Eosinophil activation markers in blood and urine in preterms developing bronchopulmonary dysplasia

Purpose@#Eosinophil-derived neurotoxin (EDN) is not the only a marker for eosinophil activation, but also acts as an alarm protein.Very few studies have examined the potential role of eosinophils in the development of bronchopulmonary dysplasia (BPD). This study aims to address the roles of eosinophil and EDN in the early phase of BPD development. @*Methods@#Patients were preterm neonates with respiratory distress syndrome (RDS) born at 36 weeks of gestation or less. Blood and urine samples were collected to measure total eosinophil count in the blood, serum eosinophil cationic protein (ECP), serum EDN, and urinary EDN during the first week of life. @*Results@#Fifty-two preterms were recruited, of whom 43 infants were analyzed. Comparisons were made between the RDS (n = 16) and non-RDS groups (n = 27) and between the BPD (n = 6) and non-BPD groups (n = 26). There were no differences between RDS and non-RDS group in total eosinophil count, serum ECP, serum EDN, or urinary EDN, except when compared by gestational age, birth weight and prenatal dexamethasone use. Urinary EDN was increased significantly in the BPD group compared to the non-BPD group. @*Conclusion@#We demonstrated the roles of eosinophil and EDN in the development of BPD and suggest that urinary EDN may be utilized as a noninvasive factor predicting the development of BPD.

Comparison of Maternal and Child Health Statistics between South and North Korea

Purpose@#This study aimed to investigate the extent of the difference in health status between South Korea (SK) and North Korea (NK) by comparing indicators relevant to maternal and child health. @*Methods@#The maternal and child health status of SK and NK considering population, birth, and mortality was reviewed using 2 Korean statistics, United Nations Children’s Fund, and United Nations databases from 1950 to 2017. @*Results@#The annual number of total live births in SK had decreased from 1,006,600 in 1970 to 326,900 in 2018, and that in NK had declined from 530,000 in 1970 to 360,000 in 2015. The percentage of children among the total population was higher in NK than in SK, and the decrease in the percentage of children in SK is remarkable, which is related to a low fertility rate in the last few decades. However, the mortality rates related to children were higher in NK than in SK. In 2017, neonatal mortality rates (per 1,000 live births) in SK and NK were 1.5 and 9.0, respectively. The fertile female population of SK and NK in 2015 was 50.2% and 52.0%, respectively, and SK and NK’s aging index (%) in 2017 was 107.3 and 46.1, re spectively. @*Conclusion@#This study shows the different population distributions and maternal and child health statuses between SK and NK, which may have a negative impact on social integration after reunification. Therefore, it is important to understand the indicators of maternal and child health to become the powerbase of effi cient healthcare system integration by minimizing the impact at the beginning of the reunification.

Trends in Birth Weight and the Incidence of Low Birth Weight and Advanced Maternal Age in Korea between 1993 and 2016

BACKGROUND: As the aging society progresses, the average age of mothers is also increasing. Advanced maternal age has been known to be associated with perinatal outcomes, as well as birth weight (BW). In this study, we aimed to investigate the perinatal factors associated with low birth weight infants (LBWIs) using birth statistics of the Korean population. METHODS: Birth statistics between 1993 and 2016 from the Korean Statistical Information Service were reviewed. We investigated 12,856,614 data points, which included the number of births, BWs, percentage of preterm births and LBWIs, multiple pregnancies, and maternal age. RESULTS: The proportion of LBWIs delivered by mothers of advanced maternal age has gradually increased since 1993. In addition, the proportion of older mothers (≥ 35 years old) giving birth to LBWIs has increased over the years. Average BW has a negative correlation with the ratio of preterm births, LBW, multiple births, and advanced maternal age. The mean BW also has a negative correlation with maternal age. CONCLUSION: This study shows that the average BW continues to decline, and the incidence of LBWIs is increasing in Korea since 1993. This study also revealed that several perinatal factors, including percentage of preterm births, LBWIs, multiple births, and maternal age influence the mean BW. Although this study did not investigate the effects of decreasing mean BW on perinatal health, future research is worth discussing.

History of Pulmonary Surfactant Replacement Therapy for Neonatal Respiratory Distress Syndrome in Korea

Neonatal respiratory distress syndrome (RDS) is a disease that is unique to newborn infants. It is caused by a deficiency of pulmonary surfactant (PS), which is usually ready to be activated around the perinatal period. Until RDS was more clearly understood, it was not known why premature infants died from respiratory failure, although pathology revealed hyaline membranes in the alveoli. Surprisingly, the era of PS replacement therapy began only relatively recently. The first clinical trial investigating neonatal RDS was conducted in 1980. Since then, newborn survival has improved dramatically, which has led to significant advances in the field of neonatology. The present comprehensive review addresses PS, from its discovery to the application of artificial PS in newborns with RDS. It also reviews the history of PS in Korea, including its introduction, various commercial products, present and past research, newborn registries, and health insurance issues. Finally, it describes the inception of the Korean Society of Neonatology and future directions of research and treatment.

Leukocyte Adhesion Deficiency Associated with Neonatal Septic Hip in a Late Preterm Infant

Leukocyte adhesion deficiency is a rare primary immunodeficiency and autosomal recessive disorder caused by a mutation in the gene encoding CD18, which is a constituent of leukocyte integrins. Clinical features usually begin with a delay in the separation of the umbilical cord in the neonatal period, and are characterized by marked leukocytosis with infection, delayed wound healing, and repeated bacterial and fungal infections. We experienced a case of leukocyte adhesion deficiency diagnosed in the neonatal period, in which a late preterm infant admitted to neonatal intensive care unit presented with a septic hip. Flow cytometry analysis of whole blood showed a decrease in the expression of CD11b/CD18. This is the first case of leukocyte adhesion deficiency with neonatal septic hip diagnosed in Korea.

Comparison of the Birth Statistics between Multi-cultural and Korean Families in Korea (2015)

Since 2002, the number of marriages, births, and family members among multi-cultural families (MCFs) has increased. Beginning in 2006, the government initiated a planned management for such families and has implemented the MCF policy basic plan since 2010. In 2015, with multiple socio-economic and medical support initiatives for MCF being available, we analyzed the statistics for several factors related to birth, to determine whether there are significant adverse birth outcomes in MCF. We analyzed the birth data of MCFs in 2015, from Statistics Korea. This study compared the birth data of MCF and Korean families (KF) by geography, neonatal birth weight (BW), gestational age (GA), birth order of the neonates, place of delivery, cohabitation period of parents before the first child, and parental education level. The distribution of BW and the prevalence of low BW (< 2,500 g) or very low BW (< 1,500 g) were similar between both groups. The incidence of preterm birth was lower in the MCF group (6.5% vs. 7.0%, P = 0.015) than in the KF group. In the MCF group, parental education level was lower, and incidence of out-of-hospital births was higher than that of the KF group. Adverse birth outcomes, such as preterm birth and low BW in MCF are similar or better than KF. This study could be a good basis to present the status of MCF birth and newborn care in 2015.

Improvement in the Survival Rates of Very Low Birth Weight Infants after the Establishment of the Korean Neonatal Network: Comparison between the 2000s and 2010s

The survival rate (SR) of very low birth weight infants (VLBWIs) and extremely low birth weight infants (ELBWIs) is a health indicator of neonatal intensive care unit (NICU) outcomes. The Korean Neonatal Network (KNN) was established in 2013, and a system has been launched to manage the registration and quality improvement of VLBWIs. The SR of the VLBWIs significantly increased to 85.7% in the 2010s compared with 83.0% in the 2000s. There was also a significant increase in the SR of the ELBWIs from 66.1% to 70.7%. The equipment, manpower, and assistance systems of NICUs also improved in quantity and quality. In the international comparison of the SRs of VLBWIs, the SRs were 93.8%, 92.2%, 90.2%, 89.4%, 86.4%, 85.1%, and 80.6% in Japan, Australia and New Zealand, Canada, Europe, Korea, Taiwan, and United States, respectively. In conclusion, the SRs of the VLBWIs and ELBWIs improved in the 2010s compared with those in the 2000s in Korea. This improvement is considered to have been related to the role of the KNN built in 2013. However, the latest VLBWI and ELBWI SRs in 2015 are still low compared with those in Japan, Australia and New Zealand, Canada, and Europe. In the future, we must establish and develop the tasks that are presented as future tasks in this review.

A Combination of Short and Simple Surfactant Protein B and C Analogues as a New Synthetic Surfactant: In Vitro and Animal Experiments

PURPOSE: Pulmonary surfactants for preterm infants contain mostly animal-derived surfactant proteins (SPs), which are essential for lowering surface tension. We prepared artificial pulmonary surfactants using synthetic human SP analogs and performed in vitro and in vivo experiments. MATERIALS AND METHODS: We synthesized peptide analogues that resemble human SP-B (RMLPQLVCRLVLRCSMD) and SP-C (CPVHLKRLLLLLLLLLLLLLLLL). Dipalmitoylphosphatidylcholine (DPPC), phosphatidylglycerol (PG), and palmitic acid (PA) were added and mixed in lyophilized to render powdered surfactant. Synsurf-1 was composed of DPPC:PG:PA:SP-B (75:25:10:3, w/w); Synsurf-2 was composed of DPPC:PG:PA:SP-C (75:25:10:3, w/w); and Synsurf-3 was composed of DPPC:PG:PA:SP-B:SP-C (75:25:10:3:3, w/w). We performed in vitro study to compare the physical characteristics using pulsating bubble surfactometer and modified Wilhelmy balance test. Surface spreading and adsorption test of the surfactant preparations were measured. In vivo test was performed using term and preterm rabbit pups. Pressure-volume curves were generated during the deflation phase. Histologic findings were examined. RESULTS: Pulsating bubble surfactometer readings revealed following minimum and maximum surface tension (mN/m) at 5 minutes: Surfacten® (5.5±0.4, 32.8±1.6), Synsurf-1 (16.7±0.6, 28.7±1.5), Synsurf-2 (7.9±1.0, 33.1±1.6), and Synsurf-3 (7.1±0.8, 34.5±1.0). Surface spreading rates were as follows: Surfacten® (27 mN/m), Synsurf-1 (43 mN/m), Synsurf-2 (27 mN/m), and Synsurf-3 (27 mN/m). Surface adsorption rate results were as follows: Surfacten® (28 mN/m), Synsurf-1 (35 mN/m), Synsurf-2 (29 mN/m), and Synsurf-3 (27 mN/m). The deflation curves were best for Synsurf-3; those for Synsurf-2 were better than those for Surfacten®. Synsurf-1 was the worst surfactant preparation. Microscopic examination showed the largest aerated area of the alveoli in the Synsurf-3 group, followed by Synsurf-1 and Surfacten®; Synsurf-2 was the smallest. CONCLUSION: Synsurf-3 containing both SP-B and SP-C synthetic analogs showed comparable and better efficacy than commercially used Surfacten® in lowering surface tension, pressure-volume curves, and tissue aerated area of the alveoli.

Development of a Synthetic Surfactant Using a Surfactant Protein-C Peptide Analog: In Vitro Studies of Surface Physical Properties

PURPOSE: Pulmonary surfactant (PS) replacement has been the gold standard therapy for neonatal respiratory distress syndrome; however, almost all commercial PSs contain animal proteins. We prepared a synthetic PS by using a human surfactant protein (SP) analog and evaluated its in vitro properties. MATERIALS AND METHODS: A peptide sequence (CPVHLKRLLLLLLLLLLLLLLLL) of human SP-C was chosen to develop the peptide analog (SPa-C). The new synthetic SP-C PS (sSP-C PS) was synthesized from SPa-C, dipalmitoyl phosphatidylcholine, phosphatidyl glycerol, and palmitic acid. Physical properties of the sSP-C PS were evaluated by measuring the maximum and minimum surface tensions (STs), surfactant spreading, and adsorption rate. In addition, we recorded an ST-area diagram. The data obtained on sSP-C PS were subsequently compared with those of purified natural bovine surfactant (PNBS), and the commercial product, Surfacten(R). RESULTS: The sSP-C PS and Surfacten(R) were found to have maximum ST values of 32-33 mN/m, whereas that of PNBS was much lower at 19 mN/m. The minimum ST values of all three products were less than 10 mN/m. The values that were measured for the equilibrium ST of rapidly spreading sSP-C PS, Surfacten(R), and PNBS were 27, 27, and 24 mN/m, respectively. The surface adsorptions were found to be the same for all three PSs (20 mN/m). ST-area diagrams of sSP-C PS and Surfacten(R) revealed similar properties. CONCLUSION: In an in vitro experiment, the physical properties exhibited by sSP-C PS were similar to those of Surfacten(R). Further study is required to evaluate the in vivo efficacy.

The history of neonatology in Korea

Neonatology in pediatrics became a part of medical school curricula in Korea in 1954-1959. Specific treatments and procedures in the neonatal field were adopted around this period, for example, antibiotics, oxygen therapy, and the exchange transfusion procedure were established in 1950-1960. Usage of an infant incubator was implemented along with the establishment in 1960. The trend of separation between a premature infant care unit and newborn nursery room enabled the specialized treatment of high-risk infants in the 1970s. Assisted ventilation with continuous positive airway pressure and phototherapy was initiated in 1978. The recent concept of a neonatal intensive care unit was established in 1980, and it made so-called neonatal intensive care such as mechanical ventilation and intensive monitoring available. The Korean Society of Neonatology was founded in 1993. The usage of pulmonary surfactant in the 1990s, accelerated the improvement of respiratory distress syndrome survival, and it resulted in the nationwide opening of neonatal intensive care unit in hospitals. The high frequency ventilator and inhaled nitric oxide were introduced in the 2000s. The Korean Neonatal Network was commenced as a nationwide systemic database for very low birth weight infant registry in 2010. Accordingly, the history of Korean neonatology can be summarized as 50 years in total, and 35 years in a narrow sense. During this era, neonatal care in Korea has improved remarkably and has achieved a great survival rate for high-risk neonates, preterm infants, and micro-premies. In this review, we intend to provide an overview of the history, efforts, and outcomes of Korean neonatology activity that have led to these achievements.

The Experience of Human Milk Banking for 8 Years: Korean Perspective

Human milk banks are a solution for mothers who cannot supply their own breast milk to their sick or hospitalized infants; premature infants, in particular, are unable to receive a full volume of breast milk for numerous reasons. As of December 2015, there was only one milk bank in a university hospital in Korea. We reviewed the basic characteristics of donors and recipients, and the amounts and contamination of breast milk donated at the Human Milk Bank in Kyung Hee University Hospital at Gangdong in Korea from 2008 to 2015. The donor pool consisted of 463 first-time donors and 452 repeat donors who made 1,724 donations. A total of 10,820 L of breast milk was collected, and 9,541.6 L were processed. Detectable bacteria grew in 12.6% after pasteurization and 52.5% had cytomegalovirus DNA before pasteurization in donated milk. There were 836 infant and 25 adult recipients; among new infant recipients, 48.5% were preterm; the groups received 8,009 and 165.7 L of donor milk, respectively. There was an increase in the percentage of preterm infants among new infant recipients in 2015 (93.1%) compared to 2008 (8.5%). Based on the number of premature infants in Korea, the number of potential recipients is not likely to diminish anytime soon, despite efforts to improve the breastfeeding rate. Sustainability and quality improvement of the milk bank need long-term financial support by health authorities and a nationwide network similar to blood banking will further contribute to the progress of milk banking.

The Clinical and Experimental Vaccine Research has been selected for coverage in Emerging Sources Citation Index of Web of Science

No abstract available.

Percentile Distributions of Birth Weight according to Gestational Ages in Korea (2010-2012)

The Pediatric Growth Chart (2007) is used as a standard reference to evaluate weight and height percentiles of Korean children and adolescents. Although several previous studies provided a useful reference range of newborn birth weight (BW) by gestational age (GA), the BW reference analyzed by sex and plurality is not currently available. Therefore, we aimed to establish a national reference range of neonatal BW percentiles considering GA, sex, and plurality of newborns in Korea. The raw data of all newborns (470,171 in 2010, 471,265 in 2011, and 484,550 in 2012) were analyzed. Using the Korean Statistical Information Service data (2010-2012), smoothed percentile curves (3rd-97th) by GA were created using the lambda-mu-sigma method after exclusion and the data were distinguished by all live births, singleton births, and multiple births. In the entire cohort, male newborns were heavier than female newborns and singletons were heavier than twins. As GA increased, the difference in BW between singleton and multiples increased. Compared to the previous data published 10 years ago in Korea, the BW of newborns 22-23 gestational weeks old was increased, whereas that of others was smaller. Other countries' data were also compared and showed differences in BW of both singleton and multiple newborns. We expect this updated data to be utilized as a reference to improve clinical assessments of newborn growth.

Changes in Survival Rate for Very-Low-Birth-Weight Infants in Korea: Comparison with Other Countries

Recently the Korean Neonatal Network (KNN) was established in order to enhance treatment outcomes further through the registration of very-low-birth-weight infants (VLBWI) data. The present study was conducted on 2,606 VLBWI, 2,386 registered and 220 un-registered, in the KNN participating centers, with the objective of reporting on recent survival rates of VLBWI in Korea and verifying the changing trends in survival rates with data from the 1960s and beyond. The study also aimed to compare the premature infants' survival rate in Korea with those reported in neonatal networks of other countries. The recent survival rate of VLBWI increased more than twice from 35.6% in the 1960s to 84.8%, and the survival rate of the extremely low birth weight infants (ELBWI) increased by more than 10 times, indicating improvement of the survival rate in premature infants with lower birth weight and gestational age. Comparison of VLBWI between countries showed improved survival rates according to each birth weight group in Canada, Australia-New Zealand, and European countries with Japan at the head, but in terms of comparison based on gestational age, differences, except for Japan, have been reduced. Efforts to increase the survival rate of premature infants in Korea with low birth rate are inevitable, and they should be the foundation of academic and clinical development based on its network with advanced countries.

Early Prophylactic versus Late Selective Use of Surfactant for Respiratory Distress Syndrome in Very Preterm Infants: A Collaborative Study of 53 Multi-Center Trials in Korea

Pulmonary surfactant (PS) therapy was proven to be highly successful for the treatment of respiratory distress syndrome in premature infants. As a results, early prophylactic (EP) PS therapy has been introduced recently in Europe, the US and Korea. However, no multi-center study was compared EP and late selective (LS) PS therapies in Korea. We performed a retrospective multi-center study to compare the outcomes of EP and LS PS therapies in very preterm infants. We analyzed clinical morbidity and mortality for 1,291 infants in 2010 (LS group) and 1,249 infants in 2011 (EP group); the infants were born <30 weeks of gestation and had birth weight < or =1,250 g, and were chosen from 53 neonatal intensive care units in Korea. Compared to the LS group (22.5%), the overall mortality was better in the EP group (19.9%) and there was no increased need for retreatment.There were additional benefits in the EP group such as fewer associated complications. To the best of knowledge, our study is the first nationwide Korean study to compare the outcomes of EP and LS therapies, and it provides evidences that EP PS therapy is important in very preterm infants to improve for survival and reduce morbidities.

Early Prophylactic versus Late Selective Use of Surfactant for Respiratory Distress Syndrome in Very Preterm Infants: A Collaborative Study of 53 Multi-Center Trials in Korea

Pulmonary surfactant (PS) therapy was proven to be highly successful for the treatment of respiratory distress syndrome in premature infants. As a results, early prophylactic (EP) PS therapy has been introduced recently in Europe, the US and Korea. However, no multi-center study was compared EP and late selective (LS) PS therapies in Korea. We performed a retrospective multi-center study to compare the outcomes of EP and LS PS therapies in very preterm infants. We analyzed clinical morbidity and mortality for 1,291 infants in 2010 (LS group) and 1,249 infants in 2011 (EP group); the infants were born <30 weeks of gestation and had birth weight < or =1,250 g, and were chosen from 53 neonatal intensive care units in Korea. Compared to the LS group (22.5%), the overall mortality was better in the EP group (19.9%) and there was no increased need for retreatment.There were additional benefits in the EP group such as fewer associated complications. To the best of knowledge, our study is the first nationwide Korean study to compare the outcomes of EP and LS therapies, and it provides evidences that EP PS therapy is important in very preterm infants to improve for survival and reduce morbidities.

Changes in the Cesarean Section Rate in Korea (1982-2012) and a Review of the Associated Factors

Although Cesarean section (CS) itself has contributed to the reduction in maternal and perinatal mortality, an undue rise in the CS rate (CSR) has been issued in Korea as well as globally. The CSR in Korea increased over the past two decades, but has remained at approximately 36% since 2006. Contributing factors associated with the CSR in Korea were an improvement in socio-economic status, a higher maternal age, a rise in multiple pregnancies, and maternal obesity. We found that countries with a no-fault compensation system maintained a lower CSR compared to that in countries with civil action, indicating the close relationship between the CSR and the medico-legal system within a country. The Korean government has implemented strategies including an incentive system relating to the CSR or encouraging vaginal birth after Cesarean to decrease CSR, but such strategies have proved ineffective. To optimize the CSR in Korea, efforts on lowering the maternal childbearing age or reducing maternal obesity are needed at individual level. And from a national view point, reforming health care system, which could encourage the experienced obstetricians to be trained properly and be relieved from legal pressure with deliveries is necessary.

Erratum: Changes in the neonatal and infant mortality rate and the causes of death in Korea / 소아과

We found an error in our published article. We have corrected the table.

A Case of Paenibacillus-induced Sepsis Complicated with Pneumatocele in a Very Low Birth Weight Infant

Paenibacillus spp. are gram-positive, rod-shaped, facultative anaerobic bacteria found in nature and rarely cause diseases in humans. We report our experience with Paenibacillus-induced sepsis complicated with pneumatocele in a very low birth weight male infant with a gestational age of 29 weeks and 5 days and a birth weight of 1,380 g, who was born by cesarean section with because of preterm labor and premature rupture of membrane. On day 12 after admission, the patient presented oxygen desaturation without apnea and fever. We identified pleural effusion on chest radiography and diagnosed pneumatocele on low-dose chest computed tomography. An empirical antibiotic was administered to treat the infection. The patient's blood culture revealed gram-positive rods, and Paenibacillus spp. was identified using16s rRNA sequencing.

A Case of Subcutaneous Fat Necrosis of the Newborn with Hypoglycemia and Meconium Aspiration Syndrome / 대한주산의학회잡지

Subcutaneous fat necrosis of the newborn is a rare, benign disease usually found in full-term infants. It occurs usually in a few weeks after birth, as one or multiple indurated nodules or plaques on the fat pads-rich fraction of the body and disappeared after few weeks to months. Complications such as hypercalcemia, pain, lipid abnormalities (dyslipidemia), renal failure, and subcutaneous atrophy may occur. We report a case of subcutaneous fat necrosis associated with hypoglycemia and meconium aspiration syndrome in the term infant and review the associated literatures.