ABSTRACT
BACKGROUND: Currently, there is a lack of effective treatments or preventive strategies for bronchopulmonary dysplasia (BPD). Pre-clinical studies with mesenchymal stromal cells (MSCs) have yielded encouraging results. The safety of administering repeated intravenous doses of umbilical cord tissue-derived mesenchymal stromal cells (UC-MSCs) has not yet been tested in extremely-low-gestational-age newborns (ELGANs). AIMS: to test the safety and feasibility of administering three sequential intravenous doses of UC-MSCs every 7 days to ELGANs at risk of developing BPD. METHODS: In this phase 1 clinical trial, we recruited ELGANs (birth weight ≤1250 g and ≤28 weeks in gestational age [GA]) who were on invasive mechanical ventilation (IMV) with FiO2 ≥ 0.3 at postnatal days 7-14. Three doses of 5 × 106/kg of UC-MSCs were intravenously administered at weekly intervals. Adverse effects and prematurity-related morbidities were recorded. RESULTS: From April 2019 to July 2020, 10 patients were recruited with a mean GA of 25.2 ± 0.8 weeks and a mean birth weight of 659.8 ± 153.8 g. All patients received three intravenous UC-MSC doses. The first dose was administered at a mean of 16.6 ± 2.9 postnatal days. All patients were diagnosed with BPD. All patients were discharged from the hospital. No deaths or any serious adverse events related to the infusion of UC-MSCs were observed during administration, hospital stays or at 2-year follow-up. CONCLUSIONS: The administration of repeated intravenous infusion of UC-MSCs in ELGANs at a high risk of developing BPD was feasible and safe in the short- and mid-term follow-up.
ABSTRACT
Antenatal corticosteroids reduce mortality and respiratory distress syndrome (RDS) in preterm newborns. These benefits decrease after a week of administration, recommending a rescue therapy if there is a new threat of premature delivery. Repeated administration of antenatal corticosteroids may have deleterious effects and their benefits are controversial in intrauterine growth restriction (IUGR). OBJECTIVE: to verify the effects in the IUGR population of antenatal betamethasone rescue therapy on neonatal morbidity and mortality, RDS, and neurodevelopment at 2 years. PATIENTS AND METHOD: Retrospective study including ≤ 34 weeks and ≤ 1,500g preterm newborns divided according to antenatal betamethasone exposure: Single-cycle (2 doses) vs Rescue therapy (3 doses). Subgroups were created for those ≥ 30 weeks. Both cohorts were followed up to 24 months of corrected age. The Ages & Stages Questionnaires (ASQ)® was administered to assess neurodevelopment. RESULTS: 62 preterm infants with a diagnosis of IUGR were included. The rescue therapy group compared with the single-dose group showed no differences in morbidity and mortality and less intubation rate at birth (p = 0.02), with no differences in respiratory support at 7 days of life. Preterm newborns ≥ 30 weeks exposed to rescue therapy showed higher morbidity and mortality (p = 0.03) and bronchopulmonary dysplasia (BPD) (p = 0.02), showing no differences in RDS. The rescue therapy group showed worse mean scores on the ASQ-3 scale, with no significant differences in cerebral palsy or sensory deficits. CONCLUSIONS: Rescue therapy reduces intubation at birth but does not reduce morbidity and mortality. However, at > 30 weeks, this benefit is not observed and the IUGR population exposed to rescue therapy presented more BPD and lower scores on the ASQ-3 scale at 2 years. Future studies should be aimed at the individualization of antenatal corticosteroid therapy.
Subject(s)
Infant, Newborn, Diseases , Respiratory Distress Syndrome, Newborn , Infant , Infant, Newborn , Humans , Female , Pregnancy , Betamethasone/therapeutic use , Infant, Premature , Retrospective Studies , Fetal Growth Retardation/drug therapy , Adrenal Cortex Hormones/therapeutic use , Infant, Newborn, Diseases/drug therapy , Respiratory Distress Syndrome, Newborn/drug therapyABSTRACT
BACKGROUND: Benefits of antenatal corticosteroids have been established for preterm infants who have received the full course. In imminent preterm labours there is no time to administer the second dose 24 h later. OBJECTIVE: To determine whether the administration of two doses of betamethasone in a 12 h interval is equivalent to the effects of a full maturation. METHODS: We performed a retrospective cohort study including preterm infants ≤34 weeks gestational age at birth and ≤1500 g, admitted to an NICU IIIC level in a tertiary hospital from 2015 to 2020. The population was divided into two cohorts: complete maturation (CM) (two doses of betamethasone 24 h apart), or advanced maturation (AM) (two doses of betamethasone 12 h apart). The primary outcomes were mortality or survival with severe morbidities. The presence of respiratory distress syndrome and other morbidities of prematurity were determined. These variables were analysed in the neonates under 28 weeks gestational age cohort. Neurodevelopment at 2 years was evaluated with the validated Ages and Stages Questionnaires®, Third Edition (ASQ®-3). Multiple regression analyses were performed and adjusted for confounding factors. RESULTS: A total of 275 preterm neonates were included. Serious outcomes did not show differences between cohorts, no increased incidence of morbidity was found in AM. A lower percentage of hypotension during the first week (p = 0.04), a tendency towards lower maximum FiO2 (p = 0.14) and to a shorter mechanical ventilation time (p = 0.14) were observed for the AM cohort. Similar results were found in the subgroup of neonates under 28 weeks gestational age. There were no differences in cerebral palsy or sensory deficits at 24 months of corrected age, although the AM cohort showed a trend towards better scores on the ASQ3 scale. CONCLUSIONS: Administration of betamethasone every 12 h showed similar results to the traditional pattern with respect to mortality and severe morbidities. No deleterious neurodevelopmental effects were found at 24 months of corrected age. Earlier administration of betamethasone at 12 h after the first dose would be an alternative in imminent preterm delivery. Further studies are needed to confirm these results.
ABSTRACT
BACKGROUND: A complete course of prenatal corticosteroids reduces the possibility of morbimortality and neonatal respiratory distress syndrome (RDS). Occasionally, it is not possible to initiate or complete the maturation regimen, and the preterm neonate is born in a non-tertiary hospital. This study aimed to assess the effects of a single dose of betamethasone within 3 h before delivery on serious outcomes (mortality and serious sequelae) and RDS in preterm neonates born in tertiary vs. non-tertiary hospitals. MATERIALS AND METHODS: Preterm neonates who were <35 weeks and ≤1500 g, treated during a period of five years in a level IIIC NICU, were included in this retrospective cohort study. Participants were divided into groups as follows: NM, non-matured; PM, partial maturation (one dose of betamethasone up to 3 h antepartum). They were further divided based on their place of birth (NICU-IIIC vs. non-tertiary hospitals). The morbimortality rates and the severity of neonatal RDS were evaluated. RESULTS: A total of 76 preterm neonates were included. A decrease in serious outcomes was found in the PM group in comparison to the NM group (OR = 0.2; 95%CI (0.07-0.9)), as well as reduced need for mechanical ventilation (54% vs. 68%). The mean time between maternal admission and birth was similar in both cohorts. The mean time from the administration of betamethasone to delivery was 1 h in the PM cohort. With regard to births in NICU-IIIC, the PM group performed better in terms of serious outcomes (32% vs. 45%) and the duration of mechanical ventilation (117.75 vs. 132.18 h) compared to the NM group. In neonates born in non-tertiary hospitals with PM in comparison to the NM group, a trend towards a reduced serious outcome (28.5% vs. 62.2%) and a decreased need for mechanical ventilation (OR = 0.09; 95%CI (0.01-0.8)) and maximum FiO2 (p = 0.01) was observed. CONCLUSIONS: A single dose of betamethasone up to 3 h antepartum may reduce the rate of serious outcomes and the severity of neonatal RDS, especially in non-tertiary hospitals.
ABSTRACT
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