Mortality of very low birth weight infants by neonatal intensive care unit workload and regional group status.

Background: Very low birth weight infants (VLBWIs) continue to face high mortality risk influenced by the care quality of neonatal intensive care units (NICUs). Understanding the impact of workload and regional differences on these rates is crucial for improving outcomes. Purpose: This study aimed to assess how the structural and staffing attributes of NICUs influence the mortality rates of VLBWIs, emphasizing the significance of the availability of medical personnel and the regional distribution of care facilities. Methods: Data from 69 Korean NICUs collected by the Korean Neonatal Network between January 2015 and December 2016 were retrospectively analyzed. The NICUs were classified by various parameters: capacity (small, medium, large), nurse-to-bed ratio (1-4), and regional location (A, B, C). Pediatrician staffing was also analyzed and NICUs categorized by beds per pediatrician into low (≤10), medium (11-15), and high (≥16). The NICUs were classified by mortality rates into high-performance (1st and 2nd quartiles) and low-performance (3rd and 4th quartiles). Demographic, perinatal, and neonatal outcomes were analyzed using multivariate logistic regression to explore the association between NICU characteristics and mortality rates. Results: This study included 4,745 VLBWIs (mean gestational age, 28.4 weeks; mean birth weight, 1,088 g; 55.4% male) and found significant variations in survival rates across NICUs linked to performance and staffing levels. High-performing NICUs, often with lower bed-to-staff ratios and advanced care levels, had higher survival rates. Notably, NICUs with two rather than one neonatologist were associated with reduced mortality rates. The study also underscored regional disparities, with NICUs in certain areas showing less favorable survival rates. Conclusion: Adequate NICU staffing and proper facility location are key to lowering the number of VLBWI deaths. Enhancing staffing and regional healthcare equity is crucial for improving the survival of this population.

Mitochondrial DNA mutations in extremely preterm infants with bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a serious chronic lung disease affecting extremely preterm infants. While mitochondrial dysfunction has been investigated in various medical conditions, limited research has explored mitochondrial DNA (mtDNA) gene mutations, specifically in BPD. This study aimed to evaluate mitochondrial mtDNA gene mutations in extremely preterm infants with BPD. In this prospective observational study, we enrolled a cohort of extremely preterm infants diagnosed with BPD. Clinical data were collected to provide comprehensive patient profiles. Peripheral blood mononuclear cells were isolated from whole-blood samples obtained within a defined timeframe. Subsequently, mtDNA extraction and sequencing using next-generation sequencing technology were performed to identify mtDNA gene mutations. Among the cohort of ten extremely preterm infants with BPD, mtDNA sequencing revealed the presence of mutations in seven patients, resulting in a total of twenty-one point mutations. Notably, many of these mutations were identified in loci associated with critical components of the respiratory chain complexes, vital for proper mitochondrial function and cellular energy production. This pilot study provides evidence of mtDNA point mutations in a subset of extremely preterm infants with BPD. These findings suggest a potential association between mitochondrial dysfunction and the pathogenesis of BPD. Further extensive investigations are warranted to unravel the mechanisms underlying mtDNA mutations in BPD.

Outcomes at 18-24 Months of Infants with Birth Weight under 500 g Born in Korea during 2013-2017: A Nationwide Cohort Study.

INTRODUCTION: This study aimed to investigate the outcomes of infants at 18-24 months born in the Korean Neonatal Network with a birth weight <500 g. METHODS: The anthropometric and neurodevelopmental data of infants with a birth weight <500 g at a gestational age of ≥22 weeks who were registered in the Korean Neonatal Network 2013-2017 and followed up at a corrected age of 18-24 months were reviewed. Neurodevelopmental impairment was defined as the presence of any of the following: (1) cerebral palsy; (2) severe visual impairment; (3) hearing impairment; or (4) cognitive impairment. Cognitive impairment was defined as (1) a Bayley Scales of Infant Development-II Mental Development Index score <70; and (2) Bayley Scales of Infant and Toddler Development-III Cognitive and Language Composite scores <85. Cognitive testing was performed for infants with suspected problems upon clinician's referral to developmental specialists. RESULTS: At a median corrected age of 20 months, 26/52 (50%) of included infants had neurodevelopmental impairment. Cerebral palsy, severe visual impairment, wearing of glasses, hearing impairment, and cognitive impairment occurred in 22%, 0%, 8%, 5%, and 57% of the included infants, respectively. The proportions of infants with <2 standard deviations of weight, length, and head circumference were 54%, 52%, and 56%, respectively. The majority (70%) of infants were rehospitalized, and the most common cause was respiratory problems. CONCLUSION: Half of infants with a birth weight <500 g in Korea may exhibit neurodevelopmental impairment and growth retardation at a corrected age of 18-24 months. Multidisciplinary follow-up along with continuous rehabilitation will be needed to improve neurological and physical development in this special population.

Wide-wavelength-tunable distributed Bragg reflector laser diode with high thermal efficiency.

We proposed a thermally-tuned distributed Bragg reflector (DBR) laser diode that has a high tuning efficiency over a wide wavelength tuning range. The laser diode is composed of a gain, a phase control (PC), and a DBR region, and its wavelength is tuned coarsely and finely by the micro-heaters on the DBR and PC regions, respectively. To improve the tuning efficiency, we developed a technique for fabricating a thermal isolation structure through a reverse mesa etching process, replacing the complex process that uses an InGaAs sacrificial layer. The DBR laser diodes (DBR-LD) fabricated using this method effectively confines heat generated by the heater, resulting in an approximate tuning range of 40 nm. This technology, which has achieved nearly four times larger wavelength tuning range than the thermally-tuned DBR-LDs without a thermal isolation structure, is considered suitable for the cost-effective development of wide-wavelength-tuning DBR-LD light sources.

Prevention of human milk-acquired cytomegalovirus infection in very-low-birth-weight infants.

BACKGROUND: The aim of the study was to determine the rate of cytomegalovirus virolactia in the human milk (HM) of mothers of VLBW infants, compare the CMV infection rates and the changes in CMV DNA viral load and nutrient profile among different HM preparation methods. METHODS: A prospective randomized controlled study was performed in infants with gestational age < 32 weeks or birth-weight < 1500 g admitted to neonatal intensive care unit of Asan Medical Center and Haeundae Paik Hospital who were given mother's own milk. Enrolled infants were randomized into three groups according to the HM preparation methods: freezing-thawing (FT), FT + low-temperature Holder pasteurization (FT + LP), and FT + high-temperature short-term pasteurization (FT + HP). Urine CMV culture and PCR were obtained at birth and at 4, 8, and 12 weeks. HM CMV culture and PCR were obtained at birth and at 3, 6, 9, and 12 weeks. Changes in macronutrients in HM was obtained at 4 ~ 6 weeks. RESULTS: Of 564 infants, 217 mothers (38.5%) produced CMV PCR positive milk. After exclusion, a total of 125 infants were randomized into the FT (n = 41), FT + LP (n = 42), and FT + HP (n = 42) groups, whose rate of HM-acquired CMV infection was 4.9% (n = 2), 9.5% (n = 4), and 2.4% (n = 1), respectively. Out of seven CMV infected infants, two infants fed with FT + LP HM developed CMV infection- associated symptoms. Ages at diagnoses were earlier (28.5 days after birth) and at younger post conceptional age (< 32 weeks) in comparison to infants with asymptomatic CMV infection. CMV DNA viral load significantly decreased after pasturizations, especially in FT + HP group. CONCLUSIONS: HM-acquired symptomatic CMV infection rate is low and its impact on clinical course was not serious in our VLBW infants. However, evidences showing poor neurodevelopmental outcome in later life, we need to generate a guideline to protect VLBW infant form HM transmitted CMV infection. Based on our small sized study, we did not find any superiority in pasteurizing HM with frequently used LP in comparison to frozen or HP HM. More research is needed to determine the method and duration of pasteurization to reduce the HM-acquired CMV infection.

Wearable Surface-Lighting Micro-Light-Emitting Diode Patch for Melanogenesis Inhibition.

Wearable light-emitting diode (LED)-based phototherapeutic devices have recently attracted attention as skin care tools for wrinkles, acne, and hyperpigmentation. However, the therapeutic effectiveness and safety of LED stimulators are still controversial due to their inefficient light transfer, high heat generation, and non-uniform spot irradiation. Here, a wearable surface-lighting micro-LED (SµLED) photostimulator is reported for skin care and cosmetic applications. The SµLEDs, consisting of a light diffusion layer (LDL), 900 thin film µLEDs, and polydimethylsiloxane (PDMS), achieve uniform surface-lighting in 2 × 2 cm2 -sized area with 100% emission yields. The SµLEDs maximize photostimulation effectiveness on the skin surface by uniform irradiation, high flexibility, and thermal stability. The SµLED's effect on melanogenesis inhibition is evaluated via in vitro and in vivo experiments to human skin equivalents (HSEs) and mouse dorsal skin, respectively. The anti-melanogenic effect of SµLEDs is confirmed by significantly reduced levels of melanin contents, melan-A, tyrosinase, and microphthalmia-associated transcription factor (MITF), compared to a conventional LED (CLED) stimulator.

Hair methylmercury levels are inversely correlated with arterial stiffness.

BACKGROUND AND AIMS: Cardiovascular diseases (CVD), including coronary heart disease, are the leading cause of death worldwide. Several studies investigating the relationship between fish intake, methylmercury exposure, and CVDs in adults have reported inconsistent results. This study aimed to determine the association between hair methylmercury levels and arterial stiffness using brachial-ankle pulse wave velocity (baPWV). METHODS: This cross-sectional study included 891 seemingly healthy Korean adults (418 men and 473 women). The anthropometric and biochemical profiles, including methylmercury levels in the hair, were measured. Arterial stiffness was measured using baPWV, wherein high baPWV was defined as >1375 cm/s (>75th percentile). The odds ratios for high baPWVs were examined using multivariable logistic regression analysis after adjusting for potential confounders across the quintiles of hair methylmercury levels (Q1 = ≤0.6, Q2 = 0.6-0.8, Q3 = 0.8-1.1, Q4 = 1.1-1.5, and Q5=>1.5 µg/g). RESULTS: After adjusting for multiple confounders-age, sex, height, body weight, smoking status, weekly alcohol consumption, total metabolic equivalent of task, mean arterial blood pressure, resting heart rate, triglycerides, low density lipoprotein cholesterol, fasting plasma glucose, uric acid and white blood cell count-the odds ratios (95% confidence intervals) for high baPWVs in each quintile of hair methylmercury levels were 1.00, 0.36 (0.17-0.76), 0.38 (0.20-0.76), 0.28 (0.13-0.61), and 0.49 (0.24-0.99), respectively. CONCLUSIONS: Within non-toxic low levels, higher hair methylmercury levels are independently associated with lower arterial stiffness in seemingly healthy Korean adults regardless of classical cardiovascular risk factors.

Neonatal sepsis-causing bacterial pathogens and outcome of trends of their antimicrobial susceptibility a 20-year period at a neonatal intensive care unit.

BACKGROUND: Due to increases in the number of infants born with younger gestational age (GA) and lower birth weight, the incidence of neonatal sepsis is increasing. PURPOSE: We investigated the changes in the prevalence of bacterial pathogens, their antimicrobial susceptibility, and sepsis-related mortality during 20 years at a neonatal intensive care unit. METHODS: The study period was divided into two 10-year phases (1998-2007 vs. 2008-2017). Medical records were reviewed to gather data on demographics, causative microbial pathogens, incidence of multidrug-resistant organisms, antimicrobial susceptibility, and rates of sepsis-related mortality. RESULTS: In both study phases, the most common pathogens for neonatal sepsis were coagulase-negative Staphylococcus (CoNS) (28.6%) and Enterobacter cloacae (16.1%) for early-onset sepsis (EOS, ≤72 hours after birth) and CoNS (54.7%) and Staphylococcus aureus (12.9%) for late-onset sepsis (LOS, >72 hours after birth). CoNS and S. aureus showed 100% sensitivity to vancomycin in both phases. The susceptibility of S. aureus to oxacillin increased from 19.2% to 57.9% in phase II than phase I. K. pneumonia and E. cloacae showed increases in its susceptibility to gentamicin, cefotaxime and ceftriaxone in phase II than phase I. In both phases, the most common pathogens that caused sepsis-related death were K. pneumoniae (18.2%) and Pseudomonas aeruginosa (13.6%). Sepsis-related mortality rate was higher in infants with GA <37 weeks than those with GA over 37 weeks (P=0.016). In addition, the mortality rate of neonatal sepsis caused by gram-negative bacteria was significantly higher than that caused by gram-positive bacteria (P<0.001). CONCLUSIONS: CoNS was the most common pathogen for EOS and LOS. While we found significant changes in antimicrobial sensitivities over time. GA below 37 weeks and gram-negative organisms are associated with mortality rate.

Prenatal prognostic factors for isolated right congenital diaphragmatic hernia: a single center's experience.

BACKGROUND: Right-sided congenital diaphragmatic hernia (RCDH) is relatively rare compared with left-sided congenital diaphragmatic hernia (LCDH). Clinical data of RCDH, especially with respect to antenatal prediction of neonatal outcome, are lacking. The aim of this study was to report the treatment outcomes of patients with antenatally diagnosed RCDH and to evaluate the predictability of observed-to-expected lung area-to-head circumference ratio (O/E LHR) for perinatal outcomes, focused on mortality or extracorporeal membrane oxygenation (ECMO) requirement. METHODS: We retrospectively reviewed the medical records of newborn infants with isolated RCDH. We analyzed and compared the clinical and prenatal characteristics including the fetal lung volume, which was measured as the O/E LHR, between the survivors and the non-survivors. RESULTS: A total of 26 (66.7%) of 39 patients with isolated RCDH survived to discharge. The O/E LHR was significantly greater in survivors (64.7 ± 21.2) than in non-survivors (40.5 ± 23.4) (P =.027). It was greater in survivors without ECMO requirement (68.3 ± 15.1) than non-survivors or those with ECMO requirement (46.3 ± 19.4; P = .010). The best O/E LHR cut-off value for predicting mortality in isolated RCDH was 50. CONCLUSIONS: The findings in this study suggest that O/E LHR, a well-characterized prognostic indicator in LCDH, could be applied to a fetus with antenatally diagnosed RCDH. A large cohort study is required to verify the association between O/E LHR values and the graded severity of RCDH.

Survival and Morbidities in Infants with Birth Weight Less than 500 g: a Nationwide Cohort Study.

BACKGROUND: This study aimed to investigate the survival and morbidities of infants in the Korean Neonatal Network (KNN) with birth weight (BW) < 500 g. METHODS: The demographic and clinical data of 208 live-born infants with a BW < 500 g at a gestational age of ≥ 22 weeks who were treated in the neonatal intensive care units of the KNN between 2013 and 2017 were reviewed. RESULTS: The survival rate of the infants was 28%, with a median gestational age and BW of 243/7 weeks (range, 220/7-336/7) and 440 g (range, 220-499), respectively. Multivariable Cox proportional hazards analysis demonstrated that survival to discharge was associated with longer gestation, higher BW, female sex, singleton gestation, use of any antenatal corticosteroids, and higher Apgar scores at 5 minutes. The overall survival rates were significantly different between the BW categories of < 400 g and 400-499 g. However, there was no significant difference in the incidence of any morbidity between the BW groups. Half of the deaths of infants with BW < 500 g occurred within a week of life, mainly due to cardiopulmonary and neurologic causes. The major causes of death in infants after 1 week of age were infection and gastrointestinal disease. Among the surviving infants, 79% had moderate to severe bronchopulmonary dysplasia, 21% underwent surgical ligation of patent ductus arteriosus, 12% had severe intraventricular hemorrhage (grade III-IV), 38% had sepsis, 9% had necrotizing enterocolitis (stage ≥ 2), and 47% underwent laser treatment for retinopathy of prematurity. The median length of hospital stay was 132 days (range, 69-291), and 53% required assistive devices at discharge. CONCLUSION: Despite recent advances in neonatal intensive care, the survival and morbidity rates of infants with BW < 500 g need further improvement.