Less invasive surfactant administration is associated with a higher need for nonpharmacological pain-relieving interventions compared to the intubation-surfactant extubation technique in preterm infants.

LISA procedure compared to INSURE technique was associated with a higher need for pain-relieving interventions in the first three days of life. Prospective randomized controlled trials are needed to optimize this less invasive method for surfactant application with special focus on pain in neonates.