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Antibody-Induced Anemia in Fetal Sheep: Model for Hemolytic Disease of the Fetus and Newborn

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Abstract

Objective

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

Methods

Antierythrocyte antibodies were infused intravascularly into late-gestation ovine fetuses over a 10-day period. Fetal blood was sampled dialy for complete blood cell counts, blood gases, iron, erythropietin (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.

Results

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 Po2 (P < .001). As fetal hematocrit declined below 25%, lactate and reticulocytes also increased (P < .001). Plasma iron concentration was not significantly altered (P = .47).

Conclusions

The chronically catheterized fetal sheep is a viable model for studying immunologically induced fetal anemia as hematocrit can be tirated 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, PO2, and lactate appeared unresponsive until hematocrit fell below 25%.

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Authors and Affiliations

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

    Richard B. Wolf DO, Kenneth J. Moise Jr. MD & Robert A. Brace PhD

  2. Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA

    Richard B. Wolf DO, Kenneth J. Moise Jr. MD & Robert A. Brace PhD

Authors
  1. Richard B. Wolf DO
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  2. Kenneth J. Moise Jr. MD
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  3. Robert A. Brace PhD
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Corresponding author

Correspondence to Robert A. Brace PhD.

Additional information

The authors are grateful to Rachel Howe and Jesse Trujillo for technical assistance in this study, to Annelle Graham and Karen Dorman for assistance with antibody production, and to John Widness and Robert Schmidt for performing the EPO and iron concentration measurements.

Supported in part by National Institute of Health Grants HD20295 and HD33499 from the National Institute of Child Health and Human Development.

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Wolf, R.B., Moise, K.J. & Brace, R.A. Antibody-Induced Anemia in Fetal Sheep: Model for Hemolytic Disease of the Fetus and Newborn. Reprod. Sci. 8, 224–232 (2001). https://doi.org/10.1177/107155760100800407

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