Determining the optimal timing of screening spinal cord ultrasonography to detect filum terminale lipoma in infants

Purpose@#The purpose of this study was to identify the optimal timing for screening spinal cord ultrasonography (US) to detect filum terminale lipoma in infants. @*Methods@#We retrospectively reviewed infants (<12 months old) who underwent repeated spinal cord US between April 2011 and January 2019. We excluded infants if they only had one US examination, or if they had lesions other than filum terminale lipoma. Infants with filum terminale lipoma on magnetic resonance imaging were included in the lipoma group and the others in the control group. A linear mixed model was used to assess differences in the growth pattern of filum terminale thickness by age and group. The cutoff thickness on US and its diagnostic performance were assessed according to age. @*Results@#Among 442 infants with 901 US examinations, 46 were included in the lipoma group and 58 in the control group. Sixty-seven infants had unmeasurable filum terminale thickness on initial US, including 55 neonates (82.1%) before 1 month of age. The lipoma group had significantly greater filum terminale thickness than the control group (P<0.001). Thickness increased with age in the lipoma group (P=0.027). The sensitivity of US was 87.5% and the area under the receiver operating characteristic curve was 0.949 (95% confidence interval, 0.849 to 0.991) with a cutoff value of 1.1 mm in 4- to 6-month-old infants. @*Conclusion@#Screening spinal cord US could effectively diagnose filum terminale lipoma in 4- to 6-month-old infants with a cutoff thickness of 1.1 mm. Spinal cord US can be used to screen young infants with intraspinal abnormalities.

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.

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.

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.

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.

The efficacy and safety of Montelukast sodium in the prevention of bronchopulmonary dysplasia / 소아과

PURPOSE: The purpose of this study was to evaluate the efficacy and safety of Montelukast sodium in the prevention of bronchopulmonarydysplasia (BPD). METHODS: The Interventional study was designed as a multicenter, prospective, and randomized trial, with open labeled and parallel-experimental groups, 66 infants were enrolled and allocated to either the case group (n=30) or the control group (n=36) based on gestational age (GA). Infants in the case group were given Montelukast sodium (Singulair) based on their body weight (BW). Zero week was defined as the start time of the study. RESULTS: The incidence of moderate to severe BPD was not different between the groups (case group: 13 of 30 [43.3%] vs. control group: 19 of 36 [52.8%], P=0.912). Additionally, secondary outcomes such as ventilation index, mean airway pressure and resort to systemic steroids were not significantly different. There were no serious adverse drug reactions in either group, and furthermore the rate of occurrence of mild drug related-events were not significantly different (case group: 10 of 42 [23.8%] vs. control group: 6 of 48 (15.8%), P=0.414). CONCLUSION: Montelukast was not effective in reducing moderate or severe BPD. There were no significant adverse drug events associated with Montelukast treatment.

Efficacy and Safety of Kangaroo Mother Care in Preterm Infants in Korea / 대한주산의학회잡지

PURPOSE: This study aimed to identify the safety of Kangaroo Mother Care (KMC) and to analyze its medical and psychological effects. METHODS: Forty five preterm infants, admitted to Gangnam Severance Hospital NICU from October 2012 to September 2013, were recruited. KMC was performed for 1 hour daily until the discharge by either mother or father. The medical effects in KMC group were compared with historical control group. Psychological effects in KMC group were made a comparison with the non-KMC group. RESULTS: The mean gestational age was 31.3+/-3.5 weeks, and the mean birth weight was 1,080+/-250 g. KMC was started at the mean age of 18.3+/-8.4 days. No event of hypothermia, bradycardia, desaturation, or hypotension occurred. There was no event of death or sepsis. Four patients (9%) had apnea but recovered after the tactile stimulation. Duration of the hospitalization in KMC group was significantly shorter than control group (P=0.041). Spielberger's anxiety scale decreased from 49.7 to 48.5. Muller's maternal attachment inventory increased from 98.4 to 99.5. Reduction of the self-happiness score improved from 5% to 70%. The score for Spielberger's anxiety scale tended to be lower in the KMC group than in the control group without statistically significant. Muller's maternal attachment inventory score was significantly higher in the KMC group. CONCLUSION: KMC is a safe method to Korean preterm infants. Due to reduction of hospitalization and beneficial psychological effect, we believe that offering KMC to more preterm infants as a supplement therapy will be useful.

Nutritional Outcomes in Children with Epidermolysis Bullosa: The Experiences of Two Centers in Korea

PURPOSE: Epidermolysis bullosa (EB) is associated with variable risks of extracutaneous manifestations and death. Currently, there is limited information on the clinical course and prognosis of EB in Korea. This study analyzed the nutritional outcomes, clinical morbidity, and mortality of children with EB. MATERIALS AND METHODS: Thirty patients, admitted to Severance Hospital and Gangnam Severance Hospital, from January 2001 to December 2011, were retrospectively enrolled. All patients were diagnosed with EB classified by dermatologists. RESULTS: Among the 30 patients, 5 patients were diagnosed with EB simplex, four with junctional EB, and 21 with dystrophic EB. Wound infection occurred in 47% of the patients, and blood culture-proven sepsis was noted in 10% of the patients. Two (9.2%) patients had esophageal stricture and 11 (52.4%) of the dystrophic EB patients received reconstructive surgery due to distal extremity contracture. There were five mortalities caused by sepsis, failure to thrive, and severe metabolic acidosis with dehydration. According to nutrition and growth status, most of the infants (97%) were born as appropriate for gestational age. However, at last follow-up, 56% of the children were below the 3rd percentile in weight, and 50% were below the 3rd percentile in weight for height. Sixty percent of the children had a thrive index below -3. CONCLUSION: Postnatal growth failure is a serious problem in children with EB. Strategies to maximize nutritional support could alleviate growth failure in children with EB, and thus improve clinical outcomes.

Risk Factors of Pulmonary Hypertension in Preterm Infants with Chronic Lung Disease

PURPOSE: Pulmonary hypertension (PH) is known as a major risk factor for preterm infants deaths, and associated with low gestational age, low birth weight, longer duration of oxygen therapy, low Apgar scores, and oligohydramnios. The aim of this study was to determine the risk factors for PH in preterm infants with chronic lung disease. METHODS: A retrospective review was performed of data from 86 infants ( or =G3) and severe chronic lung disease was higher in PH group than control group. According to multivariate analysis, IVH (> or =G3) (OR=5.00, 95% CI=1.10-22.63, P=0.037) and severe BPD (OR=2.43, 95% CI=1.03-15.41, P=0.045) were found to be significant risk factors for PH in preterm infants with chronic lung disease. CONCLUSION: Pulmonary hypertension was significantly increased in preterm infants with chronic lung disease when associated with IVH (> or =G3). We suggest that effort for early diagnosis and management for PH would be helpful in preterm infants with chronic lung disease when severe IVH was combined.

Parenteral Nutrition Associated Cholestasis Is Earlier, More Prolonged and Severe in Small for Gestational Age Compared with Appropriate for Gestational Age Very Low Birth Weight Infants

PURPOSE: We hypothesized that parenteral nutrition associated cholestasis (PNAC) would be more severe in small for gestational age (SGA) compared with appropriate for gestational age (AGA) very low birth weight (VLBW) infants. MATERIALS AND METHODS: Sixty-one VLBW infants were diagnosed as PNAC with exposure to parenteral nutrition with elevation of direct bilirubin > or =2 mg/dL for > or =14 days. Twenty-one SGA infants and 40 AGA infants matched for gestation were compared. RESULTS: Compared with AGA infants, PNAC in SGA infants was diagnosed earlier (25+/-7 days vs. 35+/-14 days, p=0.002) and persisted longer (62+/-36 days vs. 46+/-27 days, p=0.048). Severe PNAC, defined as persistent elevation of direct bilirubin > or =4 mg/dL for more than 1 month with elevation of liver enzymes, was more frequent in SGA than in AGA infants (61% vs. 35%, p=0.018). The serum total bilirubin and direct bilirubin levels during the 13 weeks of life were significantly different in SGA compared with AGA infants. SGA infants had more frequent (76% vs. 50%, p=0.046), and persistent elevation of alanine aminotransferase. CONCLUSION: The clinical course of PNAC is more persistent and severe in SGA infants. Careful monitoring and treatment are required for SGA infants.

Risk of Surgery for Retinopathy of Prematurity in Very Low Birth Weight Infants

PURPOSE: The main postnatal risk factors of retinopathy of prematurity (ROP) were described as prolonged oxygen therapy and lower gestational age. Recent data suggest poor early weight gain during the first weeks of life, which can be an additional predictor of severe ROP. We aimed to analyze the risk factors associated with requiring operation for ROP in preterm infants with very low birth weight (VLBW). METHODS: In a retrospective case control study, from January 2004 to June 2010, 140 VLBW infants diagnosed as ROP by the International classification of ROP were recruited. There were 14% of infants with stage 1 disease, 65.7% stage 2, and 20% stage 3 or more. A group requiring a laser surgery for ROP was 66 infants, and a group not requiring surgery was 74 infants. RESULTS: By a univariate analysis, antenatal steroid, chorioamnionitis, gestational age, birth weight, days on oxygen, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalasia and sepsis were significantly associated with ROP requiring surgery. Weight differences between birth and each from 4 to 12 weeks were significantly lower in the infants requiring surgery (P<0.05). However, after adjustment for gestational age in logistic regression, weight difference between birth and 8th week was a significant predictive factor for the requirement of surgery in infants with ROP (OR, 0.998; 95% CI, 0.996-0.999, P=0.013). CONCLUSION: We suggest that careful monitoring of weight change and aggresive nutritional support for poorly growing infants, during the first 8 weeks of life, may possibly prevent laser surgery of ROP in preterm VLBW infants.

Analysis of the Macronutrient Composition of Breast Milk from Korean Women and Growth of Infants / 대한주산의학회잡지

PURPOSE: The aim of this study was to determine the effect of the macronutrient composition of breast milk from Korean women on the growth of infants. METHODS: 173 healthy lactating women and breast-fed infants who visited Gangnam Severance Hospital and two breast-feeding centers in Seoul from October 2011 to March 2012 were recruited. We checked the birth weight and body weight of infants while collecting breast milk from the mothers, and analyzed the macronutrient component of breast milk with a mid-infrared milk analyzer (MIRIS(R) Human Milk Analyzer, HMA, Miris AB, Uppsala, Sweden). Group analysis was performed depending on more or less than 5 percentile and 25 percentile of body weight. RESULTS: The amount of daily intake/RDA for calories, proteins, lipids and carbohydrates of breast milk were significantly lower in the less than 5 percentile and 25 percentile group (P<0.05). Using multiple logistic regression analysis, the significant nutrient component that was insufficient in the less than 5 percentile and less than 25 percentile of body weight group respectively was carbohydrates (P<0.05). CONCLUSION: We conclude that each macronutrient level of breast milk is statistically low in infants with less body weight. These results suggest that nutritional consideration of breast milk is necessary for the growth of breast-fed infants.

High Incidence of Rickets in Extremely Low Birth Weight Infants with Severe Parenteral Nutrition-Associated Cholestasis and Bronchopulmonary Dysplasia

Risk factors for rickets of prematurity have not been re-examined since introduction of high mineral formula, particularly in ELBW infants. We analyzed the incidence and the risk factors of rickets in extremely low birth weight (ELBW) infants. As a retrospective case-control study from 2004 to 2008, risk factors were analyzed in 24 patients with rickets versus 31 patients without. The frequency of rickets in ELBW infants was 24/55 (44%). Infants with rickets were diagnosed at 48.2 +/- 16.1 days of age, and improved by 85.3 +/- 25.3 days. By radiologic evaluation, 29% were grade 1 rickets, 58% grade 2 and 13% grade 3. In univariate analysis, infants with rickets had significantly higher incidence of patent ductus arteriosus, parenteral nutrition associated cholestasis (PNAC), severe PNAC and moderate/severe bronchopulmonary dysplasia (BPD). In multiple regression analysis, after adjustment for gestation and birth weight, rickets significantly correlated with severe PNAC and with moderate/severe BPD. Serum peak alkaline phosphatase levels were significantly elevated in rickets (P < 0.001). In ELBW infants, the incidence of rickets of prematurity remains high and the incidence of severe PNAC and moderate/severe BPD was significantly increased 18 and 3 times, respectively.

Acute treatment of hyperammonemia by continuous renal replacement therapy in a newborn patient with ornithine transcarbamylase deficiency / 소아과

Ornithine transcarbamylase (OTC) deficiency is well known as the most common inherited disorder of the urea cycle, and 1 of the most common causes of hyperammonemia in newborns. We experienced a case of a 3-day-old boy with OTC deficiency who appeared healthy in the first 2 days of life but developed lethargy and seizure soon afterwards. His serum ammonia level was measured as >1700 microg/dL (range, 0 to 45 microg/dL). Continuous renal replacement therapy (CRRT) in the mode of continuous venovenous hemodiafiltration was immediately applied to correct the raised ammonia level. No seizure occurred after the elevated ammonia level was reduced. Therefore, CRRT should be included as 1 of the treatment modalities for newborns with inborn errors of metabolism, especially hyperammonemia. Here, we report 1 case of successful treatment of hyperammonemia by CRRT in a neonate with OTC deficiency.

Epidemiology of central venous catheter related blood stream infections in pediatric patients / 소아과

PURPOSE: The purpose of this study is to investigate the pathogens of central venous catheter-related blood stream infections and search for the association among the insertion site, the duration and the underlying conditions with the prevalence of central venous catheter-related blood stream infections under 15 years old. METHODS: A retrospective study was performed from Jan, 2003 to Dec, 2003 in Severance Hospital on 112 patients who undertook central venous catheter insertions. RESULTS: We examined 112 patients who undertook central venous catheter insertion. The mean age of patients was 4.77+/-4.12 years old. Coagulase negative Staphylococci was the most common organism of central venous catheter-related blood stream infections accounting for 33.9 percent, followed by Eenterococcus faecium(9.3 percent), and Staphylococcus aureus(7.5 percent), The most common insertion site was the right femoral vein, followed by the right jugular vein and the left femoral vein. The mean insertion period was 14.17+/-12.00 days. CONCLUSION: Central venous catheter-related blood stream infections were not only related to the underlying conditions, but also to the insertion site. We need to study the clinical importance of coagulase negative Staphylococci as it is part of the normal flora of the skin. In future, more studies are needed to take preventive measures and improve treatment methods.