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.

Association of newer definitions of bronchopulmonary dysplasia with pulmonary hypertension and long-term outcomes.

Background: The definition of bronchopulmonary dysplasia (BPD) has been evolved recently from definition by the National Institute of Child Health and Human Development in 2001 (NICHD 2001) to the definition reported in 2018 (NICHD 2018) and that proposed by Jensen et al. in 2019 (NICHD 2019). The definition was developed based on the evolution of non-invasive respiratory support and to achieve better prediction of later outcomes. Our objective was to evaluate the association between different definitions of BPD and occurrence of pulmonary hypertension (PHN) and long term outcomes. Methods: This retrospective study enrolled preterm infants born at < 32 weeks of gestation between 2014 and 2018. The association between re-hospitalization owing to a respiratory illness until a corrected age (CA) of 24 months, neurodevelopmental impairment (NDI) at a CA of 18-24 months, and PHN at a postmenstrual age (PMA) of 36 weeks was evaluated, with the severity of BPD defined based on these three definitions. Results: Among 354 infants, the gestational age and birth weight were the lowest in severe BPD based on the NICHD 2019 definition. In total, 14.1% of the study population experienced NDI and 19.0% were re-hospitalized owing to a respiratory illness. At a PMA of 36 weeks, PHN was identified in 9.2% of infants with any BPD. Multiple logistic regression analysis showed that the adjusted odds ratio (OR) for re-hospitalization was the highest for Grade 3 BPD of the NICHD 2019 criteria (5.72, 95% confidence interval [CI]: 1.37-23.92), while the adjusted OR of Grade 3 BPD was 4.96 (95% CI: 1.73-14.23) in the NICHD 2018 definition. Moreover, no association of the severity of BPD was found in the NICHD 2001 definition. The adjusted ORs for NDI (12.09, 95% CI: 2.52-58.05) and PHN (40.37, 95% CI: 5.15-316.34) were also the highest for Grade 3 of the NICHD 2019 criteria. Conclusion: Based on recently suggested criteria by the NICHD in 2019, BPD severity is associated with long-term outcomes and PHN at a PMA of 36 weeks in preterm infants.

Risk factors of early pulmonary hypertension and its clinical outcomes in preterm infants: a systematic review and meta-analysis.

The aim of this meta-analysis was to determine the incidence and risk factors of early pulmonary hypertension (PHT) in preterm infants and evaluate the association of early PHT with morbidities such as bronchopulmonary dysplasia (BPD), late PHT, and in-hospital mortality. We searched the PubMed (1980-2021), Embase (1968-2021), CINAHL (2002-2021), Cochrane library (1989-2021), and KoreaMed (1993-2021). Observational studies on the association between early PHT diagnosed within the first 2 weeks after birth and its clinical outcomes in preterm infants born before 37 weeks of gestation or with very low birth weight (< 1500 g) were included. Two authors independently extracted the data and assessed the quality of each study using a modified Newcastle-Ottawa Scale. We performed meta-analysis using Comprehensive Meta-Analysis version 3.3. A total of 1496 potentially relevant studies were found, of which 8 studies (7 cohort studies and 1 case-control study) met the inclusion criteria comprising 1435 preterm infants. The event rate of early PHT was 24% (95% confidence interval [CI] 0.174-0.310). The primary outcome of our study was moderate to severe BPD at 36 weeks postmenstrual age, and it was associated with early PHT (6 studies; odds ratio [OR] 1.682; 95% CI 1.262-2.241; P < 0.001; heterogeneity: I2 = 0%; P = 0.492). Preterm infants with early PHT had higher OR of in-hospital mortality (6 studies; OR 2.372; 95% CI 1.595-3.528; P < 0.001; heterogeneity: I2 = 0%; P = 0.811) and developing late PHT diagnosed after 4 weeks of life (4 studies; OR 2.877; 95% CI 1.732-4.777; P < 0.001; heterogeneity: I2 = 0%; P = 0.648). Infants with oligohydramnios (4 studies; OR 2.134; 95% CI 1.379-3.303; P = 0.001) and those who were small-for-gestational-age (5 studies; OR 1.831; 95% CI 1.160-2.890; P = 0.009) had an elevated risk of developing early PHT. This study showed that early PHT is significantly associated with mortality and morbidities, such as BPD and late PHT. Preterm infants with a history of oligohydramnios and born small-for-gestational-age are at higher risk for developing early PHT; however, high-quality studies that control for confounders are necessary.

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.

Factors associated with the follow-up of high risk infants discharged from a neonatal intensive care unit.

BACKGROUND: The study aimed to identify factors associated with compliance to follow-up (FU) appointments among infants following their discharge from the neonatal intensive care unit (NICU). METHODS: This retrospective cohort study reviewed 657 infants (birth weight <1500 g or gestational age [GA] <32 weeks), born between 2011 and 2015. A total of 525 eligible infants were classified into two groups: the compliant group (n = 360), who attended clinics from 18 to 24 months, and the non-compliant group (n = 165), who were lost to FU before 18 months. RESULTS: The non-compliant group was more likely to have higher usage rate of assisted reproductive technology (p = 0.023), GA (p < 0.001), weight (p < 0.001), height (p < 0.001), and head circumference (p < 0.001) at birth. The sibling number was higher in the non-compliant group (p = 0.011). Moreover, the non-compliant group demonstrated higher Apgar scores at 1 min and 5 min (p = 0.002 and p = 0.031, respectively). The compliant group was more likely to live in metropolitan or larger cities with a borderline significance (p = 0.056). Furthermore, the non-compliant group was less likely to suffer from respiratory distress syndrome (p < 0.001), patent ductus arteriosus (p = 0.002), retinopathy of prematurity (p = 0.007), necrotizing enterocolitis (p = 0.019), and bronchopulmonary dysplasia (p < 0.001). Moreover, it demonstrated lower postmenstrual age at discharge (p = 0.005) and a shorter length of stay in the NICU (p < 0.001). The compliance with FU appointment varied with the assigned doctor (p < 0.001). The multivariate regression analysis mentioned that the birth weight (OR = 0.903), residence in metropolitan or larger cities (OR = 1.495), and an experience of magnetic resonance imaging (OR = 1.920) were associated with compliance. The compliance to FU appointments was different according to the assigned doctor at admission (OR = 0.357). CONCLUSION: The birth weight, residence in metropolitan or larger cities, an experience of MRI, and the assigned doctors were associated with compliance to FU at a corrected age of 18-24 months.

Association between birth weight and neurodevelopmental disorders assessed using the Korean National Health Insurance Service claims data.

The risk of neurodevelopmental disorders in low birth weight (LBW) infants has gained recognition but remains debatable. We investigated the risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in school-aged children according to their birth weight. We conducted a retrospective cohort study using the Korean National Health Insurance claims data of 2,143,652 children who were born between 2008 and 2012. Gestational age of infants was not available; thus, outcomes were not adjusted with it. Not only infants with birth weights of < 1.5 kg, but also 2.0-2.4 kg and 1.5-1.9 kg were associated with having ADHD; odds ratio (OR), 1.41 (95% confidence interval [CI] 1.33-1.50), and 1.49 (95% CI 1.33-1.66), respectively. The OR in infants with birth weights of 2.0-2.4 kg and 1.5-1.9 kg was 1.91 (95% CI 1.79-2.05) and 3.25 (95% CI 2.95-3.59), respectively, indicating increased odds of having ASD. Subgroup analysis for children without perinatal diseases showed similar results. In this national cohort, infants with birth weights of < 2.5 kg were associated with ADHD and ASD, regardless of perinatal history. Children born with LBW need detailed clinical follow-up.

Effect of selenium-free parenteral nutrition on serum selenium of neonates and infants maintained on long-term parenteral nutrition.

BACKGROUND: The risk of selenium deficiency increases for infants receiving long-term parenteral nutrition (PN). This study analyzed selenium deficiency in neonates and infants requiring long-term PN and evaluated the effect of intravenous (IV) selenium provision. METHODS: This study was a retrospective study of neonates and infants who were admitted to a neonatal intensive care unit from January 2010 to December 2019, received PN for ≥2 weeks, and had their serum selenium concentration measured. Patients were divided into two groups, depending on their serum selenium concentration, a deficient group (n = 55) and a nondeficient group (n = 47). RESULTS: Of the study participants, 53.9% (55 of 102) were deficient in selenium. No difference in demographic and clinical characteristics existed except bronchopulmonary dysplasia. A subgroup analysis was performed for patients (n = 29). The average dose of IV selenium administered to patients was 2.7 ± 1.0 mcg/kg/day. The average initial serum selenium concentration was 36.5 ± 18.0 mcg/L, and the serum concentration significantly increased to 52.5 ± 19.1 mcg/L after IV selenium administration (P < .001). The correlation between the average IV selenium dose and the change in serum selenium concentrations was statistically significant (r = .423; P = .022). CONCLUSION: Selenium deficiency is common in neonates and infants receiving long-term PN. Serum selenium concentration increased proportionally as the IV selenium dose increased. Therefore, it is recommended to supply a proper dose of IV selenium depending on the degree of selenium deficiency.

Head Growth and Neurodevelopment of Preterm Infants with Surgical Necrotizing Enterocolitis and Spontaneous Intestinal Perforation.

Spontaneous intestinal perforation (SIP) and surgical necrotizing enterocolitis (NEC) are intestinal conditions requiring surgical intervention in preterm infants. We aimed to compare the head growth and neurodevelopment of preterm infants with SIP and surgical NEC. A retrospective single-center study was performed in preterm infants born at less than 32 weeks of gestation and who had undergone surgery for NEC or SIP. Data from the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) at 24 months of corrected age (CA) and the Korean Ages and Stages Questionnaire (K-ASQ) or Korean Developmental Screening Test (K-DST) at 36 months were collected. Among 82 eligible infants, 60 infants had surgical NEC, and 22 infants were diagnosed with SIP. Head growth was faster until CA 4 months in preterm infants with SIP than in those with surgical NEC. At 36 months, abnormal findings in the K-ASQ or K-DST were more prevalent in the NEC group than in the SIP group in the gross motor (48.2% vs. 0%, p = 0.015), fine motor (40.7% vs. 0%, p = 0.037), cognitive (55.6% vs. 12.5%, p = 0.047), and social domains (44.4% vs. 0%, p = 0.032). More studies evaluating the neurodevelopmental outcomes of preterm infants with surgical NEC and SIP are required.

Capillary partial pressure of carbon dioxide for predicting rehospitalization in preterm infants under noninvasive respiratory support with severe bronchopulmonary dysplasia.

BACKGROUND: The severity of bronchopulmonary dysplasia (BPD) is an important predictor of prognosis in preterm infants. However, the severity of BPD was determined mainly by the degree of oxygen supplementation and mode of respiratory support. OBJECTIVES: This retrospective study aimed to examine the role of partial pressure of carbon dioxide (pCO2 ) in predicting rehospitalization among preterm infants with severe BPD without invasive ventilation at 36 weeks' postmenstrual age (PMA). METHODS: We assessed preterm infants aged <32 gestational weeks with severe BPD who were receiving noninvasive respiratory support at 36 weeks' PMA. Patients were compared after stratifying them according to the history of rehospitalization owing to respiratory infection before a corrected age (CA) of 1 year and pCO2 measured by capillary blood gas analysis at 36 weeks' PMA. RESULTS: Among 54 infants who had severe BPD with noninvasive respiratory support at 36 weeks' PMA, 16 (29.6%) experienced rehospitalization due to respiratory problems. At 36 weeks' PMA, the amount of oxygen supplementation (0.30 vs. 0.28, p = 0.021) and pCO2 (62.1 vs. 53.6 mmHg, p = 0.006) were higher in the rehospitalization group than in the no rehospitalization group. Multivariate logistic analysis findings indicated that pCO2 ≥ 57.4 mmHg was the only factor associated with rehospitalization (adjusted odds ratio: 8.017, 95% confidence interval 1.239-51.859). CONCLUSION: High pCO2 during noninvasive respiratory support at 36 weeks' PMA in severe BPD was associated with rehospitalization. Consideration of the degree of impairment in ventilatory capacity may improve the prediction of later respiratory outcomes in infants with BPD.

Association of Severe Retinopathy of Prematurity and Bronchopulmonary Dysplasia with Adverse Neurodevelopmental Outcomes in Preterm Infants without Severe Brain Injury.

Although impaired neurodevelopment is strongly associated with severe brain injury, most preterm infants survive without severe brain injury. In this study, the association of impaired neurodevelopment and neonatal morbidities of preterm infants was assessed after excluding those with severe brain injury. This was a retrospective study of very low birthweight infants in a single tertiary center. After excluding infants with severe brain injury, the study population was categorized as infants without intraventricular hemorrhage (IVH) and with low-grade IVH. Neurodevelopmental outcomes at a corrected age (CA) of 18-24 months were evaluated using the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III). Cerebral palsy (CP), hearing impairment and blindness were also assessed and compared. Of 240 infants, 25 (11.6%) infants had combined neurodevelopmental impairment (NDI). In the multivariate analysis for combined NDI, small for gestational age (SGA) (adjusted OR 6.820, 95% confidence intervals (CI) 1.770-26.307), moderate to severe bronchopulmonary dysplasia (BPD) (aOR 3.21, 95% CI 1.032-9.999) and severe retinopathy of prematurity (ROP) (aOR 5.669, 95% CI 1.132-28.396) were associated with combined NDI. Among neonatal morbidities, moderate to severe BPD and severe ROP were associated with adverse neurodevelopmental outcomes in preterm infants without severe brain injury.

Antenatal magnesium sulfate and intestinal morbidities in preterm infants with extremely low gestational age.

BACKGROUND: Antenatal magnesium sulfate is widely used as a tocolytic, for maternal seizures, and for seizure prophylaxis in preeclampsia. Recent studies have suggested that antenatal magnesium sulfate use is associated with favorable neurodevelopmental outcomes in preterm infants. However, there are concerns regarding the effects of antenatal magnesium sulfate on neonates, especially regarding gastrointestinal morbidities. This study aims to explore the effects of antenatal magnesium sulfate on intestinal morbidities requiring surgery in preterm infants. METHODS: This was a retrospective cohort study of 181 preterm infants who were born at less than 28 weeks of gestational age. Subjects were categorized as infants exposed to antenatal magnesium sulfate and those not exposed to antenatal magnesium sulfate. RESULTS: Antenatal magnesium sulfate was associated with a decreased risk of surgical conditions of the intestine (OR 0.393, 95% CI 0.170-0.905). The multivariate analysis showed that the duration of antenatal magnesium sulfate use was associated with surgical conditions of the intestine (adjusted OR 0.766, 95% CI 0.589-0.997). In the <26 weeks of gestational age subgroup, the use of antenatal magnesium sulfate was significantly associated with decreased intestinal morbidities requiring surgery (adjusted OR 0.234, 95% CI 0.060-0.922). CONCLUSION: Antenatal magnesium sulfate use appears to have a protective effect on intestinal morbidities requiring surgery in preterm infants in a duration-dependent manner. Association of antenatal magnesium sulfate use and decreased intestinal morbidities requiring surgery was more distinct in preterm infants <26 weeks of gestational age.

New modified version of the Risk Adjustment for Congenital Heart Surgery category and mortality in premature infants with critical congenital heart disease.

BACKGROUND: Despite advances in neonatal intensive care and surgical procedures, perinatal mortality rates for premature infants with congenital heart disease (CHD) remain relatively high. PURPOSE: We aimed to describe the outcomes of premature infants with critical CHD and identify the risk factors including the new modified version of the Risk Adjustment for Congenital Heart Surgery (M-RACHS) category associated with in-hospital mortality in a Korean tertiary center. METHODS: This was a retrospective cohort study of premature infants with critical CHD admitted to the neonatal intensive care unit from January 2005 to December 2016. RESULTS: A total of 78 premature infants were enrolled. The median gestational age (GA) at birth was 34.9 weeks (range, 26.7-36.9 weeks), and the median birth weight was 1.91 kg (range, 0.53-4.38 kg). Surgical or percutaneous intervention was performed in 68 patients with a median GA at birth of 34.7 weeks (range, 26.7-36.8 weeks) and a median birth weight of 1.92 kg (range, 0.53-4.38 kg). The in-hospital survival rate was 76.9% among all enrolled preterm infants and 86.8% among patients who received an intervention. Very low birth weight (VLBW), persistent pulmonary hypertension of the newborn (PPHN), bronchopulmonary dysplasia (BPD), and M-RACHS category 5 or higher (more complex CHD) were independently associated with in-hospital mortality. For the 68 premature infants undergoing cardiac interventions, independent risk factors for mortality were VLBW, BPD, and CHD complexity. Late preterm infant and age at intervention were not associated with patient survival. CONCLUSION: For premature infants with critical CHD, VLBW, PPHN, BPD, and M-RACHS category ≥5 were risk factors for mortality. A careful approach to surgical intervention and prenatal care should be taken according to CHD type and neonatal condition.

Proteomic identification of early urinary-biomarkers of acute kidney injury in preterm infants.

The immature preterm kidney is likely to be vulnerable to acute kidney injury (AKI). However, the biomarkers currently used for AKI are not sensitive or specific and are also inadequate for the timely detection of AKI in preterm infants. The objectives of this study were to identify novel urinary biomarkers of AKI using proteomic techniques, and to verify and validate that the candidates can serve as early predictive biomarkers for AKI. In total, 1,810 proteins were identified in the discovery phase. Among those proteins, 174 were selected as the 1st targeted proteins. A total of 168 proteins were quantified, and the levels of 6 were significantly increased in the AKI group in the verification phase. Using a clinical assay, the results were confirmed and validated using samples of the first urine after birth from the biorepository. Finally, enzyme-linked immunosorbent assays revealed that the levels of annexin A5, neutrophil gelatinase-associated lipocalin (NGAL), and protein S100-P were significantly higher in the samples of the first urine from patients with AKI than in those from patients without AKI. In conclusion, urinary annexin A5, NGAL and protein S100-P levels are promising biomarkers for early, accurate prediction of AKI in preterm infants.

The Association of Pregnancy-induced Hypertension with Bronchopulmonary Dysplasia - A Retrospective Study Based on the Korean Neonatal Network database.

The prevalence of pregnancy-induced hypertension (PIH) and preeclampsia (PE) are 5-10% and 2-4%, respectively. PIH might affect angiogenesis in preterm neonates, but its association with bronchopulmonary dysplasia (BPD) remains controversial. This study evaluated the association between PIH and BPD in very low-birth weight infants. We retrospectively analysed the maternal, perinatal, and neonatal data of preterm infants born before 30 weeks of gestation, selected from the nationwide registry of very low-birth weight infants, between January 2013 and December 2014. As a result, 1,624 infants without maternal PIH (gestational age: 27.3 ± 1.8 weeks) and 203 infants with maternal PIH (28.0 ± 1.4 weeks, p < 0.001) were included. Birth weight was higher in the non-PIH group, compared with the PIH group (1027.4 ± 250.2 vs. 876.4 ± 261.5 g, p < 0.001). Multivariate logistic regression showed that PIH was associated with BPD (adjusted OR 1.474, 95% confidence interval 1.025-2.121), after adjusting for confounders, including small-for-gestation age (SGA). The result of present study is consistent with the current concept of BPD as an early form of pulmonary vascular disease, for both PIH and BPD are attributed by abnormal vascular formation.

Early postnatal cardiac manifestations are associated with perinatal brain injury in preterm infants with twin to twin transfusion syndrome.

Altered hemodynamics associated with twin to twin transfusion syndrome (TTTS) can be manifested in the fetal and neonatal heart. This study evaluated the association between cardiac manifestations immediately after birth and brain injury in preterm infants with TTTS. Medical records of preterm infants who were born at <35 weeks of gestation with TTTS and admitted to the neonatal intensive care unit at Seoul National University Children's Hospital between January 2011 and January 2018 were reviewed. TTTS was prenatally diagnosed and staged according to the Quintero criteria. Echocardiographic findings, brain ultrasound and MRI imaging findings were analyzed. Fifty-three infants were enrolled in this study. Thirty-two infants (60.3%) were treated by fetoscopic laser coagulation. Brain injury developed in 15 infants (28.3%). Hypotension within the first week and immediate postnatal cardiac manifestations were more prevalent in the brain injury group. In the multivariate analysis, acute kidney injury and cardiac manifestations, such as ventricular dysfunction and tricuspid regurgitation, were statistically associated with brain injury in the study population. Immediate postnatal cardiac manifestations, such as ventricular dysfunction and tricuspid regurgitation, can serve as surrogate markers for perinatal hemodynamic disturbance, which are associated with early neonatal brain injury in preterm infants with TTTS.

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.

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.

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.

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.