Preclinical assessment of thrombin-preconditioned human Wharton's jelly-derived mesenchymal stem cells for neonatal hypoxic-ischaemic brain injury.

Hypoxic-ischaemic encephalopathy (HIE) is a type of brain injury affecting approximately 1 million newborn babies per year worldwide, the only treatment for which is therapeutic hypothermia. Thrombin-preconditioned mesenchymal stem cells (MSCs) exert neuroprotective effects by enriching cargo contents and boosting exosome biogenesis, thus showing promise as a new therapeutic strategy for HIE. This study was conducted to evaluate the tissue distribution and potential toxicity of thrombin-preconditioned human Wharton's jelly-derived mesenchymal stem cells (th-hWJMSCs) in animal models before the initiation of clinical trials. We investigated the biodistribution, tumorigenicity and general toxicity of th-hWJMSCs. MSCs were administered the maximum feasible dose (1 × 105 cells/10 µL/head) once, or at lower doses into the cerebral ventricle. To support the clinical use of th-hWJMSCs for treating brain injury, preclinical safety studies were conducted in newborn Sprague-Dawley rats and BALB/c nude mice. In addition, growth parameters were evaluated to assess the impact of th-hWJMSCs on the growth of newborn babies. Our results suggest that th-hWJMSCs are non-toxic and non-tumorigenic in rodent models, survive for up to 7 days in the brain and hold potential for HIE therapy.

The Clinical Risk Index for Babies II for Prediction of Time-Dependent Mortality and Short-Term Morbidities in Very Low Birth Weight Infants.

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.

The impact of neonatal care resources on regional variation in neonatal mortality among very low birthweight infants in Korea.

BACKGROUND: Faced with extremely low fertility rates and increasing numbers of low-birthweight births in Korea, we examined the factors affecting the mortality of very-low-birthweight (VLBW) infants in Korea. METHODS: A survey was conducted in 91 of 93 hospitals providing neonatal intensive care in Korea in 2009. Data included information on number of neonatal intensive care unit (NICU) beds, medical workforce, resources in the NICU, birth and death. RESULTS: There was approximately one NICU per 4888 births, one NICU bed per 355 births, one mechanical ventilator per 739 births, one incubator per 327 births and one board-certified neonatologist per 4683 births. Regional disparity existed in neonatal care resources and consequently in mortality rates. VLBW infants' mortality was related to the NICU facility level, volume of VLBW infants and geographic regions. The capital city, Seoul, has the best NICU facilities and workforce, and the least mortality. Overall mortality rates before hospital discharge for <750, 750-999 and 1000-1499 g were 44.8%, 20.4% and 6.5% respectively. There was a two to threefold difference in the mortality rates across the regions. However, following adjustments for NICU facility level and volume of VLBW infants admissions, regional difference in mortality rates was markedly reduced in the <750 g and disappeared in the larger VLBW groups. CONCLUSIONS: Regional disparity in mortality of VLBW infants in Korea is most marked in the lowest-birthweight group, <750 g. This disparity is primarily due to lack of resources for neonatal intensive care in most of provincial areas.