognitive scores. However, only IVH (grade ≥ 3) and PVL were consistently associated with an increased risk of abnormal neurodevelopment at the corrected age of 18–24 months. Conclusion: In our study, despite the consistent association between cognitive developmental delays in VLBWI who underwent PDA ligation, we observed that sicker and more vulnerable VLBWIs, specifically those experincing severe IVH, consistently exhibited an increased risk for both PDA ligation and abnormal neurodevelopment at the corrected age of 18–24 months. [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]

Background: Longer hospitalizations for preterm infants with bronchopulmonary dysplasia (BPD) delay developmental outcomes, increase the risk for hospital-acquired complications, and exert a substantial socioeconomic burden. This study aimed to identify factors associated with an extended length of stay (LOS) at different levels of severity of BPD. Methods: A cohort study was conducted using the Korean Neonatal Network registry of very low birth weight infants with BPD between 2013 and 2017 through retrospective analysis. Results: A total of 4263 infants were diagnosed with BPD. For mild BPD, infants requiring surgical treatment for patent ductus arteriosus needed a longer LOS [eadjusted β coefficients (adj β) 1.041; 95% confidence interval (CI): 0.01–0.08] and hydrocephalus (eadj β 1.094; 95% CI 0.01–0.17). In moderate BPD, infants administered steroids or with intraventricular hemorrhage required a longer LOS (eadj β 1.041; 95% CI 0.00–0.07 and eadj β 1.271; 95% CI 0.11–0.38, respectively). In severe BPD, infants with comorbidities required a longer LOS: pulmonary hypertension (eadj β 1.174; 95% CI 0.09–0.23), administrated steroid for BPD (eadj β 1.116; 95% CI 0.07–0.14), sepsis (eadj β 1.062; 95% CI 0.01–0.11), patent ductus arteriosus requiring surgical ligation (eadj β 1.041; 95% CI 0.00–0.08), and intraventricular hemorrhage (eadj β 1.016; 95% CI 0.05–0.26). Additionally, the higher the clinical risk index score, the longer the LOS needed for infants in all groups. Conclusions: The factors affecting LOS differed according to the severity of BPD. Individualized approaches to reducing LOS may be devised using knowledge of the various risk factors affecting LOS by BPD severity. [ABSTRACT FROM AUTHOR]

Advances in perinatal care have led to the increased survival of preterm infants with subsequent neonatal morbidities, such as retinopathy of prematurity (ROP). This study aims to compare the differences of neonatal healthcare systems, resources, and clinical practice concerning ROP in Asia with review of current literature. An on-line survey at the institutional level was sent to the directors of 336 neonatal intensive care units (NICU) in 8 collaborating national neonatal networks through the Asian Neonatal Network Collaboration (AsianNeo). ROP screening was performed in infants born at < 34 weeks in Indonesia and Japan. In South Korea, Malaysia, and Taiwan, most screened for ROP in infants born at < 32 weeks. In all networks, majority of NICUs conducted ROP screening to infants with birth weight < 1500 g. In most NICU's in-hospital ophthalmologists performed indirect ophthalmoscopy and some were supplemented with digital imaging. Both laser photocoagulation and anti-vascular endothelial growth factor injection are performed for treatment and, vitreous surgeries are conducted less frequently in all countries. Despite limited information collected by the survey, this first study to compare ROP practices implemented in eight Asian countries through AsianNeo will enable an understanding of the differences and facilitate quality improvement by sharing better practices. [ABSTRACT FROM AUTHOR]

Advances in perinatal care have led to the increased survival of preterm infants with subsequent neonatal morbidities, such as retinopathy of prematurity (ROP). This study aims to compare the differences of neonatal healthcare systems, resources, and clinical practice concerning ROP in Asia with review of current literature. An on-line survey at the institutional level was sent to the directors of 336 neonatal intensive care units (NICU) in 8 collaborating national neonatal networks through the Asian Neonatal Network Collaboration (AsianNeo). ROP screening was performed in infants born at < 34 weeks in Indonesia and Japan. In South Korea, Malaysia, and Taiwan, most screened for ROP in infants born at < 32 weeks. In all networks, majority of NICUs conducted ROP screening to infants with birth weight < 1500 g. In most NICU's in-hospital ophthalmologists performed indirect ophthalmoscopy and some were supplemented with digital imaging. Both laser photocoagulation and anti-vascular endothelial growth factor injection are performed for treatment and, vitreous surgeries are conducted less frequently in all countries. Despite limited information collected by the survey, this first study to compare ROP practices implemented in eight Asian countries through AsianNeo will enable an understanding of the differences and facilitate quality improvement by sharing better practices. [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]

Background: Several studies have suggested that adverse neurodevelopment could be induced by systemic inflammation in preterm infants. We aimed to investigate whether preterm infants with systemic inflammation would have impaired neurodevelopment and which biomarkers and neurophysiologic studies during inflammation are associated with poor neurodevelopment.Methods: This prospective cohort study enrolled infants born before 30 weeks of gestation or with birth weight < 1250 g. Infants were grouped according to the presence of systemic inflammation: Control (no inflammation, n = 49), I (systemic inflammation, n = 45). Blood and cerebrospinal fluid samples for markers of brain injury and inflammation were collected and amplitude-integrated electroencephalography (aEEG) was performed within 4 h of septic workup. We evaluated aEEG at 35 weeks postmenstrual age (PMA), head circumference at 36 weeks PMA, and brain MRI at discharge. The Bayley Scales of Infant and Toddler Development III (Bayley-III) was performed at a corrected age (CA) of 18 months.Results: The I group had more white matter injuries (2 vs. 26.7%, Control vs. I, respectively) at the time of discharge, lower brain functional maturation (9.5 vs. 8), and smaller head size (z-score - 1.45 vs. -2.12) at near-term age and poorer neurodevelopment at a CA of 18 months than the control (p < 0.05). Among the I group, the proportion of immature neutrophils (I/T ratios) and IL-1 beta levels in the CSF were associated with aEEG measures at the day of symptom onset (D0). Seizure spike on aEEG at D0 was significantly correlated with motor and social-emotional domains of Bayley-III (p < 0.05). The I/T ratio and CRP and TNF-α levels of blood at D0, white matter injury on MRI at discharge, head circumference and seizure spikes on aEEG at near-term age were associated with Bayley-III scores at a CA of 18 months.Conclusions: Systemic inflammation induced by clinical infection and NEC are associated with neurodevelopmental impairment in preterm infants. The seizure spike on aEEG, elevated I/T ratio, CRP, and plasma TNF-alpha during inflammatory episodes are associated with poor neurodevelopment. [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]