Nucleated Red Blood Cells as a Marker of Acute and Chronic Fetal Hypoxia in a Rat Model.

Victoria K Minior,Asaf Ferber,Michael Y Divon,Seth Guller,Brian Levine

doi:10.5041/rmmj.10302

Abstract

ObjectiveTo examine the relationship between duration of fetal hypoxia, nucleated red blood cell (NRBC) count, and fetal growth.MethodsPregnant rats were exposed to a severe hypoxia (9.5%–10% O2) for varying time intervals (2, 6, 12, 24, 48, and 120 hours; n=4 for each time interval) immediately prior to delivery at term. Normoxic controls were exposed to room air (21% O2) and matched for all other study variables (n=4 rats for each time interval). Pups were delivered via hysterotomy while maintaining exposure gas concentrations. Blood gas analysis and NRBC counts were performed, and fetal body and liver weights were recorded. Student’s t test and simple regression were used for statistical analysis.ResultsAs the duration of hypoxia increased, fetal weight, liver weight, blood bicarbonate, and base excess levels decreased significantly; concomitantly, NRBC counts increased. This increase in NRBCs became statistically significant after 24 hours of exposure. After 48 hours of hypoxia there was a 2.5-fold rise in NRBC count, and after 120 hours of hypoxia there was a 4.5-fold rise in NRBC count over control levels. After 12 or more hours of hypoxia, fetal body weights were significantly reduced; 120 hours of hypoxia resulted in a 35% reduction in fetal body weight, a 34% reduction in fetal liver weight, and 356% increase in NRBC count.ConclusionIn a pregnant rat model, chronic maternal hypoxia (≥24 hours) results in a significant increase in fetal NRBC counts as well as reduced fetal body weight and organ growth.

Highlights

After 48 hours of hypoxia there was a 2.5-fold rise in nucleated red blood cell (NRBC) count, and after 120 hours of hypoxia there was a 4.5-fold rise in NRBC count over control levels
After 12 or more hours of hypoxia, fetal body weights were significantly reduced; 120 hours of hypoxia resulted in a 35% reduction in fetal body weight, a 34% reduction in fetal liver weight, and 356% increase in NRBC count
The presence of elevated levels of nucleated red blood cells (NRBCs) in the peripheral blood of newborns has been traditionally attributed to “asphyxial conditions.”[1,2,3] Increased numbers of these cells have been demonstrated in association with acidemia at birth[4,5] and conditions associated with “placental insufficiency” such as fetal growth restriction[6,7,8,9] as well as “intrapartum fetal distress.”[10,11] elevated NRBCs have been noted in the newborns of mothers who smoke cigarettes and mothers exposed to excessive air pollution.[12,13]

Summary

Introduction

Human newborns with elevated levels of NRBCs at birth have been shown to suffer a significant increase in both short-term morbidity and mortality and long-term disability. Neonatal complications such as severe respiratory distress, circulatory instability,[7,8] necrotizing enterocolitis,[15] retinopathy of prematurity,[16] hypoxic-ischemic encephalopathy,[17] early-onset neonatal seizures,[18] prolonged neonatal intensive care unit stay, and neonatal demise[10] have been reported in association with elevated NRBCs at birth. Significant associations between elevated NRBCs at birth and lifelong complications such as developmental delay[17] and cerebral palsy[1,19,20] have been described

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