Purpose: We investigated the effects of early postnatal administration of erythropoietin (EPO) on neurodevelopmental outcomes and morbidities in preterm infants with severe grades of intraventricular hemorrhage (IVH). Methods: We retrospectively reviewed the medical records of preterm infants of gestational age 23+0 weeks to 31+6 weeks, who were diagnosed with severe grades of IVH and received EPO over at least 2 weeks. We compared clinical characteristics, major complications, and neurodevelopmental impairment between the two groups. The primary outcome was severe neurodevelopmental impairment at 18 to 26 months of corrected age. Severe neurodevelopmental impairment was defined as a mental developmental index or psychomotor developmental index of <70 on the Bayley Scales of Infant Development II or diagnosis of cerebral palsy. Results: The study included 33 preterm infants (mean gestational age 25.2±1.6 weeks and mean birth weight 775.1±224.5 g). EPO was administered at a dose of 400 or 1,000 IU/kg thrice weekly and was maintained over a mean period of 58.6± 25.9 days beginning from 10.7±6.9 days after birth. We observed no difference in perinatal characteristics between the EPO (n=14) and the control group (n=19). Similarly, severe neurodevelopmental impairment rates did not differ between the EPO (85.7%) and control groups (78.9%). The incidence of neonatal morbidities including bronchopulmonary dysplasia, necrotizing enterocolitis, and retinopathy of prematurity was also similar between the EPO and control groups. Conclusion Early administration of EPO did not reduce the risk of severe neurodevelopmental impairment in preterm infants with severe IVH.

Purpose: Extremely low birth weight (ELBW) infants exhibit immature thermoregulation and are easily exposed to hypothermia. We investigated the association between hypothermia on admission with short- and long-term outcomes. Methods: Medical records of ELBW infants admitted to the neonatal intensive care unit of a tertiary medical center between June 2012 and February 2017 were retrospectively analyzed. Upon admission, the axillary body temperature was measured. Moderate hypothermia was defined as admission temperature below 36 ℃. Results: A total of 208 infants with gestational age of 26.4±2.3 weeks and birth weight of 746.7±154.9 g were included. Admission temperature ranged from 33.5 to 36.8 ℃ (median 36.1 ℃). Univariate analyses of maternal and infant characteristics were performed for moderately hypothermic and control (normothermic to mildly hypothermic) infants. Lower gestational age, lower birth weight, and vaginal delivery correlated with moderate hypothermia. Logistic regression analyses adjusted for confounders revealed that the incidence of hemodynamically significant patent ductus arteriosus (hsPDA) was associated with moderate hypothermia in ELBW infants. Moreover, abnormal mental developmental index scores on the Bayley Scales of Infant Development II at a corrected age of 18 to 24 months were associated with moderate hypothermia, but not with the psychomotor developmental index, incidence of blindness, deafness, or cerebral palsy. Conclusion Moderate hypothermia at admission is not only correlated with short-term neonatal morbidities such as hsPDA, but may also be associated with long-term neurodevelopmental impairment in ELBW infants. Future large-scale studies are required to clarify the long-term consequences of hypothermia upon admission.

Purpose: The aim of this study was to estimate the effect of targeting risk factors for the control of central line-associated bloodstream infection (CLABSI) among high-risk infants in a tertiary neonatal intensive care unit (NICU). Methods: Infants admitted to the NICU and diagnosed with CLABSI from January to December 2013 were eligible for inclusion to the study. The CLABSI group (n=47) was matched in a 1:2 ratio to the control group (n=94) based on gestational age, birth weight, and Score for Neonatal Acute Physiology-II. Risk factors for CLABSI were identified using the Cox proportional hazard model, and analysis of the effect of these risk factors targeting infection control was performed. Results: The risk factors associated with CLABSI were prolonged central line dwell days (adjusted hazard ratio [HR], 1.028; 95% confidence interval [CI], 1.011 to 1.045; P=0.001), use of a silicone catheter (adjusted HR, 5.895; 95% CI, 1.893 to 18.355; P=0.002), surgical treatment (adjusted HR, 3.793; 95% CI, 1.467 to 9.805; P=0.006), and less probiotic supplementation (adjusted HR, 0.254; 95% CI, 0.068 to 0.949; P=0.042). By targeting these risk factors with a quality improvement initiative, the mean CLABSI incidence rate per 1,000 catheter-days decreased from 6.6 to 3.1 (P=0.004). Conclusion Targeting risk factors for infection control significantly reduced the rate of CLABSI among high-risk infants in the NICU.

Purpose: The aim of this study was to estimate the effect of targeting risk factors for the control of central line-associated bloodstream infection (CLABSI) among high-risk infants in a tertiary neonatal intensive care unit (NICU). Methods: Infants admitted to the NICU and diagnosed with CLABSI from January to December 2013 were eligible for inclusion to the study. The CLABSI group (n=47) was matched in a 1:2 ratio to the control group (n=94) based on gestational age, birth weight, and Score for Neonatal Acute Physiology-II. Risk factors for CLABSI were identified using the Cox proportional hazard model, and analysis of the effect of these risk factors targeting infection control was performed. Results: The risk factors associated with CLABSI were prolonged central line dwell days (adjusted hazard ratio [HR], 1.028; 95% confidence interval [CI], 1.011 to 1.045; P=0.001), use of a silicone catheter (adjusted HR, 5.895; 95% CI, 1.893 to 18.355; P=0.002), surgical treatment (adjusted HR, 3.793; 95% CI, 1.467 to 9.805; P=0.006), and less probiotic supplementation (adjusted HR, 0.254; 95% CI, 0.068 to 0.949; P=0.042). By targeting these risk factors with a quality improvement initiative, the mean CLABSI incidence rate per 1,000 catheter-days decreased from 6.6 to 3.1 (P=0.004). Conclusion Targeting risk factors for infection control significantly reduced the rate of CLABSI among high-risk infants in the NICU.

Purpose: To determine the efficacy of inhaled nitric oxide (iNO) in very low birth weight (VLBW) infants with early pulmonary hypertension (PH). Methods: We reviewed the medical records of 22 preterm infants who were born <30 weeks of gestational age with birth weight <1,500 g, diagnosed with early PH, and treated with iNO within the first 72 hours after birth. Responders were defined by a reduction in FiO 2 >20% and/or oxygenation index (OI) >20% from the baseline values at 1 hour after beginning iNO therapy. Cardiorespiratory support indices including OI, oxygen saturation index, and vasoactive-inotropic score (VIS) were serially obtained for 96 hours following iNO therapy. Results: The mean gestational age of the patients was 26.1±2.0 weeks and the mean birth weight was 842±298 g. The mean OI at the start of iNO was 63.8±61.0. Impro vement in oxygenation indicated by prompt decrease in FiO 2 and OI from the base line values were observed 1 hour after beginning iNO therapy and lasted up to 96 hours. After iNO therapy, VIS increased until 24 hours and decreased thereafter. At 1 hour after iNO, 16 patients (73%) were classified as responders and six (27%) as nonresponders. Compared with nonresponders, responders did not demonstrate the beneficial effect of iNO in terms of short-term survival and neonatal complications.The 1-year mortality rate did not differ between responders (56%) and nonresponders (67%). Conclusion Although iNO treatment immediately improved oxygenation in most VLBW infants with early severe PH, the long-term mortality rate was high. A largescale study is needed to determine whether the initial response to iNO can predict patients’ survival.

Necrotizing enterocolitis (NEC) characterized by inflammatory intestinal necrosis is a major cause of mortality and morbidity in newborns. Deep RNA sequencing (RNA-Seq) has recently emerged as a powerful technology enabling better quantification of gene expression than microarrays with a lower background signal. A total of 10 transcriptomes from 5 pairs of NEC lesions and adjacent normal tissues obtained from preterm infants with NEC were analyzed. As a result, a total of 65 genes (57 down-regulated and 8 up-regulated) revealed significantly different expression levels in the NEC lesion compared to the adjacent normal region, based on a significance at fold change ≥ 1.5 and P ≤ 0.05. The most significant gene, DPF3 (P < 0.001), has recently been reported to have differential expressions in colon segments. Our gene ontology analysis between NEC lesion and adjacent normal tissues showed that down-regulated genes were included in nervous system development with the most significance (P = 9.3 × 10⁻⁷; P(corr) = 0.0003). In further pathway analysis using Pathway Express based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, genes involved in thyroid cancer and axon guidance were predicted to be associated with different expression (P(corr) = 0.008 and 0.020, respectively). Although further replications using a larger sample size and functional evaluations are needed, our results suggest that altered gene expression and the genes' involved functional pathways and categories may provide insight into NEC development and aid in future research.
Axons ; Colon ; Enterocolitis, Necrotizing* ; Gene Expression Profiling* ; Gene Expression* ; Gene Ontology ; Genome ; Humans* ; Infant, Newborn ; Infant, Premature ; Mortality ; Necrosis ; Nervous System ; Pilot Projects* ; Sample Size ; Sequence Analysis, RNA ; Thyroid Neoplasms ; Transcriptome

The ex utero intrapartum treatment (EXIT) procedure was introduced to reduce fetal hypoxic damage while establishing an airway in fetuses with upper and lower airway obstruction. Delivery of the fetal head and shoulders while maintaining the uteroplacental circulation offers time to secure the fetal airway. Here, we report two cases of EXIT procedure for fetal airway obstruction, which were successfully managed with extensive preoperative planning by a professional multidisciplinary team.
Airway Obstruction* ; Fetal Therapies ; Fetus* ; Head ; Laryngeal Diseases ; Lymphangioma ; Placental Circulation ; Prenatal Diagnosis ; Shoulder

Objective: To report our experience with management of fetuses with congenital high airway obstruction syndrome (CHAOS). Methods: We retrospectively reviewed the cases of fetuses who were prenatally diagnosed and postnatally confirmed with CHAOS between 2010 and 2019 at Asan Medical Center, Seoul, Korea. Results: Of 13 fetuses prenatally diagnosed with CHAOS, 7 were lost to follow-up and 6 were postnatally confirmed as having CHAOS. All fetuses, except one were delivered via cesarean section with an ex utero intrapartum treatment (EXIT) procedure. Two patients had coexisting congenital heart diseases requiring several cardiac surgeries following birth. Both of these patients demonstrated developmental delay; however, the remaining 4 had a normal development except for expressive language. Two infants died of respiratory complications, and the remaining 4 were alive at the end of the follow-up period. All 4 live patients underwent tracheostomy with planned reconstruction surgery. Three children are now able to phonate, and 1 can maintain a conservation. Conclusion The proper management of CHAOS using the EXIT procedure results in high survival and low hypoxemia-induced complication rates. Therefore, an accurate prenatal diagnosis is necessary for an appropriate perinatal management.