Neonatal nucleated red blood cells and the prediction of cerebral white matter injury in preterm infants

OBJECTIVE: To estimate whether neonates with cerebral white matter injury have significant elevations in nucleated red blood cell counts and to estimate their predictive ability in identifying injury. METHODS: This case-control study identified 176 infants born at 23-34 weeks of gestation between November 1994 and October 2004 at a single university hospital and with cerebral white matter injury characterized by periventricular leukomalacia (PVL) or ventriculomegaly due to white matter atrophy. A control was matched to each case using the subsequent delivery within 7 days of that gestational age without brain injury. RESULTS: The gestational age at birth was 27 weeks for both groups, but the cases had a significantly lower birth weight (mean ± standard deviation: 958 ± 306 g compared with 1,038 ± 381 g, P = .001). There was no difference in cesarean delivery (48% cases compared with 44% controls, P = .59). The cases had a significant increase in nucleated red blood cells per 100 white blood cells (WBC) (median, 5th percentile and 95th percentile: 22, 3 and 374 cases compared with 14, 1 and 312 controls; P = .02). Markers of chronic hypoxia, such as intrauterine growth restriction and oligohydramnios, and markers of acute hypoxia, such as an umbilical arterial pH less than 7.0 or base excess less than -12 mM, were both associated with significantly elevated neonatal nucleated red blood cell counts. A neonatal nucleated red blood cell count of 18 per 100 WBCs had a sensitivity of 56.9%, specificity of 57.9%, positive predictive value of 57.9%, and negative predictive value of 56.9% in predicting the development of cerebral white matter injury in this matched case-control sample. CONCLUSION: Preterm neonates with cerebral white matter injury have significant increases in nucleated red blood cell counts. Both acute and chronic hypoxia-ischemia can increase these counts, which limits their usefulness in timing injury. The predictive value of nucleated red blood cell counts at birth in identifying injury is poor.