Development and Validation of a Mortality Prediction Model in Extremely Low Gestational Age Neonates.

INTRODUCTION: Understanding factors that associate with neonatal death may lead to strategies or interventions that can aid clinicians and inform families. OBJECTIVE: The aim of the study was to develop an early prediction model of neonatal death in extremely low gestational age (ELGA, <28 weeks) neonates. METHODS: A predictive cohort study of ELGA neonates was derived from the Swedish Neonatal Quality Register between the years 2011 to May 2021. The goal was to use readily available clinical variables, collected within the first hour of birth, to predict in-hospital death. Data were split into a train cohort (80%) to build the model and tested in 20% of randomly selected neonates. Model performance was assessed via area under the receiver operating characteristic curve (AUC) and compared to validated mortality prediction models and an external cohort of neonates. RESULTS: Among 3,752 live-born extremely preterm infants (46% girls), in-hospital mortality was 18% (n = 685). The median gestational age and birth weight were 25.0 weeks (interquartile range [IQR] 24.0, 27.0) and 780 g (IQR 620, 940), respectively. The proposed model consisted of three variables: birth weight (grams), Apgar score at 5 min of age, and gestational age (weeks). The BAG model had an AUC of 76.9% with a 95% confidence interval (CI) (72.6%, 81.3%), while birth weight and gestational age had an AUC of 73.1% (95% CI: 68.4%,77.9%) and 71.3% (66.3%, 76.2%). In the validation cohort, the BAG model had an AUC of 68.9%. CONCLUSION: The BAG model is a new mortality prediction model in ELGA neonates that was developed using readily available information.

Intranasal delivery of human umbilical cord Wharton's jelly mesenchymal stromal cells restores lung alveolarization and vascularization in experimental bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a devastating lung condition that develops in premature newborns exposed to prolonged mechanical ventilation and supplemental oxygen. Significant morbidity and mortality are associated with this costly disease and effective therapies are limited. Mesenchymal stem/stromal cells (MSCs) are multipotent cells that can repair injured tissue by secreting paracrine factors known to restore the function and integrity of injured lung epithelium and endothelium. Most preclinical studies showing therapeutic efficacy of MSCs for BPD are administered either intratracheally or intravenously. The purpose of this study was to examine the feasibility and effectiveness of human cord tissue-derived MSC administration given via the intranasal route. Human umbilical cord tissue MSCs were isolated, characterized, and given intranasally (500 000 cells per 20 µL) to a hyperoxia-induced rat model of BPD. Lung alveolarization, vascularization, and pulmonary vascular remodeling were restored in animals receiving MSC treatment. Gene and protein analysis suggest the beneficial effects of MSCs were attributed, in part, to a concerted effort targeting angiogenesis, immunomodulation, wound healing, and cell survival. These findings are clinically significant, as neonates who develop BPD have altered alveolar development, decreased pulmonary vascularization and chronic inflammation, all resulting in impaired tissue healing. Our study is the first to report the intranasal delivery of umbilical cord Wharton's jelly MSCs in experimental BPD is feasible, noninvasive, and an effective route that may bear clinical applicability.

Upcycling umbilical cords: bridging regenerative medicine with neonatology.

Preterm birth is a major health concern that affects 10% of all worldwide deliveries. Many preterm infants are discharged from the hospital with morbidities that lead to an increased risk for neurodevelopmental impairment, recurrent hospitalizations, and life-long conditions. Unfortunately, the treatment of these conditions is palliative rather than curative, which calls for novel and innovative strategies. Progress in regenerative medicine has offered therapeutic options for many of these conditions. Specifically, human umbilical cord mesenchymal stem cells (MSCs) and cord blood (UCB) cells have shown promise in treating adult-onset diseases. Unlike bone-marrow and embryonic derived stem cells, umbilical cord-derived cells are easily and humanely obtained, have low immunogenicity, and offer the potential of autologous therapy. While there are several studies to uphold the efficacy of umbilical cord MSCs in adult therapies, there remains an unmet need for the investigation of its use in treating neonates. The purpose of this review is to provide a summary of current information on the potential therapeutic benefits and clinical applicability of umbilical cord MSCs and UCB cells. Promising preclinical studies have now led to a research movement that is focusing on cell-based therapies for preterm infants.