Effect of same dose varying concentration poractant alfa on outcomes in preterm infants under 32 weeks of age

Introduction . We proposed a hypothesis that prognosis in preterm infants may be affected by concentration of the administered surfactant preparation able to determine its viscosity and, therefore, even distribution throughout the lungs. Aim : to assess an effect of poractant alfa (PA) administered at low (40 mg/mL) vs. standard (80 mg/mL) concentration without changing recommended dosage (200 mg/kg) on outcomes of preterm infants at gestational age (GA) under 32 weeks receiving various respiratory support. Materials and Methods . A prospective randomized controlled multicenter study was conducted. A total of 325 infants under 32 weeks of GA in five perinatal centers were randomized. The inclusion criteria were met by 264 patients: required respiratory therapy, had indications for surfactant administration at birth/within the first 30 minutes of life, and informed parental consent. Patients were excluded if they had no indications for surfactant preparations at the age of the first 30 minutes of life, had chromosomal and genetic abnormalities, congenital malformations, early neonatal sepsis, or gross deviations from the study protocol. Two groups were formed and compared: Low concentration (LC) group – PA concentration was 40 mg/mL (n = 111) and Standard concentration (SC) group (control) – PA concentration was 80 mg/mL (n = 153). Additionally, we compared two subgroups with surfactant preparation administered by minimally invasive methods in spontaneously breathing infants (using LISA – a less invasive method of introducing surfactant through a thin catheter or endotracheal tube): subgroup LC – PA concentration was 40 mg/mL (n = 27) and subgroup SC (control) – PA concentration was 80 mg/mL (n = 34). Results . It was found that development of pulmonary hemorrhages in LC and SC groups was significantly less common in infants who received PA at concentration of 40 mg/mL vs. 80 mg/mL: 3.6 (4/111) % vs. 13.1 (20/153) % (p = 0.008). While comparing subgroups with minimally invasive PA administration (LISA or endotracheal tube), we found that treatment with 40 mg/mL significantly decreased total respiratory therapy duration– 142 [70.0; 219.0] hours vs. 250 [141.0; 690.0] hours (p = 0.008), incidents of bronchopulmonary dysplasia – 4.0 (1/27) % vs. 29.0 (10/34) % (p = 0.009), length of stay in neonatal intensive care unit and hospital – 8.0 [7.5; 13.0] days vs. 14.0 [8.0; 33.75] days (p = 0.014) and 38.0 [26.5; 48.5] days vs. 50.5 [36.25; 62.5] days (p = 0.014), respectively. Conclusion . PA administered at concentration of 40 mg/mL without changing the recommended dose did not aggravate nursing of preterm infants at GA under 32 weeks. Minimally invasive PA administration at concentration of 40 mg/mL, lowered risk of bronchopulmonary dysplasia, and when used in infants on mechanical lung ventilation, it lowered a risk of pulmonary hemorrhage. All the discussed findings require to be further assessed in large prospective, multicenter, randomized studies in large patient cohort.