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Background: We previously performed a phase II randomised double-blind clinical trial of mesenchymal stromal cell (MSCs) transplantation to prevent bronchopulmonary dysplasia in extremely premature infants. Subsequently, we followed the infants enrolled in this clinical trial to determine the safety and effectiveness of MSCs against bronchopulmonary dysplasia at 5-year follow-up., Methods: We evaluated infants at 5 years of age receiving placebo or MSCs in a prospective follow-up study., Results: In terms of the primary end point of composite respiratory morbidities, including respiratory problem-related readmission, emergency department visits or oxygen therapy, the MSC group had a rate of 60.7% for composite morbidities, while the control group showed a tendency of higher rate of 83.9% for the same outcomes without statistical significance. In terms of the secondary outcomes, the MSC group infants showed a tendency of being less likely to visit emergency department (control 67.7% vs MSC 35.7%) and to receive oxygen therapy (control 29.0% vs MSC 3.6%). No difference was observed in the incidence of respiratory problem-related hospital readmission or wheezing episodes between the groups., Conclusion: Intratracheally instilled MSCs showed the possibility of potential to decrease respiratory symptom-related emergency department visits and oxygen therapy episodes in infants born extremely preterm during the 5 years after a phase II randomised controlled, double-blind trial of MSCs transplantation for bronchopulmonary dysplasia. This small size study suggests preliminary insights that can be further tested using larger sample sizes., Trial Registration Number: NCT01897987., Competing Interests: Competing interests: Samsung Medical Center and MEDIPOST have issued or filed patents for ‘Method of treating lung diseases using cells separated or proliferated from umbilical cord blood’ under the name of YSC and WSP. The relevant application number is PCT/KR2007/000535., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine the outcomes of very low birth weight infants (VLBWIs) following maternal mid-trimester prolonged preterm premature rupture of membranes (PPROM) and subsequent early pulmonary hypertension (PH)., Design: Prospective cohort study., Setting: A nationwide web-based registry of VLBWIs from 67 neonatal intensive care units., Patients: VLBWIs registered on the Korean Neonatal Network and born between 23 and 34 gestational weeks., Methods: VLBWIs exposed to maternal PPROM prior to 25 gestational weeks and lasting ≥7 days (PPROM25, n  = 402) were matched 1:1 with infants not exposed or exposed within 24 h to PPROM (CON, n  = 402), using propensity score matching. The PPROM25 group was subdivided into PPROM25 groups with or without early PH, defined as exposure to inhaled nitric oxide or other pulmonary vasodilators to treat PH within 3 days of life. Clinical variables and major outcomes were compared, and risk factors for mortality and morbidities were analyzed., Results: Of 1790 infants with maternal PPROM, the PPROM25 group comprised 402 (22.5%) infants. Survival rates were similar between the CON and PPROM25 groups (71.6% vs 74.4%); however, the incidence of bronchopulmonary dysplasia (BPD) differed (47.8% and 60.2%, p  < .05). Infants in the PPROM25 group with early PH had higher mortality (55.6%) and more severe intraventricular hemorrhage (IVH) (31.7%) than infants in the PPROM25 group without early PH (21.9% and 14.3%, respectively; p  < .05). In multivariate analysis, lower 5 min Apgar score and the presence of oligohydramnios increased the risk of development of early PH. The presence of PPROM25 was founded to be a significant risk factor for BPD and early PH in relation to mortality and severe IVH, respectively., Conclusions: In VLBWIs, prolonged exposure to maternal mid-trimester PPROM increased the risk of BPD. Subsequent early PH immediately after birth increased mortality and severe IVH, thus, requires special attention.

We previously demonstrated the safety and feasibility of mesenchymal stem cell (MSC) transplantation for bronchopulmonary dysplasia (BPD) in preterm infants in a phase I clinical trial. We thus investigated the therapeutic efficacy of MSCs for BPD in premature infants. A phase II double-blind, randomized, placebo-controlled clinical trial was conducted on preterm infants at 23 to 28 gestational weeks (GW) receiving mechanical ventilator support with respiratory deterioration between postnatal days 5 and 14. Infants were stratified by 23 to 24 GW and 25 to 28 GW and randomly allocated (1:1) to receive stem cells (1 × 10 7 cells/kg, n = 33) or placebo (n = 33). Although the inflammatory cytokines in the tracheal aspirate fluid were significantly reduced with MSCs, the primary outcome of death or severe/moderate BPD in the control group (18/33, 55%) was not significantly improved with MSC transplantation (17/33, 52%). In the subgroup analysis, the secondary outcome of severe BPD was significantly improved from 53% (8/15) to 19% (3/16) with MSC transplantation in the 23 to 24 GW group but not in the 25 to 28 GW subgroup. In summary, although MSC transplantation might be safe and feasible, this small study was underpowered to detect its therapeutic efficacy in preterm infants at 23 to 28 GW. Accordingly, we are now conducting an additional larger and controlled phase II clinical trial focusing on infants at 23 to 24 GW (NCT03392467). ClinicalTrials.gov identifier: NCT01828957., (© 2021 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Objective: To investigate the risk factors for BPD severity by gestational age (GA) and identify a way to reduce the incidence of moderate-to-severe BPD., Study Design: This was a retrospective cohort study of very-low-birth-weight-infants (VLBWIs) delivered at 24 to 28 weeks GA from Korean Neonatal Network registry between 2013 and 2016. BPD was defined using the National Institutes of Health criteria. Study populations were divided by GA and subdivided into no/mild BPD and moderate/severe BPD. The initial statuses of all infants, including those who died before BPD diagnosis and the maternal and neonatal factors of the live infants were compared. Statistical methods included descriptive statistics, comparative tests, and logistic regression., Results: Of 3,976 infants, 3,717 were included (24weeks, n = 456; 25 weeks, n = 650, 26 weeks, n = 742; 27 weeks, n = 836; 28 weeks, n = 1,033). The overall mortality rate was 18% and the rates by GA were 43%, 29%, 11%, and 6% in the 24-, 25-, 26-, 27-, 28-GA groups, respectively. Small for GA (SGA), treated patent ductus arteriosus (PDA), hypotension, and late-onset sepsis were significant risk factors for developing moderate/severe BPD in the 25 to 28-week GA groups in the multivariate analyses. However, for infants born at 24 weeks GA, there were no significant risk factors apart from initial resuscitation., Conclusions: Effective initial resuscitation was the most important factor for infants delivered at 24 weeks GA determining the severity of BPD. For infants delivered between 25 and 28 weeks, judicious care of SGA infants, aggressive treatment for PDA and hypotension, and intense efforts to decrease the sepsis rate are needed to reduce the development of moderate-to-severe BPD., Competing Interests: The authors have declared that no competing interests exist.

Background: A simple predictive indicator of mortality and morbidities is essential to assess neonatal illness severity and plan proper management. Objective: This study aimed to test the time-dependent performance of the Clinical Risk Index for Babies (CRIB) II in predicting mortality and major short-term morbidities among very low birth weight infants (VLBWIs). Methods: This population-based prospective study from 67 Korean Neonatal Network centers performed between 2013 and 2016 included 5,296 VLBWIs with CRIB II calculation and 6,398 infants with CRIB II calculation but without the base excess (CRIB II-BE). A regression model predicting time-dependent mortality and morbidities using the CRIB II score was designed. The discriminate ability of the CRIB II and CRIB II-BE scores in predicting mortality and morbidities was explored using receiver-operating characteristic analysis. Results: CRIB II performed significantly better in predicting mortality than did gestational age or birth weight alone. The time-dependent performance of CRIB II was good in the first 30 days (area under the curve [AUC], 0.8435) and at 31–90 days (AUC, 0.8458). However, it was poor after 90 days (AUC, 0.6576). Specific CRIB II cutoffs were associated with severe intraventricular hemorrhage (AUC, 0.81), bronchopulmonary dysplasia (AUC, 0.77), and mortality or major morbidities (AUC, 0.80), respectively. The model using CRIB II-BE showed similar performance in predicting mortality and morbidities to that of the CRIB II model. Conclusion: Certain CRIB II cutoffs were significantly associated with time-dependent mortality, particularly within the first 90 days after birth as well as with short-term morbidities. [ABSTRACT FROM AUTHOR]

As increased oxidative stress causes increased mortality and morbidities like bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) in very low birth weight infants (VLBWIs), the conundrum of improved survival but increased ROP observed with the high oxygen saturation target range of 91–95% is difficult to explain. To determine the survival rate-dependent variation in ROP treatment rate, 6292 surviving eligible VLBWIs registered in the Korean Neonatal Network were arbitrarily grouped according to the survival rate of infants at 23–24 weeks' gestation as group I (> 70%, n = 1626), group II (40–70%, n = 2984) and group III (< 40%, n = 1682). Despite significantly higher survival and lower BPD rates in group I than in groups II and III, the ROP treatment rate was higher in group I than in groups II and III. However, the adjusted odds ratios for ROP treatment were not significantly different between the study groups, and the ROP treatment rate in the infants at 23–24 weeks' gestation was 21-fold higher than the infants at ≥ 27 weeks' gestation. The controversial association between improved survival and reduced BPD reflecting quality improvement of neonatal intensive care but increased ROP treatment rate might be primarily attributed to the improved survival of the most immature infants. [ABSTRACT FROM AUTHOR]