At what stage of lung development is exogenous surfactant therapy most effective in preterm infants?

From the Guidelines

Exogenous surfactant therapy is most effective when administered during the saccular stage of lung development in preterm infants, typically between 24-36 weeks gestation, as evidenced by a study published in Pediatrics in 2014 1. This stage is critical because the lungs are developing primitive alveoli but have not yet achieved full surfactant production capability. Preterm infants born during this stage often have respiratory distress syndrome (RDS) due to surfactant deficiency. Key points to consider include:

• Early administration, ideally within the first 2 hours of life for symptomatic infants or as prophylaxis for extremely premature infants (less than 28 weeks), provides the greatest benefit, as supported by a study published in Pediatrics in 2008 1.
• Common surfactant preparations include natural surfactants like beractant (Survanta), poractant alfa (Curosurf), and calfactant (Infasurf), typically administered via endotracheal tube at doses specific to each preparation.
• The effectiveness of surfactant therapy during this developmental stage stems from the fact that it supplements the infant's inadequate endogenous surfactant production, reducing surface tension in the alveoli, preventing atelectasis, improving lung compliance, and enhancing gas exchange until the infant's own type II pneumocytes mature enough to produce sufficient surfactant, as discussed in a study published in Pediatrics in 2008 1.
• Antenatal steroids and postnatal surfactant replacement independently and additively reduce mortality, the severity of respiratory distress syndrome, and air leaks in preterm infants, as noted in a study published in Pediatrics in 2008 1.
• The use of antenatal steroids may reduce the need for prophylactic and early rescue surfactant replacement in infants born after 27-28 weeks’ gestation, although this has not been proven in large randomized controlled trials, as mentioned in a study published in Pediatrics in 2008 1. Overall, the administration of exogenous surfactant therapy during the saccular stage of lung development, in conjunction with other treatments such as antenatal steroids, can significantly improve outcomes for preterm infants with respiratory distress syndrome.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Stages of Lung Development and Exogenous Surfactant Therapy

• The effectiveness of exogenous surfactant therapy in preterm infants is closely related to the stage of lung development 2.
• Preterm infants born at less than 30 weeks' gestation are at a higher risk of respiratory distress syndrome (RDS) and may benefit from prophylactic surfactant administration 2.
• The use of surfactant therapy in preterm infants has been shown to decrease the risk of pneumothorax, pulmonary interstitial emphysema, and neonatal mortality 2.

Surfactant Therapy Guided by Tests for Lung Maturity

• Rapid tests for lung maturity, such as the click test, lamellar body counts, and stable microbubble test, may guide the identification of preterm infants who require surfactant administration 3.
• Surfactant treatment guided by rapid tests for surfactant deficiency may result in little to no difference in bronchopulmonary dysplasia, surfactant utilization, and any pneumothorax compared to surfactant therapy provided to infants with RDS diagnosed on clinical and radiologic criteria 3.

Minimally Invasive Surfactant Therapy

• Minimally invasive surfactant therapy has been shown to improve outcomes in preterm infants at 29-32 weeks gestation, with reductions in CPAP failure, average days of intubation, and pneumothorax 4.
• Selective use of minimally invasive surfactant therapy permits a primary CPAP strategy to be pursued with a high rate of success and a low risk of pneumothorax 4.

Antenatal Dexamethasone Administration

• Antenatal dexamethasone administration may have an additive effect with exogenous surfactant therapy in reducing the incidence and severity of RDS in preterm infants 5.
• The combination of antenatal dexamethasone and exogenous surfactant therapy may be particularly beneficial in selected cases, such as singleton pregnancies and infants between 28 and 32 weeks' gestation 5.

Lung Ultrasound-Guided Surfactant Therapy

• Lung ultrasound score (LUS) may be used as a decision tool for surfactant replacement therapy (SRT) in preterm infants affected by RDS, allowing for the reduction of the incidence of BPD or death 6.
• The use of LUS as a guide for SRT may decrease the time to administer surfactant therapy and reduce the risk of BPD and mortality in preterm infants 6.