Does Neonatal Microbiome Research Encompass the Placental Transfer Pathway?

The word “microbiome” is a combination of “microbiota” and “genome,” which represents the genomic concept of microbiota. The bacterial culture method is the mainstay of identifying microbes, while polymerase chain reaction adds diagnostic value. However, in the era of next-generation sequencing, achieving high-throughput microbiota footprints is extremely sensitive. This sensitivity often leads to confusion, as it can detect specific microbes genomes, even in sterile samples, such as blood, placenta, breast milk, skin, vagina, and stool. The neonatal microbiome remarkably influences both fetal and neonatal life related to health status and disease outcome. However, its origins pose a question: does it stem from a direct gateway or through a breakdown of barriers? This review provides a brief overview of evidence and speculative insights.

A Multi-Center Educational Research Regarding Breastfeeding for Pediatrics Residents in Korea

Purpose@#Pediatricians have a significant responsibility to educate mothers about the importance of breastfeeding. However, there have been minimal efforts in the courses of resident training in Korea. The purpose of this study is to evaluate the change in knowledge and attitude before and after a 4-week breastfeeding educational intervention among multicenter residents. @*Methods@#Prospective interventional educational research was designed for residents at eight training hospitals in Korea. Institutional reviews were obtained in each hospital. The education curriculum consisted of 14 courses regarding breastfeeding theory and practice. These materials were used to teach pediatric residents for 4 weeks. Knowledge-based tests were administered before the course, and re-tests were administered after the course using different test items of similar levels. Test scores and survey responses were compared before and after the intervention. @*Results@#A total of 73 residents (1st year 20, 2nd year 23, 3rd year 16, and 4th year residents 14) from eight training hospitals completed the intervention. Their average age was 30.3±2.9 years, 17 (23.3%) were male, 22 (30.1%) were married, and eight had more than one child of their own. The mean pre-test score was 61.8±13.4 and the mean post-test score was 78.3±7.5 (P<0.001). The inter-grade difference in the score was significant in the pre-test (P=0.005), but not significant in the post-test (P=0.155). There were more responses of obtaining confidence after the intervention (P<0.001). @*Conclusion@#In our study, pediatric residents showed improvement in their knowledge and confidence level after 4 weeks of the breastfeeding curriculum. This will provide a basis for future policymaking in the training of pediatric residents regarding breastfeeding in Korea.

Current Status of Neonatologist Staffing and Workload in Korean Neonatal Intensive Care Units

Purpose@#To identify the recent status of the neonatologist and their workload in neonatal intensive care unit (NICU) in Korea. @*Methods@#On October 2018, a survey was conducted on the statistics of the workforce including the census of certified neonatologists, NICU beds, nursing staffing ratings, bed occupancy rate, annual admission of very low birth weight infant (VLBWI), infant acuity score of nursing, and the proportion of out-born patients. The level of neonatal care was self-rated. @*Results@#A total of 68 centers responded to the survey. An average number of cer tified neonatologists and the number of NICU beds per center was 1.9 (range, 0 to 5) and 23.1 (range, 0 to 30), respectively. Thirty-eight percent (n=26) of NICUs were being operated with only one (n=24) or no (n=2) certified neonatologist and only 19% (n=13) of NICUs had ≥3 neonatologists. The average ratio of NICU beds to neonatologists rated 13.4±6.2. The higher the level of neonatal care, the higher the number of tertiary referral hospitals, neonatologists, NICU volume, infant acuity scores of nursing, and annual VLBWI admissions. However, there was no difference in the beds to neonatologist ratio between level 2 (n=9, 9.5±3.1), level 3 (n=44, 14.0± 6.9), and level 4 (n=14, 13.7±4.2). The infant acuity score was proportional to the NICU volumes, but not related to the beds to neonatologist ratio. @*Conclusion@#Compared with the international standards, most Korean NICUs were understaffed in terms of the certified neonatologist and were unable to provide ‘continuity of care’ for high-risk newborns.

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.

Potential Capacity of Korean Neonatal Transport Team Model Accompanying Doctors: Citizen Security Medical Service Development Project Experience

Neonatal transport teams provide a well-established medical service in developed countries. However, these services are associated with high costs and expenses. With the lowest birth rate in the world, South Korea is facing a population decrease that is reaching a crisis level. Management of neonatal patients by neonatal transport teams is one mechanism to minimize neonatal mortality and morbidity and help overcome this population crisis. This review highlights the need to organize neonatal transport teams in Korea and addresses potential regional pitfalls and challenges.

Potential Capacity of Korean Neonatal Transport Team Model Accompanying Doctors: Citizen Security Medical Service Development Project Experience

Neonatal transport teams provide a well-established medical service in developed countries. However, these services are associated with high costs and expenses. With the lowest birth rate in the world, South Korea is facing a population decrease that is reaching a crisis level. Management of neonatal patients by neonatal transport teams is one mechanism to minimize neonatal mortality and morbidity and help overcome this population crisis. This review highlights the need to organize neonatal transport teams in Korea and addresses potential regional pitfalls and challenges.

Remission of diffuse ulcerative duodenitis in a patient with ulcerative colitis after infliximab therapy: a case study and review of the literature

Although ulcerative colitis (UC) is confined to colonic and rectal mucosa in a continuous fashion, recent studies have also demonstrated the involvement of upper gastrointestinal tract as diagnostic endoscopy becomes more available and technically advanced. The pathogenesis of UC is not well established yet. It might be associated with an inappropriate response of host mucosal immune system to gut microflora. Although continuous and symmetric distribution of mucosal inflammation from rectum to colon is a typical pattern of UC, clinical feature and course of atypically distributed lesions in UC might also help us understand the pathogenesis of UC. Herein, we report a case of duodenal involvement of UC which successfully remitted after infliximab therapy. Endoscopic and pathologic findings before and after administration of anti-tumor necrosis factor suggest that the pathogenesis of upper gastrointestinal involvement of UC may be similar to that of colon involvement.

The Relationship between Parental Stress and Nurses' Communication as Perceived by Parents of High-risk Newborns

PURPOSE: This study aimed to characterize the relationship between parental stress and nurses' communication as perceived by parents of high-risk newborns in a neonatal intensive care unit (NICU). METHODS: The participants were 54 parents of high-risk newborns in a NICU. Data were collected from January to March 2018. Parental stress and parents' perceptions of nurses' communication ability and styles were measured using a questionnaire. RESULTS: The average scores for parental stress and nurses' communication ability were 3.39 and 4.38 respectively, on a 5-point scale. Parents most commonly reported that nurses showed a friendly communication style, followed by informative and authoritative styles. Mothers and fathers reported significantly different levels of parental stress. Parental stress showed a negative correlation with nurses' perceived verbal communication ability. Higher scores for nurses' verbal communication ability and for friendly and informative communication styles were associated with lower parental stress induced by the environment, the baby's appearance and behaviors, and treatments in the NICU. CONCLUSION: The findings of this study suggest that nurses need to offer proper information for parents and to support parents by encouraging them to express their emotions of stress and by providing parents with therapeutic communication and opportunities to participate in care.

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.

Neonatal Sepsis and Meningitis Caused by Neisseria meningitidis Serogroup B: a Case Report

Sepsis and meningitis caused by Neisseria meningitidis are rare in neonates, but neonatal sepsis and meningitis are associated with a high rate of mortality. Meningococcal disease is commonly reported in older children and adolescents and is known to be more prevalent in community settings. In this study, a 16-day-old neonate was diagnosed with serogroup B meningococcal sepsis and meningitis. The baby was treated with antibiotics at the early stages of the infection and was discharged in good condition without any complications. This case report can serve to raise awareness of the incidence and importance of meningococcal infection in neonates, especially serogroup B.

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.

Clinical Characteristics and Incidence of Perianal Diseases in Patients With Ulcerative Colitis

PURPOSE: While perianal disease (PAD) is a characteristic of patients with Crohn disease, it has been overlooked in patients with ulcerative colitis (UC). Thus, our study aimed to analyze the incidence and the clinical features of PAD in patients with UC. METHODS: We reviewed the data on 944 patients with an initial diagnosis of UC from October 2003 to October 2015. PAD was categorized as hemorrhoids, anal fissures, abscesses, and fistulae after anoscopic examination by experienced proctologists. Data on patients’ demographics, incidence and types of PAD, medications, surgical therapies, and clinical course were analyzed. RESULTS: The median follow-up period was 58 months (range, 12–142 months). Of the 944 UC patients, the cumulative incidence rates of PAD were 8.1% and 16.0% at 5 and 10 years, respectively. The incidence rates of bleeding hemorrhoids, anal fissures, abscesses, and fistulae at 10 years were 6.7%, 5.3%, 2.6%, and 3.4%, respectively. The cumulative incidence rates of perianal sepsis (abscess or fistula) were 2.2% and 4.5% at 5 and 10 years, respectively. In the multivariate analyses, male sex (risk ratio [RR], 4.6; 95% confidence interval [CI], 1.7–12.5) and extensive disease (RR, 4.2; 95% CI, 1.6–10.9) were significantly associated with the development of perianal sepsis. CONCLUSION: Although the clinical course of PAD in patients with UC is not serious, in clinical practice, PAD is not rare in such patients. Therefore, careful examination and appropriate management for PAD is needed if the quality of life for patients with UC is to be improved.

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.

Can Treatment of Patent Ductus Arteriosus with Ibuprofen Compared to Supportive Management Affect Regional Brain Volume in Very Low Birth Weight Infants? A Pilot Study

PURPOSE: This study aimed to compare cerebral hemispheric volumes between pharmacologic treatment and supportive management of patent ductus arteriosus (PDA). METHODS: The study was conducted retrospectively. The subjects of period 1 group were very low birth weight infants whose PDA were treated with pharmacologic closure. Period 2 group were treated with supportive management. Regional brain volumes measured using magnetic resonance imaging were compared between the two groups. RESULTS: total of 12 infants were included. Their median gestational age was 27⁺⁶ (range: 24⁺¹–31⁺¹) weeks and birth weight was 1,065 g (range: 690–1,380). Between the two groups, there was no difference in Apgar score, incidence of bronchopulmonary dysplasia, necrotizing enterocolitis, and culture proven sepsis. The regional brain volumes such as gray matter (Period 1 group, 76,833 mm³ [55,759–100,388] vs. Period 2 group, 79,870 mm³ [59,957–113,018], P=0.59), white matter (82,993 mm³ [63,130–121,311] vs. 92,576 mm³ [77,200–104,506], P=0.18), cerebrospinal fluid (17,167 mm³ [9,279–22,760] vs. 14,348 mm³ [7,018–27,604], P=0.94), basal ganglia (2,065 mm³ [1,697–2,482] vs. 2,306 mm³ [2,065–3,009], P=0.18), and cerebellum (18,374 mm³ [14,843–24,657] vs. 18,096 mm³ [16,134–23,627], P=0.94) were not different between the two groups. CONCLUSION: Regional brain volumes were not different between pharmacological and conservative treatment in infants with PDA. Further wellcontrolled studies are required to evaluate the advantages or disadvantages of supportive management without pharmacologic treatment of PDA.

A Case of Partial Short Arm Deletion in Chromosome 9 with Inguinal Hernia, Testicular Cystic Lesion, and Arthrogryposis Multiplex Congenita

Chromosome 9p syndrome is a rare chromosomal abnormality caused by a partial deletion in chromosome 9. It was first described in 1973 by Alfi et al., and has since been shown to have diverse clinical phenotypes. Here, we reported a case of a male infant with joint contracture of the extremities, dysmorphic face, inguinal hernia, and testicular cystic masses. Chromosomal analysis revealed a terminal deletion at the short arm of chromosome 9. The major clinical features of the 9p deletion syndrome are trigonocephaly, small palpebral fissures, a flat nasal bridge, and mental retardation. To the best of our knowledge, this is the first reported case of a patient with 9p24 deletion presenting with arthrogryposis multiplex congenita.

Fetal and preterm infant microbiomes: a new perspective of necrotizing enterocolitis / 소아과

Necrotizing enterocolitis (NEC) is a devastating condition of hospitalized preterm infants. Numerous studies have attempted to identify the cause of NEC by examining the immunological features associated with pathogenic microorganisms. No single organism has proven responsible for the disease; however, immunological studies are now focused on the microbiome. Recent research has investigated the numerous bacterial species residing in the body and their role in diseases in preterm infants. The timing of initial microbial colonization is a subject of interest. The microbiome appears to transfer from the mother to the newborn, as well as to the fetus. Cross-talk between the fetus and fetal microbiome takes place continuously to generate a unique immune system. This review examined the transfer of the microbiome to the human fetus, and its potential relationship with NEC.

Does Breast-feeding Relate to Development of Atopic Dermatitis in Young Korean Children?: Based on the Fourth and Fifth Korea National Health and Nutrition Examination Survey 2007–2012

PURPOSE: There have been conflicting reports concerning the relationship between breast-feeding and the development of atopic dermatitis (AD) in early childhood. The objective of this study was to investigate the associations between breast-feeding and the risk of AD in early childhood in Korea. METHODS: We combined the fourth and fifth Korea National Health and Nutrition Examination Survey data collected from 2007 to 2012 and analyzed 2,015 children at 1 to 3 years old. Regression analysis was used to determine the association of the following variables: AD, feeding types, duration of breast-feeding, and others. RESULTS: The annual prevalence of exclusive breast-feeding and AD decreased. Parents with allergic diseases preferred breast-feeding and extended duration of feeding compared with those without. In multiple logistic regression analyses, exclusive breast-feeding in feeding type I (P=0.070; adjusted odds ratio [OR]=1.990), exclusive breast-feeding in feeding type II (P=0.095; adjusted OR=1.495) and breast-feeding duration (P=0.430; adjusted OR=1.013) were not significantly related to AD. CONCLUSIONS: Breast-feeding was not found to be associated with an occurrence of AD in young children. Rather, parents with histories of allergic diseases tended to prefer breast-feeding and extend its duration. To clarify the role of breast-feeding in the development of AD, a nation-wide prospective study is needed.

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 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.