Neonatal respiratory distress syndrome (RDS) is a condition of respiratory insufficiency occurring in neonates, secondary to deficient or dysfunctional surfactant.1,2 Pulmonary surfactant lowers alveolar surface tension and aids in maintaining the functional residual capacity of the lung.2
Bronchopulmonary dysplasia (BPD) is a chronic respiratory condition primarily affecting infants born at the extremes of prematurity. BPD is defined clinically and multiple diagnostic criteria currently exist,3-5 creating significant variability in the reported incidence of BPD and presenting difficulties when comparing the effectiveness of potential therapies.6 The reported incidence of BPD is between 35% and 50% in infants born at less than 28 weeks.7-10 The management of these two neonatal conditions is closely entwined as they share common risk factors, and interventions prompted by RDS may alter the risk of BPD.
Exogenous surfactant administration is an essential treatment in the effective management of RDS in preterm neonates. More than 30 randomized trials have been conducted and demonstrate that exogenous surfactant is effective at reducing the incidence of pneumothorax, as well as reducing neonatal mortality. Controversy still exists regarding the best surfactant preparation, optimal timing, and mode of administration.1 Early evidence suggested that prophylactic administration of surfactant was the preferable approach, compared to treating only infants with established RDS. Prophylactic surfactant reduced air leaks, mortality, and the combined outcome of BPD or death. However, these early studies did not include current practices involving stabilization of preterm neonates using continuous positive airway pressure (CPAP) and widespread use of antenatal steroids. Additionally, prophylactic surfactant and the required preceding intubation are not without risk and are not necessary in all very preterm infants.1,2 The (reviewed herein) meta-analysis by Rojas-Reyes and colleagues, which includes recent studies with high antenatal corticosteroid use and early CPAP, indicates that selective surfactant therapy is associated with reduced BPD and death in neonates, compared with prophylactic surfactant. Those caring for preterm neonates must now strive to find the balance between avoiding mechanical ventilation when feasible and providing exogenous surfactant as early as possible to preterm infants with RDS.1
BPD is a multifactorial disease process that is associated with long-term health consequences, including poor neurodevelopmental outcome and chronic respiratory conditions such as asthma and pulmonary hypertension. The paucity of effective therapies, with acceptable side effect profiles, has resulted in the incidence of BPD remaining unchanged or possibly increased in recent years. Current treatment strategies primarily attempt to reduce the post-natal injury inflicted on the premature lung.11
Caffeine is recognized as a standard of care in the treatment of apnea of prematurity and has been shown to reduce the incidence of BPD, likely by reducing exposure to positive pressure ventilation.12 Dexamethasone is an effective therapy for BPD, but it has been associated with adverse neurodevelopmental outcomes. The analysis by Doyle et al assists in identifying infants most likely to obtain a net benefit from postnatal corticosteroid therapy.
Another approach to reducing lung injury in preterm neonates is the increased use of noninvasive ventilation as a primary mode of respiratory support. The reviewed article by Schmölzer et al supports the use of CPAP in the delivery room as a means to reduce the occurrence of BPD in preterm infants less than 32 weeks' gestation at birth. Lung injury secondary to oxidative stress is implicated in the pathogenesis of BPD, and researchers are attempting to identify the optimal postnatal oxygen saturation range for preterm neonates. Early studies indicated that a restricted approach to oxygen exposure was safe and beneficial in reducing the incidence of retinopathy of prematurity (ROP) and BPD. The meta-analysis by Saugstad and Aune provides further information by summarizing studies of low (85%-89%) vs high (91%-95%) oxygen saturation targeting in preterm neonates less than 28 weeks. While the authors did not discover a significant difference in the primary outcome of death or major disability at 18-24 months or in the secondary outcome of BPD, they identified a reduction in severe ROP and a concerning increased risk of mortality and necrotizing enterocolitis (NEC) in the low-targeted oxygen saturation group. This meta-analysis highlights important potential complications of targeting oxygen saturations less than 90% in infants born at less than 28 weeks' gestational age.
BPD is one of the most common and serious complications of extreme premature birth. Survivors of preterm birth with BPD are at increased risk for long-term neurodevelopmental and pulmonary morbidity. Innovative strategies are needed, and stem cell-based therapies represent a promising and novel approach. Stem cell research and literature have expanded at rapidly over the past decade, with a variety of cell types undergoing exploration for therapeutic benefit.13 Mesenchymal stromal cells (MSC) have received particular attention as a potential new therapeutic intervention for BPD. Chang et al have published the first clinical trial demonstrating the feasibility of MSC therapy for BPD and providing evidence for the short-term safety of this therapy in preterm neonates. The authors intend to complete further clinical trials investigating the efficacy and safety of MSC transplantation for prevention of BPD. While results of these trials are anxiously awaited, ongoing research is required to elucidate the mechanisms by which MSCs function, and continued rigorous preclinical research is required to verify long-term safety.
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