Respiratory distress syndrome (RDS) is primarily due to decreased production of pulmonary surfactant, and it is associated with significant neonatal morbidity and mortality. Exogenous pulmonary surfactant therapy is currently the treatment of choice for RDS, as it demonstrates the best clinical and economic outcomes. Studies confirm the benefits of surfactant therapy to include reductions in mortality, pneumothorax, and pulmonary interstitial emphysema, as well as improvements in oxygenation and an increased rate of survival without bronchopulmonary dysplasia. Phospholipids (PL) and surfactant-associated proteins (SP) play key roles in the physiological activity of surfactant. Different types of natural and synthetic surfactant preparations are currently available. To date, natural surfactants demonstrate superior outcomes compared to the synthetic surfactants, at least during the acute phase of RDS. This disparity is often attributed to biochemical differences including the presence of surfactant-associated proteins in natural products that are not found in the currently available synthetic surfactants. Comparative trials of the natural surfactants strive to establish the precise differences in clinical outcomes among the different preparations. As new surfactants become available, it is important to evaluate them relative to the known benefits of the previously existing surfactants. In order to elucidate the role of surfactant therapy in the management of RDS, it is important to review surfactant biochemistry, pharmacology, and outcomes from randomized clinical trials.

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