Skip to main content
SpringerLink
Log in

Differential Effects of Maternal and Fetal Betamethasone Injections in Late-Gestation Fetal Sheep

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

Abstract

Objective

TO determine the effects of single or repeated intramuscular injections of betamethasone, given maternally or directly to the fetus, on chronically catheterized, late-gestation fetal sheep.

Methods

Fetal or maternal sheep received either repeated intramuscular injections of betamethasone (0.5 mg/kg body weight at 104, 111, and 118 days’ gestation), single betamethasone injection (at 104 days’ gestation, followed by saline at 111 and 118 days’ gestation), or repeated saline injections; n = 6 or 7 per group. At approximately 130 days’ gestation fetuses were catheterized for serial measurements of heart rate, arterial pressure, blood gases, metabolites, and electrolytes.

Results

Repeated maternal betamethasone injections reduced birth weight (P =.03) without fetal hypoxemia or hypoglycemia. Circulating fetal calcium and lactate concentrations were reduced (P =.002 and P =.014, respectively) by repeated maternal betamethasone only. Fetal hematocrit tended to be lower after fetal (P =.3) and maternal (P =.07) betamethasone.

Conclusion

Growth restriction caused by repeated maternal betamethasone treatments is not due to overt chronic placental insufficiency but may be caused by alterations in hormonal mediators of fetal growth or impairment of placental transport of specific nutrients.

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. National Institutes of Health Consensus Development Panel. Antenatal corticosteroids revisited: Repeat courses—National Institutes of Health Consensus Development Conference Statement, August 17-18, 2000. Obstet Gynecol 2001;98:144–150.

    Article  Google Scholar 

  2. Crowley P. Prophylactic corticosteroids for preterm birth. Cochrane Database of Systematic Reviews 2002;1.

    Google Scholar 

  3. Quinlivan JA, Evans SF, Dunlop SA, Beazley LD, Newnham JP. Use of corticosteroids by Australian obstetricians-A survey of clinical practice. Aust NZJ Obstet Gynecol 1998;38:1–7.

    Article  CAS  Google Scholar 

  4. Newnham JP, Moss TJ. Antenatal glucocorticoids and growth: Single versus multiple doses in animal and human studies. Semin Neonatol 2001;6:285–92.

    Article  CAS  PubMed  Google Scholar 

  5. Aghajafari F, Murphy K, Matthews S, Olson A, Amankwah K, Hammah M. Repeated doses of antenatal corticosteroids in animals: A systemic review. Am J Obstet Gynecol 2002;186:843–9.

    Article  CAS  PubMed  Google Scholar 

  6. French NP, Hagan R, Evans SF, Godfrey M, Newnham JP. Repeated antenatal corticosteroids: Size at birth and subsequent development. Am J Obstet Gynecol 1999;180:114–21.

    Article  CAS  PubMed  Google Scholar 

  7. Banks BA, Cnaan A, Morgan MA, et al. Multiple courses of antenatal corticosteroids and outcome of premature neonates. Am J Obstet Gynecol 1999;181:709–17.

    Article  CAS  PubMed  Google Scholar 

  8. Walfisch A, Hallak M, Mazor M. Multiple courses of antenatal steriods: Risks and benefits. Obstet Gynecol 2001;98:491–7.

    CAS  PubMed  Google Scholar 

  9. Aghajafari F, Murphy K, William A, et al. Multiple courses of antenatal corticosteriods: A systematic review and meta-analysis. Am J Obstey Gynecol 2001;185:1073–80.

    Article  CAS  Google Scholar 

  10. Elimian A, Verma U, Visintainer P, Tejani N. Effectiveness of multidose antenatal steroids. Obstet Gynecol 2000;95:34–6.

    CAS  PubMed  Google Scholar 

  11. Thorp JA, Jones AMH, Hunt C, Clark R. The effect of multi-dose antenatal betamethasone on maternal and infant outcomes. Am J Obstet Gynecol 2001;184:196–202.

    Article  CAS  PubMed  Google Scholar 

  12. Shelton SD, Boggess KA, Murtha AP, Groff AO, Herbert WNP. Repeated fetal betamethasone treatment and birth weight and head circumference. Obstet Gynecol 2001;97:301–4.

    CAS  PubMed  Google Scholar 

  13. Newnham JP, Evans SF, Godfrey M, Huang W, Ikegami M, Jobe A. Maternal, but not fetal, administration of corticosteroids restricts fetal growth. J Matern Fetal Med 1999;8:81–7.

    CAS  PubMed  Google Scholar 

  14. Moss TJM, Sloboda DM, Gurrin LC, Harding R, Challis JRG, Newnham JP. Programming effects in sheep of prenatal growth restriction and glucocorticoid exposure. Am J Physiol 2001;281: R960–70.

    CAS  Google Scholar 

  15. Berry LM, Polk DH, Ikegami M, Jobe AH, Padbury JF, Ervin MG. Preterm newborn lamb renal and cardiovascular responses after fetal or maternal antenatal betamethasone. Am J Physiol 1997;272:R1972–9.

    CAS  PubMed  Google Scholar 

  16. Rebello CM, Ikegami M, Polk DH, Jobe AH. Postnatal lung responses and surfactant function after fetal or maternal corticosteroid treatment. J Appl Physiol 1996;80:1674–80.

    Article  CAS  PubMed  Google Scholar 

  17. Bauer MK, Harding JE, Bassett NS, et al. Fetal growth and placental function. Mol Cell Endocrinol 1998;140:115–20.

    Article  CAS  PubMed  Google Scholar 

  18. Fowden A. Growth and metabolism. In: Harding R, Bocking A, eds. Fetal growth and development. Cambridge: Cambridge University Press, 2001;44–69.

    Google Scholar 

  19. Newnham JP, Polk DH, Kelly RW, et al. Catecholamine response to ultrasonographically guided percutaneous blood sampling in fetal sheep. Am J Obstet Gynecol 1994;171:460–5.

    Article  CAS  PubMed  Google Scholar 

  20. Lima M, Kallfelz F, Krook L, Nathanielsz P. Humeral skeletal development and plasma constituent changes in fetuses of ewes maintained on a low calcium diet from 60 days of gestation. Calcif Tissue Int 1993;52:283–90.

    Article  CAS  PubMed  Google Scholar 

  21. Hosking DJ. Calcium homoestasis in pregnancy. Clin Endocrinol 1996;45:1–6.

    Article  CAS  Google Scholar 

  22. Kovacs CS, Ho-Pao CL, Hunzelman JL, et al. Regulation of murine fetal- placental metabolism by the calcium-sensing receptor. J Clin Invest 1998;101:2812–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Glatz J, Heath J, Southby J, et al. Dexamethasone regulation of parathyroid hormone-related protein (PTHrP) expression in a squamous cancer cell line. Mol Cell Endocrinol 1994; 101:295–306.

    Article  CAS  PubMed  Google Scholar 

  24. Rizzoli R, Feyen J, Grau G, Wohlwend A, Sappino A, Bonjour J. Regulation of parathyroid hormone-related protein production in a human lung squmous cell carcinoma line. J Endocrinol 1994;143:333–41.

    Article  CAS  PubMed  Google Scholar 

  25. Liu B, Goltzman D, Rabbani S. Regulation of parathyroid hormone-related peptide production in vitro by the rat hypercalcemic Leydig cell tumor H-500. Endocrinology 1993;132:1658–64.

    Article  CAS  PubMed  Google Scholar 

  26. Dvir R, Golander A, Jaccard N, et al. Amniotic fluid and plasma levels of parathyroid hormone-related protein and hormonal modulation of its secretion by amniotic fluid cells. Eur J Endocrinol 1995;133:272–4.

    Article  Google Scholar 

  27. Paspaliaris V, Petersen DN, Thiede MA. Steroid regulation of parathyroid hormone- related protein expression and action in the rat uterus. J Steroid Biochem Mol Biol 1995;53:259–65.

    Article  CAS  PubMed  Google Scholar 

  28. Mosier HD, Dearden LC, Roberts RC, Jansons RA, Biggs CS. Regional differences in the effects of glucocorticoids on maturation of the fetal skeleton in rats. Teratology 1981;23:15–24.

    Article  CAS  PubMed  Google Scholar 

  29. Jensen EC, Gallaher BW, Breier BH, Harding JE. The effect of a chronic maternal. Cortisol infusion on the late-gestation fetal sheep 2002;174:27–36.

    CAS  Google Scholar 

  30. Moss T, Nitsos I, Harding R, Newnham J. The acute and longer-term differential effects of maternal and fetal betamethasone treatments in chronically catheterised sheep. Czech Gynecol 2002;67:4.

    Google Scholar 

  31. Westgren M, Kruger K, Ek S et al. Lactate compared with pH analysis at fetal scalp blood sampling: A prospective randomised study. Br J Obstet Gynaecol 1998;105:29–33.

    Article  CAS  PubMed  Google Scholar 

  32. Kruger K, Hallberg B, Blennow M, Kublickas M, Westgren M. Predictive value of fetal scalp blood lactate concentration and pH as markers of neurologic disability. Am J Obstet Gynecol 1999; 181:1072–8.

    Article  CAS  PubMed  Google Scholar 

  33. Jobe AH, Wada N, Berry LM, Ikegami M, Ervin MMG. Single and repetitive maternal glucocorticoid exposures reduce fetal growth in sheep. Am J Obstet Gynecol 1998;178:880–5.

    Article  CAS  PubMed  Google Scholar 

  34. Moritz KM, Lim GB, Wintour EM. Developmental regulation of erythropoietin and erythropoiesis. Am J Physiol 1997;273: R1829–44.

    CAS  PubMed  Google Scholar 

  35. Roodman G, Lee J, Gidari A. Effects of dexamethasone on erythroid colony and burst formation from human fetal liver and adult marrow. Br J Haematol 1983;53:621–8.

    Article  CAS  PubMed  Google Scholar 

  36. Wintour E, Clemons G, Butkus A, Horvath A, Moritz K, Towstowless M. Immunoreactive erythropoietin concentration and haemoglobin type in the perinatal period in sheep of various haemoglobin genotypes. J Dev Physiol 1990;14:259–65.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Women’s and Infants’ Healch, University of Western Australia, Perth, Western Australia, Australia

    Timothy J. M. Moss PhD, Ilias Nitsos PhD, Richard Harding DSc & John P. Newnham MD

  2. Deparonent of Physiology, Monash University, Clayton, Victoria, Australia

    Timothy J. M. Moss PhD, Ilias Nitsos PhD, Richard Harding DSc & John P. Newnham MD

Authors
  1. Timothy J. M. Moss PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ilias Nitsos PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Richard Harding DSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John P. Newnham MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Timothy J. M. Moss PhD.

Additional information

Supported by The National Health and Medical Research Council of Australia (project grant 110301).

The authors thank Mr. Adrian Jonker for providing valuable technical assistance and are grateful for the infrastructural support provided by the Women and Infants Research Foundation of Western Australia.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Moss, T.J.M., Nitsos, I., Harding, R. et al. Differential Effects of Maternal and Fetal Betamethasone Injections in Late-Gestation Fetal Sheep. Reprod. Sci. 10, 474–479 (2003). https://doi.org/10.1016/S1071-55760300152-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/S1071-55760300152-7

Key words

Search

Navigation