Use of Macrogol to Accelerate Feeding Advancement in Extremely Preterm Infants

Introduction: Delayed enteral nutrition is associated with a higher risk for adverse outcomes in extremely preterm infants. Limited evidence exists on therapeutic options to support meconium evacuation and increase gastrointestinal motility. The aim of this study was to determine the effect of macrogol on feeding tolerance and microbiome establishment in preterm infants <27 weeks of gestation. Methods: We investigated the impact of early macrogol administration in two observational cohort studies: the multi-center German-Neonatal-Network (GNN) study comparing extremely preterm infants born in neonatal intensive care units (NICUs) using macrogol in the first week of life in >30% of their infants as compared to the remaining units, and the single-center Immunoregulation-of-the-Newborn (IRoN) study including gut microbiome assessment of infants born before and after implementation of macrogol use in this NICU. Results: In the GNN study cohort including 4,290 infants, advancement to full enteral feedings was significantly faster in macrogol-using NICUs compared to the remaining NICUs (median/IQR: 14/12 vs. 16/14 days, p = 0.001). Risk for short-term outcomes such as sepsis or abdominal complications was not elevated in units with regular use of macrogol. In the IRoN cohort (n = 68), macrogol treated infants had a shorter time to reach full enteral feeding (median/IQR: macrogol 12/6, control 16/6 days, p = 0.004). Higher Bifidobacterium longum abundance in the gut microbiome correlated with acceleration to full enteral nutrition. Conclusion: Our observational data suggests that early off-label use of macrogol may support feeding advancement in highly vulnerable babies. These data provide a basis for a randomized controlled trial.