Revised reference ranges for circulating neutrophils in very-low-birth- weight neonates

Objective. Healthy very-low-birth-weight neonates (VLBW, ≤1500 g) exhibit a high incidence of neutropenia according to Manroe's reference ranges for neutrophil indices. Since these reference ranges may be inappropriate for VLBW neonates, we determined the reference ranges for circulating peripheral neutrophils in VLBW neonates between birth and 28 days of age. Methods. Serial, timed peripheral white blood cell counts (n = 1788) were prospectively obtained between birth and 28 days from 193 inborn, VLBW neonates delivered between January 1 and December 31, 1990. Data were divided into neutrophil counts obtained prior to (n = 630) and after (n = 1158) 60 hours of age. After excluding counts from neonates with perinatal and/or neonatal complications, values from 'normal' neonates were compared to Manroe's reference ranges. Where indicated new ranges were developed. Results. Although immature neutrophil (ATI) and immature:total neutrophil (I:T) values were within Manroe's reference ranges (P > .1) throughout the neonatal period, 67% of total neutrophil values (ATN) obtained prior to 60 hours of age were outside (P < .001) and 95% were considered neutropenic. Newly developed ATN reference ranges for VLBW neonates have a wider range of distribution compared to Manroe's results, primarily reflecting a decrease in the lower boundary. ATN values between 61 hours and 28 days also differed (P < .001), and new ranges had upper and lower boundaries of 6000 and 1100/mm³, respectively. Maternal hypertension was associated with neonatal neutropenia (P < .001) without abnormalities of ATI or I:T prior to day 3 of life; however, neutrophilia predominated after day 7. Between birth and 28 days >70% of ATN values were abnormal in neonates with apnea, neutrophilia occurring in >90% of counts; I:T values, however, were normal between 61 hours and 28 days. Conclusions. Normal preterm VLBW neonates have ATN reference ranges that differ significantly from that for larger, older neonates, demonstrating the effects of development on neutrophil dynamics. The predictability of neonatal infection using these new reference ranges requires additional study.