Skip to main content

Advertisement

SpringerLink
Log in

Fetal Cardiorespiratory and Neurobehavioral Response to Zidovudine (AZT) in the Baboon

  • Original Articles
  • Published:
The Journal of the Society for Gynecologic Investigation: JSGI Aims and scope Submit manuscript

Abstract

Objective

To evaluate the effects of intravenous of zidovudine (AZT) at a dose and duration of infusion comparable to that used clinically on parameters reflective of fetal well-being.

Methods

Tliirteen chronically instrumented noninfected baboons were monitored during intravenous infusions of AZT. Fetal cardiorespiratory activity and neurobehavioral function were assessed with 4—48-hour infusion of AZT to ten mothers (0.5-2.1 mg/kg per hour) and three fetuses (2-6 mg/h), which resulted in fetal plasma concentrations of AZT of 194—3100 ng/ml.

Results

No significant differences were found in the mean values in control periods, before and after infusion with values during infusion for parameters of fetal heart rate and rate variability (n = 7), breathing activity (n = 8), electroencephalographic activity (n = 8), and behavioral state (n = 7). No correlations were found with drug level.

Conclusions

The absence of associations between exposure of the fetal baboon to AZT and changes in parameters reflective of fetal condition suggests that comparable exposure of the human fetus during intravenous infusion of drug would not confound clinical monitoring used to assess fetal well-being. These findings supplement conclusions from clinical research in support of U.S. Public Health Service recommen-dations that intrapartum fetal monitoring be performed as clinically indicated, not specifically because pregnant patients are treated with intravenous AZT. (J Soc Gynecol Invest 1997;4:183-190) Copyright © 1997 by the Society for Gynecologic Investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Connor EM, Sperling RS, Gelber R, et al. Reduction of ma-ternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med 1994;331:1173–80.

    Article  CAS  Google Scholar 

  2. Public Health Service Task Force on the use of zidovudine to reduce perinatal transmission of human immunodeficiency virus. MMWR Morb Mortal Wkly Rep 1994;43:1–20.

    Google Scholar 

  3. Connor EM, Mofenson LM. Zidovudine for the reduction of perinatal human immunodeficiency virus transmission: Pediatric AIDS clinical trials group protocol 076 results and treatment recommendations. Pediatr Infect Dis J 1995;14:536–41.

    Article  CAS  Google Scholar 

  4. Connor E, Sperling R, Shapiro D, et al. Long term effects of zidovudine (ZDV) exposure among uninfected infants born to HIV-infected mothers in ACTG protocol 076. Prog Abst ICAAC 1995:11,205.

    Google Scholar 

  5. Garland M, Szeto HH, Daniel SS, Tropper P, Myers MM, Stark RI. Zidovudine kinetics in the pregnant baboon. J Acquir Im-mune Defic Syndr 1996;11:117–27.

    Article  CAS  Google Scholar 

  6. Manning FA. Fetal medicine principles and practice. Norwalk, CT: Appleton and Lange, 1995.

    Google Scholar 

  7. Domanski MJ, Sloas MM, Follmann DA, Scalise PP 3rd, Tucker EE, Egan D, Pizzo PA. Effect of zidovudine and didanosine treatment on heart function in children infected with human immunodeficiency virus. J Pediatr 1995;127:137–46.

    Article  CAS  Google Scholar 

  8. Mofenson LM. A critical review of studies evaluating the rela-tionship of mode of delivery to perinatal transmission of human immunodeficiency virus. Pediatr Infect Dis J 1995;14:169–77.

    Article  CAS  Google Scholar 

  9. Peckham C, Gibb D. Mother-to-child transmission of the human immunodeficiency virus. N Engl J Med 1995;333:298–302.

    Article  CAS  Google Scholar 

  10. Stark RI, Daniel SS, James LS, et al. Chronic instrumentation and longterm investigation in the fetal and maternal baboon: Tether system, conditioning procedures and surgical techniques. Lab Animal Sci 1989;39:25–32.

    CAS  Google Scholar 

  11. Myers MM, Fifer W, Haiken J, Stark RI. Relationships between breathing activity and heart rate in fetal baboons. Am J Physiol 1990;258:R1479–85.

    CAS  PubMed  Google Scholar 

  12. Myers MM, Stark RI, Fifer WP, et al. A quantitative method for classification of EEG in the fetal baboon. Am J Physiol 1993;265: R706–14.

    CAS  PubMed  Google Scholar 

  13. Stark RI, Daniel SS, Kim YI, Leung K, Rey HR, Tropper PJ. Patterns of development in fetal breathing activity in the latter third of gestation of the baboon. Early Hum Develop 1993;32:31–47.

    Article  CAS  Google Scholar 

  14. Stark RI, Daniel SS, Garland M, et al. Fetal hiccups in the baboon. Am J of Physiol 1994;267:R1479–87.

    CAS  Google Scholar 

  15. Grieve PG, Myers MM, Stark RI. Behavioral states in the fetal baboon. Early Hum Develop 1994;39:159–75.

    Article  CAS  Google Scholar 

  16. Fletcher KL, Leung K, Myers MM, Stark RI. Diurnal rhythms in cardiorespiratory function of the fetal baboon. Early Hum Develop 1996;46:27–42.

    Article  CAS  Google Scholar 

  17. Editorial. Zidovudine for mother, fetus, and child: Hope or poison? Lancet 1994;344:207–9.

    Article  Google Scholar 

  18. O’Sullivan MJ, Boyer PJJ, Scott GB, et al. The pharmacokinetics and safety of zidovudine in the third trimester of pregnancy for women infected with human immunodeficiency virus and their infants: Phase I acquired immunodeficiency syndrome clinical trials group study (protocol 082). Am J Obstet Gynecol 1993;168:1510–6.

    Article  Google Scholar 

  19. Lipshultz SE, Orav EJ, Sanders SP, Hale AR, Mcintosh K, Colan SD. Cardiac structure and function in children with human immunodeficiency virus infection treated with zidovudine. N Engl J Med 1992;327:1260–5.

    Article  CAS  Google Scholar 

  20. Pindado MTC, Bravo AL, Martinez-Rodriguez R, et al. Histo-chemical and ultrastructural changes induced by zidovudine in mitochondria of rat cardiac muscle. Eur J Histochem 1994;38:311–8.

    Google Scholar 

  21. Lewis W, Simpson JF, Meyer RR. Cardiac mitochondrial DNA polymerase-gamma is inhibited competitively and noncompeti-tively by phosphorylated zidovudine. Circ Res 1994;74:344–8.

    Article  CAS  Google Scholar 

  22. Dawes G, Meir YJ, Mandruzzto GP. Computerized evaluation of fetal heart-rate patterns. J Perinatal Med 1994;22(6):491–9.

    Article  CAS  Google Scholar 

  23. Vintzileos AM, Knuppel RA. Multiple parameter biophysical testing in the prediction of fetal acid-base status. Clinics in Perinatol 1994;21:823–48.

    Article  CAS  Google Scholar 

  24. Hooper SB. Fetal metabolic responses to hypoxia. Reproduc Fertil Devel 1995;7(3):527–38.

    Article  CAS  Google Scholar 

  25. Albrecht H, Stellbrink HJ. Hiccups in people with AIDS [letter]. J Acquir Immune Defic Syndr 1994;7: 735.

    CAS  PubMed  Google Scholar 

  26. Nozyce M, Hittelman J, Muenz L, Durako SJ, Fischer ML, Willoughby A. Effect of perinataUy acquired human immunodeficiency virus infection on neurodevelopment in children during the first two years of life. Pediatr 1994;94:883–91.

    CAS  Google Scholar 

  27. Chase C, Vibbert M, Pelton SI, Coulter DL, Cabral H. Early neurodevelopmental growth in children with vertically transmitted human immunodeficiency virus infection. Arch Pediatr Ado-lesc Med 1995;149:850–5.

    Article  CAS  Google Scholar 

  28. Holmes GL, Lombroso CT. Prognostic value of background patterns in the neonatal EEG. J Clin Neurophysiol 1993;10:323–52.

    Article  CAS  Google Scholar 

  29. Myers MM, Schulze KS, Fifer WP, Stark RI. Methods for quantifying state specific patterns of EEG activity in fetal baboons and immature human infants. In: Lecanuet JP, Fifer WP, Krasnegor NA, Smotherman WP, eds. Fetal behavior: A psychobio-logical perspective. Hillsdale, New Jersey, Earlbaum, 1994:35–49.

    Google Scholar 

  30. Bocking AD. Fetal behavioral states: Pathological alteration with hypoxia. Seminars in Perinatology 1992;16(4):252–7.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Columbia College of Physicians and Surgeons, 622 West 168th Street, New York, NY, 10032, USA

    Raymond I. Stark MD, Marianne Garland MB, ChB, Salha S. Daniel PhD, Kenneth Leung MS, EE, Michael M. Myers PhD & Pamela J. Tropper MD

  2. Department of Obstetrics and Gynecology, Roosevelt St. Luke’s Hospital Center, New York, New York, USA

    Raymond I. Stark MD, Marianne Garland MB, ChB, Salha S. Daniel PhD, Kenneth Leung MS, EE, Michael M. Myers PhD & Pamela J. Tropper MD

Authors
  1. Raymond I. Stark MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marianne Garland MB, ChB
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Salha S. Daniel PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kenneth Leung MS, EE
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael M. Myers PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pamela J. Tropper MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by the National Institute of Allergy and Infectious Diseases, grant no. AI 32314 and the National Institute of Child Health and Human Development, grant no. HD 13063.

We wish to thank Burroughs Wellcome for the zidovudine used in this study and Mr. T. Cooper, New York State Psychiatric Institute, for carrying out the zidovudine assay.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stark, R.I., Garland, M., Daniel, S.S. et al. Fetal Cardiorespiratory and Neurobehavioral Response to Zidovudine (AZT) in the Baboon. Reprod. Sci. 4, 183–190 (1997). https://doi.org/10.1177/107155769700400403

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/107155769700400403

Key words

Search

Navigation