Longitudinal Change of Cup to Disc Ratio in Premature Infants with Enlarged Cup to Disc Ratio and Normal Intraocular Pressure.

PURPOSE: To evaluate the longitudinal change of cup to disc ratio (CDR) in premature infants with enlarged CDR and normal intraocular pressure (IOP). METHODS: This retrospective, observational study included 283 eyes of 283 premature infants at single center. Infants were divided into enlarged CDR and control groups. Data on demographics, gestational age (GA), birth weight (BW), vertical cup to disc ratio (vCDR), IOP, and corneal diameter were analyzed. RESULTS: Of the 283 patients, 38 (13.4%) and 245 (86.6%) were in the enlarged CDR and control groups, respectively. In the enlarged CDR group, the vCDR and baseline IOP was 0.63 ± 0.12 and 12.7 ± 2.2 mmHg, respectively. In the control group, the vCDR and baseline IOP was 0.18 ± 0.05 and 10.9 ± 1.7 mmHg, respectively. The IOP at a GA of 40 weeks and at 1 and 2 years of age were significantly lower than that at baseline. The differences in vCDR between baseline and each follow-up visit were not significant. vCDR was negatively correlated with GA and BW; however, these correlations were not significant. CONCLUSIONS: The vCDR did not significantly change up to age of 2 years of age in premature infants with enlarged CDR and normal IOP. However, close follow-up is needed until other reliable glaucoma examinations, such as optical coherence tomography and visual fields, can be possible.

Recent Changes in End-of-Life Decisions for Newborns in a Korean Hospital.

INTRODUCTION: Despite recent advances in neonatal intensive care in Korea, few studies exist on the end-of-life decisions in newborns. In this study, we sought to examine the status of end-of-life decisions in neonates, changes over time, and affecting factors. METHODS: This is a retrospective study of neonates who died between 2001 and 2015 in the neonatal intensive care unit of Dong-A University Hospital in Busan. The types of end-of-life decisions were divided into active resuscitation, withholding treatment, and withdrawing treatment. The study period was divided into 3 time frames using 5-year intervals to investigate changes over time. To identify the associated factors, we analyzed the demographic and clinical characteristics of the neonates and their parents using the χ2 test and independent t test. RESULTS: Of the neonatal deaths included in the analysis (n = 222), active resuscitation, withholding treatment, and withdrawing treatment groups accounted for 73.4%, 25.2%, and 1.4% of cases, respectively. When comparing changes over time, between period 1 (2001-2005), 2 (2006-2010), and 3 (2011-2015), the proportion of active resuscitation decreased significantly, from 80.9% to 60.8%, while that of nonactive resuscitation increased significantly from 19.1% to 39.2%. The factors associated with end-of-life decisions were the clinical condition of the neonate at the time of death, rather than general characteristics or socioeconomic factors. CONCLUSIONS: In Korea, changes in the decisions on end-of-life care in neonates are shifting from active resuscitation to nonactive resuscitation based on clinical conditions.

Enteral nutrition for optimal growth in preterm infants.

Early, aggressive nutrition is an important contributing factor of long-term neurodevelopmental outcomes. To ensure optimal growth in premature infants, adequate protein intake and optimal protein/energy ratio should be emphasized rather than the overall energy intake. Minimal enteral nutrition should be initiated as soon as possible in the first days of life, and feeding advancement should be individualized according to the clinical course of the infant. During hospitalization, enteral nutrition with preterm formula and fortified human milk represent the best feeding practices for facilitating growth. After discharge, the enteral nutrition strategy should be individualized according to the infant's weight at discharge. Infants with suboptimal weight for their postconceptional age at discharge should receive supplementation with human milk fortifiers or nutrient-enriched feeding, and the enteral nutrition strategy should be reviewed and modified continuously to achieve the target growth parameters.

Current Status of Therapeutic Strategies for Patent Ductus Arteriosus in Very-Low-Birth-Weight Infants in Korea.

This study aimed to investigate current therapeutic strategies for patent ductus arteriosus (PDA) in very-low-birth-weight (VLBW) infants in Korea. A total of 2,254 VLBW infants among 2,386 from Korean Neonatal Network cohort born from January 2013 to June 2014 were included. No PDA was seen for 1,206 infants (53.5%) and the infants diagnosed or treated for PDA were 1,048 infants (46.5%). The proportion of infants with PDA was decreased according to the increase in gestational age (GA) and birthweight. Infants with PDA were divided into groups according to the therapeutic strategies of PDA: prophylactic treatment (PT, n = 69, 3.1%), pre-symptomatic treatment (PST, n = 212, 9.4%), symptomatic treatment (ST, n = 596, 26.4%), and conservative treatment (CT, n = 171, 7.6%). ST was the most preferred treatment modality for preterm PDA and the proportion of the patients was decreased in the order of PST, CT, and PT. Although ST was still the most favored treatment in GA < 24 weeks group, CT was more preferred than PST or ST when compared with GA ≥ 32 weeks group [CT vs. PST, OR 5.3, 95% CI 1.56-18.18; CT vs. ST, OR 2.9, 95% CI 1.03-8.13]. A total of 877 infants (38.9%) received pharmacological or surgical treatment about PDA, and 35.5% (801 infants) received pharmacological treatment, mostly with ibuprofen. Seventy-six infants (3.4%) received primary ligation and 8.9% (201 infants) received secondary ligation. Diverse treatment strategies are currently used for preterm PDA in Korea. Further analyses of neonatal outcomes according to the treatment strategies are necessary to obtain a standardized treatment guideline for preterm PDA.

Brainstem auditory evoked potentials in late preterm infants at term-equivalent age.

To detect differences between late preterm and term infants in the brainstem auditory evoked response (BAER) variables that predispose to neurodevelopmental abnormalities, 36 late preterm infants and 87 term infants were recruited. Data collected with the click level at 70 dB nHL were used for analysis. The latencies of waves I (2.74±0.20 msec vs. 2.74±0.42 msec), III (5.55±0.33 msec vs. 5.53±0.45 msec) and V (7.55±0.34 msec vs. 7.59±0.44 msec), and the interpeak intervals for late preterm infants were similar to those for term infants. There were no significant differences between late preterm and term infants in amplitudes I (0.26±0.11 µV vs. 0.24±0.10 µV) and V (0.25±0.06 µV vs. 0.28±0.11 µV), and in the V/I amplitude ratio (1.10±0.47 vs. 1.23±0.46). There were no significant differences in the BAER variables between late preterm infants and term infants. Late preterm birth does not appear to have marked effects on neonatal BAER or development of the brainstem.

De novo interstitial deletion of 15q22q23 with global developmental delay and hypotonia: the first Korean case.

Interstitial deletions involving the chromosome band 15q22q24 are very rare and only nine cases have been previously reported. Here, we report on a 12-day-old patient with a de novo 15q22q23 interstitial deletion. He was born by elective cesarean section with a birth weight of 3,120 g at 41.3-week gestation. He presented with hypotonia, sensory and neural hearing loss, dysmorphism with frontal bossing, flat nasal bridge, microretrognathia with normal palate and uvula, thin upper lip in an inverted V-shape, a midline sacral dimple, severe calcanovalgus at admission, and severe global developmental delay at 18 months of age. Fluorescence in situ hybridization findings confirmed that the deleted regions contained at least 15q22. The chromosome analysis revealed a karyotype of 46,XY,del(15) (q22q23). Parental chromosome analysis was performed and results were normal. After reviewing the limited literature on interstitial 15q deletions, we believe that the presented case is the first description of mapping of an interstitial deletion involving the chromosome 15q22q23 segment in Korea. This report adds to the knowledge of the clinical phenotype associated with the 15q22q23 deletion.

Bronchiolitis obliterans caused by CMV in a previously healthy Asian infant.

Cytomegalovirus (CMV) is currently the most common cause of congenital infection and the leading infectious cause of brain damage and hearing loss in children. Perinatal CMV infection rarely causes clinical manifestations in normal individuals and usually follows a benign course in immunocompetent infants. However, ~15-25% of infected preterm infants may develop pneumonia, hepatitis or sepsis-like illness, bradycardia, hepatosplenomegaly, distended bowel, anemia, or thrombocytopenia. Bronchiolitis obliterans (BO) is a rare, fibrosing form of chronic obstructive lung disease that follows severe insults to the lower respiratory tract and results in narrowing and/or complete obliteration of the small airways. In non-transplant children, the most common form of BO is a severe lower respiratory tract infection, especially of adenovirus. We experienced a case of a 37-day-old male who was diagnosed as BO on chest computed tomography (CT) after CMV pneumonia. To our best knowledge, this is the first case of BO caused by CMV pneumonia in a healthy infant.

The effects of inhaled albuterol in transient tachypnea of the newborn.

PURPOSE: Transient tachypnea of the newborn (TTN) is a disorder caused by the delayed clearance of fetal alveolar fluid. ß-adrenergic agonists such as albuterol (salbutamol) are known to catalyze lung fluid absorption. This study examined whether inhalational salbutamol therapy could improve clinical symptoms in TTN. Additional endpoints included the diagnostic and therapeutic efficacy of salbutamol as well as its overall safety. METHODS: From January 2010 through December 2010, we conducted a prospective study of 40 newborns hospitalized with TTN in the neonatal intensive care unit. Patients were given either inhalational salbutamol (28 patients) or placebo (12 patients), and clinical indices were compared. RESULTS: The duration of tachypnea was shorter in patients receiving inhalational salbutamol therapy, although this difference was not statistically significant. The duration of supplemental oxygen therapy and the duration of empiric antibiotic treatment were significantly shorter in the salbutamol-treated group. No adverse effects were observed in either treatment group. CONCLUSIONS: Inhalational salbutamol therapy reduced the duration of supplemental oxygen therapy and the duration of empiric antibiotic treatment, with no adverse effects. However, the time between salbutamol therapy and clinical improvement was too long to allow definitive conclusions to be drawn. Further studies examining a larger number of patients with strict control over dosage and frequency of salbutamol inhalations are necessary to better direct the treatment of TTN.

Autosomal dominant familial neurohypophyseal diabetes insipidus caused by a mutation in the arginine-vasopressin II gene in four generations of a Korean family.

Autosomal dominant neurohypophyseal diabetes insipidus is a rare form of central diabetes insipidus that is caused by mutations in the vasopressin-neurophysin II (AVP-NPII) gene. It is characterized by persistent polydipsia and polyuria induced by deficient or absent secretion of arginine vasopressin (AVP). Here we report a case of familial neurohypophyseal diabetes insipidus in four generations of a Korean family, caused by heterozygous missense mutation in exon 2 of the AVP-NPII gene (c.286G>T). This is the first report of such a case in Korea.

The impact of neonatal care resources on regional variation in neonatal mortality among very low birthweight infants in Korea.

BACKGROUND: Faced with extremely low fertility rates and increasing numbers of low-birthweight births in Korea, we examined the factors affecting the mortality of very-low-birthweight (VLBW) infants in Korea. METHODS: A survey was conducted in 91 of 93 hospitals providing neonatal intensive care in Korea in 2009. Data included information on number of neonatal intensive care unit (NICU) beds, medical workforce, resources in the NICU, birth and death. RESULTS: There was approximately one NICU per 4888 births, one NICU bed per 355 births, one mechanical ventilator per 739 births, one incubator per 327 births and one board-certified neonatologist per 4683 births. Regional disparity existed in neonatal care resources and consequently in mortality rates. VLBW infants' mortality was related to the NICU facility level, volume of VLBW infants and geographic regions. The capital city, Seoul, has the best NICU facilities and workforce, and the least mortality. Overall mortality rates before hospital discharge for <750, 750-999 and 1000-1499 g were 44.8%, 20.4% and 6.5% respectively. There was a two to threefold difference in the mortality rates across the regions. However, following adjustments for NICU facility level and volume of VLBW infants admissions, regional difference in mortality rates was markedly reduced in the <750 g and disappeared in the larger VLBW groups. CONCLUSIONS: Regional disparity in mortality of VLBW infants in Korea is most marked in the lowest-birthweight group, <750 g. This disparity is primarily due to lack of resources for neonatal intensive care in most of provincial areas.

Factors affecting exclusive breast-feeding during the first 6 months in Korea.

BACKGROUND: The aim of this study was to identify the status of exclusive breast-feeding (EBF) in Korea and analyze the factors affecting exclusive breast-feeding at 6 months of age. METHOD: This study was based on data obtained from the Korea National Health and Nutrition Examination Survey (KNHANES) IV, conducted from January 2007 to December 2008. A total of 404 mother-infant pairs were recruited. Exclusive breast-feeding was defined according to the criteria established by the World Health Organization. RESULT: The rate of EBF was 60.9% for 1 month, 55.0% for 3 months, 35.4% for 6 months, 3.7% for 9 months and 1.2% for 12 months after birth. According to a stepwise logistic regression analysis, factors that were positively associated with EBF at 6 months were younger maternal age (odds ratio [OR] = 0.85, 95% confidence interval [CI]: 0.79-0.92), higher maternal education level (OR = 2.29, 95%CI: 1.17-4.46) and living in a capital city (OR = 2.64, 95%CI: 1.46-4.75). CONCLUSION: The rate of EBF in Korea is still suboptimal. To promote EBF, persistent and systematic education and campaigns for breast-feeding should be provided, particularly in vulnerable regions.

A de novo proximal 6q deletion confirmed by array comparative genomic hybridization.

Deletions of chromosome 6q, particularly in the proximal region, are relatively rare. Here, we report on a de novo interstitial deletion of (6)(q13q16.2) in a girl with facial dysmorphism, congenital hip dislocation, porencephaly, and brain atrophy. Array comparative genomic hybridization analysis showed arr 6q13q16.2(73,378,824?99,824,130), demonstrating higher resolution than the conventional cytogenetic findings, del(6)(q12q15). The clinical data were analyzed and compared with those of similar patients previously reported in the literature.

Hypertension caused by renal arteriovenous fistula.

We describe a case of secondary hypertension caused by renal arteriovenous fistula. An 8-year old girl was hospitalized with a severe headache, vomiting, and seizure. Renal angiography demonstrated multiple renal arteriovenous fistula and increased blood renin concentration in the left renal vein. Thus, left renal arteriovenous fistula and renin induced secondary hypertension were diagnosed. Her blood pressure was well controlled by medication with angiotensin converting enzyme inhibitor.

Granulocyte stimulating factor attenuates hypoxic-ischemic brain injury by inhibiting apoptosis in neonatal rats.

PURPOSE: This study was undertaken to determine the neuroprotective effect of granulocyte stimulating factor (G-CSF) on neonatal hypoxic-ischemic brain injury. MATERIALS AND METHODS: Seven-day-old male newborn rat pups were subjected to 110 minutes of 8% oxygen following a unilateral carotid artery ligation. Apoptosis was identified by performing terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining and flow cytometry with a combination of fluorescinated annexin V and propidium iodide (PI) and JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolyl-carbocyanine iodide). The extent of cerebral infarction was evaluated at 2 weeks after recovery. RESULTS: With a single dose (50microg/kg) of G-CSF treatment immediately after hypoxic-ischemic insult, hypoxia-ischemia induced increase in TUNEL-positive cells, annexinV+/PI- and JC-1 positive apoptotic cells in the ipsilateral cerebral cortex was significantly reduced at 24 hours, measured by flow cytometry, and the extent of cerebral infarction at 2 weeks after recovery was also significantly attenuated compared to the hypoxia-ischemia control group. CONCLUSION: Our data suggest that G-CSF is neuroprotective by inhibiting apoptosis, thereby reducing the ensuing cerebral infarction in a newborn rat pup model of cerebral hypoxia-ischemia (HI).

Erythropoietin attenuates brain injury, subventricular zone expansion, and sensorimotor deficits in hypoxic-ischemic neonatal rats.

The aim of this study was to investigate the effect of erythropoietin (EPO) on histological brain injury, subventricular zone (SVZ) expansion, and sensorimotor function deficits induced by hypoxia-ischemia (HI) in newborn rat pups. Seven-day-old male rat pups were divided into six groups: normoxia control, normoxia EPO, hypoxia control, hypoxia EPO, HI control, and HI EPO group. Sham surgery or HI was performed in all animals. HI was induced by ligation of the right common carotid artery followed by 90 min of hypoxia with 8% oxygen. Recombinant human EPO 3 U/g or saline was administered intraperitoneally, immediately, at 24- and 48-hr after insult. At two weeks after insult, animals were challenged with cylinder-rearing test for evaluating forelimb asymmetry to determine sensorimotor function. All animals were then sacrificed for volumetric analysis of the cerebral hemispheres and the SVZ. The saline-treated HI rats showed marked asymmetry by preferential use of the non-impaired, ipsilateral paw in the cylinder-rearing test. Volumetric analysis of brains revealed significantly decreased preserved ipsilateral hemispheric volume and increased ipsilateral SVZ volume compared with the sham-operated animals. Treatment of EPO significantly improved forelimb asymmetry and preserved ipsilateral hemispheric volume along with decreased expansion of ipsilateral SVZ following HI compared to the saline-treated HI rats. These results support the use of EPO as a candidate drug for treatment of neonatal hypoxic-ischemic brain damage.

Outcome following surgical closure of patent ductus arteriosus in very low birth weight infants in neonatal intensive care unit.

PURPOSE: The aims of this study were to determine the factors affecting the outcome of patent ductus arteriosus ligation in very low birth weight infants (VLBWI) and demonstrate the safety of PDA ligation in VLBWI performed in the neonatal intensive care unit (NICU). MATERIALS AND METHODS: From October 1994 to July 2006, medical records of 94 VLBWI weighing <1,500 g who underwent PDA ligation in the NICU of Samsung Medical Center were reviewed retrospectively. Factors affecting the final outcome of PDA ligation were evaluated by dividing the infants into 3 groups according to mortality and major morbidities as follows: mortality group (Mo), major morbidity group (Mb), and no major morbidity group (NM). RESULTS: In the Mo group, birth weight was significantly lower and the preoperative mean FiO2 and mean dopamine dose were significantly higher than those in the other 2 groups. There was no significant difference in gestational age, incidence of RDS, number of courses of indomethacin, surgery-related factors, including weight and age at surgery, perioperative vital signs, and complications after surgery between the 3 groups. During surgery in the NICU, there were no significant hemodynamic instability or serious acute complications. CONCLUSION: The factors affecting the outcome of surgery in VLBWI are not the factors related to surgery but the preoperative conditions related to the underlying prematurity. PDA ligation of VLBWI performed in the NICU is safe without serious complications.