Clinical features and prognostic factors of early-onset sepsis: a 7.5-year experience in one neonatal intensive care unit / 소아과

PURPOSE: In this study, we investigated the clinical features and prognostic factors of early-onset sepsis (EOS) in neonatal intensive care unit (NICU) patients. METHODS: A retrospective analysis was conducted on medical records from January 2010 to June 2017 (7.5 years) of a university hospital NICU. RESULTS: There were 45 cases of EOS (1.2%) in 3,862 infants. The most common pathogen responsible for EOS was group B Streptococcus (GBS), implicated in 10 cases (22.2%), followed by Escherichia coli, implicated in 9 cases (20%). The frequency of gram-positive sepsis was higher in term than in preterm infants, whereas the rate of gram-negative infection was higher in preterm than in term infants (P < 0.05). The overall mortality was 37.8% (17 of 45), and 47% of deaths occurred within the first 3 days of infection. There were significant differences in terms of gestational age (26.8 weeks vs. 35.1 weeks) and birth weight (957 g vs. 2,520 g) between the death and survival groups. After adjustments based on the difference in gestational age and birth weight between the 2 groups, gram-negative pathogens (odds ratio [OR], 42; 95% confidence interval [CI], 1.4–1,281.8) and some clinical findings, such as neutropenia (OR, 46; 95% CI, 1.3–1,628.7) and decreased activity (OR, 34; 95% CI, 1.8–633.4), were found to be associated with fatality. CONCLUSION: The common pathogens found to be responsible for EOS in NICU patients are GBS and E. coli. Gram-negative bacterial infections, decreased activity in the early phase of infection, and neutropenia were associated with poor outcomes.

Lung Ultrasonography Score as a Respiratory Parameter of Respiratory Distress Syndrome in Very Preterm Infants: A Single Center Experience

PURPOSE: Comparison between lung ultrasound (LUS) score and indices of respiratory severity in very preterm infants born at 28 to 31 weeks' gestation. METHODS: We retrospectively reviewed medical records of 32 very preterm infants born at 28 to 31 weeks' gestation at Keimyung University Dongsan Medical Center. Before surfactant administration, bedside LUS in the neonatal intensive care unit was recorded within the first hour of life. Partial pressure of capillary oxygen to fraction of inspired oxygen ratio (PcO2)/FiO2, alveolar-arterial gradient (A-aO2), modified oxygenation index (OI), and arterial to alveolar ratio were calculated. Correlation between LUS score and indices of respiratory severity were analyzed between the intubation and nasal continuous positive airway pressure (NCPAP) groups depending on the presence or absence of endotracheal intubation. RESULTS: Mean LUS scores, A-aO2, and modified OI in the intubation group were significantly higher than those in the NCPAP group. Conversely, PcO2/FiO2 and arterial to alveolar ratios in the intubation group were significantly lower than those in the NCPAP group. LUS score was found to be significantly correlated with A-aO2 (r=0.448, P>0.05) and modified OI (r=0.453, P>0.05), but not with PcO2/FiO2 ratio (r=−0.205, P0.05). CONCLUSION: The LUS score is well correlated with indices of respiratory severity in very preterm infants born at 28 to 31 weeks' gestation. Further investigation is needed to use LUS as an alternative tool in infants with respiratory distress.

Amino Acid-Based Formula in Premature Infants with Feeding Intolerance: Comparison of Fecal Calprotectin Level / 대한소아소화기영양학회지

PURPOSE: We investigated fecal calprotectin (FC) levels in preterm infants with and without feeding intolerance (FI), and compared the FC levels according to the type of feeding. METHODS: The medical records of 67 premature infants were reviewed retrospectively. The fully enteral-fed infants were classified into two groups; the FI group (29 infants) and the control group (31 infants). Seven infants with necrotizing enterocolitis, sepsis, and perinatal asphyxia were excluded. If breast milk (BM) or preterm formula (PF) could not be tolerated by infants with FI, amino acid-based formula (AAF) was tried temporarily. Once FI improved, AAF was discontinued, and BM or PF was resumed. We investigated the FC levels according to the type of feeding. RESULTS: Significant differences were found in gestational age, birth weight, age when full enteral feeding was achieved, and hospital stay between the FI and control group (p 0.05). CONCLUSION: The FC levels in AAF-fed infants with FI showed significantly lower than those in the BM- or PF-fed infants with FI. The mitigation of gut inflammation through the decrease of FC levels in AAF-fed infants with FI could be presumed.

Lung Ultrasonography for the Diagnosis of Respiratory Distress Syndrome in Late Preterm Infants: Changing Incidence – A Single Center Experience

PURPOSE: Ultrasonography is non-ionizing, easy to operate, and performed at bedside in neonatal intensive care unit (NICU). We investigated the incidence of respiratory distress syndrome (RDS) with or without using lung ultrasound (LUS) in late preterm infants with postnatal respiratory difficulties. METHODS: We retrospectively reviewed medical records of 494 late preterm infants born at 34–36 weeks' gestation at Keimyung University Dongsan Medical Center. Fifty infants with postnatal respiratory difficulties were admitted to the NICU between May 2015 to October 2015 (period I), and forty-one were between November 2015 to February 2016 (period II). The diagnosis of RDS was based on chest radiography in period I. LUS was additionally performed at bedside in period II. All infants with RDS were received exogenous surfactant therapy. RESULTS: The overall incidence of RDS with surfactant replacement therapy was decreased in period II period II (9.4%, 20/212) compared to period I (14.5%, 41/282) (P=0.088). In terms of infants with postnatal respiratory difficulties, the incidence of RDS in period II (48.8%, 20/41) was significantly lower than that in period I (82.0%, 41/50) (P=0.001). There are no difference in the rate of reintubation, repeated doses of surfactant, oxygen demand at 48 hours after birth, air leak syndrome, pulmonary hemorrhage, persistent pulmonary hypertension of newborn, and mortality (P> 0.05). CONCLUSION: We could decrease the incidence of RDS with surfactant replacement therapy by using LUS in late preterm infants with postnatal respiratory difficulties. Further prospective studies are needed to apply LUS clinically to diagnose RDS.

Neuroprotective effects of erythropoietin against hypoxic injury via modulation of the mitogen-activated protein kinase pathway and apoptosis / 소아과

PURPOSE: Hypoxic-ischemic encephalopathy is a significant cause of neonatal morbidity and mortality. Erythropoietin (EPO) is emerging as a therapeutic candidate for neuroprotection. Therefore, this study was designed to determine the neuroprotective role of recombinant human EPO (rHuEPO) and the possible mechanisms by which mitogen-activated protein kinase (MAPK) signaling pathway including extracellular signal-regulated kinase (ERK1/2), JNK, and p38 MAPK is modulated in cultured cortical neuronal cells and astrocytes. METHODS: Primary neuronal cells and astrocytes were prepared from cortices of ICR mouse embryos and divided into the normoxic, hypoxia (H), and hypoxia-pretreated with EPO (H+EPO) groups. The phosphorylation of MAPK pathway was quantified using western blot, and the apoptosis was assessed by caspase-3 measurement and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. RESULTS: All MAPK pathway signals were activated by hypoxia in the neuronal cells and astrocytes (P<0.05). In the neuronal cells, phosphorylation of ERK-1/-2 and apoptosis were significantly decreased in the H+EPO group at 15 hours after hypoxia (P<0.05). In the astrocytes, phosphorylation of ERK-1/-2, p38 MAPK, and apoptosis was reduced in the H+EPO group at 15 hours after hypoxia (P<0.05). CONCLUSION: Pretreatment with rHuEPO exerts neuroprotective effects against hypoxic injury reducing apoptosis by caspase-dependent mechanisms. Pathologic, persistent ERK activation after hypoxic injury may be attenuateed by pretreatment with EPO supporting that EPO may regulate apoptosis by affecting ERK pathways.

Pulmonary Outcomes of Early Extubation in Extremely Premature Infants (Gestational Age: 25-26 Weeks) with Synchronized Nasal Intermittent Positive-Pressure Ventilation

PURPOSE: To investigate the pulmonary outcomes of early extubation (within the first 24 hours of life) with synchronized nasal intermittent positive pressure ventilation (NIPPV) in extremely premature infants born at 25-26 weeks' gestation. METHODS: Medical records of extremely premature infants (gestational age: 25-26 weeks) born and admitted to the Keimyung University Dongsan Medical Center between January 2015 and December 2015 (n=42) were reviewed retrospectively. The early extubation group included infants who were extubated within the first 24 hours of life and was compared with a control group that included infants who remained ventilated beyond the first 24 hours of life. Extubation failure was defined as the need for reintubation within 72 hours after extubation. RESULTS: Of the 35 enrolled infants, 22 (62.9%) were extubated within the first 24 hours of life. No significant differences in perinatal factors were observed between the early extubation and control groups. Between the two groups, the incidence rates of extubation failure (18.2% [4/22] vs. 7.7% [1/13], P=0.39), reintubation (50.0% [11/ 22] vs. 46.2% [6/13], P=0.84), mortality (18.2% [4/22] vs. 15.4% [2/13], P=0.83), and the combined rates of clinical bronchopulmonary dysplasia (BPD) or death (40.9% [9/22] vs. 38.5% [5/13], P=0.89) did not significantly differ. CONCLUSION: Early extubation (within the first 24 hours of life) with synchronized NIPPV is safe and effective in the extremely premature infants born at 25-26 weeks' gestation, and does not indicate increased risks of extubation failure and other morbidities.

Insulin and glucagon levels of umbilical cord blood in appropriate for gestational age - preterm infants with or without postnatal hypoglycemia

PURPOSE: To determine whether serum insulin and glucagon levels of umbilical cord blood correlate with subsequent postnatal hypoglycemia in appropriate for gestational age (AGA) - preterm infants at different gestational ages (GAs). METHODS: The serum insulin and glucagon levels of umbilical cord blood were measured using magnetic bead based multiplex immunoassay in 69 AGA - premature infants, stratified according to GA: GA 23-30 weeks, early preterm (EP, n=31); GA 31-34 weeks, late preterm (LP, n=38). Postnatal hypoglycemia was defined as a capillary glucose level <40 mg/dL within the first 60 minutes of life, regardless of GA. RESULTS: The capillary glucose concentration in EP infants (65.5±21.2 mg/dL) was significantly higher than that of LP infants (55.9±17.3 mg/dL) (P=0.043). The serum glucagon level in EP infants (44.3±28.7 pg/mL) was significantly higher than that in LP infants (28.1±13.6 pg/mL) (P=0.006). There was not a significant difference in serum insulin level between EP and LP infants (372.7±254.2 pg/mL vs. 372.4±209.1 pg/mL, P=0.996). There was a significant difference in the serum glucagon level between infants with and without hypoglycemia (27.7±8.9 mg/dL vs. 36.8±24.6 mg/dL, P=0.036), but not in the serum insulin level (451.9±256.9 pg/mL vs. 357.4±222.2 pg/mL, P=0.211). Postnatal glucose concentration within the first 60 minutes of life had a significant positive correlation with serum glucagon levels (r=0.256, P=0.034), but not with serum insulin levels (r=-0.020, P=0.867). CONCLUSION: Lower glucagon levels of cord blood were seen in premature infants with higher GA, which might contribute to the occurrence of postnatal hypoglycemia.

Insulin and glucagon levels of umbilical cord blood in appropriate for gestational age - preterm infants with or without postnatal hypoglycemia

PURPOSE: To determine whether serum insulin and glucagon levels of umbilical cord blood correlate with subsequent postnatal hypoglycemia in appropriate for gestational age (AGA) - preterm infants at different gestational ages (GAs). METHODS: The serum insulin and glucagon levels of umbilical cord blood were measured using magnetic bead based multiplex immunoassay in 69 AGA - premature infants, stratified according to GA: GA 23-30 weeks, early preterm (EP, n=31); GA 31-34 weeks, late preterm (LP, n=38). Postnatal hypoglycemia was defined as a capillary glucose level <40 mg/dL within the first 60 minutes of life, regardless of GA. RESULTS: The capillary glucose concentration in EP infants (65.5±21.2 mg/dL) was significantly higher than that of LP infants (55.9±17.3 mg/dL) (P=0.043). The serum glucagon level in EP infants (44.3±28.7 pg/mL) was significantly higher than that in LP infants (28.1±13.6 pg/mL) (P=0.006). There was not a significant difference in serum insulin level between EP and LP infants (372.7±254.2 pg/mL vs. 372.4±209.1 pg/mL, P=0.996). There was a significant difference in the serum glucagon level between infants with and without hypoglycemia (27.7±8.9 mg/dL vs. 36.8±24.6 mg/dL, P=0.036), but not in the serum insulin level (451.9±256.9 pg/mL vs. 357.4±222.2 pg/mL, P=0.211). Postnatal glucose concentration within the first 60 minutes of life had a significant positive correlation with serum glucagon levels (r=0.256, P=0.034), but not with serum insulin levels (r=-0.020, P=0.867). CONCLUSION: Lower glucagon levels of cord blood were seen in premature infants with higher GA, which might contribute to the occurrence of postnatal hypoglycemia.

Clinical Findings According to Feeding Diets in Very Low Birth Weight Infants: Human Breast Milk versus Bovine Milk-Based Formula

PURPOSE: We aimed to compare the clinical findings, including morbidity, duration of parenteral nutrition, and length of hospital stay between very low birth weight infants (VLBWIs) fed bovine milk-based formula (BOV) and VLBWIs fed human breast milk (HBM) in a neonatal intensive care unit (NICU). METHODS: VLBWIs admitted to the NICU of Dongsan Medical Center, Keimyung University, were enrolled. Infants born from March to August 2014 (n=28) were fed BOV (the BOV group), and those born from September to December 2014 (n=18) were fed HBM (the HBM group). Pasteurized (heating at 62.5degrees C for 30 minutes) donor human milk was used if the mother's own milk was not available because of insufficient breast milk production. RESULTS: The gestational age (28.0+/-1.7 weeks vs. 27.8+/-1.4 weeks) and birth weight (1,055+/-265 g vs. 1,175+/-187 g), of the infants in the BOV and HBM, groups were similar. In addition, perinatal characteristics were similar between the groups. The duration of parenteral nutrition (36.4 days vs. 24.1 days, P=0.038), length of hospital stay (74.3 days vs.61.1 days, P=0.037), and incidence of nosocomial sepsis (53.6% vs. 22.2%, P=0.035), significantly differed between the BOV and HBM groups. Furthermore, the frequency of feeding intolerance was higher in the BOV group than in the HBM group, but this difference was not significant. Perinatal cytomegalovirus infection was not detected in any of the infants fed pasteurized donor human milk. CONCLUSION: Human-breast-milk-based diet for VLBWIs significantly reduces the incidence of nosocomial sepsis, duration of parenteral nutrition, and length of hospital stay.

Early-onset Pericardial Effusion after Peripherally Inserted Central Venous Catheterization in a Preterm Infant / 대한주산의학회잡지

Peripherally inserted central venous catheters (PICC) are commonly used to provide long term intravascular access for parenteral nutrition and medications in preterm infants, but rarely life-threatening complications associated with malposition of catheter tip such as pericardial effusion may be developed. We report a preterm case of early-onset pericardial effusion related to PICC of which the distal part is angulated and located in the right atrium of heart.

The Effect of Combination Treatment of Melatonin and Hypothermia on Hypoxic-Ischemic Brain Injury in Neonatal Rats

PURPOSE: Melatonin is a naturally occurring hormone produced by the pineal gland. Melatonin has many pharmacological effects in different tissues or organs. Melatonin is especially known to have antioxidant and neuroprotective effects. Hypothermia is a therapeutic tool against hypoxia-ischemia (HI) of the brain. This study examines the effect of combined therapy using melatonin and hypothermia in neonatal rats with HI. METHODS: Seven-day old rats were subjected to HI and randomized into four groups : vehicle, melatonin alone, vehicle and hypothermia, and melatonin and hypothermia. Melatonin (30 mg/kg) was intraperitoneally administered in two doses: immediately following HI, and 24 h later. Hypothermia consisted of whole-body cooling (3 hours, 27degrees C). Sham-treated animals not subjected to HI were also studied. P10, P14, and P35 rats were sacrificed for experiments. RESULTS: Vehicle-treated P10 rats increased in brain infarction compared to controls in TTC staining study. And also, P35 rats decreased in brain volume of injured hemisphere in H&E stain. Melatonin or hypothermia alone did not show any protective effect against HI. However, a combination of melatonin and hypothermia effectively reduced the brain injury. In addition, the results of in situ zymography, TUNEL assay and immunofluorescence studies showed that neuroprotective effects were achieved only with combined therapy. CONCLUSION: Melatonin may contribute to synergistic effects to neuroprotection of hypothermia on brain damage after HI.

Oculocutaneous Albinism Type 1 Diagnosed by Genetic Study in a Newborn Infant / 대한주산의학회잡지

Oculocutaneous Albinism (OCA) is a heterogenous autosomal recessive disorder characterized by defective melanin biosynthesis. Physical findings including white scalp hair and depigmented skin of whole body in newborn infants are important clinical features of OCA 1. We report a newborn case of OCA 1 with two different TYR mutations, and gene defects of the baby revealed to be originated from both parents carriers of OCA.

Comparison of Clinical Findings of Gastric Perforation between Preterm and Term Neonates / 대한주산의학회잡지

PURPOSE: The purpose of this study was to compare the clinical findings and mortality of gastric perforation between preterm and term infants. METHODS: The medical records of neonates, admitted to the neonatal intensive care unit of Dongsan Medical Center for gastric perforation between July 1992 and June 2012, were reviewed retrospectively. The admission records of clinical findings and mortality were reviewed and statistically analyzed between preterm and term infants. RESULTS: Nine infants were diagnosed with neonatal gastric perforation. Of the nine infants, the number of term infants was five and the number of male was eight. Of the four infants diagnosed with spontaneous gastric perforation, the number of preterm and term infants was three and one respectively. The anatomical location of perforation was greater curvature in all four preterm infants. However, various sites such as greater curvature (three infants) and antrum (two infants) were observed in five term infants. Mortality rate was tended to be lower in preterm infants compared to term infants, without statistical significance (25.0% vs. 40.0%, P>0.1). There was no mortality in four infants diagnosed with spontaneous gastric perforation. However, two infants diagnosed with necrotizing enterocolitis (NEC) all died. CONCLUSION: There was no significant difference in clinical findings and mortality of gastric perforation between preterm and term infants. The prognosis of spontaneous gastric perforation was good, however, mortality rate was tended to be higher in NEC than other causes (P=0.083).

Surfactant Therapy in Severe Meconium Aspiration Syndrome

Meconium is a strong inactivator of pulmonary surfactant. The deficiency of surfactant or surfactant dysfunction may contribute to respiratory failure in a wide group of disorders, including meconium aspiration syndrome (MAS). We reviewed the effect of pulmonary surfactant therapy for severe MAS in ours as well as other countries. In general, surfactant therapy improves pulmonary oxygenation (oxygenation index or arterial/alveolar oxygen tension) and reduces the requirement for ventilation, and oxygen supplementation or hospitalization time. However, its effects on mortality and pulmonary or extrapulmonary complications are variable. In Korean studies, outborn infants are five times more common than inborn infants; therefore, the initial hospital care at delivery including adequate tracheal suctioning is important to improve the outcome of patients with severe MAS. To confirm the effect of surfactant therapy in MAS, additional well-designed, multicenter, randomized, controlled trials are needed. In addition, determining the optimal type of surfactant therapy (bolus, lavage, or combined) and the appropriate dose and duration of therapy is important.

Invasive Candida Infections in Extremely Preterm Infants

Invasive Candida infections (ICI) have become the third most common cause of late-onset infection among extremely preterm infants in the neonatal intensive care unit. Candida colonization of the skin and gastrointestinal tract is an important first step in the pathogenesis of invasive disease. Factors such as exposure to broad spectrum antimicrobials, especially third generation cephalosporin, parenteral nutrition including lipid emulsion, central venous catheter, and abdominal surgery increase the risk of invasive infection. A definite diagnosis of ICI requires isolation the organism from blood or other sterile body fluid. Thrombocytopenia is very common in neonatal candidiasis, but it is also often seen in babies with bacteremia. Candida is capable of invading all vital organs and following candidemia, therefore a thorough evaluation to rule out end organ dissemination is important. Amphotericin-B is the drug of choice for treating ICI. Antifungal susceptibility test is increasingly used to manage ICI, especially in situations refractory to initial antifugal therapy. Invasive candidiasis among extremely preterm infants is associated with chronic lung disease, severe retinopathy of prematurity, and neurodevelopmental impairment at infancy.

Breast Feeding Rates and Factors Influencing Breast Feeding Practice in Late Preterm Infants: Comparison with Preterm Born at Less than 34 Weeks of Gestational Age

PURPOSE: This study was done to compare breast feeding rates and factors influencing feeding practice between late preterm (34< or =GA<37) and preterm infants (GA<34). METHODS: A survey was done of 207 late preterm and 117 preterm infants in neonatal intensive care units (NICU) of 4 university hospitals in D city. Data were collected from July 2009 to June 2010 from 324 medical records in the NICU. Breast-feeding at home was checked either by telephone survey or questioning during hospital visits. RESULTS: Rate of breast feeding for late preterm infants was significantly lower than for preterm infants. There was no significant difference in breast-feeding at home. We found differences in factors influencing breast feeding between the two groups. Factors influencing feeding for late preterm infants were type of delivery, mothers' occupation, feeding type during hospitalization, time elapse from hospital discharge, total admission days, infant's body weight at first feeding and length of NPO (nothing by mouth). Factors influencing feeding for preterm infants were birth order, maternal disease and obstetric complications, and one-minute Apgar score. CONCLUSION: Results of the study show low rates of breast-feeding for late preterm infants indicating a need for breast-feeding education for mothers of these infants.

Clinical Features and Outcomes of Renal Mycetoma Complicated by Candida Sepsis in Newborn Infants

PURPOSE: The kidney is a common site of end organ involvement in patients with candidemia. This study was undertaken to investigate clinical features and outcomes of renal mycetoma complicated by Candida sepsis in neonates. METHODS: A retrospective analysis of the medical records and radiologic images was conducted in a neonatal intensive care unit over a 9-year period (2002-2010). RESULTS: During the study period, there were 69 episodes of Candida sepsis. C. albicans was the most common pathogen (49.2%), and C. parapsilosis was the second (42%), but emerging. Of the 42 patients who underwent ultrasound examination in early phase of infection, renal mycetoma was observed in 8 cases (19.1%). Renal mycetoma was more frequently developed in patients with C. albicans sepsis than those with non-albicans candidemia, but the result was not significant. The demographic characteristics of the two groups of patients who had Candida sepsis (with renal mycetoma vs. without renal mycetoma) were similar. Candiduria was more common in the mycetoma group (P<0.01). In addition, the duration of antifungal medication was longer in patients with mycetoma (P<0.001). On follow-up ultrasounds, improvement and resolution of renal echogenic lesions took a median time of 2 and 5 months respectively for the mycetoma group. CONCLUSION: Candiduria may be an initial sign of renal mycetoma complicated by Candida sepsis in newborn infants. Echogenic foci on the renal ultrasound are persistent for a considerable period after antifungal therapy, and therefore follow-up evaluations are important.

Clinical Features and Outcomes of Meconium Intestinal Obstruction in Preterm Infants / 대한주산의학회잡지

PURPOSE: This study was undertaken to investigate the clinical features and outcomes of meconium intestinal obstruction (MIO) in preterm infants. METHODS: A retrospective analysis of medical records and radiologic images was conducted in a neonatal intensive care unit over a 3-year period (2009-2011). In addition, birth year- and gestational age-matched babies were selected by random sampling with twice the number as the control group. RESULTS: There were 43 infants with MIO who were appropriate as subjects. In perinatal factors, a maternal history of hypertension and the use of magnesium sulfate were more frequent in patients with MIO, but not significant. Feeding intolerance was more common in the MIO group than the control (86% vs. 24.4%; P<0.001). The frequency of gastrografin enema was once in all but one of the patients, and the microcolon was detected in 7 cases (16.3%. Radiographic change after enema was seen earlier than clinical improvement (P<0.05).The patients with MIO took longer to achieve full enteral feeding, and had a more prolonged hospital stay (P<0.001). CONCLUSION: Feeding intolerance in preterm infants may be an early clinical finding of MIO. Meconium obstruction causes a delay of full enteral feeding and extension of hospital stay.

Haddad Syndrome with PHOX2B Gene Mutation in a Korean Infant

Congenital central hypoventilation syndrome with Hirschsprung's disease, also known as Haddad syndrome, is an extremely rare disorder with variable symptoms. Recent studies described that congenital central hypoventilation syndrome had deep relation to the mutation of the PHOX2B gene in its diagnosis and phenotype. We report a newborn male infant with clinical manifestations of recurrent hypoventilation with hypercapnea and bowel obstruction. These clinical manifestations were compatible with congenital central hypoventilation syndrome and Hirschsprung's disease, and polyalanine 26 repeats in the PHOX2B gene supported the diagnosis of congenital central hypoventilation. We described a first case of Haddad syndrome in Korean and its clinical and genetic characteristics were discussed.

Clinical Features of Late-Onset Sepsis with Fatal Outcome in Early Phase of Infection in Neonatal Intensive Care Unit Patients and Impact of Initial Antibiotic Therapy / 대한주산의학회잡지

PURPOSE: Late-onset sepsis (LOS) is a serious problem in the neonatal intensive care unit (NICU). This study was undertaken to investigate clinical features of LOS (occurring after 72 hours of age) with fatal outcome (lethal within 72 hours of onset) in early phase of infection in NICU patients and impact of initial antibiotic therapy. METHODS: Retrospective analysis of the medical records was conducted to find LOS in patients in a NICU of university hospital over an 8-year period (2001-2008). RESULTS: There were 455 episodes of blood culture-proven LOS in 388 (6.9%) of 5,608 infants who survived beyond 3 days of age. Gram-positive bacteria were the most common pathogen, accounting for 265 cases (58.2%), and were followed by fungi with 101 cases (22.2%) and Gram-negative bacteria with 89 cases (19.6%). Fatal outcome in early phase of infection occurred in 14 cases (3.1%), and the most prevalent organism of fatal infection was Klebsiella, accounting for 7 cases (50%). Both Candida and S. aureus caused 2 cases of sepsis with fatal outcome, and also Acinetobacter, E. coli and Enterococcus caused 1 case respectively. The fatal outcome was more frequently developed in patients with Gram-negative sepsis than those with Gram-positive or fungal infections (10.1% vs. 2.0% vs. 1.1%; P <0.05). In clinical findings of patients with fatal outcome, the median of age at onset of infection was 19 days (range: 6-94 days), and the interval between onset and death was 29 hours (range: 10-58 hours). Severe sepsis at onset of infection was developed in 7 cases (50.0%), and the use of adequate empirical antibiotics was done in 10 cases (71.4%) of them. CONCLUSION: LOS by Gram-negative bacteria may easily complicate with fatal outcome in neonates. It cannot be prevented with adequate empirical antibiotic therapy, and additional countermeasures against fatal infection are necessary in NICU.