Growth Pattern With Morbidities From Birth to 5 Years of Age in Very Low Birth Weight Infants: Comparison of the Korean National Network and National Health Insurance Service

Background@#Long-term growth data of very low birth weight (VLBW) infants are currently collected in the Korean Neonatal Network (KNN) and National Health Insurance Service (NHIS) database. However, variance in the number of infants, check-up time, and check-up parameters led to decreased credibility of cumulated data. We aimed to compare the data on serial growth outcomes by major morbidities from birth to 5 years in VLBW infants between the KNN and NHIS databases. @*Methods@#We combined the NHIS and KNN data of VLBW infants born between 2013 and 2015. The check-up times in the NHIS database were at 4–6, 9–12, 18–24, 30–36, 42–48, and 54–60 months of age, whereas in the KNN were at 18–24 months of corrected age and at 36 months of age.Result: Among 8,864 VLBW infants enrolled based on the birth certificates from the Statistics Korea, 6,086 infants (69%) were enrolled in the KNN, and 5,086 infants (57%) participated in the NHIS health check-up. Among 6,068 infants, 3,428 infants (56%) were enrolled at a corrected age of 18–24 months and 2,572 infants (42%) were enrolled at a chronological age of 33–36 months according to the KNN follow-up registry. However, based on the national birth statistics data, the overall follow-up rate of the KNN at 36 months of age was as low as 29%. The NHIS screening rate was lower at first (23%); however, it increased over time to exceed the KNN follow-up rate. Growth failure (weight under 10th percentile) at corrected ages of 18–24 months and 36 months were more common in the NHIS than KNN (42% vs. 20%, 37% vs. 34.5%). Infants with bronchopulmonary dysplasia and periventricular leukomalacia showed similar rates of growth failure at 2 years but varying rates at 3 years between the KNN and NHIS. @*Conclusion@#By integrating the KNN and NHIS data indirectly at continuous time points according to morbidities, we found that there are discontinuities and discrepancies between the two databases among VLBW infants. Establishing an integrated system by patient level linking the KNN and NHIS databases can lead to better understanding and improved neonatal outcomes in VLBW infants in Korea.

Epidemiology of Macrosomia in Korea: Growth and Development

Background@#Macrosomia, as an infant with birth weight over 4 kg, can have several perinatal, and neonatal complications. This study aimed to estimate the incidence of macrosomia in Korea and to identify the growth and developmental outcomes and other neonatal complications. @*Methods@#In total, 397,203 infants who were born in 2013 with birth weight ≥ 2.5 kg and who underwent infant health check-up between their 1 st and 7 th visit were included from the National Health Insurance Service database. The information was obtained by the International Classification of Diseases-10 codes or self-reported questionnaires in the National Health Screening Program. @*Results@#The distribution of infants by birth weight was as follows: 384,181 (97%) infants in the 2.5–3.99 kg (reference) group, 12,016 (3%) infants in the 4.0–4.49 kg group, 772 (0.2%) infants in the 4.5–4.99 kg group, and 78 (0.02%) infants in the ≥ 5 kg group. Macrosomia showed significantly higher incidence of sepsis, male sex, and mothers with GDM and birth injury. There was a significant difference in weight, height, and head circumference according to age, birth weight group, and combination of age and birth weight, respectively (P < 0.001). The number of infants with the weight above the 90 th percentile in macrosomia at each health check-up showed higher incidence than in reference group. The mean body mass index significantly differed among the groups, as 50.6 in infants with 2.5–3.99 kg of birth weight, 63.5 with 4.0–4.49 kg, 71.0 with 4.5–4.99 kg, and 73.1 with ≥ 5 kg. There was a significant difference in the incidence of poor developmental results between infants with macrosomia and the reference group at 24, 36 and 48 month of age. @*Conclusion@#Macrosomia was significantly associated with the risk of sepsis, birth injury, obesity and developmental problem especially in a boy born from mothers with gestational diabetes mellitus. Careful monitoring and proper strategies for monitoring growth and development are needed.

Hearing Impairments in Preterm Infants: Factors Asso ciated with Discrepancies between Screening and Con firmatory Test Results

Purpose@#The aim of the study was to investigate risk factors of hearing impairments in preterm infants and analyze factors associated with discrepancies between neonatal hearing screening (NHS) and confirmatory test results. @*Methods@#We analyzed the medical records of 352 preterm infants born at 23 to 32 weeks’ gestational age (GA) who underwent both automated auditory brainstem response (aABR) and confirmatory ABR (cABR). @*Results@#Mean GA, mean birth weight, the incidence of small for GA and cesarean section birth were significantly different between the pass and refer groups on aABR and the normal and abnormal groups of cABR. On univariate analysis, bronchopul monary dysplasia (odds ratio [OR], 2.74; 95% confidence interval [CI], 1.00 to 7.48), intraventricular hemorrhage (OR, 7.02; 95% CI, 1.59 to 31.05), and use of furosemide (OR, 3.84; 95% CI, 1.38 to 10.73) were the factors related to refer results on aABR. Peri ventricular leukomalacia (PVL; OR, 4.00; 95% CI, 1.39 to 11.52) and use of vancomycin (OR, 2.86; 95% CI, 1.22 to 6.73) were associated with abnormal cABR. Twenty-five (7.9%) infants had discrepant aABR and cABR results, particularly males and those in whom vancomycin was used. @*Conclusion@#PVL and use of vancomycin were confirmed as independent risk factors for hearing loss in infants born at less than 32 weeks’ GA. Also, discrepancies between the screening and confirmatory test may occur, especially among male infants and those in whom vancomycin was used. The hearing of infants must be assessed more carefully in such groups regardless of NHS results.

Cellular Response of Ventricular-Subventricular Neural Progenitor/Stem Cells to Neonatal Hypoxic-Ischemic Brain Injury and Their Enhanced Neurogenesis

Purpose@#To elucidate the brain’s intrinsic response to injury, we tracked the response of neural stem/progenitor cells (NSPCs) located in ventricular-subventricular zone (V-SVZ) to hypoxic-ischemic brain injury (HI). We also evaluated whether transduction of V-SVZ NSPCs with neurogenic factor NeuroD1 could enhance their neurogenesis in HI. @*Materials and Methods@#Unilateral HI was induced in ICR neonatal mice. To label proliferative V-SVZ NSPCs in response to HI, bromodeoxyuridine (BrdU) and retroviral particles encoding LacZ or NeuroD1/GFP were injected. The cellular responses of NSPCs were analyzed by immunohistochemistry. @*Results@#Unilateral HI increased the number of BrdU+ newly-born cells in the V-SVZ ipsilateral to the lesion while injury reduced the number of newly-born cells reaching the ipsilateral olfactory bulb, which is the programmed destination of migratory V-SVZ NSPCs in the intact brain. These newly-born cells were directed from this pathway towards the lesions. HI significantly increased the number of newly-born cells in the cortex and striatum by the altered migration of V-SVZ cells. Many of these newly-born cells differentiated into active neurons and glia. LacZ-expressing V-SVZ NSPCs also showed extensive migration towards the non-neurogenic regions ipsilateral to the lesion, and expressed the neuronal marker NeuN. NeuroD1+/GFP+ V-SVZ NSPCs almost differentiated into neurons in the peri-infarct regions. @*Conclusion@#HI promotes the establishment of a substantial number of new neurons in non-neurogenic regions, suggesting intrinsic repair mechanisms of the brain, by controlling the behavior of endogenous NSPCs. The activation of NeuroD1 expression may improve the therapeutic potential of endogenous NSPCs by increasing their neuronal differentiation in HI.

Pulmonary Surfactant Replacement Therapy for Respiratory Distress Syndrome in Neonates: a Nationwide Epidemiological Study in Korea

Background@#Pulmonary surfactant (PS) replacement therapy, as a safe and effective treatment for respiratory distress syndrome (RDS) may have further increased with the extended insurance coverage since 2011 in Korea. Thus, this study aimed to investigate the epidemiologic data of PS replacement therapy for RDS in Korea and to analyze the complications associated with RDS. @*Methods@#We included 19,442 infants who were treated with PS and diagnosed with RDS (International Classification of Diseases-10 codes: P22.0) between 2014 and 2018 from the Health Insurance Review and Assessment database. Birth certificate data from Statistics Korea were used to estimate the incidence of RDS. @*Results@#The average incidence of RDS within the study period was 0.99% among live births.Repeated doses of PS were administered to 1,688 infants (8.7%), ranging from 2 doses in 929 infants (4.8%) to 9 doses in 1 infant (0.01%). The incidence of RDS in term infants markedly increased over 5 years from 0.2% to 0.34%. The incidence was similarly increased among the preterm infants. The RDS mortality rate was 6.3% and showed a decreasing trend according to year. The mortality rate was significantly higher in the lower gestational age group. A decreasing trend was observed in the incidence of the complications, such as patent ductus arteriosus, intraventricular hemorrhage, and bronchopulmonary dysplasia, except for pneumothorax in term infants. The complications were also higher in the lower gestational age group and the lower birth weight group. However, pneumothorax was the most frequent complication in the term infant group and in infants with birth weight ≥ 2,500 g. @*Conclusion@#Advancements in neonatal care and extended insurance coverage have increased the use of PS replacement therapy for RDS. This, in turn, decreased neonatal mortality and the incidence of the associated complications. The appropriate therapeutic strategy for RDS should be decided according to the gestational age and lung pathology.

Evaluation of Newborn Infants with Prenatally Diagnosed Congenital Pulmonary Airway Malformation: A Single-Center Experience

PURPOSE: Congenital pulmonary airway malformation (CPAM)—a rare developmental anomaly—affects the lower respiratory tract in newborns. By comparing the reliability of diagnostic tools and identifying predictive factors for symptoms, we provide comprehensive clinical data for the proper management of CPAM. METHODS: We reviewed the medical records of 66 patients with prenatally diagnosed CPAM delivered at Severance Children's Hospital between January 2005 and July 2017. RESULTS: We enrolled 33 boys and 33 girls. Their mean gestational age and birth weight were 38.8 weeks and 3,050 g, respectively. Prenatal ultrasonography and postnatal radiography, lung ultrasonography, and chest computed tomography (CT) showed inconsistent findings. Chest CT showed superior sensitivity (100%) and positive predictive value (90%). Among the 66 patients, 59 had postnatally confirmed CPAM, three had pulmonary sequestration, one had cystic teratoma, and one had a normal lung. Of the 59 patients with CPAM, 21 (35%; mean age, 23.4 months) underwent surgery, including 15 who underwent video-assisted thoracoscopy. Twenty-five and 12 patients exhibited respiratory symptoms at birth and during infancy, respectively. Apgar scores and mediastinal shift on radiography were significantly associated with respiratory symptoms at birth. However, none of the factors could predict respiratory symptoms during infancy. CONCLUSION: Radiography or ultrasonography combined with chest CT can confirm an unclear or inconsistent lesion. Apgar scores and mediastinal shift on radiography can predict respiratory symptoms at birth. However, symptoms during infancy are not associated with prenatal and postnatal factors. Chest CT combined with periodic symptom monitoring is important for diagnosing and managing patients with prenatally diagnosed CPAM and to guide appropriate timing of surgery.

Implementation of a Targeted Next-Generation Sequencing Panel for Constitutional Newborn Screening in High-Risk Neonates

PURPOSE: Newborn screening (NBS) programs are important for appropriate management of susceptible neonates to prevent serious clinical problems. Neonates admitted to neonatal intensive care units (NICU) are at a potentially high risk of false-positive results, and repetitive NBS after total parenteral nutrition is completely off results in delayed diagnosis. Here, we present the usefulness of a targeted next-generation sequencing (TNGS) panel to complement NBS for early diagnosis in high-risk neonates. MATERIALS AND METHODS: The TNGS panel covered 198 genes associated with actionable genetic and metabolic diseases that are typically included in NBS programs in Korea using tandem mass spectrometry. The panel was applied to 48 infants admitted to the NICU of Severance Children's Hospital between May 2017 and September 2017. The infants were not selected for suspected metabolic disorders. RESULTS: A total of 13 variants classified as likely pathogenic or pathogenic were detected in 11 (22.9%) neonates, including six genes (DHCR7, PCBD1, GAA, ALDOB, ATP7B, and GBA) associated with metabolic diseases not covered in NBS. One of the 48 infants was diagnosed with an isobutyl-CoA dehydrogenase deficiency, and false positive results of tandem mass screening were confirmed in two infants using the TNGS panel. CONCLUSION: The implementation of TNGS in conjunction with conventional NBS can allow for better management of and earlier diagnosis in susceptible infants, thus preventing the development of critical conditions in these sick infants.

Glial Cell Line-derived Neurotrophic Factor-overexpressing Human Neural Stem/Progenitor Cells Enhance Therapeutic Efficiency in Rat with Traumatic Spinal Cord Injury

Spinal cord injury (SCI) causes axonal damage and demyelination, neural cell death, and comprehensive tissue loss, resulting in devastating neurological dysfunction. Neural stem/progenitor cell (NSPCs) transplantation provides therapeutic benefits for neural repair in SCI, and glial cell line-derived neurotrophic factor (GDNF) has been uncovered to have capability of stimulating axonal regeneration and remyelination after SCI. In this study, to evaluate whether GDNF would augment therapeutic effects of NSPCs for SCI, GDNF-encoding or mock adenoviral vector-transduced human NSPCs (GDNF-or Mock-hNSPCs) were transplanted into the injured thoracic spinal cords of rats at 7 days after SCI. Grafted GDNF-hNSPCs showed robust engraftment, long-term survival, an extensive distribution, and increased differentiation into neurons and oligodendroglial cells. Compared with Mock-hNSPC- and vehicle-injected groups, transplantation of GDNF-hNSPCs significantly reduced lesion volume and glial scar formation, promoted neurite outgrowth, axonal regeneration and myelination, increased Schwann cell migration that contributed to the myelin repair, and improved locomotor recovery. In addition, tract tracing demonstrated that transplantation of GDNF-hNSPCs reduced significantly axonal dieback of the dorsal corticospinal tract (dCST), and increased the levels of dCST collaterals, propriospinal neurons (PSNs), and contacts between dCST collaterals and PSNs in the cervical enlargement over that of the controls. Finally grafted GDNF-hNSPCs substantially reversed the increased expression of voltage-gated sodium channels and neuropeptide Y, and elevated expression of GABA in the injured spinal cord, which are involved in the attenuation of neuropathic pain after SCI. These findings suggest that implantation of GDNF-hNSPCs enhances therapeutic efficiency of hNSPCs-based cell therapy for SCI.

Human Neural Stem Cells: Translational Research for Neonatal Hypoxic-Ischemic Brain Injury

Neonatal hypoxic-ischemic (HI) brain injury is a major cause of neonatal mortality and long-term neurodevelopmental disabilities. Although promising neuroprotective interventions have been studied, the current management of HI brain injury has been limited to supportive measures and induced hypothermia. In addition to engrafting, migrating toward the damage sites and differentiating into multiple lineages, multipotent neural stem/progenitor cells (NSPCs) also provide trophic/immunomodulatory factors and integrate into the host neurons upon implantation into an HI-injured brain. However, NSPC-based therapies have shown poor cell survival and integration, poor differentiation or restricted differentiation into the glial lineages. Furthermore, to achieve full functional recovery following brain injury, the optimization of cell therapy is needed to recapitulate the precise migration of stem cells to the region of interest and the neural rewiring present in the brain microenvironment. Therefore, the efficacy of NSPCs in the treatment of CNS injury is currently insufficient. Human NSPCs (hNSPCs) were isolated from the forebrain of an aborted fetus at 13 weeks of gestation with full parental consent and the approval of the Institutional Review Board of the Yonsei University College of Medicine. Here, to enhance the regenerative ability of hNSPCs in HI brain injury, cells were either pretreated with pharmacological agents or engineered to serve as vehicles for gene delivery. Furthermore, when combined with a poly (glycolic acid)-based synthetic scaffold, hNSPCs provide a more versatile treatment for neonatal HI brain injury. Finally, hNSPCs transfected with zinc-doped ferrite magnetic nanoparticles for controlling both cell migration and differentiation offer a simple and smart tool for cell-based therapies.

Successful Treatment of Neonatal Pylorospasm with Intravenous Atropine

Pylorospasm is a cause of delayed gastric emptying in young infants. As in patients with hypertrophic pyloric stenosis, most pylorospasm patients present with projectile vomiting. However, unlike that in case of hypertrophic pyloric stenosis, no persistent pyloric stenotic lesions are present. As such, follow-up using serial gastrointestinal fluoroscopy or ultrasonography can be helpful in diagnosing patients with clinical signs of gastroparesis. Most cases can be treated conservatively, but some patients require pharmacologic treatment. Antispasmodics have been proposed as a treatment for pylorospasm, but their use in neonates and infants has rarely been reported. Herein, we present a case of pylorospasm diagnosed in the neonatal period and successfully treated with intravenous atropine.

Genitopatellar Syndrome Secondary to De Novo KAT6B Mutation: The First Genetically Confirmed Case in South Korea

Genitopatellar syndrome (GPS) is a rare disorder characterized by patellar hypoplasia, flexion contractures of the lower limbs, psychomotor retardation and genital and renal anomalies. We report the case of a female infant diagnosed with GPS to a KAT6B gene mutation, which was identified using whole exome sequencing.

The impact of a quality improvement effort in reducing admission hypothermia in preterm infants following delivery / 소아과

PURPOSE: Hypothermia at admission is associated with increased mortality and morbidity in preterm infants. We performed a quality improvement (QI) effort to determine the impact of a decrease in admission hypothermia in preterm infants. METHODS: The study enrolled very low birth weight (VLBW) infants born at Gangnam Severance Hospital between January 2013 and December 2016. This multidisciplinary QI effort included the use of occlusive wraps, warm blankets, and caps; the delivery room temperature was maintained above 23.0℃, and a check-list was used for feedback. RESULTS: Among 259 preterm infants, the incidence of hypothermia (defined as body temperature <36.0℃) decreased significantly from 68% to 41%, and the mean body temperature on neonatal intensive care unit admission increased significantly from 35.5℃ to 36.0℃. In subgroup analysis of VLBW infants, admission hypothermia and neonatal outcomes were compared between the pre-QI (n=55) and post-QI groups (n=75). Body temperature on admission increased significantly from 35.4℃ to 35.9℃ and the number of infants with hypothermia decreased significantly from 71% to 45%. There were no cases of neonatal hyperthermia. The incidence of pulmonary hemorrhage was significantly decreased (P=0.017). Interaction analysis showed that birth weight and gestational age were not correlated with hypothermia following implementation of the protocol. CONCLUSION: Our study demonstrated a significant reduction in admission hypothermia following the introduction of a standardized protocol in our QI effort. This resulted in an effective reduction in the incidence of massive pulmonary hemorrhage.

Effective Tidal Volume for Normocapnia in Very-Low-Birth-Weight Infants Using High-Frequency Oscillatory Ventilation

PURPOSE: Removal of CO₂ is much efficient during high-frequency oscillatory ventilation (HFOV) for preterm infants. However, an optimal carbon dioxide diffusion coefficient (DCO₂) and tidal volume (VT) have not yet been established due to much individual variance. This study aimed to analyze DCO₂ values, VT, and minute volume in very-low-birth-weight (VLBW) infants using HFOV and correlates with plasma CO₂ (pCO₂). MATERIALS AND METHODS: Daily respiratory mechanics and ventilator settings from twenty VLBW infants and their two hundred seventeen results of blood gas analysis were collected. Patients were treated with the Dräger Babylog VN500 ventilator (Drägerwerk Ag & Co.) in HFOV mode. The normocapnia was indicated as pCO₂ ranging from 45 mm Hg to 55 mm Hg. RESULTS: The measured VT was 1.7 mL/kg, minute volume was 0.7 mL/kg, and DCO₂ was 43.5 mL²/s. Mean results of the blood gas test were as follows: pH, 7.31; pCO₂, 52.6 mm Hg; and SpO₂, 90.5%. In normocapnic state, the mean VT was significantly higher than in hypercapnic state (2.1±0.5 mL/kg vs. 1.6±0.3 mL/kg), and the mean DCO₂ showed significant difference (68.4±32.7 mL²/s vs. 32.4±15.7 mL²/s). The DCO₂ was significantly correlated with the pCO₂ (p=0.024). In the receiver operating curve analysis, the estimated optimal cut-off point to predict the remaining normocapnic status was a VT of 1.75 mL/kg (sensitivity 73%, specificity 80%). CONCLUSION: In VLBW infants treated with HFOV, VT of 1.75 mL/kg is recommended for maintaining proper ventilation.

Clinical Pharmacokinetics of Caffeine in Korean Preterm Infants with Apnea of Prematurity

PURPOSE: Caffeine shows wide interindividual pharmacokinetic (PK) variation, and therapeutic drug monitoring (TDM) may be needed. The PK profile of caffeine in Korean preterm neonates was investigated, and factors influencing the clearance of caffeine were analyzed. METHODS: Fifty-nine preterm neonates receiving caffeine for apnea of prematurity were enrolled in the study (gestational age, 29.5±2.2 weeks and birth weight [BW], 1,318±358 g). Caffeine (20 mg/kg) was intravenously administered to each neonate as a loading dose, followed by a maintenance dose of 5-10 mg/kg/d. A total of 190 serum concentrations were measured for population PK analysis and modeling using nonlinear mixed-effects model (NONMEM®) software. RESULTS: The mean serum concentration of caffeine was 15.4±4.5 mg/L (range 7.8-33.0 mg/L). High serum concentrations (>20 mg/L) were noted in 36 samples (29%). At the first measurement of serum caffeine, the mean postmenstrual age was 33.9±2.3 weeks, mean BW was 1,802±471 g, mean duration of treatment was 7.4±9.4 days, and mean sampling time after the last dose was 21.8±2.1 hours. In the population PK analysis, the clearance was 0.033 L/h and volume of distribution was 0.371 L. Typical clearance was calculated as 0.0293×(BW/70)1.33. Among the subjects receiving 5 mg/kg/d caffeine, the most significant risk factor associated with high serum concentrations (>20 mg/L) was low BW (P=0.024). CONCLUSION: BW was the only covariate that influenced caffeine clearance in preterm neonates. Preterm neonates with low BW should be carefully monitored for apnea and adverse reactions in addition to undergoing TDM.

Postdischarge growth assessment in very low birth weight infants / 소아과

PURPOSE: The goal of nutritional support for very-low-birth-weight (VLBW) infants from birth to term is to match the in utero growth rates; however, this is rarely achieved. METHODS: We evaluated postdischarge growth patterns and growth failure in 81 Korean VLBW infants through a retrospective study. Weight and height were measured and calculated based on age percentile distribution every 3 months until age 24 months. Growth failure was defined as weight and height below the 10th percentile at 24 months. For the subgroup analysis, small-for-gestational age (SGA) and extremely low birth weight (ELBW) infants were evaluated. The growth patterns based on the Korean, World Health Organization (WHO), or Centers for Disease Control and Prevention (CDC) standard were serially compared over time. RESULTS: At postconception age (PCA) 40 weeks, 47 (58%) and 45 infants (55%) showed growth failure in terms of weight and height, respectively. At PCA 24 months, 20 infants (24%) showed growth failure for weight and 14 (18%) for height. Growth failure rates were higher for the SGA infants than for the appropriate-weight-for-gestational age infants at PCA 24 months (P=0.045 for weight and P=0.038 for height). Growth failure rates were higher for the ELBW infants than for the non-ELBW infants at PCA 24 months (P<0.001 for weight and P=0.003 for height). Significant differences were found among the WHO, CDC, and Korean standards (P<0.001). CONCLUSION: Advancements in neonatal care have improved the catch-up growth of VLBW infants, but this is insufficient. Careful observation and aggressive interventions, especially in SGA and ELBW infants, are needed.

Experience and pharmacokinetics of Levetiracetam in Korean neonates with neonatal seizures / 소아과

PURPOSE: The aims of this study were to evaluate the safety and pharmacokinetics of levetiracetam (LEV) in neonates with seizures and to establish a population pharmacokinetics (PPK) model by using the software NONMEM. METHODS: A retrospective analysis of 18 neonatal patients with seizures, who were treated with LEV, including 151 serum samples, was performed. The mean loading dose was 20 mg/kg, followed by a mean maintenance dose of 29 mg/kg/day. RESULTS: Seventeen neonates (94%) had seizure cessation within 1 week and 16 (84%) remained seizure-free at 30 days under the LEV therapy. The mean serum concentration of LEV was 8.7 µg/mL. Eight samples (5%) were found above the therapeutic range. No serious adverse effects were detected. In the PPK analysis for Korean neonates, the half-life was 9.6 hours; clearance, 0.357 L/hr; and volume of distribution, 4.947 L, showing differences from those in adults. CONCLUSION: LEV is a safe and effective option for the treatment of neonatal seizures with careful therapeutic drug monitoring.

A Case of Pulmonary Interstitial Emphysema Treated by Percutaneous Catheter Insertion in Extremely Low Birth Weight Infant

The pulmonary interstitial emphysema (PIE) is a life-threatening illness in premature infants with mechanical ventilation. While most are managed conservatively, decompression would be necessary. Here, we report the first case of PIE treated by percutaneous catheter insertion in an extremely low birth weight (ELBW) infant in Korea. The patient, born with 660 g in 23+2 weeks of gestation, showed PIE in left lower lung on postnatal day 12. Percutaneous catheter insertion was performed on postnatal day 25. The size of PIE decreased, but didn't disappear completely. On postnatal day 42, we exchanged catheter and inserted additional catheter in pleural space. However, sudden desaturation and pneumothorax occurred on postnatal day 44. We changed catheter in pleural space, and pneumothorax and PIE improved. Finally, we successfully removed catheters, and weaned patient out. As in our case, percutaneous catheter insertion would be a useful option for ELBW infants with PIE.

A Case of Pulmonary Interstitial Emphysema Treated by Percutaneous Catheter Insertion in Extremely Low Birth Weight Infant

The pulmonary interstitial emphysema (PIE) is a life-threatening illness in premature infants with mechanical ventilation. While most are managed conservatively, decompression would be necessary. Here, we report the first case of PIE treated by percutaneous catheter insertion in an extremely low birth weight (ELBW) infant in Korea. The patient, born with 660 g in 23+2 weeks of gestation, showed PIE in left lower lung on postnatal day 12. Percutaneous catheter insertion was performed on postnatal day 25. The size of PIE decreased, but didn't disappear completely. On postnatal day 42, we exchanged catheter and inserted additional catheter in pleural space. However, sudden desaturation and pneumothorax occurred on postnatal day 44. We changed catheter in pleural space, and pneumothorax and PIE improved. Finally, we successfully removed catheters, and weaned patient out. As in our case, percutaneous catheter insertion would be a useful option for ELBW infants with PIE.

Diagnosis of Severe Protein C Deficiency Confirmed by Presence of Rare PROC Gene Mutation

Protein C (PROC) deficiency is caused by mutations in the PROC gene on chromosome 2q14.3. Patients with PROC deficiency typically present distinguished purpura, intracerebral and intravascular coagulopathy, and ophthalmologic complications. Here, we report a rare severe form of PROC deficiency resulting from a compound heterozygosity in PROC. The patient was a 5-day-old female neonate born at 39 weeks of gestation with a birth weight of 2,960 g. She was transferred to our hospital with running a fever at 38.5℃ and with dark red patches on her feet. At admission, a complete blood count showed no specific findings, but levels of PROC and protein S were abnormally low (1% and 68%, respectively). Magnetic resonance imaging revealed intracerebral hemorrhaging and parenchymal damage with dysplasia of the brain. Ophthalmologic examination revealed vitreous hemorrhaging with retinal detachment. Genetic testing revealed a missense mutation (Arg211Trp) and a frameshift mutation (Gly239Serfs*8) in PROC, inherited from the father and mother, respectively. The patient recovered from purpura after undergoing ventriculoperitoneal shunting and treatment with fresh frozen plasma, warfarin sodium, and PROC concentrate. This is the first report of severe neonatal PROC deficiency with purpura fulminans, vitreous hemorrhage, and intracerebral hemorrhage confirmed via PROC genetic testing, which identified a rare compound heterozygosity of PROC.

Usefulness of serum cystatin C to determine the dose of vancomycin in neonate / 소아과

PURPOSE: The vancomycin dosage regimen is regularly modified according to the patient's glomerular filtration rate (GFR). In the present study, we aimed to assess the usefulness of serum cystatin C (Cys-C) concentration, compared with serum creatinine (SCr) concentration, for predicting vancomycin clearance (CLvcm) in neonates. METHODS: We retrospectively analyzed the laboratory data of 50 term neonates who were admitted to the neonatal intensive care unit and received intravenous vancomycin, and assessed the pharmacokinetic profiles. Creatinine clearance (CLcr) and GFR based on Cys-C (GFRcys-c) were estimated using the Schwartz and Larsson formulas, respectively. RESULTS: The mean CLvcm (+/-standard deviation) was 74.52+/-31.17 L/hr, the volume of distribution of vancomycin was 0.67+/-0.14 L, and vancomycin half-life was 9.16+/-17.42 hours. The SCr was 0.46+/-0.25 mg/dL and serum Cys-C was 1.43+/-0.34 mg/L. The peak and trough concentrations of vancomycin were 24.65+/-14.84 and 8.10+/-5.35 mcg/mL, respectively. The calculated GFR based on serum creatinine concentration (GFR-Cr) and GFRcys-c were 70.2+/-9.45 and 63.6+/-30.18 mL/min, respectively. The correlation constant for CLvcm and the reciprocal of Cys-C (0.479, P=0.001) was significantly higher than that for CLvcm and the reciprocal of SCr (0.286, P=0.044). GFRcys-c was strongly correlated with CLvcm (P=0.001), and the correlation constant was significantly higher than that for CLvcm and CLcr (0.496, P=0.001). Linear regression analysis showed that only GFRcys-c was independently and positively correlated with CLvcm (F=41.9, P<0.001). CONCLUSION: The use of serum Cys-C as a marker of CLvcm could be beneficial for more reliable predictions of serum vancomycin concentrations, particularly in neonates.