Abstract 1606 Poster Session II, Sunday, 5/2 (poster 113)

Nucleated red blood cells (NRBCs), precursors to circulating mature erythrocytes, are not normally present in peripheral blood smears of children. However, NRBCs may be found in newborn infants under certain recognized conditions (e.g. chronic fetal asphyxia, placental insufficiency, maternal diabetes, fetal hemolytic disease, and early gestation). We investigated the possibility that early-onset neonatal sepsis was another, previously unrecognized, correlate of elevated NRBCs on the first day of life (DOL).

Methods: We determined the NRBC values and blood culture status on DOL 1 for 909 infants with gestational ages 23 - 42 weeks admitted to our NICU. Using logistic regression analysis, and accounting for birthweight (BW) and gestational age (GA), we determined the odds ration (OR) of the presence of early-onset sepsis as a function of progressively increased values of NRBC (expressed as % of circulating neutrophils). Recognizing the skewed distribution of NRBCs in early neonatal period, we also determined the risk of sepsis, controlling for BW and GA, as a function of the natural log transform of NRBC.

Results: 837 infants in our study population were not septic at birth, while 72 infants had positive blood cultures for recognized pathogens. For NRBC values above 5%, the odds ratio for the presence of early-onset sepsis was always greater than 1. At 5% NRBC, OR = 1.80 (95% CI 0.99 - 3.3; p=0.05); at 10% NRBC, OR = 1.54 (95% CI 0.92 - 2.6; p=0.10); at 15% NRBC, OR = 1.73 (95% CI 1.03 - 2.9; p=0.04); at 20% NRBC, OR = 1.76 (95% CI 1.04 - 3.0; p=0.04). Analyzing the natural log transform of NRBC for the overall population, the odds ratio for sepsis was 1.21 (95% CI 1.02 - 1.42; p=0.03). After adjusting for BW and GA, this OR increased to 1.31 (95% CI 1.1 - 1.57; p < 0.005). Consequently, this phenomenon resembled more closely a 'dose effect' model than a 'threshold' model -- that is, the likelihood of early-onset sepsis increased as the percentage of NRBC values increased, roughly doubling for every 10-fold increase in NRBC. As expected, below 34 weeks gestation, there was a significant inverse correlation of NRBC with birthweight and gestational age -- above 34 weeks / 1500 grams, this correlation disappeared.

Conclusions: 1) Adjusting for BW and GA, elevated NRBC values in peripheral blood are significantly associated with an increased risk of early-onset newborn sepsis. 2) The mechanism for NRBC elevation in septic infants remains incompletely elucidated.