Fetal “nonreassuring status” is associated with elevation of nucleated red blood cell counts and interleukin-6

Objective Previous studies have established the association between fetal hypoxia and elevated nucleated red blood cells (NRBCs). Animal studies have demonstrated that a rise in plasma erythropoietin (EPO) is not detectable until 4 to 6 hours after the initiation of hypoxia. In contrast, interleukin-6 (IL-6) has the capacity to directly induce erythroid maturation. Therefore, we set forth to evaluate the role of EPO and IL-6 as potential mediators of elevated fetal NRBCs in response to acute hypoxia. Study design Low-risk pregnancies with a normal fetal heart rate at admission to labor and delivery were eligible for participation. Deliveries for “nonreassuring fetal status” comprised the study group. All other deliveries served as controls. Umbilical cord blood was prospectively collected for blood gas analysis, NRBC counts, EPO, and IL-6. Results One hundred women participated in the study. Nonparametric univariate analysis demonstrated a significant association between elevated NRBC counts and Apgar scores, arterial cord blood pH, base excess, EPO, and IL-6 levels (all P values <.01). Stepwise regression analysis identified only pH, IL-6, and EPO as independent variables associated with elevated NRBC counts at birth (all P values <.0001 with R2 of 0.27, 0.42, and 0.46, respectively). A significant increase in NRBC counts was noted in study patients. IL-6 was significantly increased in study patients, whereas there was no difference in EPO between groups. Conclusion The fact that NRBC counts were elevated in fetuses who were delivered for “nonreassuring fetal status” with EPO being normal and IL-6 being elevated implies that IL-6 may have a unique, short-term role in elevating fetal NRBC counts.