[show abstract][hide abstract] ABSTRACT: There were many reports of longitudinal changes in the causative organisms of neonatal sepsis in Western countries but few in Asia. We aimed to study longitudinal trends in the epidemiology of neonatal sepsis at Seoul National University Children's Hospital (SNUCH), a tertiary center in Korea, and compared the results to previous studies of Western countries. The medical records of all of the neonates who were hospitalized at SNUCH from 1996 to 2005 with positive blood cultures were reviewed. We also compared the findings to previous 16-yr (1980-1995). One hundred and forty-nine organisms were identified in 147 episodes from 134 infants. In comparison with the previous 16-yr studies, there was a decrease in the number of Escherichia coli infections (16.2% vs 8.7%: odds ratio [OR] 0.495; 95% confidence interval [CI], 0.255-0.962; P = 0.035), but an increase in Staphylococcus aureus (16.6% vs 25.5%: OR 1.720; 95% CI, 1.043-2.839; P = 0.033) and fungal infections (3.3% vs 18.7%: OR 6.740; 95% CI, 2.981-15.239; P < 0.001), predominantly caused by Candida species. In conclusion, the incidence of sepsis caused by E. coli decreases, but S. aureus and fungal sepsis increases significantly. Compared with Western studies, the incidence of sepsis caused by S. aureus and fungus has remarkably increased.
Journal of Korean medical science 02/2011; 26(2):284-9. · 0.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: To test the hypothesis that intrauterine inflammation increases prostaglandin production and may be a risk factor for persistent ductus arteriosus after therapy with indomethacin, a nonselective cyclooxygenase inhibitor.
Indomethacin therapy was started after confirming ductus arteriosus within 24 hours after birth in extremely low birth weight infants. After one cycle of therapy, infants with closed ductus were classified as responders, and those with patent ductus were classified as nonresponders. Multiple logistic regression analysis was used to determine important perinatal factors associated with persistent ductus arteriosus. Immunohistochemistry with cyclooxygenase antibodies and radioimmunoassay by 6-keto prostaglandin F(1α) kit were used to determine the relationship between intrauterine inflammation and ductal patency.
Forty-one infants were responders, and 37 infants were nonresponders. Responders were frequently small for gestational age; nonresponders frequently had lower gestational age, respiratory distress syndrome, and intrauterine inflammation. By multiple logistic regression analysis, respiratory distress syndrome and intrauterine inflammation were more frequent in nonresponders. Cyclooxygenase-1 expression in the umbilical arteries and plasma 6-keto prostaglandin F(1α) levels were higher in nonresponders.
Respiratory distress syndrome and intrauterine inflammation were independent risk factors for persistent ductus arteriosus after indomethacin therapy in extremely low-birth weight infants. Intrauterine inflammation may have a negative influence on ductus arteriosus closure via increased cyclooxygenase-1 activity.
The Journal of pediatrics 11/2010; 157(5):745-50.e1. · 4.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: to investigate serial changes of lung morphology and biochemical profiles in a rat model of bronchopulmonary dysplasia (BPD) induced by intra-amniotic lipopolysaccharide (LPS) administration and postnatal hyperoxia (85%).
we evaluated histological changes of the lungs and compared the levels of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and protein carbonyl in lung tissue on days 1, 7, and 14 after birth in a rat model of BPD.
the inhibition of alveolarization was sustained in the LPS plus hyperoxia group from day 7 to 14, whereas alveolarization resumed in the hyperoxia group after oxygen exposure was withdrawn at day 7. Administration of LPS alone did not adversely affect lung morphometry. IL-6 levels showed transient overexpression at day 1 in the LPS-treated groups, but decreased at days 7 and 14. VEGF protein levels were elevated in the LPS-treated groups, but not in the hyper-oxia and control groups at days 1, 7, and 14. Exposure to hyperoxia affected protein carbonyl levels in the hyperoxia group at days 7 and 14.
lung injury induced by intra-amniotic inflammation and postnatal hyperoxia may be due to inhibition of alveolarization without recovery even after withdrawal of oxygen.
Journal of Perinatal Medicine 11/2010; 38(6):675-81. · 1.95 Impact Factor
[show abstract][hide abstract] ABSTRACT: Perinatal stroke in neonates can lead to disability in later life. However, its etiology and prognosis are poorly understood. The aim of this study was to describe clinical presentations and neurodevelopmental outcomes of our case series of perinatal stroke in Korea. Thirteen term and preterm neonates who were diagnosed with perinatal stroke in two university hospitals from March 2003 to March 2007 were enrolled. Seven term and 6 preterm neonates were diagnosed with perinatal stroke, based on the brain MRI findings. Perinatal stroke presented with seizure (4/13), perinatal distress (3/13) in term neonates, whereas stroke in preterm neonates did not present with noticeable clinical symptoms. Only one neonate had positive thrombophilic test (homozygous C677T polymorphism for MTHFR). Ten neonates had infarctions in the territory of the middle cerebral artery (MCA), and 3 neonates had borderzone infarctions between the anterior cerebral artery and MCA. Neurodevelopmental outcome was abnormal in 4 neonates. Infarction in MCA main branch or posterior limb of internal capsule showed an abnormal neurodevelopmental outcome. Our study is the first systematic study of perinatal stroke in Korea, and shows its clinical presentations and neurodevelopmental outcomes. The population-based study on incidence and prognosis of perinatal stroke in Korea is required in the future.
Journal of Korean medical science 06/2010; 25(6):888-94. · 0.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: Periventricular-intraventricular hemorrhage (PV-IVH) is a major cause of neurological disabilities in preterm newborns. This study aimed to determine the perinatal factors associated with PV-IVH. We conducted a retrospective case-control study from preterm infants born at < or =34 weeks of gestation and admitted to Neonatal Intensive Care Units of Seoul National University Children's Hospital and Seoul National University Bundang Hospital between June 2003 and December 2007. Neonates with no cranial sonographic data or infants transferred from other centers after three days of age were excluded. Of 1,044 eligible subjects, 59 infants with PV-IVH grade 2, 3, and 4 were allocated to the case group. The control group consisted of 118 infants without PV-IVH who were matched for gestational age and birth weight to each case of PV-IVH. At the multivariate logistic regression model, metabolic acidosis (odds ratio [OR]: 6.94; 95% confidence interval [CI]: 1.12-43.23) and use of inotropes (OR: 3.70; 95% CI: 1.16-11.84) were associated with an increased risk of PV-IVH. Maternal use of antenatal corticosteroids decreases the risk of PV-IVH (OR: 0.36; 95% CI: 0.14-0.92).
Journal of Korean medical science 03/2010; 25(3):418-24. · 0.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: With the increasing survival of preterm infants, pulmonary hypertension (PH) related to bronchopulmonary dysplasia (BPD) has become an important complication. The aim of this study was to investigate the characteristics and outcome of PH in preterm infants with BPD and to identify the risk factors for PH.
We reviewed the records of 116 preterm infants with BPD cared for at a single tertiary center between 2004 and 2008.
Twenty-nine (25%) infants had PH >2 months after birth. PH occurred initially at a median age of 65 days (range, 7-232 days). Severe BPD, a birth weight <800 g, long-term ventilator care and oxygen supplementation, a high ventilator setting, infection, and a patent ductus arteriosus (PDA) were related to PH based on univariate analysis (p<0.05). The infants who had longer oxygen supplementation were significantly more likely to have PH (odds ratio, 18.5; 95% confidence interval, 4.1-84.6; p<0.001). PH was improved in 76% of infants after a median of 85 days (range, 20-765 days). Four infants (14%) died. The death of 3 infants was attributed to PH.
BPD was frequently complicated by PH. Although PH resolved in the majority of infants, PH in preterm infants with BPD can be fatal. Regular screening for PH and adequate management are required.
[show abstract][hide abstract] ABSTRACT: The purpose of this study was to examine the clinical applicability of Doppler sonography by evaluating Doppler sonographic findings in an experimental rabbit model of necrotizing enterocolitis (NEC).
Necrotizing enterocolitis was experimentally induced using a combination of endotoxin, hypoxia, and cold stress in 23 rabbits. Doppler sonography was performed to obtain the Doppler spectrum of the superior mesenteric artery. From the flow profile, the peak systolic velocity (PSV) and resistive index (RI) were calculated at 5 time sessions: initial and 1 to 2, 3 to 4, 5 to 6, and 20 to 24 hours. Animals were divided into 2 groups based on pathologic NEC scores (NEC-positive [NEC+] group versus NEC-negative [NEC-] group). Differences between the groups with regard to RI and PSV values were evaluated for each time session.
Comparison of RI and PSV values between the NEC+ and NEC- groups revealed a significant increase in the PSV in the NEC+ group during the 1- to 2-hour session (P = .0199). Comparison of RI and PSV differences revealed a significant increase in RI and PSV differences in the NEC+ group during the 1- to 2-hour session (P = .0095 and .0013, respectively). In the other time sessions, there was no difference between the groups.
The NEC+ group showed a significant increase in the PSV and RI during the 1- to 2-hour period.
Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 03/2010; 29(3):379-86. · 1.40 Impact Factor
[show abstract][hide abstract] ABSTRACT: The use of amplitude-integrated electroencephalography (aEEG) is increasing during the neonatal intensive care of preterm infants.
This prospective study was designed to assess factors that affect the maturation of aEEG activity in preterm infants with a gestational age (GA) of <32 weeks.
aEEGs with cerebral function monitoring were performed weekly in preterm infants, and the recordings were evaluated and scored to assess the degree of continuity, the degree of sleep-wake cycling, and the amplitude of the lower border. Subjects with any of the following conditions were excluded: intraventricular hemorrhage or periventricular leukomalacia on cranial ultrasonography, sedation, hypotension, or respiratory instability (FiO(2) >50%).
The authors analyzed 207 recordings in 35 infants (GA 24-31 weeks, birth weight 440-1,980 g, postmenstrual age 25-38 weeks). At postmenstrual age 34-36 weeks, the aEEG total score was higher in preterm infants with a GA from 24 to 28 weeks than in less premature infants with a GA from 29 to 31 weeks (aEEG total score 12 vs. 10, p < 0.05). Logistic regression analysis revealed that the sleep-wake cycling was more prominent in infants with higher postnatal age (OR 3.32, 95% CI 2.40-4.59) or those receiving aminophylline (OR 3.28, 95% CI 1.06-10.08).
The maturation of aEEG activity was found to be significantly correlated with postnatal age and with aminophylline use in clinically stable preterm infants. Most notably, aminophylline was found to be significantly associated with the degree of sleep-wake cycling as indicated by aEEG activity.
[show abstract][hide abstract] ABSTRACT: The authors previously demonstrated the priming effect of intra-amniotic lipopolysaccharide (LPS) on hyperoxic lung injury in a rat model of bronchopulmonary dysplasia (BPD).
To investigate the mechanism underlying this priming effect by determining biochemical profiles in a rat model of BPD.
The rat model involved intra-amniotic LPS administration and postnatal hyperoxia (85%). The mRNA expressions of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), basic fibroblast growth factor (bFGF), and transforming growth factor beta(1) (TGF-beta(1)), as well as the protein levels of IL-6, VEGF, and protein carbonyl in lung tissue were compared between the LPS plus hyperoxia, the LPS only, the hyperoxia only, and the control groups.
Morphometric analysis of lung tissues demonstrated that alveolarization was significantly inhibited only in the LPS plus hyperoxia group. IL-6 protein levels and its mRNA expression in the lungs were significantly increased only in the LPS plus hyperoxia group. Neither LPS nor hyperoxia increased IL-6 in the lungs independently. bFGF mRNA expression was significantly decreased in the LPS-treated groups. VEGF protein levels were significantly reduced by hyperoxia, whereas protein carbonyl levels were increased by intra-amniotic LPS or hyperoxia. No additional significant change to VEGF or protein carbonyl levels was produced by intra-amniotic LPS or hyperoxia. There were no significant differences in the mRNA expressions of VEGF, VEGFR-2, and TGF-beta(1).
The priming effect of intra-amniotic LPS on hyperoxic lung injury may be associated with IL-6 elevation in the lungs.
[show abstract][hide abstract] ABSTRACT: Neonatal hypoxic-ischemic brain injury (HIE) remains a major cause of neurologic disabilities. However, many experimental therapies have shown limited successes. We assessed whether human mesenchymal stem cells (MSCs) could be transplanted in the HIE rat brain to improve neurologic disabilities. P7 SD rats were either subjected to left carotid artery ligation and hypoxic exposure [hypoxia-ischemia (HI)] or sham operation and normoxic exposure (sham). On P10, rat pubs received either PKH26-labeled MSCs or buffer via intracardial injection, resulting in four experimental groups: sham-buffer, sham-MSC, HI-buffer, and HI-MSC. Cylinder test and accelerating rotarod test were performed 14, 20, 30, and 40 d after injection. Six weeks after injection, cresyl violet and double immunofluorescence staining were performed. MSCs were transplanted to the whole brain mainly after HI. Glial fibrillary acidic protein and OX42 were more abundantly colocalized with MSC than neuronal specific nuclear protein or myelin basic protein. There were no significant differences in the total amounts and cell types between the lesioned and nonlesioned hemisphere. The lesioned hemispheric volume was decreased after HI (p = 0.012) but not restored by MSC. Neurologic performance was significantly impaired only on the cylinder test after HI (p = 0.034), and MSC transplants improved it (p = 0.010). These suggest MSC can be a candidate for the treatment of neonatal HIE.
Pediatric Research 10/2009; 67(1):42-6. · 2.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: Differentiation of serious bacterial infection (SBI) from self-limiting viral illness in febrile infants younger than three months is a significant challenge for clinicians. We aimed to assess the risk factors for SBI in febrile infants. Data were obtained from 221 infants younger than three months who visited a single community referral hospital for fever and underwent a complete sepsis workup between August 2003 and July 2006. The causes of fever were febrile illness without a documented cause (FISDC, 65%), urinary tract infection (UTI, 12%), aseptic meningitis (12%), bacteremia (4%), bacterial meningitis (2%). Cerebrospinal fluid enterovirus polymerase chain reaction was positive in 28% of FISDC and 48% of aseptic meningitis cases. When UTI was excluded, the risk factors for SBI were 1) C-reactive protein (CRP) level of > or =1.87 mg/dL and 2) fevers of > or =38.9 degrees C. The specificity and negative predictive values of risk factors 1) and 2) for the diagnosis of SBI were 94% and 95%, respectively. We concluded that enteroviral infection may be a major cause of febrile episodes in infants younger than three months. If UTI could be excluded, the presence of CRP levels > or =1.87 mg/dL and fevers of > or =38.9 degrees C can be used as criteria to rule out SBI in these infants.
Journal of Korean medical science 10/2009; 24(5):844-8. · 0.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: To determine the validity of a repeat thyroid function test for preterm infants, and to investigate factors that influence thyroid function of preterm infants, thyroid functions of 105 infants born at <32 weeks' gestational age were evaluated. Initial serum free thyroxine (fT4) and thyrotropin (TSH) levels were measured during the first 10 days of life, and repeated tests were performed more than 2 weeks apart. We analyzed the effects of gestational age, systemic diseases, and nutrition on the development of thyroid dysfunction. Thirty-one infants (30%) had low fT4 levels (<0.7 ng/dL) in the absence of elevated TSH levels (<7 microU/mL). Thirteen infants (12%) had hypothyroidism (fT4 <0.7 ng/dL, TSH >or=10 microU/mL) and mean age at diagnosis was 28+/-17 days. Twelve infants had moderately elevated TSH (TSH 10-30 microU/mL) with normal fT4 levels after 1 week of postnatal life. The history of undergone surgical procedure which needed iodine containing disinfectants was significantly frequent in the infant with hypothyroidism and transient TSH elevation. Repeated thyroid function tests are necessary for preterm infants, even though they initially show normal thyroid function, and are especially important for infants who have been exposed to excessive or insufficient levels of iodine.
Journal of Korean medical science 08/2009; 24(4):627-31. · 0.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: The pathogenesis of coarctation of the aorta (CoA) has not been clearly elucidated. It is hypothesized that CoA patients have abnormal extension of ductal tissue into the aorta which plays some pathogenic role. The aim of this study was to investigate the extension of ductal tissue into the aorta in CoA patients by comparative analysis of ductal and aortic tissue histopathology, smooth muscle cell (SMC) phenotypes and apoptosis.
Fifteen cases of surgically resected specimens including coarctation segment (CS), ductus arteriosus (DA) and transition zone (TZ) were histologically reviewed. SMC phenotypes were determined by immunohistochemistry for myosin heavy chain isoforms SM1, SM2, SMemb and α-smooth muscle actin. Apoptotic cell death was estimated by the TUNEL method.
A considerable amount of ductal tissue was found in CS and TZ in all investigated cases. CS showed a histologic pattern similar to that of closing DA. CS showed the least differentiated SMC phenotype and TZ intima displayed SMC phenotype more similar to that of DA than that of the normal aorta. TUNEL-positive cell deaths were frequently found in the media of both CS and DA, but absent in TZ.
Abnormal extension of ductal tissue into the aorta in CoA patients was indicated by similar histology and shared apoptosis. SMC phenotypic modulation may be involved in the formation of CoA. Our results strongly support the hypothesis that abnormal extension of ductal tissue in the aorta plays a crucial role in the pathogenesis of CoA.
International journal of cardiology 07/2009; 145(2):177-82. · 7.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Antenatal inflammation is a known risk factor of bronchopulmonary dysplasia. The authors hypothesized that lipopolysaccharide (LPS) administration amplifies hyperoxia-induced lung injury in neonatal rats. LPS (0.5 or 1.0 microg) or normal saline was injected into the amniotic sacs of pregnant rats at 20 d gestation (term 22.5 d). After birth, rats were exposed to 85% oxygen or room air for 1 or 2 wk. Morphometric analysis of lungs was performed on 14 d. One week of hyperoxia without LPS administration resulted in modest lung injury. LPS at 0.5 microg alone did not alter lung morphology, but amplified the effect of 1 wk of hyperoxia resulting in marked inhibition of alveolarization (airspaces were enlarged and alveolar surface areas further reduced). LPS at 1.0 microg independently induced modest lung injury and also amplified the effect of 1 wk of hyperoxia. However, this sensitizing effect of LPS was not observed in rats subjected to 2 wks of hyperoxia, which in itself caused extensive lung injury (possibly masking the effect of LPS). The authors concluded that intra-amniotic LPS sensitizes neonatal rat lungs, and thus, amplifies the hyperoxia-induced inhibition of alveolarization.
Pediatric Research 04/2009; 65(3):323-7. · 2.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: Functional closure and subsequent remodeling of the ductus arteriosus (DA) are essential for postnatal adaptation. Very preterm infants often fail to accomplish this process spontaneously. Histologic studies on human DA have shown that the closing ductus exhibits progressive intimal thickening and cell death of muscle media, which was verified by recent animal studies.
To analyze the histologic findings of preterm infants' DA in relation to their clinical parameters and to investigate the histologic difference between preterm and term DAs.
Histology of 14 preterm DAs and 13 term DAs obtained from surgery was analyzed. We examined hematoxylin and eosin staining and van Gieson staining for the elastic tissue. Cell death was determined with the in situ apoptosis detection technique.
The histologic findings of preterm DAs showed apparent correlations with clinical parameters, especially birth weight. Preterm DA histology was significantly different from that of term DAs in the extent and degree of intimal thickening. Cytolytic necrosis where TUNEL-positive cell deaths were prominent was observed mainly in term DAs.
The results of this study indicate that insufficient intimal thickening and scarcity of cell deaths in the DA may play a significant role in the pathogenesis of the persistently patent DA in preterm infants.
Early human development 12/2008; 85(3):181-6. · 2.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: Maternal chorioamnionitis has been associated with abnormal lung development. We examined the effect of maternal chorioamnionitis on the expression of transforming growth factor-beta1 (TGF-beta1) in the lungs of preterm infants. A total of 63 preterm (<or=34 weeks) infants who were intubated in the delivery room were prospectively enrolled. Their placentas were examined for the presence of chorioamnionitis. Bronchoalveolar lavage (BAL) fluid and cells were obtained shortly after birth. TGF-beta1 was measured in BAL fluid and TGF-beta1 mRNA expression was determined by reverse transcription polymerase chain reaction (RT-PCR) in BAL cells. TGF-beta1 mRNA expression in BAL cells showed a positive correlation with gestational age (r=0.414, p=0.002). TGF-beta1 mRNA expression was significantly decreased in the presence of maternal chorioamnionitis (0.70+/-0.12 vs. 0.81+/-0.15, p=0.007). Adjustment for gestational age, birth weight, and delivery mode did not nullify the significance. TGF-beta1 mRNA expression was marginally significantly decreased in preterm infants who developed bronchopulmonary dysplasia (BPD) later (0.75+/-0.11 vs. 0.82+/-0.15, p=0.055). However, adjustment for gestational age, patent ductus arteriosus (PDA), and maternal chorioamnionitis nullified the significance. These results might be an indirect evidence that maternal chorioamnionitis may inhibit normal lung development of fetus.
Journal of Korean Medical Science 09/2008; 23(4):609-15. · 1.25 Impact Factor
[show abstract][hide abstract] ABSTRACT: A considerable number of preterm infants may have been exposed to inflammation in utero and may be born with an inflamed lung.
To determine the impact of antenatal lung injury and inflammatory response on the pathogenesis of bronchopulmonary dysplasia (BPD) according to its clinical pattern, using KL-6 (as a lung injury marker) and C-reactive protein (CRP) (as a marker of inflammatory response).
In this case-control study, a total of 74 infants (<32 weeks of gestation) including BPD with minimal early lung disease ('atypical'; 21 infants), BPD with significant early lung disease ('classic'; 29 infants) and the non-BPD (24 infants) groups underwent KL-6 and CRP in cord blood determinations.
The cord plasma KL-6 levels were significantly higher in the atypical and the total BPD groups than in the non-BPD group (median = 60.9 vs. 34.5 U/ml, p = 0.031; 43.5 vs. 34.5 U/ml, p = 0.02). However, the cord plasma CRP levels were not significantly different among the study groups. The cord plasma KL-6 levels in patients with atypical BPD were significantly higher in infants with moderate or severe BPD than in infants with mild BPD (median = 88.3 vs. 41.5 U/ml, p = 0.041) and were found to be significantly correlated with the duration of oxygen therapy (r = 0.502, p = 0.024).
The present study shows that cord plasma KL-6, a specific lung injury marker, is increased and objectively reflects disease severity in atypical BPD.