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PEDIATRICS Vol. 102 No. 5 November 1998, pp. 1116-1125

Fetal Versus Maternal and Gestational Age Effects of Repetitive Antenatal Glucocorticoids

Received Dec 2, 1997; accepted Apr 22, 1998.

Alan H. Jobe*, John NewnhamDagger , Karen Willet§, Peter Sly§, and Machiko Ikegami*

From the * Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio; the Dagger  Department of Obstetrics, University of Western Australia, Perth, Australia; and § TVW Telethon, Division of Clinical Sciences, Institute for Child Health Research, Perth, Western Australia.

Background.  Although single courses of antenatal glucocorticoids decrease respiratory distress syndrome and mortality, repetitive courses of antenatal glucocorticoids are being given to women at risk of preterm delivery without evidence of benefit or appreciation of potential risks.

Objectives.  To evaluate the effects of single and repetitive antenatal glucocorticoid exposures on fetal growth and postnatal lung function in sheep.

Methods.  Pregnant ewes were randomized to three protocols that included one or three doses (at 7-day intervals) of 0.5 mg/kg of betamethasone (beta ) given to the ewe or fetus beginning at gestations ranging from 104 to 128 days' gestation with delivery at 125, 135, and 146 days' gestation. Postnatal assessments included measurements of gas exchange, compliance, ventilation efficiency, static lung volume, and lung tissue and alveolar wash saturated phosphatidylcholine.

Results.  Single or repetitive maternal beta  but not fetal beta  caused fetal growth retardation at delivery at 125, 135, and 146 days' gestation. Single-dose fetal beta  had no effect on postnatal lung function whereas single-dose maternal beta  significantly increased compliance, lung volume, and tissue and alveolar surfactant after preterm delivery. Although three-dose fetal beta  improved all indicators of postnatal lung function, three-dose maternal beta  resulted in larger responses. The added benefits of repetitive beta  relative to a single-dose beta on postnatal lung function after preterm delivery were not as great when therapy was begun later in gestation. Postnatal lung function after delivery at 146 days' gestation (term is 150 days) was improved after repetitive maternal beta  at early gestational age.

Conclusions.  In sheep, single or repetitive maternal beta  causes growth retardation from 104 to 121 days' gestation and the growth retardation persists to term. In contrast, single or repetitive fetal beta  does not cause fetal growth retardation and is less potent at improving postnatal lung function and increasing surfactant pools. There are potential benefits as well as risks for the use of repetitive antenatal glucocorticoids. Randomized, controlled trials in humans are essential given the widespread use of repetitive courses of antenatal glucocorticoids in women at risk of preterm delivery. respiratory distress syndrome, maturation, prematurity, growth retardation, surfactant. .




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