Long-term outcomes of very low birth weight infants with intraventricular hemorrhage: a nationwide population study from 2011 to 2019.

BACKGROUND: Advancements in neonatal care have increased preterm infant survival but paradoxically raised intraventricular hemorrhage (IVH) rates. This study explores IVH prevalence and long-term outcomes of very low birth weight (VLBW) infants in Korea over a decade. METHODS: Using Korean National Health Insurance data (NHIS, 2010-2019), we identified 3372 VLBW infants with IVH among 4,129,808 live births. Health-related claims data, encompassing diagnostic codes, diagnostic test costs, and administered procedures were sourced from the NHIS database. The results of the developmental assessments  are categorized into four groups based on standard deviation (SD) scores. Neonatal characteristics and complications were compared among the groups. Logistic regression models were employed to identify significant changes in the incidence of complications and to calculate odds ratios with corresponding 95% confidence intervals for each risk factor associated with mortality and morbidity in IVH. Long-term growth and development were compared between the two groups (years 2010-2013 and 2014-2017). RESULTS: IVH prevalence was 12% in VLBW and 16% in extremely low birth weight (ELBW) infants. Over the past decade, IVH rates increased significantly in ELBW infants (P = 0.0113), while mortality decreased (P = 0.0225). Major improvements in certain neurodevelopmental outcomes and reductions in early morbidities have been observed among VLBW infants with IVH. Ten percent of the population received surgical treatments such as external ventricular drainage (EVD) or a ventriculoperitoneal (VP) shunt, with the choice of treatment methods remaining consistent over time. The IVH with surgical intervention group exhibited higher incidences of delayed development, cerebral palsy, seizure disorder, and growth failure (height, weight, and head circumference) up to 72 months of age (P < 0.0001). Surgical treatments were also significantly associated with abnormal developmental screening test results. CONCLUSIONS: The neurodevelopmental outcomes of infants with IVH, especially those subjected to surgical treatments, continue to be a matter of concern. It is imperative to prioritize specialized care for patients receiving surgical treatments and closely monitor their growth and development after discharge to improve developmental prognosis. Supplementary file2 (MP4 77987 kb).

Oligohydramnios affects pulmonary functional/structural abnormalities in school-aged children with bronchopulmonary dysplasia.

BACKGROUND: The relationship between early life factors and childhood pulmonary function and structure in preterm infants remains unclear. PURPOSE: This study investigated the impact of bronchopulmonary dysplasia (BPD) and perinatal factors on childhood pulmonary function and structure. METHODS: This longitudinal cohort study included preterm participants aged ≥5 years born between 2005 and 2015. The children were grouped by BPD severity according to National Institutes of Health criteria. Pulmonary function tests (PFTs) were performed using spirometry. Chest computed tomography (CT) scans were obtained and scored for hyperaeration or parenchymal lesions. PFT results and chest CT scores were analyzed with perinatal factors. RESULTS: A total 150 children (66 females) aged 7.7 years (6.4-9.9 years) were categorized into non/mild BPD (n=68), moderate BPD (n=39), and severe BPD (n=43) groups. The median z score for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced midexpiratory flow (FEF25%-75%) were significantly lower in the severe versus non/mild BPD group (-1.24 vs. -0.18, -0.22 vs. 0.41, -1.80 vs. -1.12, and -1.88 vs. -1.00, respectively; all P<0.05). The median z scores of FEV1, FEV1/ FVC, and FEF25%-75% among asymptomatic patients were also significantly lower in the severe versus non/mild BPD group (-0.82 vs. 0.09, -1.68 vs. -0.87, -1.59 vs. -0.61, respectively; all P<0.05). The severe BPD group had a higher median (range) CT score than the non/mild BPD group (6 [0-12] vs. 1 [0-10], P<0.001). Prenatal oligohydramnios was strongly associated with both low pulmonary function (FEV1/FVC

Factors associated with the response to postnatal dexamethasone use in very low birthweight infants: a nationwide cohort study.

BACKGROUND: Dexamethasone is widely used as a systemic corticosteroid to treat and prevent bronchopulmonary dysplasia (BPD) in preterm infants. We evaluated the current epidemiology of dexamethasone use to prevent BPD and analyse the factors associated with the response to dexamethasone in very low birthweight infants using a nationwide database. METHODS: We included very low birthweight infants born between January 2013 and December 2020 with a gestational age of 23-31 weeks using data from the Korean Neonatal Network registry. Patients were grouped based on their dexamethasone use into 'Dex' or 'No Dex' groups. Clinical variables and data were collected, and the annual trends of dexamethasone use and the proportion of patients who received dexamethasone according to gestational age were analysed. Respiratory outcomes were compared between the groups. Univariate and multivariate analyses were performed to analyse factors associated with the response to dexamethasone in BPD. RESULTS: Of 11 261 eligible infants, 2313 (20.5%) received dexamethasone, and 1714 (74.1%) of them were diagnosed with moderate-to-severe BPD. The 8-year annual prevalence of dexamethasone use was 17.7-22.3%. The 'Dex' group had more moderate-to-severe BPD, more frequent invasive ventilation use at a postmenstrual age of 36 weeks and longer ventilator duration. Birth weight, 5-minute APGAR score, pulmonary hypertension within the first 28 days, surgical treatment of patent ductus arteriosus, medical treatment of patent ductus arteriosus, pathological chorioamnionitis, hydrocortisone or budesonide use, surgical management of necrotising enterocolitis and fungal sepsis were associated with BPD after dexamethasone use. CONCLUSIONS: Approximately 20.5% of preterm infants received dexamethasone, and the frequency increased as gestational age decreased. Poor response to dexamethasone was associated with antenatal and postnatal inflammation, low birth weight and early pulmonary hypertension.

Prediction of Postnatal Growth Failure in Very Low Birth Weight Infants Using a Machine Learning Model.

Accurate prediction of postnatal growth failure (PGF) can be beneficial for early intervention and prevention. We aimed to develop a machine learning model to predict PGF at discharge among very low birth weight (VLBW) infants using extreme gradient boosting. A total of 729 VLBW infants, born between 2013 and 2017 in four hospitals, were included. PGF was defined as a decrease in z-score between birth and discharge that was greater than 1.28. Feature selection and addition were performed to improve the accuracy of prediction at four different time points, including 0, 7, 14, and 28 days after birth. A total of 12 features with high contribution at all time points by feature importance were decided upon, and good performance was shown as an area under the receiver operating characteristic curve (AUROC) of 0.78 at 7 days. After adding weight change to the 12 features-which included sex, gestational age, birth weight, small for gestational age, maternal hypertension, respiratory distress syndrome, duration of invasive ventilation, duration of non-invasive ventilation, patent ductus arteriosus, sepsis, use of parenteral nutrition, and reach at full enteral nutrition-the AUROC at 7 days after birth was shown as 0.84. Our prediction model for PGF performed well at early detection. Its potential clinical application as a supplemental tool could be helpful for reducing PGF and improving child health.

Growth and developmental outcomes of infants with hypoxic ischemic encephalopathy.

Despite advances in obstetric care, hypoxic ischemic encephalopathy (HIE) remains a significant disease burden. We determined the national trends of HIE prevalence, therapeutic hypothermia (TH) use, mortality, and outcomes from 2012 to 2019. This study included term infants diagnosed with HIE between 2012 and 2019 from the National Health Insurance Service database. The prevalence of HIE was 2.4 per 1000 births without significant change during the period. TH was performed in approximately 6.7% of infants with HIE, and the annual variation ranged from 2.4 to 12.5%. The mortality among all term infants with HIE was 4.6%. The mortality rate among infants with HIE and TH significantly declined from 40 to 16.9% during the eight years. Infants with TH had higher mortality, increased use of inhaled nitric oxide, and more invasive ventilator use, indicating greater disease severity in the TH group. Infants with TH also showed significantly poorer outcomes, including delayed development, cerebral palsy, sensorineural hearing loss, and seizure, compared to infants without TH (p < 0.0001). With the increasing application of TH, mortality and developmental outcomes among infants with HIE have been improving in the past eight years in Korea. Further efforts to improve outcomes should be needed.

Application of Machine Learning Approaches to Predict Postnatal Growth Failure in Very Low Birth Weight Infants.

PURPOSE: The aims of the study were to develop and evaluate a machine learning model with which to predict postnatal growth failure (PGF) among very low birth weight (VLBW) infants. MATERIALS AND METHODS: Of 10425 VLBW infants registered in the Korean Neonatal Network between 2013 and 2017, 7954 infants were included. PGF was defined as a decrease in Z score >1.28 at discharge, compared to that at birth. Six metrics [area under the receiver operating characteristic curve (AUROC), accuracy, precision, sensitivity, specificity, and F1 score] were obtained at five time points (at birth, 7 days, 14 days, 28 days after birth, and at discharge). Machine learning models were built using four different techniques [extreme gradient boosting (XGB), random forest, support vector machine, and convolutional neural network] to compare against the conventional multiple logistic regression (MLR) model. RESULTS: The XGB algorithm showed the best performance with all six metrics across the board. When compared with MLR, XGB showed a significantly higher AUROC (p=0.03) for Day 7, which was the primary performance metric. Using optimal cut-off points, for Day 7, XGB still showed better performances in terms of AUROC (0.74), accuracy (0.68), and F1 score (0.67). AUROC values seemed to increase slightly from birth to 7 days after birth with significance, almost reaching a plateau after 7 days after birth. CONCLUSION: We have shown the possibility of predicting PGF through machine learning algorithms, especially XGB. Such models may help neonatologists in the early diagnosis of high-risk infants for PGF for early intervention.

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.

Association between bronchopulmonary dysplasia and early respiratory morbidity in children with respiratory distress syndrome: a case-control study using nationwide data.

Bronchopulmonary dysplasia (BPD) can cause respiratory morbidity beyond the neonatal period. We aimed to analyze the association of BPD on childhood lower respiratory illness (LRI) and asthma among patients diagnosed with respiratory distress syndrome (RDS). This case-control study analyzed data between 2002 and 2015 from a nationwide database. We included 55,066 children with RDS. Two-year LRI and asthma at ages 3 and 5 were assessed. Readmission for LRIs within 2 years of birth occurred in 53.9% and 37.9% of the BPD (n = 9470) and non-BPD (n = 45,596) cases, respectively. In the BPD group, the median number of hospitalizations, mechanical ventilation and oxygen use rates were significantly higher, while the hospitalization duration was significantly longer (P < 0.001 for all). The relative risk of BPD was 1.42 (1.39-1.45) on total readmission and 6.53 (5.96-7.15) on intensive care unit readmission. Asthma prevalence was significantly higher in BPD group (57.6% vs. 48.9% at age 3 and 44.3% vs. 38.2% at age 5, P < 0.001). In children with RDS, BPD could affect repetitive and worse LRI as an independent risk factor for respiratory morbidity during the first 2 years of life. BPD may also be a crucial risk factor for asthma in preschoolers.

Association between birth weight and neurodevelopmental disorders assessed using the Korean National Health Insurance Service claims data.

The risk of neurodevelopmental disorders in low birth weight (LBW) infants has gained recognition but remains debatable. We investigated the risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in school-aged children according to their birth weight. We conducted a retrospective cohort study using the Korean National Health Insurance claims data of 2,143,652 children who were born between 2008 and 2012. Gestational age of infants was not available; thus, outcomes were not adjusted with it. Not only infants with birth weights of < 1.5 kg, but also 2.0-2.4 kg and 1.5-1.9 kg were associated with having ADHD; odds ratio (OR), 1.41 (95% confidence interval [CI] 1.33-1.50), and 1.49 (95% CI 1.33-1.66), respectively. The OR in infants with birth weights of 2.0-2.4 kg and 1.5-1.9 kg was 1.91 (95% CI 1.79-2.05) and 3.25 (95% CI 2.95-3.59), respectively, indicating increased odds of having ASD. Subgroup analysis for children without perinatal diseases showed similar results. In this national cohort, infants with birth weights of < 2.5 kg were associated with ADHD and ASD, regardless of perinatal history. Children born with LBW need detailed clinical follow-up.

The impact of neonatal morbidities on child growth and developmental outcomes in very low birth weight infants: a nationwide cohort study.

Growth in preterm infants has long-term implications for neurodevelopmental outcomes. We aimed to estimate the nationwide growth outcomes from birth to 5 years in infants born under 1500 g and to analyze the effects of major morbidities in preterm infants on growth. In total, 2961 children born in 2013 with a birth weight under 1500 g who underwent an infant health checkup between 2013 and 2018 according to the National Health Insurance Service database were included. Checkups were conducted at 4-6, 9-12, 18-24, 30-36, 42-48, and 54-60 months of age. Information was obtained from the International Classification of Diseases-10 codes or a questionnaire administered during the check-up. At 60 months of age, the mean percentiles of weight, height, and head circumference fell within only the 30-40th percentile of normal growth values. About 30% of infants had growth parameters below the 10th percentile and showed worse neurodevelopmental outcomes. Using multiple logistic regression, infants with bronchopulmonary dysplasia showed a significantly higher incidence of growth restriction in all three categories of weight (odds ratio [OR] 1.50), height (OR 1.33), and head circumference (OR 1.36) at 60 months. Sepsis was associated with growth restriction in weight (OR 1.43) and head circumference (OR 1.33). Periventricular leukomalacia infants had relatively small head circumferences (OR 1.91) and poor developmental screening results (OR 2.89).Conclusion: Catch-up growth remains a major issue in infants born under 1500 g, especially those with some morbidities from preterm birth. Regular checkups to monitor and early intervention to achieve normal growth are essential. What is Known: • Growth in preterm infants has long-term implications for neurodevelopmental and cardiometabolic outcomes. • Data are lacking on the time-serial effects of many preterm morbidities simultaneously on long-term growth outcomes. What is New: • All growth parameters of VLBW infants, including weight, height, and head circumference, fell within the 30-40th percentile of normal growth for infants at 60 months of age, indicating that catch-up growth for VLBW infants remains an issue. • VLBW infants with major preterm morbidities, including BPD, PVL, and sepsis, showed difficulties in achieving normal catch-up growth and neurodevelopment at 60 months of age.

Growth failure of very low birth weight infants during the first 3 years: A Korean neonatal network.

We aimed to evaluate risk factors for growth failure in very low birth weight (VLBW) infants at 18-24 months of corrected age (follow-up1, FU1) and at 36 months of age (follow-up2, FU2). In this prospective cohort study, a total of 2,943 VLBW infants from the Korean Neonatal Network between 2013 and 2015 finished follow-up at FU1. Growth failure was defined as a z-score below -1.28. Multiple logistic regression was used to analyze risk factors for growth failure after dividing the infants into small for gestational age (SGA) and appropriate for gestational age (AGA) groups. Overall, 18.7% of infants were SGA at birth. Growth failure was present in 60.0% at discharge, 20.3% at FU1, and 35.2% at FU2. Among AGA infants, male sex, growth failure at discharge, periventricular leukomalacia, treatment of retinopathy of prematurity, ventriculoperitoneal shunt status and treatment of rehabilitation after discharge were independent risk factors for growth failure at FU1. Among SGA infants, lower birth weight, pregnancy-induced hypertension, and treatment of rehabilitation after discharge were independent risk factors for growth failure at FU1. Mean weight z-score graphs from birth to 36 month of age revealed significant differences between SGA and non-SGA and between VLBW infants and extremely low birth weight infants. Growth failure remains an issue, and VLBW infants with risk factors should be closely checked for growth and nutrition.

Impact of neonatal resuscitation changes on outcomes of very-low-birth-weight infants.

The improvement of delivery room care, according to the 2015 International Consensus, may affect neonatal outcome, especially in very-low-birth-weight infants. We aimed to investigate the current practice of neonatal resuscitation by year and analyze the association with neonatal outcomes. A total of 8142 very-low-birth-weight infants, registered in the Korean Neonatal Network between 2014 and 2017 were included. A significant decreasing trend of intubation (64.5% vs 55.1%, P < 0.0001) and markedly increasing trend of positive pressure ventilation (PPV) (11.5% vs 22.9%, P < 0.0001) were noted. The annual PPV rate differed significantly by gestation (P < 0.0001). The highest level of resuscitation was also shown as an independent risk factor for mortality within 7 days and for bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and periventricular leukomalacia. PPV and intubation were associated with significantly decreased risk of mortality and morbidities compared to epinephrine use. When considering association, the incidence of mortality within 7 days, IVH, PVL, and BPD or mortality showed significant differences by combination of year, gestational age, and level of resuscitation. According to updated guidelines, changes in the highest level of resuscitation significantly associated with reducing mortality and morbidities. More meticulous delivery room resuscitation focusing on extreme prematurity is needed.

Identification of Growth Patterns in Low Birth Weight Infants from Birth to 5 Years of Age: Nationwide Korean Cohort Study.

This study aimed to investigate the nationwide growth pattern of infants in Korea according to the birth-weight group and to analyze the effect of growth on development. A total of 430,541 infants, born in 2013 and who received the infant health check-up regularly from 6 months to 60 months of age, were included. The weight, height, head circumferences percentiles, and neurodevelopment using screening tests results were compared among the birth-weight groups. Using longitudinal analysis, the study found a significant difference in height, weight, and head circumference, respectively, according to age at health check-up, birth weight group, and combination of age and birth weight (p < 0.001). The growth parameters at 60 months of age showed a significant correlation with those at 6 months of age especially in extremely low birth weight infants. The incidence of suspected developmental delay was significantly higher in infants with growth below the 10th percentiles than in those with growth above the 10th percentiles. Among 4571 (1.6%) infants with suspected developmental delay results at 60 months of age, birth weight, sex, and poor growth parameters were confirmed as associated factors. This nationwide Korean study shows that poor growth and neurodevelopment outcomes persisted among low-birth-weight infants at 60 months of age. Our findings provide guidance for developing a nationwide follow-up program for infants with perinatal risk factors in Korea.

Outcomes of infants born to pregnant women with syphilis: a nationwide study in Korea.

BACKGROUND: Despite the expansion of antenatal syphilis screening programs, congenital syphilis (CS) remains a concern. PURPOSE: This study aimed to analyze the manifestation and progress of CS, including treatment and follow-up, based on a nationwide study. METHODS: From the Korean National Health Insurance Service database, a total of 548 infants were examined for CS during their first year of life from 2013 to 2018. Neurosyphilis and complications were investigated using the International Classification of Diseases-10 codes. RESULTS: The birth rate of infants from mothers with syphilis was 2.8 per 10,000 live births for 5 years, which is not indicative of a decreasing trend. Overall, 148 infants were proven or highly probable or possible of having CS with treatment for 10 days; 66 infants were possible or less likely of having CS with only 1-day treatment. Jaundice (56 %) was common, followed by hearing impairment (14 %), renal disease (8 %), and mental retardation (8 %). Fourteen cases of neurosyphilis occurred. Infants with complications, including mental retardation, eye involvement, hearing impairment, or renal disease, were significantly associated with neurosyphilis (OR 8.49, P < 0.0001). Of 250 patients who received treatment, 92.8 % were treated with one medication: benzathine penicillin was used in 73 % of patients. Only four patients were re-treated due to treatment failure. In addition to the treponemal test, fluorescent treponemal antibody-absorption was the most utilized tool for diagnosis and follow-up. CONCLUSIONS: Establishing standardized guidelines for the evaluation of CS, as well as the establishment of treatment regimens and follow up-plans for the disease, at a national level would help improve maternal and neonatal care and facilitate the eradication of CS in Korea.

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.

Postdischarge growth assessment in very low birth weight infants.

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.

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.

Abnormal neurodevelopmental outcomes are very likely in cases of bilateral neonatal arterial ischaemic stroke.

AIM: Neonatal arterial ischaemic stroke (AIS) is an important cause of severe neurological disability. This study aimed to analyse the clinical manifestations and outcomes of AIS patients. METHODS: We enrolled neonates with AIS admitted to Severance Children's Hospital and Gangnam Severance Hospital between 2008 and 2015. AIS was confirmed using magnetic resonance imaging (MRI). We retrospectively reviewed the clinical manifestations, MRI findings, electroencephalography (EEG) findings and neurodevelopmental outcomes. RESULTS: The study comprised 29 neonates (18 boys). The mean follow-up period was 15.4 months (range 6-44 months), and the mean age at diagnosis was 8.1 days. Seizure was the most common symptom (66%). Bilateral involvement was more common than unilateral involvement (52%). The middle cerebral artery was the most commonly identified territory (79%). Abnormal EEG findings were noted in 93% of the cases. Neurodevelopment was normal in 11 (38%) patients, while cerebral palsy and delayed development were noted in eight (28%) and six (21%) patients, respectively. Patients with bilateral involvement were very likely to have abnormal neurodevelopmental outcomes. CONCLUSION: Our study showed that abnormal neurodevelopmental outcomes were very likely after cases of neonatal AIS with bilateral involvement, and clinicians should consider early and more effective interventions in such cases.

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.