pectant management). This is especially true in the faceof multiple observational studies such as ours thatdemonstrate that nulliparous subjects have higher ratesof cesarean deliveries with labor induction. This includesstudies that were able to assess the state of the cervix andin which preinduction ripening was used—these datashould be used in assessing the risks and benefits of in-duction, especially when done on an elective basis.

Dean V. Coonrod, MD, MPH, R. Curtis Bay, PhD, and Glen Y. Kishi, MD

Department of Obstetrics and Gynecology, Maricopa County MedicalCenter, 2601 E Roosevelt, Phoenix, AZ 85008

REFERENCE

1. Hannah ME, Hannah WJ, Hellmann J, Hewson S, Milner R,Willan A. Induction of labor as compared with serial antenatalmonitoring in post-term pregnancy: a randomized controlledtrial. N Engl J Med 1992;326:1587-92.

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Potential for brief but severe intrapartum injuryamong neonates with early-onset seizures and ele-vated nucleated red blood cell countsTo the Editors: Blackwell et al in a recent article (BlackwellSC, Refuerzo JS, Wolfe HM, Hassan SS, Berry SM, SokolRJ, et al. The relationship between nucleated red bloodcell counts and early-onset neonatal seizures. Am J ObstetGynecol 2000;182:1452-7) reported increased nucleatedred blood cell counts in neonates with early-onsetseizures relative to healthy control neonates. Blackwell etal assumed that 48 to 72 hours was required for hypoxiato cause an increase in circulating nucleated red bloodcell counts and therefore concluded that many infantswith early-onset seizures had a hypoxic episode of at leastthat duration before the intrapartum period.

Blackwell et al did not present a more likely alternativehypothesis. Elevations in nucleated red blood cell countare a function of both the severity and the duration of hy-poxia, and nucleated red blood cell counts may riserapidly after brief but severe hypoxia. It may require 48hours of hypoxia to result in de novo erythropoietic ac-tivity. However, increased circulation of nucleated redblood cells occurs rapidly after hypoxia, not from newerythropoiesis but from a release of previously stored nu-cleated red blood cells. Basic evidence indicates that thisrapid release is caused by erythropoietin-induced in-creases in marrow blood flow and an increase in theporous infrastructure of the marrow that allows easy es-cape of nucleated red blood cells.

The precise time required for acute hypoxia to causeincreased circulating nucleated red blood cell counts isnot known, but it is clearly less than 48 to 72 hours. At-shuler and Hyder1 found that nucleated red blood cellcounts increased within 2 hours of acute blood loss inhealthy term fetuses, and Benirschke2 reported the caseof a neonate with an increased nucleated red blood cellcount within 1 hour of an acute hypoxic event. Korst etal3 found elevated nucleated red blood cell counts after

such acute catastrophic intrapartum events as uterinerupture and umbilical cord prolapse. The duration of thecatastrophic event was undoubtedly less than 1 hour inmost cases.

Hanlon-Lundberg and Kirby4 documented the rela-tionship between severity of hypoxia and increased nu-cleated red blood cell count. Nucleated red blood cellcounts increased with progressive decreases in cord pHand with lower Apgar scores. Blackwell et al also found atrend toward increased nucleated red blood cell countswith decreasing cord pH values. These data support thebelief that the severity of the hypoxia influences the in-crease in circulating nucleated red blood cells.

Blackwell et al acknowledged that the assumption that48 to 72 hours of hypoxia is required to result in in-creased circulating nucleated red blood cells “remainsspeculative.” On the basis of the available evidence, it ismore than speculative; it is a dubious assumption. Pub-lished basic research and clinical data indicate that nu-cleated red blood cell counts can rise within 1 hour of se-vere hypoxia. If in fact nucleated red blood cell countscan rise so fast, the results of Blackwell et al remain valid.Infants with early-onset seizures commonly have elevatednucleated red blood cell counts. However, Blackwell et alcannot use such results to claim that these infants had in-jury before the intrapartum period. Actually, the entireinjury could have occurred in the final minutes or hoursbefore birth.

Marcus C. Hermansen, MDDartmouth Medical School, Southern New Hampshire Medical Center, 8 Prospect St, Nashua, NH 03062

REFERENCES

1. Atshuler G, Hyder SR. Nucleated erythrocytes. In: Pitkin RM,Scott JR, editors. Clinical obstetrics and gynecology. Philadel-phia: Lippincott-Raven; 1996. p. 553-6.

2. Benirschke K. Placenta pathology questions to the perinatolo-gist. J Perinatol 1994;14:371-5.

3. Korst LM, Phelan JP, Ahn MO, Martin GI. Nucleated red bloodcells: an update on the marker for fetal asphyxia. Am J ObstetGynecol 1996;175:843-6.

4. Hanlon-Lundberg KM, Kirby RS. Nucleated red blood cells as amarker for acidemia in term neonates. Am J Obstet Gynecol1999;181:196-201.

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ReplyTo the Editors: We appreciate the interest of Hermansen inour study. Our comments regarding the timing of hy-poxia and increased nucleated red blood cell countsseem to have been misinterpreted. We hypothesized thatelevated nucleated red blood cell counts (in the absenceof confounding factors) in these neonates with early-onset seizures might indicate that a hypoxic insult has oc-curred or begun ≥48 hours before delivery; but we didnot mean that this exposure necessarily persisted or ex-tended for that entire period until delivery.

Hermansen suggested that both the severity and theduration of hypoxia may affect nucleated red blood cellcounts. We are aware of the inverse relationship between

782 Letters March 2001Am J Obstet Gynecol