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Endogenous and Recombinant Erythropoietin Levels Decline in Human Amniotic Fluid and Fetal Plasma in vitro at 37°C

Journal of Perinatology volume 24, pages 218–222 (2004)Cite this article

Abstract

OBJECTIVE: To determine the in vitro stability of endogenous and recombinant erythropoietin (EPO) incubated at 37°C in amniotic fluid (AF) and fetal plasma.

STUDY DESIGN: Endogenous and recombinant EPO in AF, fetal plasma and phosphate buffer were incubated in vitro for 21 days at 37°C. Serial aliquots were analyzed for EPO and the rates of EPO decline were compared within and between groups.

RESULTS: Endogenous and recombinant EPO declined significantly in plasma and AF at 37°C. Endogenous EPO displayed a similar linear rate of decline in AF and plasma, with nearly 70% of the initial hormone concentration remaining at 21 days. Recombinant EPO incubated in buffer did not change.

CONCLUSIONS: Using the rate of decline in endogenous EPO we observed, EPO levels measured in AF or plasma within 21 days of fetal demise can be extrapolated back to the level likely present at fetal death.

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References

  1. Buescher U, Hertwig K, Wolf C, et al. Erythropoietin in amniotic fluid as a marker of chronic fetal hypoxia. Int J Gynaecol Obstet 1998;60:257–263.

    Article  CAS  Google Scholar 

  2. Widness JA, Teramo KA . Erythropoietin: significance as an indicator of fetal pathology. In: Kurjak A, editor. Textbook of Perinatal Medicine. New York: The Parthenon Publishing Group, Inc.; 1998. p. 549–558.

    Google Scholar 

  3. Teramo KA, Schwartz R, Clemons GK, et al. Amniotic fluid erythropoietin concentrations differentiate between acute and chronic causes of fetal death. Acta Obstet Gynecol Scand 2002;81:245–251.

    Article  Google Scholar 

  4. Malek A, Sager R, Eckardt K-U, et al. Lack of transport of erythropoietin across the human placenta as studied by an in vitro perfusion system. Pflügers Arch 1994;427:157–161.

    Article  CAS  Google Scholar 

  5. Teramo KA, Widness JA, Clemons GK, et al. Amniotic fluid erythropoietin correlates with umbilical plasma erythropoietin in normal and abnormal pregnancy. Obstet Gynecol 1987;69:710–716.

    CAS  PubMed  Google Scholar 

  6. Kakuya F, Shirai M, Takase M, et al. Effect of hypoxia on amniotic fluid erythropoietin levels in fetal rats. Biol Neonate 1997;72:118–124.

    Article  CAS  Google Scholar 

  7. Clapp III JF, Little KD, Appleby-Wineberg SK, et al. The effect of regular maternal exercise on erythropoietin in cord blood and amniotic fluid. Am J Obstet Gynecol 1995;172:1445–1451.

    Article  Google Scholar 

  8. Voutilainen P, Widness JA, Clemons GK, et al. Amniotic fluid erythropoietin predicts fetal distress in Rh-immunized pregnancies. Am J Obstet Gynecol 1989;160:429–434.

    Article  CAS  Google Scholar 

  9. Finne PH . Erythropoietin levels in the amniotic fluid, particularly in Rh-immunized pregnancies. Acta Paediatr 1964;53:269–281.

    Article  CAS  Google Scholar 

  10. Eckardt K-U, Kurtz A, Hirth P, et al. Evaluation of the stability of human erythropoietin in samples for radioimmunoassay. Eur J Clin Investig 1988;66:241–245.

    CAS  Google Scholar 

  11. Kendall RG, Chapman C, Hartley AE, et al. Storage and preparation of samples for erythropoietin radioimmunoassay. Clin Lab Haematol 1991;13:189–196.

    Article  CAS  Google Scholar 

  12. Veng-Pedersen P, Hong SS, Widness JA, et al. Correction for non-ideal tracer pharmacokinetic disposition by disposition decomposition analysis (DDA). Pharm Res 1998;15:1469–1473.

    Article  CAS  Google Scholar 

  13. Kakuya F, Shirai M, Takase M, et al. Relationship between erythropoietin levels both in cord serum and amniotic fluid at birth and abnormal fetal heart rate records. Pediatr Int 2002;44:414–419.

    Article  CAS  Google Scholar 

  14. Jazayeri A, Tsibris JC, Spellacy WN . Fetal erythropoietin levels in growth-restricted and appropriately grown neonates with and without abnormal fetal heart rate tracings: a comparison with cord blood gases and Apgar scores. J Perinatol 1999;19:255–259.

    Article  CAS  Google Scholar 

  15. Georgieff MK, Landon MB, Mills MM, et al. Abnormal iron distribution in infants of diabetic mothers: spectrum and maternal antecedents. J Pediatr 1990;117:455–461.

    Article  CAS  Google Scholar 

  16. Egrie JC, Cotes PM, Lane J, et al. Development of radioimmunoassays for human erythropoietin using recombinant erythropoietin as tracer and immunogen. J Immunol Methods 1987;99:235–241.

    Article  CAS  Google Scholar 

  17. Sawyer ST, Krantz SB, Goldwasser E . Binding and receptor-mediated endocytosis of erythropoietin in Friend virus-infected erythroid cells. J Biol Chem 1987;262:5554–5562.

    CAS  PubMed  Google Scholar 

  18. Calhoun DA, Richards BE, Gersting JA, et al. G-CSF and erythropoietin stability in amniotic fluid during simulated in vitro digestion conditions. J Pharm Technol 2002;18:310–315.

    Article  CAS  Google Scholar 

  19. Bonsnes R . Composition of amniotic fluid. Clin Obstet Gynecol 1966;9:440–448.

    Article  CAS  Google Scholar 

  20. Feleppa Jr. AE . Effectiveness of oral versus intraperitoneal administration of erythropoietin in stimulating erythropoiesis. Scand J Haemat 1973;10:186–188.

    CAS  PubMed  Google Scholar 

  21. Britton JR, Koldovsky O . Development of luminal protein digestion: implications for biologically active dietary polypeptides. J Pediatr Gastroent Nutr 1989;9:144–162.

    Article  CAS  Google Scholar 

  22. Richey SD, Ramin SM, Bawdon RE, et al. Markers of acute and chronic asphyxia in infants with meconium-stained amniotic fluid. Am J Obstet Gynecol 1995;172:1212–1215.

    Article  CAS  Google Scholar 

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Acknowledgements

The rabbit EPO antiserum used in the EPO radioimmunoassay was a generous gift from Gisela K. Clemons, Ph.D. The authors thank Frank Zlatnik, M.D., Janet Andrews, M.D., Ronald Strauss, M.D., and Paul Casella, M.F.A., for their critical review and suggestions on the manuscript.

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Authors and Affiliations

  1. Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA

    Nicole M Schmidt MD, Robert A Schmidt MD & John A Widness MD

  2. Department of Obstetrics and Gynecology, University Central Hospital, Helsinki, Finland

    Kari A Teramo MD

Authors
  1. Nicole M Schmidt MD
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  2. Robert A Schmidt MD
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  3. Kari A Teramo MD
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  4. John A Widness MD
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Additional information

This study was supported in part by NIH PO1 HL46925, University of Iowa General Clinical Research Center RR00059, Helsinki University Central Hospital Grant TYH-0240 and Children's Miracle Network.

Statistical review/consultation: Leon Burmeister, Ph.D., Professor, Department of Biostatistics, University of Iowa College of Public Health. M. Bridget Zimmerman, Ph.D., Department of Biostatistics, University of Iowa College of Public Health.

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Schmidt, N., Schmidt, R., Teramo, K. et al. Endogenous and Recombinant Erythropoietin Levels Decline in Human Amniotic Fluid and Fetal Plasma in vitro at 37°C. J Perinatol 24, 218–222 (2004). https://doi.org/10.1038/sj.jp.7211049

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