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J Soc Gynecol Investig. 2001 Jul-Aug;8(4):224-32.

Antibody-induced anemia in fetal sheep: model for hemolytic disease of the fetus and newborn.

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Department of Reproductive Medicine, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0802, USA.



Our purpose was to produce a condition analogous to alloimmune hemolytic disease of the fetus and newborn by infusing antierythrocyte antibodies in fetal sheep.


Antierythrocyte antibodies were infused intravascularly into late-gestation ovine fetuses over a 10-day period. Fetal blood was sampled daily for complete blood cell counts, blood gases, iron, erythropoietin (EPO), and electrolyte concentrations. Red cell mass (RCM) and blood volume were determined every other day using indicator dilution techniques. Results were compared with eight similarly aged control animals. Statistical analysis included Student t test, three-factor analysis of variance, and least squares regression.


The hematocrit in seven fetal sheep receiving antibody infusion declined significantly by 10.3 +/- 1.7%, whereas it increased in control animals 2.3 +/- 0.6% (P <.001). RCM was reduced by 18.9 +/- 3.2% over the 10-day protocol while increasing 34.1 +/- 4.2% in control animals, representing more than a 50% difference in RCM (P <.001). Fetal EPO was significantly increased with lower hematocrit and lower PO(2) (P <.001). As fetal hematocrit declined below 25%, lactate and reticulocytes also increased (P <.001). Plasma iron concentration was not significantly altered (P =.47).


The chronically catheterized fetal sheep is a viable model for studying immunologically induced fetal anemia as hematocrit can be titrated and the fall in RCM and hematocrit are associated with fetal hypoxia and elevated EPO as occurs in the anemic human fetus. Furthermore, there appears to be a threshold degree of anemia required to elicit responses as the fetal EPO, PO(2), and lactate appeared unresponsive until hematocrit fell below 25%.

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