Fast Assessment of Surfactant Deficiency to Speed up Treatment: Assessment of Lung Maturity and Prediction of RDS by Determination of L/S-ratio in Fresh Gastric Aspirates by FTIR Spectroscopy

Respiratory distress syndrome (RDS) remains a major cause of mortality and morbidity in premature infants despite the increased use of antenatal steroids and early nasal continuous positive airway pressure (nCPAP) in addition to exogenous surfactant replacement therapy(1,2). In recent years, there have been several improvements in treatment, reducing the incidence and severity of RDS and bronchopulmonary dysplasia (BPD) including early treatment with nCPAP, early targeted surfactant replacement therapy, increased used of lung protective ventilation together with an overall reduced use of mechanical ventilation(1,3,4).

However, the majority of premature infants with a gestational age of less than 30 weeks have immature lungs and approximately half still require treatment with exogenous surfactant(2). Timing of surfactant treatment seems crucial. Prophylactic surfactant treatment followed by mechanical ventilation has been widely used, but has now been shown to increase the combined mortality and incidence of BPD, as opposed to early targeted rescue treatment, especially when combined with nCPAP and avoidance of mechanical ventilation using the "Intubation, surfactant, extubation (INSURE) or "Less Invasive Surfactant Administration " (LISA) approach(5-8). In addition, evidence shows that very early targeted surfactant treatment is associated with a better outcome compared to later treatment(9).

Consequently, it is necessary to treat with surfactant selectively and very soon after birth, preferably even before classical symptoms of RDS are present, in order to further improve outcome from RDS. To be able to do so, we need a bedside test that can quickly identify which infants have surfactant deficiency to target treatment effectively(1).

Biomarkers expressing lung maturity have been identified in amniotic fluid, gastric aspirate, and oropharyngeal secretions(10-12). These fluids are partially produced in the foetal lungs as well as in the kidneys and the amniotic sac and therefore contain lung surfactant(13). The classic method to determine surfactant in amniotic fluid has been measuring lecithin/sphingomyelin ratio (L/S) with thin-layer chromatography(10,14). Sphingomyelin secretion remains fairly constant during pregnancy, whereas lecithin secretion increases in parallel with lung maturation. Consequently, L/S-ratio reflects lung maturity independently of dilution sampling effects(10)

Gastric aspirate (GAS) and oropharyngeal (OPS) secretion are easier to obtain and measure than amniotic fluid, and can be obtained within minutes from birth using routine neonatal care measures(15,16). Previously, we have measured the surfactant content in gastric aspirate with microbubble stability tests and with lamellar body counts(17,18). In a recent randomized clinical trial in very preterm infants we compared early surfactant treatment guided by lamellar body counts in gastric aspirate with traditional surfactant treatment, and found a significant reduction in the need of oxygen at six hours of age and by day 28, in addition to reduced duration of oxygen-dependency and a trend towards a lower incidence of bronchopulmonary dysplasia(19).