Enteral Granulocyte-Colony Stimulating Factor and Erythropoietin Early in Life Improves Feeding Tolerance in Preterm Infants: A Randomized Controlled Trial

Objective To evaluate the efficacy and safety of enteral recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human erythropoietin (rhEPO) in preventing feeding intolerance. Study design An interventional randomized control trial was conducted in 90 preterm infants born at <= 33 weeks gestational age. The neonates were assigned to 4 groups; 20 received rhG-CSF, 20 received rhEPO, 20 received both, and 30 received distilled water (placebo control). The test solution was given at the beginning of enteral feeding and was discontinued when enteral intake reached 100 mL/kg/day or after a maximum of 7 days, whichever came first. Feeding tolerance and adverse effects of treatment were assessed. Serum granulocyte colony-stimulating factor and erythropoietin levels were measured on days 0 and 7 of treatment. Results All neonates tolerated the treatment without side effects. Neonates who received rhG-CSF and/or rhEPO had better feeding tolerance, as reflected by earlier achievement of 75 mL/kg/day, 100 mL/kg/day, and full enteral feeding of 150 mL/kg/day with earlier weight gain and a shorter hospital stay (P <.05). The risk of necrotizing enterocolitis was reduced from 10% to 0% in all treatment groups (P <.05). There was a shorter duration of withholding of feeding secondary to feeding intolerance among neonates receiving both rhG-CSF and rhEPO compared with those receiving placebo (P <.05). Serum levels of granulocyte colony-stimulating factor and erythropoietin at 0 and 7 days did not differ across the treatment groups. Conclusions Enteral administration of rhG-CSF and/or rhEPO improves feeding outcome and decreases the risk of necrotizing enterocolitis in preterm neonates. The mechanism may involve the prevention of villous atrophy.