Development of a machine learning model to identify intraventricular hemorrhage using time-series analysis in preterm infants.

Although the prevalence of intraventricular hemorrhage (IVH) has remained high, no optimal strategy has been established to prevent it. This study included preterm newborns born at a gestational age of < 32 weeks admitted to the neonatal intensive care unit of a tertiary hospital between January 2013 and June 2022. Infants who had been observed for less than 24 h were excluded. A total of 14 features from time-series data after birth to IVH diagnosis were chosen for model development using an automated machine-learning method. The average F1 scores and area under the receiver operating characteristic curve (AUROC) were used as indicators for comparing the models. We analyzed 778 preterm newborns (79 with IVH, 10.2%; 699 with no IVH, 89.8%) with a median gestational age of 29.4 weeks and birth weight of 1180 g. Model development was performed using data from 748 infants after applying the exclusion criteria. The Extra Trees Classifier model showed the best performance with an average F1 score of 0.93 and an AUROC of 0.999. We developed a model for identifying IVH with excellent accuracy. Further research is needed to recognize high-risk infants in real time.

Integrated Structural Modulation Inducing Fast Charge Transfer in Aqueous Zinc-Ion Batteries.

Aqueous Zn-ion batteries (AZIBs) are promising energy-storage devices owing to their exceptional safety, long cycle life, simple production, and high storage capacity. Manganese oxides are considered potential cathode materials for AZIBs, primarily because of their safety, low cost, simple synthesis, and high storage capacity. However, MnO2-based cathodes tend to deteriorate structurally during long-term cycling, which reduces their reversible capacity. In this study, an advanced α-MnO2@SnO2 nanocomposite via facile hydrothermal synthesis is developed. The synergistic effects of lattice disorder and increased electron conductivity in the α-MnO2@SnO2 nanocomposite mitigate structural degradation and enhance the overall electrochemical performance. The nanocomposite exhibits a high reversible capacity of 347 mAh g-1 at a current density of 100 mA g-1 after 50 cycles. Furthermore, it exhibits excellent rate performance and stable capacity even after 1000 cycles, maintaining a capacity of 78 mAh g-1 at a high current density of 5 A g-1. This excellent electrochemical performance is attributed to the reversible Zn intercalation in α-MnO2@SnO2 nanocomposites due to the increased structural stability and fast ion/electron exchange caused by the distortion of the tunnel structure, on the basis of various ex situ experiments, density functional theory calculations, and electrochemical characterizations.

Analysis of gastric fluid in preterm newborns supports the view that the amniotic cavity is sterile before the onset of parturition: a retrospective cohort study.

OBJECTIVES: To compare the frequency of Ureaplasma-positive gastric fluid (GF) cultures based on the cause and mode of delivery in preterm newborns. METHODS: This retrospective cohort study included women with a singleton pregnancy who delivered prematurely (between 23+0 and 32+0 weeks of gestation, n=464) at a single university hospital in South Korea. The newborns' GF was obtained on the day of birth via nasogastric intubation. The frequency of Ureaplasma spp. in GF cultures was measured and compared according to the cause and mode of delivery. RESULTS: Ureaplasma spp. was detected in 20.3 % of the GF samples. The presence of Ureaplasma spp. was significantly higher in the spontaneous preterm birth group than in the indicated preterm birth group (30.2 vs. 3.0 %; p<0.001). Additionally, Ureaplasma spp. was more frequently found in the vaginal delivery group than in the cesarean delivery group, irrespective of the cause of preterm delivery [indicated preterm birth group (22.2 vs. 1.9 %, p=0.023); spontaneous preterm birth group (37.7 vs. 24.2 %, p=0.015)]. CONCLUSIONS: Ureaplasma spp. were found in 20.3 % of the GFs. However, only 1.9 % of newborns in the indicated preterm birth group with cesarean delivery had a Ureaplasma-positive GF culture.

Neonatal outcomes of early preterm births according to the delivery indications.

OBJECTIVE: To compare the neonatal outcomes of early preterm births according to delivery indications and determine the obstetric risk factors associated with adverse outcomes. METHODS: We retrospectively studied pregnancies delivered between 22 + 0 and 26 + 6 weeks at the tertiary center between April 2013 and April 2022. Stillbirths, elective termination of pregnancy, and multifetal pregnancies were excluded. Patients were classified into two groups according to delivery indications: spontaneous preterm birth (sPTB) due to premature rupture of membranes (PROM), preterm labor, or acute cervical insufficiency; and indicated preterm birth (iPTB). Obstetric and neonatal outcomes were compared between the groups. RESULTS: Of the 121 neonates, 73 % (88/121) underwent sPTB. The overall survival rates were 73 % and 49 % in the sPTB and iPTB groups, respectively (p = 0.017). Multivariate logistic regression analysis was performed with adjustment for gestational age at delivery, fetal growth restriction, cesarean section, histological chorioamnionitis, and funisitis. Moreover, in the 1-year follow-up, the proportion of body mass below the third percentile was significantly higher in the iPTB-group than in the sPTB-group (53 % vs. 20 %, p = 0.019). Furthermore, diagnoses of developmental delay and cerebral palsy were slightly higher in the iPTB-group (33 % and 20 %, respectively) than in the sPTB-group (27 % and 9 %, respectively); however, this difference was not statistically significant. CONCLUSIONS: In early preterm births, iPTB was associated with a higher neonatal mortality than sPTB.

Comprehensive characterization of maternal, fetal, and neonatal microbiomes supports prenatal colonization of the gastrointestinal tract.

In this study, we aimed to comprehensively characterize the microbiomes of various samples from pregnant women and their neonates, and to explore the similarities and associations between mother-neonate pairs, sample collection sites, and obstetrical factors. We collected samples from vaginal discharge and amniotic fluid in pregnant women and umbilical cord blood, gastric liquid, and meconium from neonates. We identified 19,597,239 bacterial sequences from 641 samples of 141 pregnant women and 178 neonates. By applying rigorous filtering criteria to remove contaminants, we found evidence of microbial colonization in traditionally considered sterile intrauterine environments and the fetal gastrointestinal track. The microbiome distribution was strongly grouped by sample collection site, rather than the mother-neonate pairs. The distinct bacterial composition in meconium, the first stool passed by newborns, supports that microbial colonization occurs during normal pregnancy. The microbiome in neonatal gastric liquid was similar, but not identical, to that in maternal amnionic fluid, as expected since fetuses swallow amnionic fluid in utero and their urine returns to the fluid under normal physiological conditions. Establishing a microbiome library from various samples formed only during pregnancy is crucial for understanding human development and identifying microbiome modifications in obstetrical complications.

Efficacy and safety of mucous fistula refeeding in preterm infants: an exploratory randomized controlled trial.

BACKGROUND: This study aimed to evaluate whether mucous fistula refeeding (MFR) is safe and beneficial for the growth and intestinal adaptation of preterm infants with enterostomies. METHODS: This exploratory randomized controlled trial enrolled infants born before 35 weeks' gestation with enterostomy. If the stomal output was ≥ 40 mL/kg/day, infants were assigned to the high-output MFR group and received MFR. If the stoma output was < 40 mL/kg/day, infants were randomized to the normal-output MFR group or the control group. Growth, serum citrulline levels, and bowel diameter in loopograms were compared. The safety of MFR was evaluated. RESULTS: Twenty infants were included. The growth rate increased considerably, and the colon diameter was significantly larger after MFR. However, the citrulline levels did not significantly differ between the normal-output MFR and the control group. One case of bowel perforation occurred during the manual reduction for stoma prolapse. Although the association with MFR was unclear, two cases of culture-proven sepsis during MFR were noted. CONCLUSIONS: MFR benefits the growth and intestinal adaptation of preterm infants with enterostomy and can be safely implemented with a standardized protocol. However, infectious complications need to be investigated further. TRIAL REGISTRATION: clinicaltrials.gov NCT02812095, retrospectively registered on June 6, 2016.

Effects of antenatal corticosteroids on neonatal outcomes in twin and singleton pregnancies: a Korean national cohort study.

OBJECTIVE: To investigate whether effects of antenatal corticosteroids on neonatal outcomes in preterm infants with very low birth weight were different by plurality. DESIGN: Nationwide prospective cohort study. PATIENTS: Twins and singletons with very low birth weight (<1500 g) who were born between 23+0 and 33+6 weeks of gestation and registered in the Korean Neonatal Network from January 2014 to December 2019. MAIN OUTCOME MEASURES: Morbidity and mortality before discharge from neonatal intensive care unit. RESULTS: Among a total of 9531 preterm infants with very low birth weight, there were 2364 (24.8%) twins and 7167 (75.2%) singletons. While 83.9% of singletons were exposed to at least one dose of antenatal corticosteroids, so were 87.9% of twins.Interaction analysis demonstrated that there was no significant difference in the effect of antenatal corticosteroids on morbidities or mortality between twins and singletons in either gestational age group (23-28 weeks or 29-33 weeks).Antenatal corticosteroids significantly decreased the risk of surfactant use (adjusted relative risk (aRR): 0.972 (95% CI: 0.961 to 0.984)), high-grade intraventricular haemorrhage (aRR: 0.621 (95% CI: 0.487 to 0.794)), periventricular leucomalacia (aRR: 0.728 (95% CI: 0.556 to 0.954)) and mortality (aRR: 0.758 (95% CI: 0.679 to 0.846)) in the gestational age group of 23-28 weeks. In the gestational age group of 29-33 weeks, antenatal corticosteroids significantly decreased the risk of surfactant use (aRR: 0.914 (95% CI: 0.862 to 0.970)) and mortality (aRR: 0.409 (95% CI: 0.269 to 0.624)) but increased the risk of sepsis (aRR: 1.416 (95% CI: 1.018 to 1.969)). CONCLUSION: This study demonstrates that effect of antenatal corticosteroids on neonatal outcomes of preterm infants with very low birth weight does not differ significantly by plurality (twin or singleton pregnancy).

Neurodevelopmental outcomes of preterm infants with very low birth weight conceived with the assistance of in vitro fertilization.

OBJECTIVE: To compare the neurodevelopmental outcomes at 18-24 months of corrected age between preterm (<32 weeks of gestational age) infants with very low birth weight (VLBW) conceived with and without the assistance of in vitro fertilization (IVF). DESIGN: Prospective cohort study. SETTING: Not applicable. PATIENT(S): In total, 4,940 infants with VLBW were born before 32 weeks of gestational age from January 2013 to December 2015. INTERVENTION(S): In vitro fertilization. MAIN OUTCOME MEASURE(S): Neuromotor or sensory disability (primary outcome) and developmental delay assessed using the Bayley Scales of Infant and Toddler Development (secondary outcome) at 18-24 months of corrected age. RESULT(S): Of the 4,940 infants with VLBW enrolled, 2,818 surviving infants who were followed up for neurodevelopmental assessment at 18-24 months of corrected age were included in the study. Of these 2,818 infants, 630 (22.4%) were conceived with the assistance of IVF, and 2,188 (77.6%) were not. After adjustment for potential confounders, no statistically significant differences were found in the rate of neuromotor or sensory disability at 18-24 months of corrected age between infants conceived with and without the assistance of IVF. After excluding infants with neuromotor or sensory disability, the rate of developmental delay was also comparable between those conceived with and without the assistance of IVF. CONCLUSION(S): This study showed comparable neurodevelopmental outcomes at 18-24 months of corrected age between preterm infants with VLBW conceived with and without the assistance of IVF.

Population pharmacokinetic analysis of sildenafil in term and preterm infants with pulmonary arterial hypertension.

Sildenafil is widely used off-label in pediatric patients with pulmonary arterial hypertension (PAH). This study was conducted to characterize the pharmacokinetics (PK) of sildenafil in term and preterm neonates with PAH, by developing a population PK model, and to suggest appropriate doses to achieve clinically effective concentrations. A population PK modelling analysis was performed using sildenafil and its metabolite N-desmethyl sildenafil (DMS) concentration data from 19 neonates with PAH, whose gestational ages ranged 24-41 weeks. They received sildenafil orally at a dose of 0.5-0.75 mg/kg, four times a day. To investigate the appropriate sildenafil dose, simulations were conducted according to body weight which was significant covariate for sildenafil clearance. A one-compartment model with first-order absorption adequately described the PKs of sildenafil and DMS. Sildenafil clearance was expected to increase rapidly with increasing body weight. In the simulation, sildenafil doses > 1 mg/kg was required to achieve and maintain target concentrations of sildenafil and to expect timely clinical effects in term and preterm infants. These results could be utilized for the safer and more effective use of sildenafil in term and preterm infants.

Noninvasive Neurally Adjusted Ventilation in Postextubation Stabilization of Preterm Infants: A Randomized Controlled Study.

OBJECTIVE: To compare the effects of noninvasive neurally adjusted ventilatory assist (NIV-NAVA) to nasal continuous positive airway pressure (NCPAP) in achieving successful extubation in preterm infants. STUDY DESIGN: This prospective, single-center, randomized controlled trial enrolled preterm infants born at <30 weeks of gestation who received invasive ventilation. Participants were assigned at random to either NIV-NAVA or NCPAP after their first extubation from invasive ventilation. The primary outcome of the study was extubation failure within 72 hours of extubation. Electrical activity of the diaphragm (Edi) values were collected before extubation and at 1, 4, 12, and 24 hours after extubation. RESULTS: A total of 78 infants were enrolled, including 35 infants in the NIV-NAVA group and 35 infants in the NCPAP group. Extubation failure within 72 hours of extubation was higher in the NCPAP group than in the NIV-NAVA group (28.6% vs 8.6%; P = .031). The duration of respiratory support and incidence of severe bronchopulmonary dysplasia were similar in the 2 groups. Peak and swing Edi values were comparable before and at 1 hour after extubation, but values at 4, 12, and 24 hours after extubation were lower in the NIV-NAVA group compared with the NCPAP group. CONCLUSIONS: In the present trial, NIV-NAVA was more effective than NCPAP in preventing extubation failure in preterm infants. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02590757.

Cooperative coupling of anisotropic phonon modes intensifies visible thermochromism in layered α-MoO3.

Applications that provide versatile, high temperature warnings require the development of thermochromic materials based on solid-state oxides. To boost the visible thermochromic properties, a fundamental approach to reveal the unclear roles of local structure on band structure modulation should be considered by scrutinizing the thermal motion of phonon modes. Herein, we demonstrate that selective coupling of intra-layer phonon modes intensifies the visible thermochromism of layered oxides α-MoO3. As a result of thermally induced band gap reduction in α-MoO3, the observed color reversibly changes from white at 25 °C to yellow at 300 °C owing to a red shift of the absorption edge with an increase of temperature. This high-temperature thermochromism is attributed to the anisotropic change of layered α-MoO3 crystal structures characterized by synchrotron X-ray diffraction. Notably, quantitative characterizations combined with theoretical calculations reveal that the cooperative coupling of active Raman modes in intra-layer [MoO6] octahedra are responsible for the band gap reduction at high temperature; this defies the general belief regarding the origin of visible thermochromism in layered oxides as the modulation of a van der Waals inter-layer distance. These original results can aid the development of a new strategy to further intensify high-temperature thermochromism by anion doping for highly sensitive temperature-indicating applications.

Breech Presentation in Twins as a Risk Factor for Developmental Dysplasia of the Hip.

INTRODUCTION: Identifying risk factors associated with developmental dysplasia of the hip (DDH) is essential for early diagnosis and treatment. Breech presentation is a major DDH risk factor, possibly because of crowding of the fetus within the uterus. In multifetal pregnancy, fetuses are generally smaller than singletons, which may obscure the effect of breech presentation on fetal hips. Only a few studies have investigated the occurrence of DDH in multifetal pregnancies. In this study, we aimed to evaluate whether the breech presentation is a major risk factor of DDH in twin pregnancies. METHODS: This retrospective study included 491 consecutive live births (after 23+0 weeks gestation) delivered through cesarean section with at least 1 baby with noncephalic presentation in single or twin pregnancies from April 2013 to October 2018. We analyzed the incidence of DDH and its associated factors, including sex, breech, and multifetal pregnancy, with a generalized linear mixed model. RESULTS: The incidence of DDH was 12.5% in singleton with breech presentation, 9.8% in twin-breech presentation, and 0.7% in twin-cephalic presentation. Multivariate analysis showed that singleton-breech presentation (P=0.003), twin-breech presentation (P=0.003), and female sex (P=0.008) were independent risk factors for DDH. CONCLUSION: Breech presentation is an independent risk factor for DDH in twin pregnancies, although twin pregnancy itself is not an independent risk factor for DDH.

Differentiation of food protein-induced enterocolitis syndrome misleading to necrotizing enterocolitis.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a rare non-immunoglobulin E-mediated food allergy with necrotizing enterocolitis (NEC)-like symptoms which requires differential diagnosis as treatments differ. OBJECTIVE: To evaluate the clinical, laboratory, and radiologic findings that differentiate FPIES from NEC in preterm and term infants. METHODS: Clinical features, comorbidities, and laboratory and radiologic findings of neonates with presumed NEC were reviewed retrospectively and compared between FPIES and NEC in preterm and term infants who were admitted to the neonatal intensive care unit at Seoul National University Bundang Hospital between May 2003 and February 2020. RESULTS: A total of 10 of 150 (6.7%) preterm and 17 of 38 (44.7%) term infants with presumed NEC were confirmed to have FPIES; the remainder had NEC by modified Bell's criteria. Demographics and comorbidities were similar between these groups. Symptoms such as hematochezia, shock, leukocytosis, peripheral eosinophilia, and feeding of extensively hydrolyzed milk formula or elemental formula after discharge were significantly different between the 2 groups in term infants (P <.05), but not in preterm infants. On abdominal ultrasonography, pneumatosis intestinalis was more common among preterm FPIES (44.4%) than NEC cases (21.6%) (P =.04). Among the preterm infants, 4 FPIES (40%) and 25 NEC (17.9%) cases required surgery (P =.10). CONCLUSION: Differentiating FPIES in neonates suspected of having NEC is important as dietary elimination of the triggering milk protein can be recommended instead of prolonged fasting and antibiotic treatment, which are indicated for NEC, in both term and preterm infants.

Cognitive and Behavioral Outcomes of School-aged Children Born Extremely Preterm: a Korean Single-center Study with Long-term Follow-up.

BACKGROUND: School-aged children born very preterm have been suggested to have worse cognitive and behavioral outcomes than children born full-term. Executive function (EF) is a higher level of cognitive function related to academic achievement. The present study aimed to evaluate the cognitive (including EF) and behavioral outcomes of Korean children born extremely preterm (EP) and to analyze any biological or socioeconomic risk factors for poor cognitive outcomes in this population. METHODS: A total of 71 infants weighing < 1,000 g at birth or born before 30 weeks of gestation (EP group) who were admitted to the neonatal intensive care unit from 2008 to 2009 were included in this study and compared with 40 term-birth controls. The Korean Wechsler Intelligence Scale for Children-Fourth Edition, Advanced Test of Attention (ATA), Stroop test, Children's Color Trails Test (CCTT), and Wisconsin Card Sorting Test (WCST) were used. Additionally, the Korean Child Behavior Checklist (K-CBCL) and Korean ADHD Rating Scale (K-ARS) were completed. Perinatal and demographic data were collected and analyzed. RESULTS: The mean full-scale intelligence quotient (FSIQ) score in the EP group was significantly lower than that of the term control group (89.1 ± 18.3 vs. 107.1 ± 12.7; P < 0.001). In the EP group, 26 (37%) children had an FSIQ score below 85, compared to only one child (3%) in the control group. Furthermore, the EP group showed significantly worse EF test results (ATA, Stroop test, CCTT, WCST). Except for the higher social immaturity subscore in the EP group, the K-CBCL and K-ARS scores were not different between the two groups. EP children who received laser treatment for retinopathy of prematurity (ROP) had an 8.8-fold increased risk of a low FSIQ score, and a 1-point increase in the discharge weight Z-score decreased the risk of a low FSIQ score by approximately half in this EP cohort. CONCLUSION: This is the first Korean study to investigate the cognitive and behavioral outcomes of school-aged children born EP. In the study cohort, EP children exhibited significantly lower FSIQ scores and EF than their full-term peers, and 37% of them had cognitive problems. Nonetheless, except for social immaturity, the behavioral problems were not different in EP children. Severe ROP and low discharge weight Z-score were identified as independent risk factors for low FSIQ score after adjusting for birth weight.

The Physiologic Significance of Early Urinary Intestinal Fatty Acid Binding Protein Levels in Preterm Infants: A Prospective Cohort Study.

Intestinal fatty acid binding protein (I-FABP) is released from mature enterocytes when cell membrane integrity is disrupted. This study aimed to prospectively investigate the physiologic significance of early urinary I-FABP and whether it might reflect intestinal compromise in preterm infants. We conducted a prospective cohort study of 100 preterm infants weighing <1250 g and collected serial urine samples at 12, 24, and 48 h after birth. The correlations between initial urinary I-FABP/urinary creatinine (creatinineu) levels and associated factors were analyzed. Among 100 patients, 15 were diagnosed with meconium obstruction of prematurity, and five were diagnosed with necrotizing enterocolitis during the hospital stay. Early urinary I-FABP/creatinineu levels were inversely correlated with both gestational age (Spearman's rank correlation coefficient (Rs) -0.381, p < 0.01) and birth weight ((Rs) -0.424, p < 0.01). Early urinary I-FABP/creatinineu levels were associated with cord pH ((Rs) -0.436, p < 0.01) and base excess ((Rs) -0.258, p = 0.021). There were significantly positive correlations between early urinary I-FABP/creatinineu levels and the time to full enteral feeding in preterm infants without specific intestinal morbidities. Therefore, a more premature gut with acute perinatal ischemia is expected to exhibit increased I-FABP levels shortly after birth. Because of small sample size, further large-scale studies are needed.

Impact of very preterm birth and post-discharge growth on cardiometabolic outcomes at school age: a retrospective cohort study.

BACKGROUND: Adverse metabolic outcomes later in life have been reported among children or young adults who were born as preterm infants. This study was conducted to examine the impact of very preterm/very low birth weight (VP/VLBW) birth and subsequent growth after hospital discharge on cardiometabolic outcomes such as insulin resistance, fasting glucose, and systolic and diastolic blood pressure (BP) among children at 6-8 years of age. METHODS: This retrospective cohort study included children aged 6-8 years and compared those who were born at < 32 weeks of gestation or weighing < 1,500 g at birth (n = 60) with those born at term (n = 110). Body size, fat mass, BP, glucose, insulin, leptin, adiponectin, and lipid profiles were measured. Weight-for-age z-score changes between discharge and early school-age period were also calculated, and factors associated with BP, fasting glucose, and insulin resistance were analyzed. RESULTS: Children who were born VP/VLBW had significantly lower fat masses, higher systolic BP and diastolic BP, and significantly higher values of fasting glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), compared to children born at term. VP/VLBW was correlated with HOMA-IR and BPs after adjusting for various factors, including fat mass index and weight-for-age z-score changes. Weight-for-age z-score changes were associated with HOMA-IR, but not with BPs. CONCLUSIONS: Although children aged 6-8 years who were born VP/VLBW showed significantly lower weight and fat mass, they had significantly higher BPs, fasting glucose, HOMA-IR, and leptin levels. The associations of VP/VLBW with cardiometabolic factors were independent of fat mass and weight gain velocity.

The association of low body mass index with neonatal morbidities in preterm infants.

Little is known about the association between body proportionality at birth and neonatal outcomes in preterm infants. Body mass index (BMI) is one of the weigh-for-length ratios that represent body proportionality. The objective of this study was to examine whether BMI at birth affects neonatal outcomes in preterm infants. We assessed 3115 preterm (< 30 weeks), very low birth weight (< 1500 g) infants born between January 2013 and December 2016 and registered in the Korean Neonatal Network database. Using gender-specific BMI for gestational age curves, z-scores of BMI at birth were calculated. Low-, normal-, and high-BMI were defined as BMI z-scores of less than - 1, from - 1 to 1, and greater than 1, respectively. Neonatal morbidities and mortality in low- and high-BMI groups were compared to those in normal-BMI group. The low-BMI group had an increased risk of bronchopulmonary dysplasia, bronchopulmonary dysplasia or death, and necrotizing enterocolitis after adjusting for baseline characteristics and the birth weight z-score. High-BMI group had comparable neonatal outcomes to those of normal-BMI group. Low BMI at birth was associated with an increased risk of bronchopulmonary dysplasia and necrotizing enterocolitis, whereas High BMI at birth was not associated with adverse neonatal outcomes.

Differences in Comorbidities and Clinical Burden of Severe Bronchopulmonary Dysplasia Based on Disease Severity.

Background: The present study compared baseline characteristics, comorbidities and clinical burden of pre-term infants with type 1 and 2 severe bronchopulmonary dysplasia (BPD) Collaborative classification. Methods: This study was a prospective cohort study of pre-term (<32 weeks) very-low-birth-weight infants. Severe BPD was divided into type 1 severe BPD requiring of ≥30% oxygen and/or non-invasive ventilation at 36 weeks post-menstrual age (PMA), and type 2 severe BPD requiring invasive mechanical ventilation at 36 weeks PMA. Baseline characteristics, comorbidities, and clinical burden were compared between these two types of severe BPD. Results: Of the 1,328 infants included, 983 (74.0%) developed type 1 severe BPD, and 345 (26.0%) developed type 2 severe BPD. Lower birth weight, small for gestational age, lesser maternal pre-mature rupture of membrane, lower 5-min Apgar score, air leak, pulmonary hemorrhage, surgical ligation of patent ductus arteriosus, necrotizing enterocolitis, and late-onset sepsis were significantly associated with type 2 severe BPD. Compared with infants with type 1 severe BPD, infants with type 2 severe BPD had an increased risk of mortality (aOR 18.64, 95% CI 10.81-32.13), pulmonary hypertension (aOR 2.16, 95% CI 1.59-2.93), and tracheostomy (aOR 10.38, 95% CI 2.05-52.49). Conclusions: Our data highlight the substantially greater mortality and clinical burden in infants with type 2 severe BPD than infants with type 1 severe BPD. A comprehensive and multidisciplinary approach is needed for infants with type 2 severe BPD.