Human Neural Stem Cells: Translational Research for Neonatal Hypoxic-Ischemic Brain Injury

Neonatal hypoxic-ischemic (HI) brain injury is a major cause of neonatal mortality and long-term neurodevelopmental disabilities. Although promising neuroprotective interventions have been studied, the current management of HI brain injury has been limited to supportive measures and induced hypothermia. In addition to engrafting, migrating toward the damage sites and differentiating into multiple lineages, multipotent neural stem/progenitor cells (NSPCs) also provide trophic/immunomodulatory factors and integrate into the host neurons upon implantation into an HI-injured brain. However, NSPC-based therapies have shown poor cell survival and integration, poor differentiation or restricted differentiation into the glial lineages. Furthermore, to achieve full functional recovery following brain injury, the optimization of cell therapy is needed to recapitulate the precise migration of stem cells to the region of interest and the neural rewiring present in the brain microenvironment. Therefore, the efficacy of NSPCs in the treatment of CNS injury is currently insufficient. Human NSPCs (hNSPCs) were isolated from the forebrain of an aborted fetus at 13 weeks of gestation with full parental consent and the approval of the Institutional Review Board of the Yonsei University College of Medicine. Here, to enhance the regenerative ability of hNSPCs in HI brain injury, cells were either pretreated with pharmacological agents or engineered to serve as vehicles for gene delivery. Furthermore, when combined with a poly (glycolic acid)-based synthetic scaffold, hNSPCs provide a more versatile treatment for neonatal HI brain injury. Finally, hNSPCs transfected with zinc-doped ferrite magnetic nanoparticles for controlling both cell migration and differentiation offer a simple and smart tool for cell-based therapies.ope

Successful Treatment of Neonatal Pylorospasm with Intravenous Atropine

Pylorospasm is a cause of delayed gastric emptying in young infants. As in patients with hypertrophic pyloric stenosis, most pylorospasm patients present with projectile vomiting. However, unlike that in case of hypertrophic pyloric stenosis, no persistent pyloric stenotic lesions are present. As such, follow-up using serial gastrointestinal fluoroscopy or ultrasonography can be helpful in diagnosing patients with clinical signs of gastroparesis. Most cases can be treated conservatively, but some patients require pharmacologic treatment. Antispasmodics have been proposed as a treatment for pylorospasm, but their use in neonates and infants has rarely been reported. Herein, we present a case of pylorospasm diagnosed in the neonatal period and successfully treated with intravenous atropine.ope

Evaluation of Newborn Infants with Prenatally Diagnosed Congenital Pulmonary Airway Malformation: A Single-Center Experience

Purpose Congenital pulmonary airway malformation (CPAM)－a rare developmental anomaly－affects the lower respiratory tract in newborns. By comparing the reliability of diagnostic tools and identifying predictive factors for symptoms, we provide comprehensive clinical data for the proper management of CPAM. Methods We reviewed the medical records of 66 patients with prenatally diagnosed CPAM delivered at Severance Children’s Hospital between January 2005 and July 2017. Results We enrolled 33 boys and 33 girls. Their mean gestational age and birth weight were 38.8 weeks and 3,050 g, respectively. Prenatal ultrasonography and postnatal radiography, lung ultrasonography, and chest computed tomography (CT) showed inconsistent findings. Chest CT showed superior sensitivity (100%) and positive predictive value (90%). Among the 66 patients, 59 had postnatally confirmed CPAM, three had pulmonary sequestration, one had cystic teratoma, and one had a normal lung. Of the 59 patients with CPAM, 21 (35%; mean age, 23.4 months) underwent surgery, including 15 who underwent video-assisted thoracoscopy. Twenty-five and 12 patients exhibited respiratory symptoms at birth and during infancy, respectively. Apgar scores and mediastinal shift on radiography were significantly associated with respiratory symptoms at birth. However, none of the factors could predict respiratory symptoms during infancy. Conclusion Radiography or ultrasonography combined with chest CT can confirm an unclear or inconsistent lesion. Apgar scores and mediastinal shift on radiography can predict respiratory symptoms at birth. However, symptoms during infancy are not associated with prenatal and postnatal factors. Chest CT combined with periodic symptom monitoring is important for diagnosing and managing patients with prenatally diagnosed CPAM and to guide appropriate timing of surgery.ope

Metabolic Bone Disease of Prematurity

Preterm infants are at significant risk of reduced bone mineral content and subsequent bone disease, variably termed osteopenia of prematurity or neonatal rickets. The prevalence varies depending on gestation, occurs up to 30% of Korean extremely low birth weight infants (ELBW). The etiology is multifactoreal: inadequate nutrient intake, prolonged parenteral nutrition, chronic co-morbidities and immobilization. In Korean ELBW infants, rickets of prematurity was significantly increased by 18 times with severe parenteral nutrition associated cholestasis, and by 3 times with moderate/severe bronchopulmonary dysplasia. Prolonged hospitalization with ventilator care could lead to lack of physical activity and muscle contraction against resistance in preterm infants, which may increase bone resorption and demineralization, resulting in osteopenia. Low serum P and high alkaline phosphatase (ALP) are suggestive of metabolic bone disease. In Korean ELBW infants, increased serum ALP (>495 IU) at the age of 5 weeks has a 81% of sensitivity and 87% of specificity for radiographic rickets. An early nutritional intervention can reduce both the prevalence and the severity of osteopenia. Provision of adequate nutrition including energy, protein and minerals, and passive physical exercise during first weeks of life may prevent abnormal bone remodeling activity in preterm infants. Early detection by vigorous monitoring of bone homeostasis and prompt treatment of osteopenia are warranted in these high-risk infants. This review is to focus on the recent advances in the understanding of bone metabolism in preterm infants and on the therapeutic approach to prevent and to treat metabolic bone disease of prematurity.ope

A Case of Newborn with Prenatally Detected Cerebral Venous Sinus Thrombosis.

Cerebral venous sinus thrombosis (CVST) in pediatric patients is rare, but the incidence of this disease is much higher in neonates. It is one of the important causes of neonatal seizures, and also can cause long term neurologic deficits. So far, there has been only one retrospective study of 10 neonatal CVST patients reported in Korea. However, there are no reported cases of prenatally diagnosed patient. We report a patient prenatally diagnosed with CVST which might cause severe neurologic complication, as we experienced significant decrease in size and number of thrombi without anticoagulation therapy and relatively benign clinical progress from birth to 1-year-old age.ope

A Case of Neonate with Acute Renal Failure after Maternal Treatment with Angiotensin II Receptor Blocker.

Hypertension is common medical problem encountered during pregnancy. However medication administered for maternal hypertension may cause fetal or neonatal complications. Angiotensin converting enzyme inhibitor or angiotensin II receptor blocker are rarely used during pregnancy, and there are few reports about the effect of them, because administration of these drugs during pregnancy may cause oligohydramnios, renal tubular dysplasia, hypocalvaria, pulmonary hypoplasia, intrauterine growth retardation, neonatal anuria and persistent ductus arteriosus. We report a case of neonatal acute renal failure by angiotensin II receptor blocker during pregnancy. In this case, the neonate with meconium aspiration was admitted to neonatal intensive care unit (NICU). During the NICU stay, neonatal anuria occurred, and there was a medical history that his mother took Candesartan Cilexeril (Atacand(R)), one of angiotensin II receptor blockers during pregnancy. The neonate showed intrinsic acute renal failure, so fluid was restricted and diuretics were administered to the neonate, and after 10 days, anuria improved.ope

The impact of a quality improvement effort in reducing admission hypothermia in preterm infants following delivery

PURPOSE: Hypothermia at admission is associated with increased mortality and morbidity in preterm infants. We performed a quality improvement (QI) effort to determine the impact of a decrease in admission hypothermia in preterm infants. METHODS: The study enrolled very low birth weight (VLBW) infants born at Gangnam Severance Hospital between January 2013 and December 2016. This multidisciplinary QI effort included the use of occlusive wraps, warm blankets, and caps; the delivery room temperature was maintained above 23.0˚C, and a check-list was used for feedback. RESULTS: Among 259 preterm infants, the incidence of hypothermia (defined as body temperature <36.0˚C) decreased significantly from 68% to 41%, and the mean body temperature on neonatal intensive care unit admission increased significantly from 35.5˚C to 36.0˚C. In subgroup analysis of VLBW infants, admission hypothermia and neonatal outcomes were compared between the pre-QI (n=55) and post-QI groups (n=75). Body temperature on admission increased significantly from 35.4˚C to 35.9˚C and the number of infants with hypothermia decreased significantly from 71% to 45%. There were no cases of neonatal hyperthermia. The incidence of pulmonary hemorrhage was significantly decreased (P=0.017). Interaction analysis showed that birth weight and gestational age were not correlated with hypothermia following implementation of the protocol. CONCLUSION: Our study demonstrated a significant reduction in admission hypothermia following the introduction of a standardized protocol in our QI effort. This resulted in an effective reduction in the incidence of massive pulmonary hemorrhage.ope

A Case of Congenital Gastric Outlet Obstruction with Serosal Fibrous Band in Prematurity

Most of the gastric outlet obstruction symptoms like vomiting and abdominal distension were caused by congenital anatomical abnormality in a neonate. Abnormal structures associated with congenital gastric outlet obstruction have been categorized by its site and extent of obstruction. We report one case of persisting vomiting in a premature infant caused by serosal fibrous band in gastric outlet lesion, excluded from the category of congenital gastric outlet obstruction.ope

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.ope

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

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