A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF RECOMBINANT HUMAN GRANULOCYTE COLONY-STIMULATING FACTOR (G-CSF) ADMINISTRATION TO WOMEN WITH AN IMMINENT PRETERM DELIVERY. • 1747

Abstract

Bacterial infection occurs in as many as 50 percent of extremely preterm infants and is a major cause of morbidity and mortality. A single dose(50μg/kg) of rG-CSF given to pregnant rats one day prior to delivery resulted in transplacental passage of G-CSF sufficient to stimulate neutrophil production, elevate blood neutrophil concentrations, and improve the outcome of pups who were inoculated with group B β-hemolytic streptococci(Medlock, Blood 1993). In our previous pilot study, transplacental passage of G-CSF appeared to occur when given 12 hours prior to delivery, but an increase in absolute neutrophil count (ANC) was only seen in infants whose mothers received rG-CSF 30 hours before delivery (Calhoun, Am J Ob Gyn, 1996). To determine whether administration of rG-CSF more than 30 hours prior to delivery would improve fetal neutrophil production and favorably effect neonatal outcome, a randomized placebo controlled trial was conducted in 20 women about to deliver at <30 weeks gestation. Serum concentrations of G-CSF and neutrophils were measured in the blood of mothers, and in the umbilical venous cord blood following a single intravenous dose (25μg/kg) of rG-CSF to women in whom delivery was not likely to occur for 30 hours. ANC's were followed for one week in the infants, bone marrow aspirations were performed at 24±8 hours of age to assess neutrophil storage pools and hematopoietic progenitor cultures, and SNAP scores were completed on days of life one and seven. Ten mothers delivered 11 infants. The G-CSF had no apparent adverse effect on pregnancy duration, maternal comfort, or maternal temperature. The bone marrow neutrophil proliferative pool was significantly increased in the G-CSF-treated neonates (23±8% vs 14±3%)(mean±SD,p<.05), but no difference was observed in ANC. Infants in the G-CSF-treated group had improvement (lowering) in SNAP scores between the first (16.3±3.1) and seventh days (7.3±6.1) (p<.05), while no significant change was noted in the control group(14.5±6.5, day 1 and 6.3±5.6, day 7). This pilot study suggests that administration of rG-CSF to certain women prior to preterm delivery might increase fetal neutrophil production and improve outcome of the infants.