Less invasive surfactant administration and complications of preterm birth

Abstract

In a large cohort study of the German Neonatal Network (GNN) we aimed to evaluate whether less invasive surfactant administration (LISA) strategy is associated with complications of preterm birth. Within the observational period n = 7533 very-low-birth-weight infants (VLBWI) with gestational age 22 0/7 to 28 6/7 weeks were enrolled in GNN; n = 1214 VLBWI never received surfactant, n = 2624 VLBWI were treated according to LISA procedure, n = 3695 VLBWI had surfactant via endotracheal tube (ETT). LISA was associated with a reduced risk for adverse outcome measures including mortality [odds ratio (OR) 0.66 (95% CI: 0.51-0.84), p < 0.001] bronchopulmonary dysplasia [BPD; OR 0.55 (95% CI: 0.49-0.62), p < 0.001], intracerebral hemorrhage (ICH) grade II-IV [OR 0.55 (95% CI: 0.48-0.64), p < 0.001] and retinopathy of prematurity [ROP; OR 0.62 (95% CI: 0.45-0.85), p < 0.001]. Notably, LISA was associated with an increased risk for focal intestinal perforation [FIP; OR 1.49 (95% CI: 1.14-1.95), p = 0.002]. The differences in FIP rates were primarily observed in VLBWI born <26 weeks (LISA: 10.0 vs. ETT: 7.4%, p = 0.029). Our observational data confirm that LISA is associated with improved outcome. In infants <26 weeks we noted an increased risk for FIP. Future randomized controlled trials including LISA need to integrate safety analyses for this particular subgroup.

Figure 1

Incidence of FIP stratified to primary surfactant management. The figure depicts the percentage of infants suffering from FIP per week of gestation according to exposure to surfactant treatment: Surfactant via ETT (white bars), Surfactant via LISA (grey bars). Numbers of infants are given below each column, i.e. surfactant treated infants via ETT/surfactant treated infants via LISA in each week of gestation.

Figure 2

FIP requiring surgery – logistic regression model. The figure depicts the data of a multivariable logistic regression model to adjust the effect of LISA strategy for known or probable confounding variables including inotropes in the first 24 hours (surrogate marker for severity of primary compromise at birth), amniotic infection syndrome as cause of preterm birth, postnatal steroid hormones (dexamethasone, hydrocortisone, (methyl)prednisolone), PDA drug treatment (indomethacin, ibuprofen), multiple birth, female gender, antenatal steroids, inborn, SGA, gestational age per week. The symbols and lines describe the odds ratios and 95% confidence interval.