Abstract
Objective
To study the effects of single and multiple courses of antenatal corticosteroids on tissue water content in ovine fetuses.
Methods
After chronic catheterization of the ewes and fetuses, the ewes were randomly assigned to receive single or multiple courses of dexamethasone or placebo beginning at 104–106 or 76-78 days’ gestation, respectively. In the single course groups, the ewes received dexamethasone (6mg, n = 6) or placebo (n = 6) as four intramuscular injections every 12 hours over 48 hours. The fetal tissues were harvested for water content determination 66 hours after the first injection of dexamethasone or placebo was given. In the multiple-course groups, the ewes received the same treatment (dexamethasone, n = 10, or placebo, n - 8), once a week for 5 weeks starting at 76–78 days’ gestation. In these groups, the tissues were harvested 66 hours after the first the injection of the fifth and last treatment course. In both groups, tissues were harvested at 106-107 days’ gestation. Tissue water content was determined by wet-to-dry weight ratio in brain (cerebral cortex, caudate nucleus, cerebellum, midbrain, and medulla) and somatic tissues (kidney, liver, muscle, and skin).
Results
Water content in the brain regions (cerebellum and medulla) was lower (P <.05) in fetuses of dexamethasone-treated ewes than placebo-treated ewes after the multiple course but not the single course. Water content of somatic tissue was lower (P <.05) in fetuses of dexamethasone-treated ewes than placebo-treated ewes after the multiple courses, and in the liver after a single course.
Conclusion
Dexamethasone treatment of ewes at 70% of gestation results in decreased regional brain water content in the fetuses after multiple but not single treatment courses, in somatic tissues (kidney, liver, muscle, and skin) after multiple courses, and in the liver after a single course. (J Soc Gynecol Investig 2004;11:166-74)
Similar content being viewed by others
References
Liggins GC. Premature delivery of foetal lambs infused with glucocorticoids. J Endocrinol 1969;45(4):515–23.
Banks BA, Cnaan A, Morgan MA, Parer JT, Merrill JD, Ballard PL, Ballard RA. Multiple courses of antenatal corticosteroids and outcome of premature neonates. North American Thyrotropin-Releasing Hormone Study Group. Am J Obstet Gynecol 1999;181(3):709–17.
Padbury JF, Polk DH, Ervin MG, Berry LM, Ikegami M, Jobe AH. Postnatal cardiovascular and metabolic responses to a single intramuscular dose of betamethasone in fetal sheep born prematurely by cesarean section. Pediatr Res 1995;38(5):709–15.
Ervin MG, Berry LM, Ikegami M, Jobe AH, Padbury JF, Polk DH. Single dose fetal betamethasone administration stabilizes postnatal glomerular filtration rate and alters endocrine function in premature lambs. Pediatr Res 1996;40(5):645–51.
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(6 Pt 2):R1972–9.
Stonestreet BS, Hansen NB, Laptook AR, Oh W. Glucocorticoid accelerates renal functional maturation in fetal lambs. Early Hum Dev 1983;8(3–4):331–41.
Petershack JA, Nagaraja SC, Guillery EN. Role of glucocorticoids in the maturation of renal cortical Na + -K+-ATPase during fetal life in sheep. Am J Physiol 1999;276(6 Pt 2):R1825–32.
Stonestreet BS, Petersson KH, Sadowska GB, Pettigrew KD, Padak CS. Antenatal steroids decrease blood-brain barrier permeability in the ovine fetus. Am J Physiol 1999;276(2 Pt 2):R283–9.
Sloboda DM, Newnham JP, Challis JR. Effects of repeated maternal betamethasone administration on growth and hypothalamic-pituitary-adrenal function of the ovine fetus at term. J Endocrinol 2000;165(1):79–91.
Antenatal corticosteroids revisited: repeat courses. NIH Consensus Statement. 2000 August 17–18; 17(2) 1–18. Available at: http://consensus.nih.gov.
Kutzler MA, Molnar J, Schlafer DH, Kuc RE, Davenport AP, Nathanielsz PW. Maternal dexamethasone increases endothe-1 in-1 sensitivity and endothelin A receptor expression in ovine foetal placental arteries. Placenta 2003;24(4):392–402.
Jobe AH, Newnham J, Willet K, Sly P, Ikegami M. Fetal versus maternal and gestational age effects of repetitive antenatal glucocorticoids. Pediatrics 1998;102(5):1116–25.
Ikegami M, Jobe AH, Newnham J, Polk DH, Willet KE, Sly P. Repetitive prenatal glucocorticoids improve lung function and decrease growth in preterm lambs. Am J Respir Crit Care Med 1997;156(1):178–84.
Huang WL, Harper CG, Evans SF, Newnham JP, Dunlop SA. Repeated prenatal corticosteroid administration delays myelination of the corpus callosum in fetal sheep. Int J Dev Neurosci 2001;19(4):415–25.
Huang WL, Beazley LD, Quinlivan JA, Evans SF, Newnham JP, Dunlop SA. Effect of corticosteroids on brain growth in fetal sheep. Obstet Gynecol 1999;94(2):213–8.
Dunlop SA, Archer MA, Quinlivan JA, Beazley LD, Newnham JP. Repeated prenatal corticosteroids delay myelination in the ovine central nervous system. J Matern Fetal Med 1997;6(6):309–13.
Yamada K, Bremer AM, West CR. Effects of dexamethasone on tumor-induced brain edema and its distribution in the brain of monkeys. J Neurosurg 1979;50(3):361–7.
Sztriha L, Joo F, Szerdahelyi P, Eck E, Koltai M. Effects of dexamethasone on brain edema induced by kainic acid seizures. Neuroscience 1986; 17(1): 107–14.
Reid AC, Teasdale GM, McCulloch J. Hormonal influence on water permeability across the blood-brain barrier. Clin Exp Neurol 1983;19:50–3.
Reid AC, Teasdale GM, McCulloch J. The effects of dexameth-asone administration and withdrawal on water permeability across the blood-brain barrier. Ann Neurol 1983;13(1):28–31.
De Souza SW, Dobbing J. Cerebral oedema in developing brain. 3. Brain water and electrolytes in immature asphyxiated rats treated with dexamethasone. Biol Neonate 1973;22(5):388–97.
Stonestreet BS, Elitt CM, Markowitz J, Petersson KH, Sadowska GB. Effects of antenatal corticosteroids on regional brain and non-neural tissue water content in the ovine fetus. J Soc Gynecol Investig 2003;10(2):59–66.
Ballabh P, Lo ES, Kumari J, Cooper TB, Zervoudakis I, Auld PA, Kraus AN. Pharmacokinetics of betamethasone in twin and singleton pregnancy. Clin Pharmacol Ther 2002;71(1):39–45.
Turrentine MA, Ramirez MM. Adverse perinatal events and subsequent cesarean rate. Obstet Gynecol 1999;94(2): 185–8.
Al-Yatama MK, Al Essa M, Omu AE, Al-Shamali I, Egbase P, Rashwan N. Effect of repeated doses of dexamethasone on the incidence and severity of respiratory distress syndrome in multifetal gestation between 24 and 34 weeks. Gynecol Obstet Invest 2001;52(1):26–33.
Stonestreet BS, Le E, Berard DJ. Circulatory and metabolic effects of beta-adrenergic blockade in the hyperinsulinemic ovine fetus. Am J Physiol 1993;265(4 Pt 2):H1098–106.
Stonestreet BS, Patlak CS, Pettigrew KD, Reilly CB, Cserr HF. Ontogeny of blood-brain barrier function in ovine fetuses, lambs, and adults. Am J Physiol 1996;271(6 Pt 2):R1594–601.
Stonestreet BS, Sadowska GB, McKnight AJ, Patlak C, Petersson KH. Exogenous and endogenous corticosteroids modulate blood-brain barrier development in the ovine fetus. Am J Physiol Regul Integr Comp Physiol 2000;279(2):R468-77.
McGowan JE, Sysyn G, Petersson KH, et al. Effect of dexamethasone treatment on maturational changes in the NMDA receptor in sheep brain. J Neurosci 2000;20(19):7424–29.
Kerzner LS, Stonestreet BS, Wu KY, Sadowska G, Malee MP. Antenatal dexamethasone: Effect on ovine placental llbeta-hydroxysteroid dehydrogenase type 2 expression and fetal growth. Pediatr Res 2002;52(5):706–12.
Hai CM, Sadowska G, Francois L, Stonestreet BS. Maternal dexamethasone treatment alters myosin isoform expression and contractile dynamics in fetal arteries. Am J Physiol Heart Circ Physiol 2002;283(5):H1743-9.
Stonestreet BS, McKnight AJ, Sadowska GB, Patlak CS, Petersson KH. Effects of repeated courses of antenatal corticosteroids on blood-brain barrier function in early gestation ovine fetuses. Pediatr Res 2000;4(2):434A.
National Institutes of Health Consensus Development Panel. Effect of corticosteroids for fetal maturation and perinatal out-comes. JAMA 1995;5:413–8.
Cserr HF, DePasquale M, Patlak CS. Regulation of brain water and electrolytes during acute hyperosmolality in rats. Am J Physiol 1987;253(3 Pt 2):F522–9.
Bloom SL, Sheffield JS, McIntire DD, Leveno KJ. Antenatal dexamethasone and decreased birth weight. Obstet Gynecol 2001;97(4):485–90.
Thorp JA, Jones AM, Hunt C, Clark R. The effect of multidose antenatal betamethasone on maternal and infant outcomes. Am J Obstet Gynecol 2001;184(2): 196-202.
Clifton VL, Wallace EM, Smith R. Short-term effects of glucocorticoids in the human fetal-placental circulation in vitro. J Clin Endocrinol Metab 2002;87(6):2838–42.
Milley JR. Fetal substrate uptake during increased ovine fetal Cortisol concentration. Am J Physiol 1996;271(1 Pt 1):E186–91.
Bennet L, Kozuma S, McGarrigle HH, Hanson MA. Temporal changes in fetal cardiovascular, behavioural, metabolic and endocrine responses to maternally administered dexamethasone in the late gestation fetal sheep. Br J Obstet Gynaecol 1999;106(4):331–9.
Cuthrell WV, Rose JC, Meis PJ. The effect of adrenocorticotropic hormone infusion on subsequent pituitary response in the sheep fetus. Am J Obstet Gynecol 1990;163(1 Pt 1):170–4.
Kleeman CR. The kidney in health and disease: X. CNS manifestations of disordered salt and water balance. Hosp Pract 1979;14(5):59–68, 73.
Strange K. Regulation of solute and water balance and cell volume in the central nervous system. J Am Soc Nephrol 1992;3(1):12–27.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was supported by National Institutes of Health grant R01-HD34618.
The authors acknowledge the excellent technical assistance of Christopher M. Elitt, BS, John Kazianis, BS, Amanda J. McKnight, BS, Maricmz Merino, BS, Stephanie Newton, BS, and Mary Oh, MD.
Rights and permissions
About this article
Cite this article
Stonestreet, B.S., Watkins, S., Petersson, K.H. et al. Effects of Multiple Courses of Antenatal Corticosteroids on Regional Brain and Somatic Tissue Water Content in Ovine Fetuses. Reprod. Sci. 11, 166–174 (2004). https://doi.org/10.1016/j.jsgi.2003.10.006
Published:
Issue Date:
DOI: https://doi.org/10.1016/j.jsgi.2003.10.006