Improved Outcomes following a Conservative Approach to Hemodynamically Significant Patent Ductus Arteriosus: A Comparison across Two Periods.

INTRODUCTION: Patent ductus arteriosus (PDA) is a commonly encountered morbidity that occurs inversely with gestational age. In response to the growing trend of avoiding PDA ligation and prophylactic interventions, our center adopted a conservative approach starting in September 2020. This approach involves more precise fluid restriction for hemodynamically significant (hs) PDA. This study aimed to evaluate whether a conservative approach to hsPDA has led to a reduction in adverse clinical outcomes for very low birth weight infants (VLBWIs) during the period of conservative treatment. METHODS: Since more conservative approach to hsPDA was adopted since September 2020, the two periods were divided into period 1 (January 2015 to August 2020) and period 2 (September 2020 to June 2023). Fluid therapy was carefully monitored and advanced from day 1 in all VLBWI, and a more conservative approach as fluid restriction was attempted in hsPDA during period 2. RESULTS: Of the 540 VLBWI with hsPDA, 348 infants were born and diagnosed with hsPDA. Period 2 demonstrated a significantly higher rate of medical treatment (79.17% vs. 19.51%) and lower PDA ligation (54.17% vs. 78.05%). Period 2 showed a greater adherence to conservative fluid restriction compared to period 1. Bronchopulmonary dysplasia (BPD) and BPD ≥ moderate, sepsis, necrotizing enterocolitis (≥ grade 2), IVH (grade ≥3) were notably lower in period 2 with lower mortality. In regard to PDA-related treatment, primary PDA ligation was significantly higher in period 1. The secondary PDA ligation after medical failure and more conservative fluid restriction were significantly higher in period 2. At corrected age of 18-24 months, cognitive score was significantly lower in VLBWI born in period 1 compared to those born in period 2. CONCLUSION: Our study demonstrated that a conservative approach to hsPDA led to better clinical outcomes and improved cognitive scores at a corrected age of 18-24 months compared to the period of active PDA ligation. This conservative strategy, involving more precise fluid restriction and the judicious use of appropriate diuretics, has shown to improve clinical outcomes with minimal intervention.

Risk factors for PDA ligation and neurodevelopmental outcomes at corrected 18-24 months in very low birth weight infants.

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.

Evaluation of a Diazo-Based Point-Of-Care Bilirubin Assay careSTART S1 Total Bilirubin Strip.

BACKGROUND: Neonatal jaundice (NNJ) affects a significant proportion of newborns globally, with an increased burden in low-resource settings. Effective health risk management of NNJ is hindered, particularly in resource-constrained environments, where early detection and treatment are challenging. The careSTART S1 Total Bilirubin Strip, a point-of-care testing (POCT) device based on a diazo-method, offers a potential solution by enabling onsite bilirubin measurement, thus, addressing the gap in early NNJ detection and management. METHODS: The current study evaluated the analytical performance of the careSTART S1 Total Bilirubin Strip for precision, linearity, method comparison, and lot-to-lot consistency following CLSI guidelines. For method comparison, 105 residual EDTA whole blood samples were analyzed with the careSTART S1 Total Bilirubin Strip and compared with reference measurements from the Roche Cobas c702 analyzer. Additionally, statistical analyses, including Passing-Bablok regression and Bland-Altman plots, were performed. RESULTS: The careSTART S1 Total Bilirubin Strip showed allowable (<10%) within-laboratory imprecision of 2.5%-3.6% across all levels and demonstrated linearity over the range of 4.16-439.3 µmol/L. Method comparison revealed a constant negative bias with a mean bias -4.19 µmol/L. However, the 95% confidence interval (-7.10 to -1.28 µmol/L) of the bias is covered by the prespecified allowable bias of 8.3%, at medical decision point. Lot-to-lot variation ranged from 0.14%-6.49%, and was within the acceptable critical difference of 8.3%. CONCLUSION: The careSTART S1 Total Bilirubin Strip provided accurate and reliable bilirubin measurements that could contribute to neonatal care in settings lacking central laboratory facilities.

Interleukin 8 may predict surgical necrotizing enterocolitis in infants born less than 1500 g.

Necrotizing enterocolitis (NEC) often leads to gastrointestinal emergency resulting high mortality in very low birth weight infants (VLBWIs) requiring surgery. To date, few studies have explored the role of serum cytokines in the development of feeding intolerance (FI) or NEC outcomes in VLBWIs. Infants born weighing <1500 g or of 32 weeks of gestational age were prospectively enrolled from May 2018 to Dec 2019. We measured several cytokines routinely within 72 h of life, even before NEC-like symptoms developed. NEC or FI group comprised 17 (27.4%) infants, and 6 (9.7%) infants had surgical NEC. The gestational age and birth weight were significantly lower in the NEC or FI group with more prematurity-related complications. The surgical NEC group also demonstrated significantly lower gestational age and birth weight along with more infants experiencing refractory hypotension within a 1 week of life, pulmonary hypertension, and patent ductus arteriosus. IL-10 levels were significantly higher in the NEC or FI group, whereas IL-8 levels were significantly higher in the infants with surgical NEC. Our findings indicated to IL-8 can predict surgical NEC while increased IL-10 can predict NEC development in VLBWIs.

Preoperative metabolic acidosis and acute kidney injury after open laparotomy in the neonatal intensive care unit.

BACKGROUND: This study evaluated potential risk factors associated with acute kidney injury (AKI) in infants undergoing bedside open laparotomy in the neonatal intensive care unit (NICU), and analyzed the association between postoperative AKI and outcomes. METHODS: Retrospective data, including neonatal characteristics, perioperative findings (i.e. vital signs and fluid status), postoperative AKI incidence, and postoperative mortality rate of infants who underwent bedside open laparotomy in the NICU between May 2013 and May 2018 were collected and analyzed. RESULTS: A total of 53 cases (26 in AKI group vs 27 in non-AKI group) were analyzed. On univariable analysis, transfusion, pre- and postoperative blood gas analysis and number of inotropic agents, cumulative postoperative percentage fluid overload (48 h), and preoperative hourly urine output were associated with the development of postoperative AKI. On multivariable logistic regression analysis, preoperative acidosis (pH <7.15 or base deficit >10; P = 0.002; OR, 11.067; 95%CI: 2.499-49.017) and preoperative urine output (P = 0.035; OR, 0.548; 95%CI: 0.314-0.959) were significant factors associated with postoperative AKI. Postoperative mortality rate 30 days after surgery was higher in the AKI group, but the difference was not significant. CONCLUSIONS: Preoperative metabolic acidosis and urine output are important factors potentially associated with the development of postoperative AKI in neonates undergoing bedside open laparotomy. Strategies such as alkali therapy, which protect the kidney from further injury, should be validated in future studies. A decreasing urine output may suggest deteriorating kidney function prior to surgery, potentially amplifying the risk of postoperative AKI.

Efficacy of levetiracetam for neonatal seizures in preterm infants.

BACKGROUND: Neonatal seizures remain a significant clinical problem, and therapeutic options are still not diverse with limited efficacy. Levetiracetam (LEV) is a relatively new and wide spectrum anti-seizure medication with favorable pharmacokinetics and safety profile. In the recent decades, LEV has been increasingly used for the treatment of neonatal seizures. The aim of this study was to describe the experience of using LEV as the first line anti-seizure medication for preterm infants. METHODS: A retrospective analysis of 37 preterm infants who were treated with LEV as the first-line anti-seizure medication was performed. RESULTS: Mean gestational age of the 37 preterm infants was 31.5 ± 1.9 weeks (range, 26 to 36+ 6 weeks). Twenty-one infants (57%) were seizure-free while given LEV at the end of the first week, and no additional anti-seizure medication was required. Loading doses of LEV ranged from 40 to 60 mg/kg (mean 56 mg/kg) and the maintenance dose ranged from 20 to 30 mg/kg (mean 23 mg/kg). No adverse effect was observed. CONCLUSIONS: Levetiracetam can be a good and safe choice for treatment of neonatal seizures in preterm infants. Prospective double blind controlled studies are needed in the future.

Expanded criteria for retinopathy of prematurity screening in moderately preterm infants: Single-center pilot study.

BACKGROUND: While developed countries seek to lower the gestational age and birthweight parameters in retinopathy of prematurity (ROP) screening, older, larger infants still develop ROP in other parts of the world. The aim of this study was therefore to define criteria to identify potential ROP developers who are outliers of the common screening range. METHODS: A retrospective medical record review was performed in 147 inborn moderately preterm infants admitted to the neonatal intensive care unit during the study period. Univariate and logistic regression analysis was carried out. RESULTS: Forty-two infants developed ROP. Gestational age (31.4 ± 1.1 vs 32.4 ± 1.0 weeks, P = 0.000) and birthweight (1607.7 ± 339.4 vs 1846.4 ± 317.2 g, P = 0.000) were lower in those who developed ROP. Respiratory distress syndrome (P = 0.026) and documented sepsis (P = 0.003) were significant comorbidities on univariate analysis. Inotrope need >72 h starting in the first week of life (P = 0.004; OR, 5.181) and more than three transfusions of packed red blood cells (P = 0.028; OR, 3.891) were also significant, both on univariate and multivariate analysis. CONCLUSIONS: In moderately preterm infants, status should be evaluated in order to effectively select candidates for ROP screening without missing potential ROP developers.

Necrotizing Enterocolitis among Very-Low-Birth-Weight Infants in Korea.

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency and remains a major cause of mortality for very-low-birth-weight infants (VLBWI) requiring surgery. To date, there have been no large-scale studies evaluating the incidence, associated clinical factors and outcomes of NEC for VLBWI in Korea. The 2,326 VLBWI of a total 2,386 Korean Neonatal Network (KNN) cohort born with a birth weight below 1,500 g between January 2013 to June 2014 were included in this analysis. The overall incidence of NEC (stage ≥ 2) among VLBWI in Korea was 6.8%; 149 infants had NEC stage ≥ 2 and 2,177 infants did not have NEC. Surgery was performed for 77 (53%) of the infants in the NEC group. NEC was related to lower gestational age (GA) and birth weight (P < 0.001). Multivariate logistic regression analysis demonstrated that NEC was consistently related to hypotension within one week after birth (OR 2.0, 95% CI 1.0-3.9). With respect to outcome, the NEC group had longer times to reach 100 mL/kg/day feeding (P < 0.001), longer TPN duration (P < 0.001) and hospitalization (P = 0.031) and higher PVL (P < 0.001) and mortality rate (P < 0.001). When the medical and surgical NEC groups were compared, GA was significantly lower and PDA was more found in the surgical NEC group. The overall incidence of NEC in Korea is similar to that of other multicenter studies. In addition to GA and birth weight, hypotension within a week of life is significantly related to NEC.

Outcomes of primary ligation of patent ductus arteriosus compared with secondary ligation after pharmacologic failure in very-low-birth-weight infants.

This study aimed to determine whether primary surgical closure of patent ductus arteriosus (PDA) is a risk factor for morbidity and mortality compared with secondary surgical ligation. The study enrolled 178 very-low-birth-weight infants. The surgical group included 34 patients who did not respond to pharmacologic intervention and eventually required ligation of their PDA as well as 35 patients who underwent direct ligation because of contraindications to the use of oral ibuprofen. The overall outcomes for the primary and secondary ligation groups were compared. The outcome during hospitalization showed no statistically significant difference in terms of morbidity and mortality between the two groups. The group that had primary ligation for PDA experienced more complications associated with premature birth such as lower gestational age and birth weight. The two groups did not differ significantly in terms of overall outcomes.

Risk factors associated with nephrocalcinosis in preterm infants.

PURPOSE: The objective was to identify the risk factors associated with nephrocalcinosis (NC) in preterm infants. METHODS: NC was diagnosed by renal sonography at 4 or 8 weeks of life, and 10 infants who had findings of type 3 or 4 NC were classified as the NC group. Various clinical and laboratory factors were compared between NC and control groups. RESULTS: Serum sodium (Na) on day 1, serum creatinine and fractional excretion of calcium (FeCa) at 1 and 2 weeks, and serum calcium (Ca), fractional excretion of sodium (FeNa), and urine Na on 2 weeks of life were significantly different between the two groups: the NC group showed significantly higher serum creatinine, FeNa, and FeCa than the control group, suggesting a greater decrease in renal function in the NC group. Differences of the laboratory findings disappeared after 4 weeks of life. The strongest risk factor was birth weight. CONCLUSION: A transient decrease in renal function during the first 2 weeks of life was associated with development of NC in preterm very low-birth-weight infants, and the risk of NC increased as birth weight decreased.

Gut Dysbiosis in the First-Passed Meconium Microbiomes of Korean Preterm Infants Compared to Full-Term Neonates.

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. ß-diversities did not appear to differ between the groups. Overall, these findings underscore the importance of GA in shaping the early gut microbiome.

Enhanced Survival of 22-25 Week Preterm Infants After Proactive Care Implementation: A Comparative Analysis of Two Time Periods.

OBJECTIVES: To investigate the impact of proactive perinatal care on periviable preterm infants before and after its implementation. METHODS: This retrospective cohort study was conducted over a period of 10 y, from 2013 to 2019, referred to as Phase I, and from 2020 to 2022, referred to as Phase II. A total of 162 eligible infants born between 220/7 and 256/7 wk of gestation were included in this analysis. RESULTS: A total of 125 infants were born in phase I, and 37 infants in phase II received proactive care with minimal handling. The mortality decreased from 54.4% to 24.3% (P = 0.001). The composite outcomes of severe brain injury or death, sepsis or death and necrotizing enterocolitis or death were also improved with proactive care. Gestational age [adjusted odds ratio (aOR) 0.900; 95% confidence interval (CI), 0.836-0.970], air leak syndrome (aOR 4.958; 95% CI, 1.681-14.624), massive pulmonary hemorrhage (aOR 4.944; 95% CI, 2.055-11.893), and birth in phase II (aOR 0.324; 95% CI, 0.115-0.912) were independently associated with mortality. CONCLUSIONS: The implementation of proactive care with minimal handling resulted in an increased survival rate and a reduction in the combined morbidities between the two time periods. The provision of proactive perinatal care with minimal handling is crucial for improving both the survival rates and clinical outcomes of these vulnerable infants.

Comparative analysis of the quantitative point-of-care CareSTART™ total bilirubin with central laboratory total bilirubin assays in neonatal blood samples.

This study aimed to assess and compare the accuracy of point-of-care CareSTART™ S1 Total Bilirubin test with a central laboratory total bilirubin assay using neonatal samples. This study was conducted using 152 paired measurements obtained from 122 neonates admitted to the neonatal intensive care unit. Total serum bilirubin (TSB) levels assayed with the central laboratory assay, laboratory bilirubinomter, trancutaneous bliribubin (TcB) instrument and CareSTART were compared using Bland-Altman analysis. The mean difference between the CareSTART and TSB values was -1.43 mg/dL and the 95% limit of agreement (LoA) was -4.25 to 1.39 mg/dL. CareSTART tended to underestimate total bilirubin concentrations compared with TcB, however, the LoA was narrower due to the smaller SD of mean difference for CareSTART. The CareSTART Total Bilirubin test provides an accurate alternative to TcB for total serum bilirubin measurement. Given its low-cost, ease-of-use, and portability, the use of CareSTART is expected to provide point-of-care measurements, especially in low-resource settings.

Dysbiosis of the initial stool microbiota increases the risk of developing necrotizing enterocolitis or feeding intolerance in newborns.

Several perinatal factors influence the intestinal microbiome of newborns during the first days of life, whether during delivery or even in utero. These factors may increase the risk of developing necrotizing enterocolitis (NEC) by causing dysbiosis linked to a NEC-associated microbiota, which may also be associated with other gastrointestinal problems. The objective of our study was to evaluate the potential risks associated with microbial shifts in newborns with gastrointestinal symptoms and identify the intestinal microbiota of neonates at risk for NEC.During the study period, 310 preterm and term newborns' first passed meconium occurring within 72 h of birth were collected, and the microbiome was analyzed. We identified the risk factors in the NEC/FI group. Regarding microbiota, we compared the bacterial abundance between the NEC/FI group at the phylum and genus levels and explored the differences in the microbial composition of the 1st stool samples. A total of 14.8% (n = 46) of the infants were diagnosed with NEC or FI. In univariate analysis, the mean gestational age and birth weight were significantly lower in the NEC/FI group (p < 0.001). Prolonged rupture of membranes (PROM) > 18 h, chorioamnionitis, and histology were significantly higher in the NEC/FI group (p < 0.001). Multivariate analysis showed that gestational age (GA), prolonged membrane rupture (> 18 h), and early onset sepsis were consistently associated with an increased risk of NEC/FI. Infants diagnosed with NEC/FI exhibited a significantly lower abundance of Actinobacteria at the phylum level than the control group (p < 0.001). At the genus level, a significantly lower abundance of Streptococcus and Bifidobacterium which belong to the Actinobacteria phylum, was observed in the NEC/FI group (p < 0.001). Furthermore, the NEC/FI had significantly lower alpha diversities (Shannon Index,3.39 vs. 3.12; P = 0.044, respectively). Our study revealed that newborns with lower diversity and dysbiosis in their initial gut microbiota had an increased risk of developing NEC, with microbiota differences appearing to be associated with NEC/FI. Dysbiosis could potentially serve as a predictive marker for NEC- or GI-related symptoms.

The effect of minimizing central line days for very low birth weight infants through quality improvement.

Blood culture proven sepsis is associated with increased mortality and morbidity. Given the extended hospitalization of very preterm infants, catheter-related blood stream infections (CRBSIs) play a substantial role in sepsis. The reported incidence of CRBSIs in neonates varies from 3.2 to 21.8 CRBSIs per 1000 catheter line days. Moreover, discrepancies in neonatal practices and potential neglect may lead to the unwarranted prolongation of central lines. This study aims to compare two distinct periods (Pre-QI vs. Post-QI) in relation to the central line insertion rate and duration, as well as blood culture proven sepsis, duration of total parenteral nutrition (TPN), and the progression of feeding. These factors are known to be associated with prolonged hospitalization and increased morbidities. A total of 210 very low birth weight infants (VLBWIs), defined as either less than 32 weeks of gestational age (GA) or weighing less than 1500 g, were admitted to the Neonatal Intensive Care Unit (NICU) at Seoul St. Mary's Hospital, The Catholic University of Korea, between January 2020 and June 2023. Fourteen infants were excluded from the study as they did not survive beyond 1 month of life, and one was excluded due to a congenital anomaly. Consequently, the analysis included 195 VLBWIs. The Quality Improvement (QI) initiative began in January 2022, marking the division into two distinct epochs: the Pre-QI period, encompassing the years 2020 to 2021, and the Post-QI period, spanning from 2022 to 2023. The primary outcome measures included PICC insertion rates, duration, and feeding advancement or feeding-related complications. The hospital outcome measures were also compared between the two periods. A total of 195 VLBWI were included in the analysis. The birth weight was significantly lower in the pre-QI period, with an average of 1023 g compared to 1218 g (P < 0.001). Severe BPD ≥ moderate was significantly lower in the post-QI period (36.2% vs. 53.9%) (P < 0.001) along with shorter mechanical ventilation days (12 ± 29 vs. 22 ± 27) (P = 0.046). The PICC insertion rate was significantly decreased from 95.6% in pre-QI period compared to 55.2% in post-QI period (P < 0.001) along with a notable reduction in blood culture-proven sepsis (25.6% vs. 10.5%, P = 0.008). CRBSI rate was reduced from 1.3 to 1.1 per 1000 catheter days in the post-QI period. Moreover, the time required to achieve full enteral feeding of 100 mL/kg/day was significantly shorter in the post-QI (24 ± 23 vs. 33 ± 25) (P = 0.006). Multivariable logistic regression analysis for sepsis revealed that both birth weight and pre/post QI consistently demonstrated an association with lower sepsis rates in the Post-QI period. QI has the potential to reduce the burden of unnecessary interventions and blood culture proven sepsis rate along with CRBSI rate, thereby, optimizing the better care of very preterm babies.

Volumetric changes in brain MRI of infants with hypoxic-ischemic encephalopathy and abnormal neurodevelopment who underwent therapeutic hypothermia.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is a severe neonatal complication that can result in 40-60 % of long-term morbidity. Magnetic Resonance Imaging (MRI) is a noninvasive method which is usually performed before discharge to visually assess acquired cerebral lesions associated with HIE and severity of lesions possibly providing a guide for detecting adverse outcomes. This study aims to evaluate the impact of HIE on brain volume changes observed in MRI scans performed at a mean 10 days of life, which can serve as a prognostic indicator for abnormal neurodevelopmental (ND) outcomes at 18-24 months among HIE infants. METHODS: We retrospectively identified a cohort of HIE patients between June 2013 and March 2017. The inclusion criteria for therapeutic hypothermia (TH) were a gestational age ≥35 weeks, a birth weight ≥1800 g, and the presence of ≥ moderate HIE. Brain MRI was performed at a mean 10 days of life and brain volumes (total brain volume, cerebral volume, cerebellar volume, brain stem volume, and ventricle volume) were measured for quantitative assessment. At 18-24 months, the infants returned for follow-up evaluations, during which their cognitive, language, and motor skills were assessed using the Bayley Scales of Infant and Toddler Development III. RESULTS: The study recruited a total of 240 infants between 2013 and 2017 for volumetric brain MRI evaluation. Among these, 83 were normal control infants, 107 were TH-treated HIE infants and 37 were HIE infants who did not receive TH due to contraindications. Clinical evaluation was further proceeded. We compared the brain volumes between the normal control infants (n = 83) with normal ND but TH-treated HIE infants (n = 76), abnormal ND TH-treated HIE infants (n = 31), and the severe HIE MRI group with no TH (n = 37). The abnormal ND TH-treated HIE infants demonstrated a significant decrease in brainstem volume and an increase in ventricle size (p < 0.001) (Table 4). Lastly, the severe brain MRI group who did not receive TH showed significantly smaller brain stem (p = 0.006), cerebellar (p = 0.006) and cerebrum volumes (p = 0.027), accompanied by larger ventricular size (p = 0.013) compared to the normal control group (Table 5). CONCLUSION: In addition to assessing the location of brain injuries in MRI scans, the reduction in brain stem volume coupled with an increase in ventricular volume in HIE infants may serve as a biomarker indicating severe HIE and adverse long-term ND outcomes among HIE infants who either received therapeutic hypothermia (TH) treatment or not.

Structural development and brain asymmetry in the fronto-limbic regions in preschool-aged children.

Early-life experiences play a crucial role in the development of the fronto-limbic regions, influencing both macro- and microstructural changes in the brain. These alterations profoundly impact cognitive, social-emotional functions. Recently, early limbic structural alterations have been associated with numerous neurological and psychiatric morbidities. Although identifying normative developmental trajectories is essential for determining brain alterations, only a few studies have focused on examining the normative trajectories in the fronto-limbic regions during preschool-aged children. The aim of this study was to investigate the structural-developmental trajectory of the fronto-limbic regions using the cortical thickness, volume, and subcortical volume in 57 healthy and typical preschool-aged children between 1 and 5 years and examined the early lateralization patterns during the development of the fronto-limbic regions. Regarding brain lateralization, remarkable asymmetry was detected in the volume of thalamus and the cortical regions excluding the lateral orbitofrontal cortex in the fronto-limbic regions. This study of preschool-aged children may fill the knowledge gaps regarding the developmental patterns and hemispheric asymmetries of the fronto-limbic regions between newborns and adolescents.

Using adenosine triphosphate bioluminescence level monitoring to identify bacterial reservoirs during two consecutive Enterococcus faecium and Staphylococcus capitis nosocomial infection outbreaks at a neonatal intensive care unit.

INTRODUCTION: This study aimed to assess the role of adenosine triphosphate (ATP) bioluminescence level monitoring for identifying reservoirs of the outbreak pathogen during two consecutive outbreaks caused by Enterococcus faecium and Staphylococcus capitis at a neonatal intensive care unit (NICU). The secondary aim was to evaluate the long-term sustainability of the infection control measures employed one year after the final intervention measures. METHODS: Two outbreaks occurred during a 53-day period in two disconnected subunits, A and B, that share the same attending physicians. ATP bioluminescence level monitoring, environmental cultures, and hand cultures from healthcare workers (HCW) in the NICU were performed. Pulsed-field gel electrophoresis (PFGE) typing was carried out to investigate the phylogenetic relatedness of the isolated strains. RESULTS: Four cases of E. faecium sepsis (patients A-8, A-7, A-9, B-8) and three cases of S. capitis sepsis (patients A-16, A-2, B-8) were diagnosed in six preterm infants over a span of 53 days. ATP levels remained high on keyboard 1 of the main station (2076 relative light unit [RLU]/100 cm2) and the keyboard of bed A-9 (4886 RLU/100 cm2). By guidance with the ATP results, environmental cultures showed that E. faecium isolated from the patients and from the main station's keyboard 1 were genotypically indistinguishable. Two different S. capitis strains caused sepsis in three patients. A total 77.8% (n = 7/9) of S. capitis cultured from HCW's hands were genotypically indistinguishable to the strains isolated from A-2 and A-16. The remaining 22.2% (n = 2/9) were genotypically indistinguishable to patient B-8. Three interventions to decrease the risk of bacterial transmission were applied, with the final intervention including a switch of all keyboards and mice in NICU-A and B to disinfectable ones. Post-intervention prospective monitoring up to one year showed a decrease in blood culture positivity (P = 0.0019) and catheter-related blood stream infection rate (P = 0.016) before and after intervention. CONCLUSION: ATP monitoring is an effective tool in identifying difficult to disinfect areas in NICUs. Non-medical devices may serve as reservoirs of pathogens causing nosocomial outbreaks, and HCWs' hands contribute to bacterial transmission in NICUs.

Variations in medical practice of retinopathy of prematurity among 8 Asian countries from an international survey.

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.

The prognosis of refractory hypotension and severe intraventricular hemorrhage in very low birth weight infants.

BACKGROUND: The increased survival rate among very low birth weight infants has resulted in a higher risk for developing neuro-complications such as intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and adverse neurodevelopmental outcomes. PURPOSE: We examined refractory hypotension experienced within a week of life in association with severe IVH (grades 3-4) among very low birth weight infants (VLBWIs). METHOD: Between Jan 2014 and Dec 2017, the clinical data of 191 VLBWIs were retrospectively chart reviewed. Of a total of 191 VLBWIs, 71.2% (136/191) had IVH, and 28.7% (55/191) had severe IVH. RESULTS: The VLBWI with severe IVH group (grade 3-4) presented with a significantly lower gestational age along with higher use of postnatal hydrocortisone for refractory hypotension within a week of life. Resuscitation at delivery, pulmonary hemorrhage, neonatal seizure, and PVL were significantly more frequent in the severe IVH group (P < .05). Higher mortality occurred in the VLBWI with severe IVH group (P < .001). The multivariable logistic regression analysis consistently showed that refractory hypotension within a week of life and neonatal seizures were significantly associated with severe IVH. Those in the severe IVH and refractory hypotension groups had significantly lower composite cognitive, language, motor scores in Bayley Scales of Infant and Toddler Development III scores at corrected 18-24 months. CONCLUSION: Refractory hypotension within a week of life and seizures were consistently associated with severe IVH and developmental delay at corrected 18-24 months. VLBWI who experienced refractory hypotension within a week of life may indicate a more vulnerable clinical setting with a higher risk for developmental delay.