Nucleated red blood cell counts in the first week of life: a critical appraisal of relationships with perinatal outcome in preterm growth-restricted neonates

Objective: Nucleated red blood cells (NRBC) are fetal hematologic markers for placental dysfunction, hypoxemia, and asphyxia. NRBC count elevation at birth or persistence is linked statistically to adverse outcome, but clinical predictive value is variable. We studied novel indices to better define overall magnitude of NRBC response. Study Design: Peripheral NRBC count was obtained from preterm (<34 weeks of gestation) growth-restricted neonates within 2 hours of life. Daily counts and duration of NRBC count >30/100 white blood cells were determined. Mean counts (NRBC-mean), area under the curve (NRBC-AUC), and declination (NRBC-slope) were analyzed over week 1. NRBC parameters were related to major morbidity (bronchopulmonary dysplasia, grade III/IV intraventricular hemorrhage, necrotizing enterocolitis included) and neonatal death (NND). Results: Twenty-two of 176 patients (12.5%) had acidosis. Complications included bronchopulmonary dysplasia (n = 36; 20.5%), intraventricular hemorrhage (n = 18; 10.2%), necrotizing enterocolitis (n = 18; 10.2%), NND (n = 18; 10.2%). NRBC-AUC and NRBC-mean correlated most strongly with pH, birthweight, and gestational age (Pearson coefficien,t -0.45 to -0.18; all P < .001). NRBC-AUC varied most between nonmorbid and morbid; NRBC-mean varied most between survivors and NND (all P < .001). NRBC persistence strongly predicted NND: clearance by day 4 was achieved by 80% of survivors and only 35% of NNDs. Logistic regression identified prematurity and persistent NRBC counts as primary morbidity determinants (r² = 0.56; P < .01). Although the importance of individual NRBC counts varied, day-4 NRBC counts of >70 predicted morbidity best (sensitivity, 82%; specificity, 96%). Presence of morbidity and birthweight were prime determinants of death (r² = 0.42; P < .01). Conclusion: Simple daily NRBC counts provide clinical information that is equivalent to more complicated methods. The importance of prematurity and growth are emphasized, but elevated NRBC counts beyond day 3 are relevant independent predictors of adverse outcome.