Short term effect of intravenous treprostinil in term and preterm infants with pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a life-threatening condition in newborns. We aimed to assess the clinical and echocardiographic responses of term and preterm infants to treprostinil. METHODS: This retrospective study included newborns diagnosed with PH and treated with treprostinil as additional therapy after inhaled nitric oxide administration in the neonatal intensive care unit of a tertiary center. Term and preterm infants were compared in terms of echocardiographic findings and clinical findings 4 weeks after treprostinil treatment. RESULTS: During the study period, 11 term and 18 preterm infants were diagnosed with PH and received treprostinil. There were no differences in the echocardiographic findings of interventricular septal deviation, direction of shunt, and ratio of estimated pulmonary artery pressure over systolic blood pressure. Congenital diaphragmatic hernia was the most common condition occurring upon PH diagnosis among term infants, while severe bronchopulmonary dysplasia was the most common in preterm infants. Improvements in echocardiographic findings were more pronounced in term infants than in preterm infants (100% vs. 55.6%, P = 0.012). The inhaled nitric oxide dose was gradually tapered for term infants and was lower than that for preterm infants at 1, 2, and 3 weeks after treprostinil. CONCLUSION: Intravenous treprostinil could be an adjuvant therapy option for term and preterm infants with PH, especially for those who cannot receive oral medication. The efficacy and safety of treprostinil in this population with PH should be investigated further.

Factors associated with acute kidney injury among preterm infants administered vancomycin: a retrospective cohort study.

BACKGROUND: Vancomycin (VCM) is a widely used antibiotic for the treatment of gram-positive microorganisms, with some nephrotoxic effects. Recent studies have suggested that piperacillin-tazobactam (TZP) aggravates VCM-induced nephrotoxicity in adults and adolescents. However, there is a lack of research investigating these effects in the newborn population. Therefore, this study investigates whether the concomitant use of TZP with VCM use increases the risk of acute kidney injury (AKI) and to explore the factors associated with AKI in preterm infants treated with VCM. METHODS: This retrospective study included preterm infants with birth weight < 1,500 g in a single tertiary center who were born between 2018 and 2021 and received VCM for a minimum of 3 days. AKI was defined as an increase in serum creatinine (SCr) of at least 0.3 mg/dL and an increase in SCr of at least 1.5 times baseline during and up to 1 week after discontinuation of VCM. The study population was categorized as those with or without concomitant use of TZP. Data on perinatal and postnatal factors associated with AKI were collected and analyzed. RESULTS: Of the 70 infants, 17 died before 7 postnatal days or antecedent AKI and were excluded, while among the remaining participants, 25 received VCM with TZP (VCM + TZP) and 28 VCM without TZP (VCM-TZP). Gestational age (GA) at birth (26.4 ± 2.8 weeks vs. 26.5 ± 2.6 weeks, p = 0.859) and birthweight (750.4 ± 232.2 g vs. 838.1 ± 268.7 g, p = 0.212) were comparable between the two groups. There were no significant differences in the incidence of AKI between groups. Multivariate analysis showed that GA (adjusted OR: 0.58, 95% CI: 0.35-0.98, p = 0.042), patent ductus arteriosus (PDA) (adjusted OR: 5.23, 95% CI: 0.67-41.05, p = 0.115), and necrotizing enterocolitis (NEC) (adjusted OR: 37.65, 95% CI: 3.08-459.96, p = 0.005) were associated with AKI in the study population. CONCLUSIONS: In very low birthweight infants, concomitant use of TZP did not increase the risk of AKI during VCM administration. Instead, a lower GA, and NEC were associated with AKI in this population.

Noninvasive Neurally Adjusted Ventilation in Postextubation Stabilization of Preterm Infants: A Randomized Controlled Study.

OBJECTIVE: To compare the effects of noninvasive neurally adjusted ventilatory assist (NIV-NAVA) to nasal continuous positive airway pressure (NCPAP) in achieving successful extubation in preterm infants. STUDY DESIGN: This prospective, single-center, randomized controlled trial enrolled preterm infants born at <30 weeks of gestation who received invasive ventilation. Participants were assigned at random to either NIV-NAVA or NCPAP after their first extubation from invasive ventilation. The primary outcome of the study was extubation failure within 72 hours of extubation. Electrical activity of the diaphragm (Edi) values were collected before extubation and at 1, 4, 12, and 24 hours after extubation. RESULTS: A total of 78 infants were enrolled, including 35 infants in the NIV-NAVA group and 35 infants in the NCPAP group. Extubation failure within 72 hours of extubation was higher in the NCPAP group than in the NIV-NAVA group (28.6% vs 8.6%; P = .031). The duration of respiratory support and incidence of severe bronchopulmonary dysplasia were similar in the 2 groups. Peak and swing Edi values were comparable before and at 1 hour after extubation, but values at 4, 12, and 24 hours after extubation were lower in the NIV-NAVA group compared with the NCPAP group. CONCLUSIONS: In the present trial, NIV-NAVA was more effective than NCPAP in preventing extubation failure in preterm infants. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02590757.

Neonatal Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (CoSTR) for neonatal life support includes evidence from 7 systematic reviews, 3 scoping reviews, and 12 evidence updates. The Neonatal Life Support Task Force generally determined by consensus the type of evidence evaluation to perform; the topics for the evidence updates followed consultation with International Liaison Committee on Resuscitation member resuscitation councils. The 2020 CoSTRs for neonatal life support are published either as new statements or, if appropriate, reiterations of existing statements when the task force found they remained valid. Evidence review topics of particular interest include the use of suction in the presence of both clear and meconium-stained amniotic fluid, sustained inflations for initiation of positive-pressure ventilation, initial oxygen concentrations for initiation of resuscitation in both preterm and term infants, use of epinephrine (adrenaline) when ventilation and compressions fail to stabilize the newborn infant, appropriate routes of drug delivery during resuscitation, and consideration of when it is appropriate to redirect resuscitation efforts after significant efforts have failed. All sections of the Neonatal Resuscitation Algorithm are addressed, from preparation through to postresuscitation care. This document now forms the basis for ongoing evidence evaluation and reevaluation, which will be triggered as further evidence is published. Over 140 million babies are born annually worldwide (https://ourworldindata.org/grapher/births-and-deaths-projected-to-2100). If up to 5% receive positive-pressure ventilation, this evidence evaluation is relevant to more than 7 million newborn infants every year. However, in terms of early care of the newborn infant, some of the topics addressed are relevant to every single baby born.

Extrauterine growth restriction in extremely preterm infants based on the Intergrowth-21st Project Preterm Postnatal Follow-up Study growth charts and the Fenton growth charts.

Growth charts are essential for monitoring the postnatal growth of preterm infants. The preterm postnatal follow-up study (PPFS) of the Intergrowth-21st Project provides new growth standards based on a longitudinal study. This study was conducted to investigate the prevalence of extrautrine growth restriction (EUGR) and the associated factors of EUGR in preterm infants, using the PPFS charts and the Fenton charts. Data of 1,356 infants with gestational age (GA) less than 28 weeks from the Korean Neonatal Network were analysed. The prevalence of small for gestational age (SGA) of weight and length was higher with the Intergrowth charts than with the Fenton charts. EUGR in weight and length was more prevalent when using the Fenton charts. Multivariate analysis showed that low GA, high birthweight z score, male, treated patent ductus arteriosus (PDA), necrotizing enterocolitis, intraventricular haemorrhage and duration of parenteral nutrition (PN) were associated with EUGR in weight by the Intergrowth charts. High birthweight z score, treated PDA and PN duration were associated with EUGR defined by the Fenton charts.Conclusion: Compared to the Fenton charts, SGA was more defined and EUGR was less prevalent in extremely low gestational infants, while EUGR defined by the Intergrowth charts categorized infants with adverse clinical courses more elaborately. What is Known: • Preterm infants are at risk of postnatal growth restriction (PGR), although optimal postnatal growth is important for the long-term outcomes. • Growth charts are essential tools to monitor the postnatal growth of preterm infants. What is New: • PGR of weight and length were less defined with the Intergrowth charts than the Fenton charts. • PGR defined by the Intergrowth preterm postnatal follow-up study (PPFS) chart categorized preterm infants with morbidities more elaborately than the Fenton charts.

Impact of very preterm birth and post-discharge growth on cardiometabolic outcomes at school age: a retrospective cohort study.

BACKGROUND: Adverse metabolic outcomes later in life have been reported among children or young adults who were born as preterm infants. This study was conducted to examine the impact of very preterm/very low birth weight (VP/VLBW) birth and subsequent growth after hospital discharge on cardiometabolic outcomes such as insulin resistance, fasting glucose, and systolic and diastolic blood pressure (BP) among children at 6-8 years of age. METHODS: This retrospective cohort study included children aged 6-8 years and compared those who were born at < 32 weeks of gestation or weighing < 1,500 g at birth (n = 60) with those born at term (n = 110). Body size, fat mass, BP, glucose, insulin, leptin, adiponectin, and lipid profiles were measured. Weight-for-age z-score changes between discharge and early school-age period were also calculated, and factors associated with BP, fasting glucose, and insulin resistance were analyzed. RESULTS: Children who were born VP/VLBW had significantly lower fat masses, higher systolic BP and diastolic BP, and significantly higher values of fasting glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), compared to children born at term. VP/VLBW was correlated with HOMA-IR and BPs after adjusting for various factors, including fat mass index and weight-for-age z-score changes. Weight-for-age z-score changes were associated with HOMA-IR, but not with BPs. CONCLUSIONS: Although children aged 6-8 years who were born VP/VLBW showed significantly lower weight and fat mass, they had significantly higher BPs, fasting glucose, HOMA-IR, and leptin levels. The associations of VP/VLBW with cardiometabolic factors were independent of fat mass and weight gain velocity.

Factors associated with neurodevelopment in preterm infants with systematic inflammation.

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.

Cognitive and Behavioral Outcomes of School-aged Children Born Extremely Preterm: a Korean Single-center Study with Long-term Follow-up.

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.

Effects of Lipopolysaccharide on Oligodendrocyte Differentiation at Different Developmental Stages: an In Vitro Study.

BACKGROUND: Lipopolysaccharide (LPS) exerts cytotoxic effects on brain cells, especially on those belonging to the oligodendrocyte lineage, in preterm infants. The susceptibility of oligodendrocyte lineage cells to LPS-induced inflammation is dependent on the developmental stage. This study aimed to investigate the effect of LPS on oligodendrocyte lineage cells at different developmental stages in a microglial cell and oligodendrocyte co-culture model. METHODS: The primary cultures of oligodendrocytes and microglia cells were prepared from the forebrains of 2-day-old Sprague-Dawley rats. The oligodendrocyte progenitor cells (OPCs) co-cultured with microglial cells were treated with 0 (control), 0.01, 0.1, and 1 µg/mL LPS at the D3 stage to determine the dose of LPS that impairs oligodendrocyte differentiation. The co-culture was treated with 0.01 µg/mL LPS, which was the lowest dose that did not impair oligodendrocyte differentiation, at the developmental stages D1 (early LPS group), D3 (late LPS group), or D1 and D3 (double LPS group). On day 7 of differentiation, oligodendrocytes were subjected to neural glial antigen 2 (NG2) and myelin basic protein (MBP) immunostaining to examine the number of OPCs and mature oligodendrocytes, respectively. RESULTS: LPS dose-dependently decreased the proportion of mature oligodendrocytes (MBP+ cells) relative to the total number of cells. The number of MBP+ cells in the early LPS group was significantly lower than that in the late LPS group. Compared with those in the control group, the MBP+ cell numbers were significantly lower and the NG2+ cell numbers were significantly higher in the double LPS group, which exhibited impaired oligodendrocyte lineage cell development, on day 7 of differentiation. CONCLUSION: Repetitive LPS stimulation during development significantly inhibited brain cell development by impairing oligodendrocyte differentiation. In contrast, brain cell development was not affected in the late LPS group. These findings suggest that inflammation at the early developmental stage of oligodendrocytes increases the susceptibility of the preterm brain to inflammation-induced injury.

Population Pharmacokinetic Study of Prophylactic Fluconazole in Preterm Infants for Prevention of Invasive Candidiasis.

Fluconazole is an antifungal agent with reported evidence for its prophylactic effect against systemic fungal infection in preterm infants. The aim of this study was to build a population pharmacokinetic model to evaluate the pharmacokinetic characteristics of intravenous and oral fluconazole in preterm infants with the current prophylactic fluconazole dosing regimen. A pharmacokinetic model was developed using 301 fluconazole concentrations from 75 preterm infants with a baseline body weight (WT) ranging from 0.5 to 1.5 kg and an estimated glomerular filtration rate (eGFR) ranging from 12.9 to 58.5 ml/min/1.73 m2 Eligible infants received an intravenous or oral dose of 3 mg/kg of body weight of fluconazole, twice weekly with a ≥72-h dose interval, for 4 weeks. The model was qualified with basic goodness-of-fit diagnostics, visual predictive checks, and bootstrapping. The fluconazole pharmacokinetics was well described with a one-compartment linear model with a proportional residual error. The population clearance (CL) and volume of distribution (V) were derived as 0.0197 × (WT/1.00)0.746 × (eGFR/25.0)0.463 × exp(η) and 1.04 × WT × exp(η), respectively. Such covariate analyses augment the awareness of the need for personalized dosing in preterm infants. (This study has been registered at ClinicalTrials.gov under identifier NCT01683760).

Phenotypic and Genetic Characteristics of Five Korean Patients with Costello Syndrome.

Costello syndrome (CS) is a rare genetic disorder characterized by distinctive facial appearance, cardiopulmonary complications, severe growth retardation, skin and skeletal defects, developmental delay, and tumor predisposition. CS is caused by heterozygous de novo mutations in the proto-oncogene HRAS, which is a component of the RAS/mitogen-activated protein kinase pathway. Herein, we reviewed the phenotypic and genetic features of 5 Korean patients who were genetically diagnosed with CS. Atrial tachycardia and polyhydramnios, which are important prenatal features for CS, were observed in 4 and 5 patients, respectively. The distinctive coarse facial appearances of the patients and presence of deep palmoplantar creases supported the clinical diagnosis of CS, which was confirmed by HRAS sequence analysis. Extremely poor postnatal growth was observed in all 5 patients. Further, all patients exhibited cardiac abnormalities; left ventricular hypertrophy and hypertrophic cardiomyopathy were observed in 3 patients. All 5 patients suffered from airway problems; 3 of them required intubation right after birth, and 2 of them received tracheostomy. One patient with a p.Gly12Ser mutation was diagnosed with retroperitoneal rhabdomyosarcoma alveolar type at the age of 5 years. Consistent with previous reports, both patients with p.Gly12Cys mutations died within the first year of life due to cardiopulmonary failure. Our study summarizes the characteristics of these 5 Korean patients with CS and, along with previous studies, provides clues for genotype-phenotype correlation in patients with CS.

TNF-α antagonist attenuates systemic lipopolysaccharide-induced brain white matter injury in neonatal rats.

BACKGROUND: Systemic inflammation is an important risk factor for neurodevelopmental impairments in preterm infants. Premyelinating oligodendrocytes are main building blocks of white matter in preterm infants and vulnerable to oxidative stress and excitotoxic stress. Tumour necrosis factor-α (TNF-α) plays important roles in systemic inflammation and local inflammation leading to apoptosis of premyelinating oligodendrocytes and white matter injury (WMI) in brain tissue. This study was conducted to investigate whether etanercept, a TNF-α antagonist, could attenuate systemic lipopolysaccharide (LPS)-induced WMI in the immature brain. RESULTS: We found that intraperitoneal LPS administration caused systemic and local inflammation in brain tissue. Subsequent etanercept treatment significantly attenuated LPS-induced inflammation in brain tissue as well as in systemic circulation. Intraperitoneal LPS also induced microgliosis and astrocytosis in the cingulum and etanercept treatment reduced LPS-induced microgliosis and astrocytosis. Additionally, systemic LPS-induced apoptosis of oligodendrocyte precursor cells was observed, which was lessened by etanercept treatment. The concentration of etanercept in the CSF was higher when it was administrated with LPS than when administrated with a vehicle. CONCLUSIONS: It appears that etanercept reduce WMI in the neonatal rat brain via attenuation of systemic and local inflammation. This study provides preclinical data suggesting etanercept-mediated modulation of inflammation as a promising approach to reduce WMI caused by sepsis or necrotizing enterocolitis in preterm infants.

Comparison of NIV-NAVA and NCPAP in facilitating extubation for very preterm infants.

BACKGROUND: Various types of noninvasive respiratory modalities that lead to successful extubation in preterm infants have been explored. We aimed to compare noninvasive neurally adjusted ventilatory assist (NIV-NAVA) and nasal continuous positive airway pressure (NCPAP) for the postextubation stabilization of preterm infants. METHODS: This retrospective study was divided into two distinct periods, between July 2012 and June 2013 and between July 2013 and June 2014, because NIV-NAVA was applied beginning in July 2013. Preterm infants of less than 30 weeks GA who had been intubated with mechanical ventilation for longer than 24 h and were weaned to NCPAP or NIV-NAVA after extubation were enrolled. Ventilatory variables and extubation failure were compared after weaning to NCPAP or NIV-NAVA. Extubation failure was defined when infants were reintubated within 72 h of extubation. RESULTS: There were 14 infants who were weaned to NCPAP during Period I, and 2 infants and 16 infants were weaned to NCPAP and NIV-NAVA, respectively, during Period II. At the time of extubation, there were no differences in the respiratory severity score (NIV-NAVA 1.65 vs. NCPAP 1.95), oxygen saturation index (1.70 vs. 2.09) and steroid use before extubation. Several ventilation parameters at extubation, such as the mean airway pressure, positive end-expiratory pressure, peak inspiratory pressure, and FiO2, were similar between the two groups. SpO2 and pCO2 preceding extubation were comparable. Extubation failure within 72 h after extubation was observed in 6.3% of the NIV-NAVA group and 37.5% of the NCPAP group (P = 0.041). CONCLUSIONS: The data in the present showed promising implications for using NIV-NAVA over NCPAP to facilitate extubation.

Developmental outcomes of preterm infants with bronchopulmonary dysplasia-associated pulmonary hypertension at 18-24 months of corrected age.

BACKGROUND: Owing to advances in the critical care of premature infants with bronchopulmonary dysplasia (BPD), BPD-associated pulmonary hypertension (PH) is becoming a growing concern. However, only few investigations were available on neurodevelopmental outcomes in preterm infants with PH. Therefore, this study aimed to identify the impact of PH on growth and neurodevelopment at 18-24 months of corrected age (CA). METHODS: We retrospectively analyzed the medical records of 394 infants (aged < 28 weeks of gestation) admitted to the neonatal intensive care unit between 2005 and 2014. Among the surviving infants, 123 returned for follow-up evaluations including the Bayley Scales of Infant and Toddler Development, third Edition (Bayley-III) screening tests and growth assessment at 18-24 months of CA. Among the 81 infants with moderate or severe BPD, 20 met the criteria for PH. Baseline characteristics and outcomes were compared in infants who developed BPD-associated PH (PH group, n = 20) and moderate or severe BPD infants who did not develop PH (non-PH group, n = 61). RESULTS: Compared to the non-PH group, the PH group showed significantly lower cognitive (85 vs. 95, p = 0.004), language (81 vs. 89, p = 0.040), and motor (88 vs. 94, p = 0.010) scores of the Bayley-III at 18-24 months of CA. Cognitive delay was found in 45.0% (9/20) of PH infants. In addition, z-scores of weight (- 1.4 ± 1.3 vs. -0.6 ± 1.1%, p = 0.011) and HC (- 1.2 ± 1.8 vs. 0.53 ± 1.0%, p = 0.035) were significantly lower in the BPD with PH group. With the subgroup analysis in infants with severe BPD only, the cognitive score was consistently lower and poorer and weight gain after discharge was identified in infants with PH and severe BPD. CONCLUSION: PH was a worsening factor of non-optimal growth and poor neurodevelopmental outcome in preterm infants with BPD at 18-24 months of CA. Our findings suggest the importance of close developmental follow-up and recognition of that risk to help optimize the outcome of preterm infants with PH.

Correction to: Respiratory severity score as a predictive factor for severe bronchopulmonary dysplasia or death in extremely preterm infants.

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Respiratory severity score as a predictive factor for severe bronchopulmonary dysplasia or death in extremely preterm infants.

BACKGROUND: Despite significant advances in neonatology, bronchopulmonary dysplasia (BPD) remains the most common cause of serious morbidity and mortality in premature infants. The aim of the present study was to determine associations between the respiratory severity score (RSS) with death or BPD in premature infants. METHODS: This was a retrospective study conducted between January 2010 and December 2014. We enrolled preterm infants with a gestational age of less than 28 weeks who were supported by mechanical ventilation for more than a week during the first 4 weeks of life. We collected the RSS scores on day of life 2, 7, 14, 21 and 28. The correlations between postnatal RSSs and death or severe BPD were analyzed using multivariate logistic regression. RESULTS: Of the 138 eligible infants, 66 infants (47.8%) either died or developed severe BPD. The RSS cut-off values for predicting severe BPD or death were 3.0 for postnatal day (PND) 14 with an odds ratio (OR) of 11.265 (p = 0.0006, 95% confidence interval (CI), 2.842 to 44.646), 3.6 for PND 21 with an OR of 15.162 (p = 0.0003, 95% CI, 3.467 to 66.316), and 3.24 for PND 28 with an OR of 10.713 (p = 0.0005, 95% CI, 2.825 to 40.630). CONCLUSION: Strong correlations were observed between the RSSs on PND 14, 21, and 28 and death or subsequent severe BPD. The RSS could provide a simple estimate of severe BPD or death., Further research with a larger study population is necessary to validate the usefulness of the RSS for predicting severe BPD or death.

Comparison of Acute Abdominal Surgical Outcomes of Extremely-Low-Birth-Weight Neonates according to Differential Diagnosis.

BACKGROUND: Improvements in perinatal intensive care have improved survival of extremely-low-birth-weight (ELBW) neonates, although the risk of acute abdomen has increased. The differential diagnosis resulting in abdominal surgery can be categorized into necrotizing enterocolitis (NEC), spontaneous intestinal perforation (SIP), meconium-related ileus (MRI), and meconium non-related ileus (MNRI). The purpose of this study was to review our experience with abdominal surgery for ELBW neonates, and to evaluate characteristics and prognosis according to the differential diagnosis. METHODS: Medical records of ELBW neonates treated between 2003 and 2015 were retrospectively reviewed. RESULTS: Of 805 ELBW neonates, 65 (8.1%) received abdominal surgery. The numbers of cases by disease category were 29 for NEC, 18 for SIP, 13 for MRI, and 5 for MNRI. Ostoma formation was performed in 61 (93.8%) patients; primary anastomosis without ostoma was performed in 4 (6.2%). All patients without ostoma formation experienced re-perforation of the anastomosis site. Seven patients had 30-day postoperative mortality (6 had NEC). Long-term survival of the surgical and non-surgical groups was not statistically different. NEC was a poor prognostic factor for survival outcome (P = 0.033). CONCLUSION: Abdominal surgery for ELBW neonates is feasible. Ostoma formation can lead to reduced complications compared to primary anastomosis.

Effects of cyclic parenteral nutrition on parenteral nutrition-associated cholestasis in newborns.

BACKGROUND AND OBJECTIVES: Parenteral nutrition (PN) is one of the main nutritional methods used in newborns; however, long-term PN may induce PN-associated cholestasis (PNAC). This study aims to evaluate the effect of cyclic PN in the prevention and improvement of PNAC in newborns requiring long-term PN. METHODS AND STUDY DESIGN: A retrospective cohort study was conducted on patients admitted at the Seoul National University Children's Hospital neonatal intensive care unit between October 2010 and September 2015 and referred to the nutrition support team with total parenteral nutrition for more than 14 days. The primary outcome was the incidence of PNAC. The incidence of hypoglycemia, changes in direct bilirubin (DB) concentrations, and length of hospital stay were investigated. RESULTS: A total of 124 patients were observed in this study. Among these, 100 patients received continuous PN, whereas 24 patients received both continuous and cyclic PN. PNAC occurred in 31.5% (39/124) of study population. The incidence rates of PNAC were 27.4% during continuous PN period and 20.8% during cyclic PN period. Cyclic PN was an independent factor that significantly decreased PNAC incidence (OR=0.154; 95% CI, 0.045-0.529, p=0.003). DB concentrations significantly decreased (p=0.049) with therapeutic cyclic PN, but remained normal with prophylactic cyclic PN. No significant difference in hypoglycemia incidence and length of hospital stay was observed in both continuous PN and continuous to cyclic PN groups. CONCLUSIONS: Cyclic PN could be effective in the prevention and improvement of PNAC and also safe in terms of hypoglycemia in newborns.

Effect of Sustained Inflations vs Intermittent Positive Pressure Ventilation on Bronchopulmonary Dysplasia or Death Among Extremely Preterm Infants: The SAIL Randomized Clinical Trial.

Importance: Preterm infants must establish regular respirations at delivery. Sustained inflations may establish lung volume faster than short inflations. Objective: To determine whether a ventilation strategy including sustained inflations, compared with standard intermittent positive pressure ventilation, reduces bronchopulmonary dysplasia (BPD) or death at 36 weeks' postmenstrual age without harm in extremely preterm infants. Design, Setting, and Participants: Unmasked, randomized clinical trial (August 2014 to September 2017, with follow-up to February 15, 2018) conducted in 18 neonatal intensive care units in 9 countries. Preterm infants 23 to 26 weeks' gestational age requiring resuscitation with inadequate respiratory effort or bradycardia were enrolled. Planned enrollment was 600 infants. The trial was stopped after enrolling 426 infants, following a prespecified review of adverse outcomes. Interventions: The experimental intervention was up to 2 sustained inflations at maximal peak pressure of 25 cm H2O for 15 seconds using a T-piece and mask (n = 215); standard resuscitation was intermittent positive pressure ventilation (n = 211). Main Outcome and Measures: The primary outcome was the rate of BPD or death at 36 weeks' postmenstrual age. There were 27 prespecified secondary efficacy outcomes and 7 safety outcomes, including death at less than 48 hours. Results: Among 460 infants randomized (mean [SD] gestational age, 25.30 [0.97] weeks; 50.2% female), 426 infants (92.6%) completed the trial. In the sustained inflation group, 137 infants (63.7%) died or survived with BPD vs 125 infants (59.2%) in the standard resuscitation group (adjusted risk difference [aRD], 4.7% [95% CI, -3.8% to 13.1%]; P = .29). Death at less than 48 hours of age occurred in 16 infants (7.4%) in the sustained inflation group vs 3 infants (1.4%) in the standard resuscitation group (aRD, 5.6% [95% CI, 2.1% to 9.1%]; P = .002). Blinded adjudication detected an imbalance of rates of early death possibly attributable to resuscitation (sustained inflation: 11/16; standard resuscitation: 1/3). Of 27 secondary efficacy outcomes assessed by 36 weeks' postmenstrual age, 26 showed no significant difference between groups. Conclusions and Relevance: Among extremely preterm infants requiring resuscitation at birth, a ventilation strategy involving 2 sustained inflations, compared with standard intermittent positive pressure ventilation, did not reduce the risk of BPD or death at 36 weeks' postmenstrual age. These findings do not support the use of ventilation with sustained inflations among extremely preterm infants, although early termination of the trial limits definitive conclusions. Trial Registration: clinicaltrials.gov Identifier: NCT02139800.

Improved Regional Disparities in Neonatal Care by Government-led Policies in Korea.

BACKGROUND: Although the number of high-risk neonates has increased in Korea, hospitals were reluctant to open or maintain neonatal intensive care unit (NICU) due to the low medical cost. Consequently, there were regional disparities in facilities, equipment, and neonatal health outcomes. For these reasons, the Korean government began to invest in neonatal care during the last decade. We identified the status of NICUs in Korea and assessed changes after the government-driven policies. METHODS: We surveyed 87 of 89 hospitals that operated NICUs in 2015. The questionnaire assessed the number of NICU beds, admission and mortality rates of very low birthweight infants (VLBWIs), personnel status, equipment and facilities, and available multidisciplinary approach. Current data was compared with the previous studies and changes in the status and function of the nationwide NICU from 2009 and 2011. RESULTS: During the last 7 years, there was an increase of 462 NICU beds, which met the required number estimated by the number of births and covered about 90% of regional VLBWI births. Status of facilities and equipment improved in all regions in Korea but there were still regional differences in multidisciplinary approach and human resources. The difference in odds ratios for mortality of VLBWI between regions decreased compared to 2009. CONCLUSION: There was improvement in regional disparities of neonatal care and mortality of premature babies with the government investment in Korea. Further supports are required for human resources and referral system.