[Show abstract][Hide abstract] ABSTRACT: Purpose
We tested whether rosiglitazone (RGZ), a peroxisome proliferator-activated receptor-γ agonist, can restore alveolar development and vascular growth in a rat model of bronchopulmonary dysplasia (BPD).
Materials and Methods
A rat model of BPD was induced through intra-amniotic delivery of lipopolysaccharide (LPS) and postnatal hyperoxia (80% for 7 days). RGZ (3 mg/kg/d, i.p.) or vehicle was given daily to rat pups for 14 days. This model included four experimental groups: No BPD+vehicle (V), No BPD+RGZ, BPD+V, and BPD+RGZ. On D14, alveolarization, lung vascular density, and right ventricular hypertrophy (RVH) were evaluated.
Morphometric analysis revealed that the BPD+RGZ group had significantly smaller and more complex airspaces and larger alveolar surface area than the BPD+V group. The BPD+RGZ group had significantly greater pulmonary vascular density than the BPD+V group. Western blot analysis revealed that significantly decreased levels of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 by the combined exposure to intra-amniotic LPS and postnatal hyperoxia were restored by the RGZ treatment. RVH was significantly lesser in the BPD+RGZ group than in the BPD+V group.
These results suggest that RGZ can restore alveolar and pulmonary vascular development and lessen pulmonary hypertension in a rat model of BPD.
Full-text · Article · Jan 2014 · Yonsei medical journal
[Show abstract][Hide abstract] ABSTRACT: Massive pulmonary hemorrhage(MPH) within the first five days after birth is a major cause of early death in extremely low birth weight(ELBW) infants. The objective of this study was to determine risk factors for MPH in ELBW infants.
[Show abstract][Hide abstract] ABSTRACT: Amplitude-integrated electroencephalography (aEEG) allows continuous brain function monitoring at bedside.
This prospective cohort study was designed to longitudinally evaluate aEEG tracings at increased postmenstrual age (PMA) in preterm infants with intraventricular hemorrhage (IVH).
Biweekly aEEG recordings were performed on preterm infants <32weeks gestational age from 24 to 36weeks PMA. The tracings were evaluated according to a scoring system adapted from Burdjalov et al.
We analyzed 496 aEEG recordings in 105 preterm infants. The control group consisted of 42 infants with no IVH, whereas the IVH grade I, II, III, and IV groups consisted of 38, 8, 3, and 14 infants, respectively. There were significant differences in the cycling and total maturation scores among the IVH groups at 36weeks PMA (p=0.010 and p=0.006, respectively). The IVH-IV patients maintained low scores in their cycling as their PMA increased, in contrast to their continuity and amplitude scores. The risk factors affecting the aEEG maturation scores at 36weeks PMA in the IVH-IV patients included seizure events with the administration of antiepileptic drugs and the insertion of external ventricular drains (β=-0.679 and β=-0.418, respectively; p=0.003).
The low cycling scores persisted until 36weeks PMA in the IVH-IV group.
No preview · Article · Sep 2013 · Early human development
[Show abstract][Hide abstract] ABSTRACT: Aim:
We investigated the combined effects of intra-amniotic lipopolysaccharide (LPS) and maternal betamethasone (BMZ) on alveolarization using a newborn rat model.
LPS (1.0 μg/sac) or vehicle was injected into the amniotic sacs of pregnant rats and BMZ (170 μg/kg) or vehicle was injected intramuscularly into the pregnant rats twice at 8-h intervals on gestation day 20. The rat pups were delivered spontaneously after 2-2.5 days and raised until the measurements were taken. Bronchoalveolar lavage was performed on days 2 and 5, and morphometric analyses of the lungs were performed on days 5 and 14.
Intra-amniotic LPS significantly increased the neutrophils in the bronchoalveolar lavage fluid (BALF) on day 2, but double exposure to LPS and BMZ significantly alleviated the neutrophil increase in the BALF. On day 5, while the neutrophils in the BALF decreased in the animals exposed to LPS alone, the neutrophil numbers in the BALF were steady in the animals exposed to both LPS and BMZ. Morphometric analyses on days 5 and 14 revealed a significant disruption of alveolarization only in the animals exposed to both LPS and BMZ.
Our results suggested that double exposure to maternal BMZ and intra-amniotic LPS induces sustained increase of neutrophils in the lungs and disrupts alveolarization.
No preview · Article · Aug 2013 · Journal of Perinatal Medicine
[Show abstract][Hide abstract] ABSTRACT: Faced with extremely low fertility rates and increasing numbers of low-birthweight births in Korea, we examined the factors affecting the mortality of very-low-birthweight (VLBW) infants in Korea.
A survey was conducted in 91 of 93 hospitals providing neonatal intensive care in Korea in 2009. Data included information on number of neonatal intensive care unit (NICU) beds, medical workforce, resources in the NICU, birth and death.
There was approximately one NICU per 4888 births, one NICU bed per 355 births, one mechanical ventilator per 739 births, one incubator per 327 births and one board-certified neonatologist per 4683 births. Regional disparity existed in neonatal care resources and consequently in mortality rates. VLBW infants' mortality was related to the NICU facility level, volume of VLBW infants and geographic regions. The capital city, Seoul, has the best NICU facilities and workforce, and the least mortality. Overall mortality rates before hospital discharge for <750, 750-999 and 1000-1499 g were 44.8%, 20.4% and 6.5% respectively. There was a two to threefold difference in the mortality rates across the regions. However, following adjustments for NICU facility level and volume of VLBW infants admissions, regional difference in mortality rates was markedly reduced in the <750 g and disappeared in the larger VLBW groups.
Regional disparity in mortality of VLBW infants in Korea is most marked in the lowest-birthweight group, <750 g. This disparity is primarily due to lack of resources for neonatal intensive care in most of provincial areas.
No preview · Article · Mar 2013 · Paediatric and Perinatal Epidemiology
[Show abstract][Hide abstract] ABSTRACT: The objective of the study was to compare the incidences of the neonatal morbidity, using the various criteria of histologic chorioamnionitis (HC) in the extremely low gestational age newborns (ELGANs), who were born before the 28 weeks of gestational age.
[Show abstract][Hide abstract] ABSTRACT: Anomalies of the fetal venous system are rare. Major portion of fetal venous anomalies are malformation of umbilical vein and ductus venosus. Abnormal umbilico-systemic shunt, bypassing the ductus venosus makes direct connection between the high-pressure umbilical system and the low-pressure systemic system. And it makes adverse to the fetal hemodynamics. Fetal hemodynamic distress may induce fetal growth retardation, hepatomegaly, cardiomegaly, hydrops fetalis and fetal death. We report a case of non-immune hydrops fetalis which was associated with abnormal umbilical vein pathway. Our patient had bifurcated umbilical veins. Main branch of umbilical vein was drained directly to the left internal iliac vein and another branch was drained to the portal vein. After birth, extrahepatic shunt through main branch of umbilical vein that bypassed the portal system was persisted and thrombocytopenia was combined due to consumption in thrombus of a dilated anomalous umbilical vein. Later this case was diagnosed as Noonan syndrome with a genetic testing.
[Show abstract][Hide abstract] ABSTRACT: Herlyn-Werner-Wunderlich syndrome (HWWS) is a very rare congenital anomaly of the urogenital tract involving Mullerian ducts and Wolffian ducts, and is characterized by the triad of uterine didelphys, unilateral obstructed hemivagina and ipsilateral renal agenesis. Generally it is diagnosed at puberty after menarche due to recurrent pelvic pain or abdominal mass. We report 2 cases of female newborns whose fetal ultrasonography (USG) showed unilateral renal agenesis and were diagnosed with HWWS by postnatal evaluation. Both cases were female newborns who were born at term by vaginal delivery. They had no perinatal problems except suspicious findings of unilateral renal agenesis from fetal USG. Abdominal ultrasonography and pelvic MRI were performed after birth, and they were diagnosed with HWWS. The potential complications of this syndrome such as pyosalpinx, pelvic adhesions and increased risk of abortion or infertility can occur, but without complication, the prognosis is very good with simple surgical treatment. If renal agenesis is detected in a fetus or a newborn, possible anomalies of urogenital tract such as HWWS should be considered; and postnatal evaluation should be performed, as a simple surgical treatment before menarche can prevent unnecessary complications of disease.
[Show abstract][Hide abstract] ABSTRACT: In the present study, we aimed to evaluate the suitability of the first screening examination for retinopathy of prematurity (ROP) in a tertiary neonatal intensive care unit (NICU).
[Show abstract][Hide abstract] ABSTRACT: To evaluate the causes of nil per os (NPO) before reaching full enteral feeding and compare the clinical outcomes of extremely low birth weight infant (ELBWI) by NPO duration.
[Show abstract][Hide abstract] ABSTRACT: Lung injury from mechanical ventilation is one of the major pathogenetic factors of bronchopulmonary dysplasia. Permissive hypercapnia (PH) is one of the strategies for reducing lung injury. However, PH is frequently infeasible in very low birth weight infants (VLBWI) due to their immature renal compensation for respiratory acidosis. The purpose of this study was to identify time when metabolic compensation for hypercapnia begin to occur in VLBWIs.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE:: To evaluate clinical applicability of noninvasive hemoglobin (Hb) measurement with a pulse CO-oximeter in neonates. DESIGN:: Prospective comparison study. SETTING:: Neonatal ICU. PATIENTS:: Fifty-six preterm and term infants with median age = 20 days (range = 1-98 days) and median weight = 1,440 g (range = 530-4,230 g). INTERVENTIONS:: Hb measurements by Pulse CO-Oximetry (Masimo Radical-7) were recorded immediately prior to venous samplings. MEASUREMENTS AND MAIN RESULTS:: The collected data were compared with the corresponding venous Hb level obtained in laboratory testing, and a total of 137 data pairs were analyzed. Noninvasive Hb values measured with a pulse CO-oximeter were significantly correlated with the venous Hb levels (correlation coefficient, r = .758; p < .001). Hb values measured with a pulse CO-oximeter were higher than those measured with a laboratory hematology analyzer (13.3 ± 2.6 g/dL vs. 12.5 ± 3.1 g/dL). In terms of the agreement between the laboratory analyzer and the pulse CO-oximeter, 94.8% of the measurements fell within two standard deviations of the mean difference. CONCLUSION:: Noninvasive Hb measurements with Pulse CO-Oximetry provide clinically acceptable accuracy, and they were significantly correlated with laboratory Hb measurement in neonates. In terms of the clinical applicability, noninvasive Hb monitoring with a pulse CO-oximeter could be useful in the early detection of Hb changes in neonates.
No preview · Article · Nov 2012 · Pediatric Critical Care Medicine
[Show abstract][Hide abstract] ABSTRACT: Mucolipidosis II (ML II) or inclusion cell disease (I-cell disease) is a rarely occurring autosomal recessive lysosomal enzyme-targeting disease. This disease is usually found to occur in individuals aged between 6 and 12 months, with a clinical phenotype resembling that of Hurler syndrome and radiological findings resembling those of dysostosis multiplex. However, we encountered a rare case of an infant with ML II who presented with prenatal skeletal dysplasia and typical clinical features of severe secondary hyperparathyroidism at birth. A female infant was born at 37(+1) weeks of gestation with a birth weight of 1,690 g (<3rd percentile). Prenatal ultrasonographic findings revealed intrauterine growth retardation and skeletal dysplasia. At birth, the patient had characteristic features of ML II, and skeletal radiographs revealed dysostosis multiplex, similar to rickets. In addition, the patient had high levels of alkaline phosphatase and parathyroid hormone, consistent with severe secondary neonatal hyperparathyroidism. The activities of β-D-hexosaminidase and α-N-acetylglucosaminidase were moderately decreased in the leukocytes but were 5- to 10-fold higher in the plasma. Examination of a placental biopsy specimen showed foamy vacuolar changes in trophoblasts and syncytiotrophoblasts. The diagnosis of ML II was confirmed via GNPTAB genetic testing, which revealed compound heterozygosity of c.3091C>T (p.Arg1031X) and c.3456_3459dupCAAC (p.Ile1154GlnfsX3), the latter being a novel mutation. The infant was treated with vitamin D supplements but expired because of asphyxia at the age of 2 months.
Full-text · Article · Nov 2012 · Korean Journal of Pediatrics
[Show abstract][Hide abstract] ABSTRACT: Background: Increased pro-inflammatory cytokines are suggested in the pathogenesis of necrotizing enterocolitis (NEC). The transcription factor, nuclear factor-ĸB (NF-ĸB), is a central regulator of inflammatory and immune responses, and recent rodent NEC models have shown that NF-ĸB may have a critical role in the disease processes that underlie NEC. Heat shock proteins have important functions in response to stress-related events in a variety of systems, including digestive organs. Objectives: We investigated whether heat shock pretreatment protects intestinal epithelial damage in the early NEC rat model. Methods: We generated human NEC-like lesions in neonatal rat ileum by administering oral endotoxin (10 mg/kg), intermittent 8% hypoxia, and hypertonic formula. Heat shock was administered by raising the chamber temperature to 42°C for 20 min, 3 h prior to endotoxin ingestion. Results: Heat shock pretreatment increased the expression of HSP70 in the ileal tissue and attenuated histological severity of early experimental NEC. NF-ĸB was activated in the ileal tissue of the NEC group and this activation was attenuated by heat shock pretreatment, which was determined by electrophoretic mobility shift assay and Western blot analysis of p50 in subcellular fractionated samples. Conclusions: Heat shock pretreatment reduced the incidence and severity of early experimental NEC in rats. A possible mechanism underlying this protective effect includes inhibition of NF-ĸB activation through increased HSP70 expression.
[Show abstract][Hide abstract] ABSTRACT: A nationwide survey was conducted to determine the incidence of bronchopulmonary dysplasia (BPD) in Korea and the intercenter differences in survival and BPD rates among preterm infants. Questionnaires were sent to all registered neonatal intensive care units (NICUs). The questionnaires inquired about the survival and BPD rates of very low birth weight (VLBW, < 1,500 g) infants who had been admitted to each NICU from 2007 to 2008. BPD was defined as requiring oxygen at 36 weeks' postmenstrual age. Almost all level III NICUs replied. During the study period, 3,841 VLBW infants were born in the NICUs that responded to the survey. The survival rate was 81% and the BPD rate was 18%. Combined outcome of BPD or death rate was 37%. The BPD rate and combined outcome of BPD or death rate varied considerably from 5% to 50% and 11% to 73%, respectively across the centers. There was no significant correlation between the survival rate and the BPD rate across the centers. In conclusion, the incidence of BPD among VLBW infants in Korea during the study period was 18%, and a considerable intercenter difference in BPD rates was noted.
Preview · Article · Aug 2012 · Journal of Korean medical science
[Show abstract][Hide abstract] ABSTRACT: To determine whether neurally adjusted ventilatory assist (NAVA), a new method of mechanical ventilation that delivers pressure assistance that is proportional to the electrical activity of the diaphragm (EAdi), could lower the inspiratory pressure and respiratory muscle load in preterm infants supported with ventilators.
Twenty-six mechanically ventilated preterm infants were randomized to crossover ventilation with NAVA and synchronized intermittent mandatory ventilation (SIMV) with pressure support (PS) for 4 hours each in a randomized order. A 1-hour interval for washout was provided between the 2 modes of ventilation. The ventilator settings were adjusted to maintain similar levels of end-tidal partial pressure of CO(2). The ventilator parameters, vital signs, and gas exchange effects under the 2 ventilatory modes were compared.
Nineteen infants completed the 9-hour crossover comparison protocol. Peak inspiratory pressure (PIP), work of breathing, and peak EAdi with NAVA were lower than those in SIMV with PS. Calculated tidal volume to peak EAdi ratio and PIP to peak EAdi ratio were higher with NAVA. There were no significant differences in mean airway pressure, inspiratory oxygen fraction, and blood gas values. The measurements of vital signs did not differ significantly between the 2 modes.
NAVA lowered PIP and reduced respiratory muscle load in preterm infants at equivalent inspiratory oxygen fraction and partial pressure of CO(2) of capillary blood in comparison with SIMV with PS.
No preview · Article · Jun 2012 · The Journal of pediatrics