Korean Neonatal Network Research Articles

The Impact of Surgical Intervention on Neurodevelopmental Outcomes in Very Low Birth Weight Infants: a Nationwide Cohort Study in Korea.

BackgroundTo investigate the incidence of surgical intervention in very low birth weight (VLBW) infants and the impact of surgery on neurodevelopmental outcomes at corrected ages (CAs) of 18–24 months, using data from the Korean Neonatal Network (KNN).MethodsData from 7,885 VLBW infants who were born and registered with the KNN between 2013 to 2016 were analyzed in this study. The incidences of various surgical interventions and related morbidities were analyzed. Long-term neurodevelopmental outcomes at CAs of 18–24 months were compared between infants (born during 2013 to 2015, n = 3,777) with and without surgery.ResultsA total of 1,509 out of 7,885 (19.1%) infants received surgical interventions during neonatal intensive care unit (NICU) hospitalization. Surgical ligation of patent ductus arteriosus (n = 840) was most frequently performed, followed by laser therapy for retinopathy of prematurity and laparotomy due to intestinal perforation. Infants who underwent surgery had higher mortality rates and greater neurodevelopmental impairment than infants who did not undergo surgery (P value < 0.01, both). On multivariate analysis, single or multiple surgeries increased the risk of neurodevelopmental impairment compared to no surgery with adjusted odds ratios (ORs) of 1.6 with 95% confidence interval (CI) of 1.1–2.6 and 2.3 with 95% CI of 1.1–4.9.ConclusionApproximately one fifth of VLBW infants underwent one or more surgical interventions during NICU hospitalization. The impact of surgical intervention on long-term neurodevelopmental outcomes was sustained over a follow-up of CA 18–24 months. Infants with multiple surgeries had an increased risk of neurodevelopmental impairment compared to infants with single surgeries or no surgeries after adjustment for possible confounders.

The Incidence and Survival Rate of Very Low Birth Weight Infants in Korea (2013–2016): A Comparison of the Statistics Korea and the Korean Neonatal Network and Improvements

The Incidence and Survival Rate of Very Low Birth Weight Infants in Korea (2013–2016): A Comparison of the Statistics Korea and the Korean Neonatal Network and Improvements

The predictors for the non-compliance to follow-up among very low birth weight infants in the Korean neonatal network.

The critical need to emphasize preterm infant follow-up after neonatal intensive care unit (NICU) discharge assures early identification of and intervention for neurodevelopmental disability. The aims of this study were to observe the follow-up rates in high-risk follow-up clinics, and analyze factors associated with non-compliance to follow-up among very low birth weight (VLBW) infants. The data was prospectively collected for 3063 VLBW infants between January 2013 and December 2014 from 57 Korean neonatal network (KNN) centers at a corrected age of 18–24 months. Correlations among demographic data, clinical variables, and neonatal intensive care unit (NICU) volume (divided into 4 quartiles) with the occurrence of non-compliance were analyzed. The overall follow-up rate at the corrected age of 18–24 month was 65.4%. The follow-up rates were inversely related to birth weight and gestational age. Apgar score, hospital stay, maternal age, and maternal education were significantly different between the compliance and non-compliance groups. The follow-up rate was higher for mothers with chorioamnionitis, abnormal amniotic fluid, multiple pregnancy, and in vitro fertilization. Infants with respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus ligation, periventricular leukomalacia, and retinopathy of prematurity were more common in the compliance group. Follow-up rates showed significant differences according to NICU volume. Using multivariate logistic regression, high birth weight, low NICU volume, siblings, foreign maternal nationality and high 5 min APGAR scores were significant independent factors associated with the non-compliance of VLBW infants for follow-up at 18–24 months of age. This is the first nation-wide analysis of follow-up for VLBW infants in Korea. Understanding factors associated with failure of compliance could help improve the long-term follow-up rates and neurodevelopmental outcomes through early intervention.

Perinatal prediction model for severe intraventricular hemorrhage and the effect of early postnatal acidosis.

Severe acidosis is one of the strongest predictors of neurologic outcomes in full-term infants with suspected hypoxic-ischemic encephalopathy. However, the relative importance of acidosis as a predictor of outcomes in preterm infants is much less clear. The goals of the present study were to examine the association between postnatal acidosis and severe intraventricular hemorrhage (IVH) and to establish a new score model including acid-base status after birth for predicting the risk of this morbidity. The study sample was very low birth weight (VLBW) infants in the Korean Neonatal Network (KNN) cohort registry, collected prospectively from January 2013 to December 2014. Infants with blood pH and base deficit (BD) values collected within the first hour after birth, and documentation of severe IVH, were included. Multivariate stepwise logistic regression analysis was used to determine the contribution of postnatal acidosis to predicting severe IVH in VLBW infants. In addition, a prediction model was developed. Data from 2518 VLBW infants were analyzed. Infants with postnatal acidosis had a higher incidence of severe IVH. The clinical model plus blood BD values improved predictive performance, compared with models using only perinatal data or blood pH. A prediction model for severe IVH was developed using the KNN registry of VLBW infants. Immediate postnatal acidosis, defined based on blood BD, was associated with a higher-risk-adjusted incidence of severe IVH.

Morbidity and Mortality of Fungal Infections in Very Low Birth Weight Infants of the Korean Neonatal Network 2013–2015

Morbidity and Mortality of Fungal Infections in Very Low Birth Weight Infants of the Korean Neonatal Network 2013–2015

Prediction of Postnatal Growth Failure among Very Low Birth Weight Infants

Postnatal growth failure (PGF) in preterm infants remains an important clinical issue. In this study, we analysed the incidence of PGF among very low birth weight (VLBW) infants and evaluated the risk factors for PGF based on the data of 2799 VLBW infants obtained from the Korean Neonatal Network database from 2013 to 2014. PGF was defined as a decrease in weight Z score between birth and discharge of more than −1.28 using the Fenton growth charts. Risk factors were evaluated in relation to birth weight for gestational age, namely small (SGA) or appropriate (AGA) for gestational age, using propensity score matching used for between-group differences. The overall incidence of PGF was 45.5%, with a rate of 68.9% in the SGA group and 36.2% in the AGA group. PGF was negatively correlated with gestation and birth weight; additionally, PGF was associated with a higher incidence of co-morbidities. Predictors of PGF in the SGA group were respiratory distress syndrome and days to attain 100 mL/kg of enteral feeding. The only predictor of PGF in the AGA group was days to attain 100 mL/kg of enteral feeding. Early initiation and aggressive progression of enteral nutrition may decrease the incidence of PGF.

National Registry Data from Korean Neonatal Network: Two-Year Outcomes of Korean Very Low Birth Weight Infants Born in 2013-2014.

BackgroundThe aim of this study was to observe long-term outcomes of very low birth weight infants (VLBWIs) born between 2013 and 2014 in Korea, especially focusing on neurodevelopmental outcomes.MethodsThe data were collected from Korean Neonatal Network (KNN) registry from 43 and 54 participating units in 2013 and 2014, respectively. A standardized electronic case report form containing 30 items related to long-term follow up was used after data validation.ResultsOf 2,660 VLBWI, the mean gestational age and birth weight were 291/7 ± 26/7 weeks and 1,093 ± 268 g in 2013 and 292/7 ± 26/7 weeks and 1,125 ± 261 g in 2014, respectively. The post-discharge mortality rate was 1.2%–1.5%. Weight < 50th percentile was 46.5% in 2013 and 66.1% in 2014. The overall prevalence of cerebral palsy among the follow up infants was 6.2% in 2013 and 6.6% in 2014. The Bayley Scales of Infant Developmental Outcomes version II showed 14%–25% of infants had developmental delay and 3%–8% of infants in Bayley version III. For the Korean developmental screening test for infants and children, the area “Further evaluation needed” was 5%–12%. Blindness in both eyes was reported to be 0.2%–0.3%. For hearing impairment, 0.8%–1.9% showed bilateral hearing loss. Almost 50% were readmitted to hospital with respiratory illness as a leading cause.ConclusionThe overall prevalence of long-term outcomes was not largely different among the VLBWI born between 2013 and 2014. This study is the first large national data study of long-term outcomes.

Quality improvement in pediatric care.

We often overlook the importance of several safety issues such as identification of patients, timeout procedure, hand hygiene, handoff communication, and many others. This ignorance, along with many other issues, leads to medical error being ranked as a third leading cause of death in the U.S. Consequently, quality improvement (QI) has become one of the major subjects in healthcare despite a relatively short history. Improving quality is about making healthcare safe, effective, patient-centered, timely, efficient, and equitable. Understanding the need and methodology of QI as well as participation is now essential for physicians. Although basic QI methodology has not changed, one of the most fascinating changes in recent QI is conducting large-scale QI projects through multicenter networks. Prospective multicenter QI projects utilizing the Korean Neonatal Network are a substantial initiation of pediatric QI in Korea. The Korean Pediatric Society should set ambitious goals for QI activities for every primary care pediatrician and pediatric subspecialist.

Changes of Mortality and Morbidity of Very Low Birth Weight Infants after Neonatal Intensive Care Unit Strategy Alteration in a Single Center: Comparison with 2015 Korean Neonatal Network Report

Changes of Mortality and Morbidity of Very Low Birth Weight Infants after Neonatal Intensive Care Unit Strategy Alteration in a Single Center: Comparison with 2015 Korean Neonatal Network Report

Gestational age-specific sex difference in mortality and morbidities of preterm infants: A nationwide study

This study aims to determine whether male sex has adverse effect on mortality and morbidities in very low birth weight infants (VLBWI) <30 weeks of gestation and to ascertain this sex effect, stratified by gestational age, adjusting for perinatal risk factors. This is a population-based study from Korean Neonatal Network for VLBWI born at 23+0 and 29+6 weeks of gestation between January 2013 and December 2014. The primary outcome was gestation-specific sex difference in the occurrence of mortality, combined morbidities, and individual morbidity. A total of 2228 VLBWI were enrolled (males, 51.7%). Mortality was not different between sexes. The risk of bronchopulmonary dysplasia and combined morbidities was significantly higher in males ≤25 weeks of gestation (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.35–3.20 and OR 2.00, CI 1.19–3.39, respectively). Males had a significantly higher incidence of periventricular leukomalacia at 23 and 29 weeks of gestation. The risk of severe retinopathy of prematurity was higher in females >25 weeks of gestation. Although both sexes have similar risk for mortality, male sex remains an independent risk for major morbidities, especially at ≤25 weeks of gestation. The risk of each outcome for males has a specific pattern with increasing gestational age.

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.

The Korean Neonatal Network: An Overview.

Currently, in the Republic of Korea, despite the very-low-birth rate, the birth rate and number of preterm infants are markedly increasing. Neonatal deaths and major complications mostly occur in premature infants, especially very-low-birth-weight infants (VLBWIs). VLBWIs weigh less than 1,500 g at birth and require intensive treatment in a neonatal intensive care unit (NICU). The operation of the Korean Neonatal Network (KNN) officially started on April 15, 2013, by the Korean Society of Neonatology with support from the Korea Centers for Disease Control and Prevention. The KNN is a national multicenter neonatal network based on a prospective web-based registry for VLBWIs. About 2,000 VLBWIs from 60 participating hospital NICUs are registered annually in the KNN. The KNN has built unique systems such as a web-based real-time data display on the web site and a site-visit monitoring system for data quality surveillance. The KNN should be maintained and developed further in order to generate appropriate, population-based, data-driven, health-care policies; facilitate active multicenter neonatal research, including quality improvement of neonatal care; and ultimately lead to improvement in the prognosis of high-risk newborns and subsequent reduction in health-care costs through the development of evidence-based neonatal medicine in Korea.

Risk Factors for Cause-specific Mortality of Very-Low-Birth-Weight Infants in the Korean Neonatal Network.

This study attempted to assess the risk factors for mortality of very-low-birth-weight (VLBW) infants in the neonatal intensive care unit (NICU, n=2,386). Using data from the Korean Neonatal Network, we investigated infants with birth weights <1,500 g and gestational ages (GAs) of 22-31 weeks born between January 2013 and June 2014. Cases were defined as death at NICU discharge. Controls were randomly selected from live VLBW infants and frequency matched to case subjects by GA. Relevant variables were compared between the cases (n=236) and controls (n=236) by Cox proportional hazards regression to determine their associations with cause-specific mortality (cardiorespiratory, neurologic, infection, gastrointestinal, and others). In a Cox regression analysis, cardiorespiratory death were associated with a foreign mother (hazard ratio, HR, 4.33; 95% confidence interval, CI, 2.08-9.02), multiple gestation (HR, 1.65; 95% CI, 1.07-2.54), small for gestational age (HR, 2.06; 95% CI, 1.25-3.41), male gender (HR, 1.69; 95% CI, 1.10-2.60), Apgar score ≤3 at 5 min (HR, 1.97; 95% CI, 1.18-3.31), and delivery room resuscitation (HR, 2.60; 95% CI, 1.53-4.40). An Apgar score ≤3 at 5 min was also associated with neurological death (HR, 2.95; 95% CI, 1.29-6.73). Death due to neonatal infection was associated with outborn delivery (HR, 5.09; 95% CI, 1.46-17.74). Antenatal steroid and preterm premature rupture of membranes reduced risk of cardiorespiratory death (HR, 0.43; 95% CI, 0.27-0.67) and gastrointestinal death (HR, 0.30; 95% CI, 0.13-0.70), respectively. In conclusion, foreign mother, multiple gestation, small gestation age, male gender, Apgar score ≤3 at 5 min, and resuscitation in the delivery room are associated with cardiorespiratory mortality of VLBW infants in NICU. An Apgar score ≤3 at 5 min and outborn status are associated with neurological and infection mortality, respectively.

Data Management and Site-Visit Monitoring of the Multi-Center Registry in the Korean Neonatal Network.

The Korean Neonatal Network (KNN), a nationwide prospective registry of very-low-birth-weight (VLBW, < 1,500 g at birth) infants, was launched in April 2013. Data management (DM) and site-visit monitoring (SVM) were crucial in ensuring the quality of the data collected from 55 participating hospitals across the country on 116 clinical variables. We describe the processes and results of DM and SVM performed during the establishment stage of the registry. The DM procedure included automated proof checks, electronic data validation, query creation, query resolution, and revalidation of the corrected data. SVM included SVM team organization, identification of unregistered cases, source document verification, and post-visit report production. By March 31, 2015, 4,063 VLBW infants were registered and 1,693 queries were produced. Of these, 1,629 queries were resolved and 64 queries remain unresolved. By November 28, 2014, 52 participating hospitals were visited, with 136 site-visits completed since April 2013. Each participating hospital was visited biannually. DM and SVM were performed to ensure the quality of the data collected for the KNN registry. Our experience with DM and SVM can be applied for similar multi-center registries with large numbers of participating centers.

Real-time Data Display System of the Korean Neonatal Network.

Real-time data reporting in clinical research networks can provide network members through interim analyses of the registered data, which can facilitate further studies and quality improvement activities. The aim of this report was to describe the building process of the data display system (DDS) of the Korean Neonatal Network (KNN) and its basic structure. After member verification at the KNN member's site, users can choose a variable of interest that is listed in the in-hospital data statistics (for 90 variables) or in the follow-up data statistics (for 54 variables). The statistical results of the outcome variables are displayed on the HyperText Markup Language 5-based chart graphs and tables. Participating hospitals can compare their performance to those of KNN as a whole and identify the trends over time. Ranking of each participating hospital is also displayed in terms of key outcome variables such as mortality and major neonatal morbidities with the names of other centers blinded. The most powerful function of the DDS is the ability to perform 'conditional filtering' which allows users to exclusively review the records of interest. Further collaboration is needed to upgrade the DDS to a more sophisticated analytical system and to provide a more user-friendly interface.

Intraventricular Hemorrhage and Post Hemorrhagic Hydrocephalus among Very-Low-Birth-Weight Infants in Korea.

Here, we aimed to evaluate the incidence and mortality of intraventricular hemorrhage (IVH) and post-hemorrhagic hydrocephalus (PHH) among very-low-birth-weight (VLBW) infants in Korea and assess the associated factors of PHH. This cohort study used prospectively collected data from the Korean Neonatal Network (KNN). Among 2,386 VLBW infants in the KNN database born between January 2013 and June 2014, 63 infants who died without brain ultrasonography results were excluded. Maternal demographics and neonatal clinical characteristics were assessed. The overall incidence of IVH in all the VLBW infants was 42.2% (987 of 2,323), while those of IVH grade 1, 2, 3, and 4 were 25.1%, 7.0%, 4.8%, and 5.5%, respectively. The incidence and severity of IVH showed a negatively correlating trend with gestational age and birth weight. PHH developed in 0%, 3.5%, 36.1%, and 63.8% of the surviving infants with IVH grades 1, 2, 3, and 4, respectively. Overall, in the VLBW infants, the IVH-associated mortality rate was 1.0% (24/2,323). Only IVH grade severity was proven to be an associated with PHH development in infants with IVH grades 3-4. This is the first Korean national report of IVH and PHH incidences in VLBW infants. Further risk factor analyses or quality improvement studies to reduce IVH are warranted.

Blood Culture Proven Early Onset Sepsis and Late Onset Sepsis in Very-Low-Birth-Weight Infants in Korea.

Neonatal sepsis remains one of the most important causes of death and co-morbidity in very-low-birth-weight (VLBW) infants. The aim of this study was to determine the current incidences of early-onset sepsis (EOS) and late-onset sepsis (LOS), the distribution of pathogens, and the impact of infection on co-morbidities in VLBW infants. We analyzed the data including sepsis episode from 2,386 VLBW infants enrolled in Korean Neonatal Network from January 2013 to June 2014. We defined EOS as a positive blood culture occurring between birth and 7 days of life and LOS after 7 days of life. Sepsis was found in 21.1% of VLBW infants. The risk of sepsis was inversely related to birth weight and gestational age. EOS was found in only 3.6% of VLBW infants, however the mortality rate was as high as 34.1%. EOS was associated with the increased odds for bronchopulmonary dysplasia and intraventricular hemorrhage. The vast majority of EOS was caused by Gram-positive organisms, particularly coagulase-negative staphylococci (30.6%). LOS developed in 19.4% of VLBW infants with a 16.1% mortality rate. Pathogens in LOS were dominated by coagulase-negative staphylococci (38.3%). Twenty-five percent and fifty percent of first LOS episode occurred after 12 days and 20 days from birth, respectively. Younger and smaller VLBW infants showed the earlier occurrence day for the 25% of first LOS episode. This study provides a recent nationwide epidemiology of sepsis in VLBW infants in Korea. Based on this study, successful strategies to reduce infections would improve survival and reduce morbidity.

Recent Changes in the Incidence of Bronchopulmonary Dysplasia among Very-Low-Birth-Weight Infants in Korea.

We investigated the incidence of bronchopulmonary dysplasia (BPD) in very-low-birth-weight (VLBW) infants in Korea using the Korean Neonatal Network (KNN) data. In total, 2,386 VLBW infants born from January 2013 to June 2014 were prospectively registered. BPD was defined as supplemental oxygen or positive pressure support at 36 weeks postmenstrual age (PMA). The overall incidence of BPD was 28.9%, and the overall mortality rate in the neonatal intensive care units (NICUs) was 11.9%. To investigate recent changes in the incidence of BPD among VLBW infants, we compared the BPD rate in the present study with the latest nationwide retrospective survey conducted between 2007 and 2008. For comparison, we selected infants (23-31 weeks of gestation) (n=1,990) to adjust for the same conditions with the previous survey in 2007-2008 (n=3,841). Among the limited data on VLBW infants (23-31 weeks of gestation), the incidence of BPD increased by 85% (from 17.8% to 33.0%) and the mortality rate in the NICU decreased by 31.4% (from 18.8% to 12.9%) compared to those in the study conducted in 2007-2008. The current trend of increase in the incidence of BPD among infants can be attributed to the increase in the survival rate of VLBW infants.

Necrotizing Enterocolitis among Very-Low-Birth-Weight Infants in Korea.

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency and remains a major cause of mortality for very-low-birth-weight infants (VLBWI) requiring surgery. To date, there have been no large-scale studies evaluating the incidence, associated clinical factors and outcomes of NEC for VLBWI in Korea. The 2,326 VLBWI of a total 2,386 Korean Neonatal Network (KNN) cohort born with a birth weight below 1,500 g between January 2013 to June 2014 were included in this analysis. The overall incidence of NEC (stage ≥ 2) among VLBWI in Korea was 6.8%; 149 infants had NEC stage ≥ 2 and 2,177 infants did not have NEC. Surgery was performed for 77 (53%) of the infants in the NEC group. NEC was related to lower gestational age (GA) and birth weight (P < 0.001). Multivariate logistic regression analysis demonstrated that NEC was consistently related to hypotension within one week after birth (OR 2.0, 95% CI 1.0-3.9). With respect to outcome, the NEC group had longer times to reach 100 mL/kg/day feeding (P < 0.001), longer TPN duration (P < 0.001) and hospitalization (P = 0.031) and higher PVL (P < 0.001) and mortality rate (P < 0.001). When the medical and surgical NEC groups were compared, GA was significantly lower and PDA was more found in the surgical NEC group. The overall incidence of NEC in Korea is similar to that of other multicenter studies. In addition to GA and birth weight, hypotension within a week of life is significantly related to NEC.

Retinopathy of Prematurity among Very-Low-Birth-Weight Infants in Korea: Incidence, Treatment, and Risk Factors.

This study was conducted to describe the incidence, risk factors, and current treatment status of retinopathy of prematurity (ROP) in very-low-birth-weight (VLBW) infants registered in the Korean Neonatal Network database. Medical records of 2,009 VLBW infants born between January 2013 and June 2014 who underwent examination by an ophthalmologist were reviewed. The total incidence of ROP was 34.1%. Of the patients, 11.6% showed ROP stage ≥ 3 and 11.5% received treatment of VLBW. Among all infants who received treatment of ROP, 63.6% underwent operation only; 16.9%, anti-vascular endothelial growth factor (anti-VEGF) treatment only; and 19.5%, both operation and anti-VEGF treatment. The mean gestational age (GA) and birth weight (BW) were significantly lower and the prevalence rates of respiratory distress syndrome, patent ductus arteriosus (PDA), invasive ventilator duration, and sepsis were significantly higher in the VLBW infants with ROP than in those without ROP. In the multivariable logistic regression analysis, PDA (odd ratio [OR], 2.1; 95% confidence interval [CI], 1.11-3.79) and invasive ventilator duration (OR, 1.0; 95% CI, 1.00-1.02) were significant risk factors of ROP and ROP stage ≥ 3. In conclusion, the high incidence of ROP is associated with low GA and BW, and attempt to reduce the aforementioned risk factors could reduce the incidence of ROP stage ≥ 3 in VLBW infants.