Postnatal Cardiovascular and Metabolic Responses to a Single Intramuscular Dose of Betamethasone in Fetal Sheep Born Prematurely by Cesarean Section

Abstract

Although the benefits of antenatal hormone treatment are well accepted, most studies have reported only pulmonary effects. There is evidence of beneficial cardiovascular and metabolic effects in studies using chronically catheterized animals; however because of the route of administration, the results are not directly applicable to clinical strategies. We previously demons trated sign ificant pulmonary effects in animals treated antenatally with a single, direct fetal, intramuscular injection of glucocorticoids . Th is study was performed to determine the effects of a single fetal injection of betamethasone (BETA) alone or in combination with thyroxine (T 4 ) on cardiovascular and metabolic respons es after preterm birth . Hemodynamic and metabolic response s at birth were determined in fetuses (126-d gestation; term = 150 d) treated with ultrasound-guided intramuscular injections of 0.5 mg/kg BETA (n = 7), BETA plus 60 g/kg T 4 (n = 7), or saline (SAL, n = 9). After 48 h, lambs were delivered by cesarean section and studied for 3 h. BETA treatment increased mean arterial blood pressure [56 ± 6 (SEM) versus 42 ± 3 mm Hg], heart rate (152 ± 5 versus 123 ± 4 beats/min), and cardiac Multiple studies have documented improved outcomes of preterm human infants born to mothers treated antenatally with glucocor ticoids. Most studies have focused primarily on pulmonary effects, although secondary outcome variables and retrospective metanalysis of clinical and other demographic data indicate beneficial effects in other organ systems (1, 2). Maternal corticosteroid treatment reduces nonrespiratory morbidities such as intraventricular hemorrhage, necrotizing enterocolitis, and patent ductus arteriosus. The mechanism(s) for these varied clinical outcomes is uncertain .In previous studies using chronically catheterized fetal sheep we demonstrated that antenatal corticosteroid infusion signifi- Responses of BETA + T 4 -treated animals were not different from animals treated with BETA alone. Glucose and FFA were simila r among all groups. The increase in catecholamine levels normally seen at birth was significantly attenuated in both the BETA and BETA + T 4 -treated animal s. A single, intramuscular injec tion of glucocorticoids 48 h before delive ry improves cardiovascular responses to preterm birth . This effect is not augmented by concomitant admi nistration of T4 ' (Pediatr Res 38: 709-715, 1995) Abbrev iations BETA, betamethasone T 4 , thyroxine T 3 , triiodothyronine SAL , saline TRH, thyrotropin-releasing hormone ANOVA, analysis of variance

Postnatal hemodynamic changes in very-low-birthweight infants

“…The protection against intraventricular hemorrhage (15,38) and necrotizing enterocolitis (3) afforded by antenatal steroid administration may result from accelerated cellular development in the brain and intestine. On the other hand, it is tempting to invoke the improved blood pressure (15,24) and cardiac output (28) observed after antenatal steroid administration as the mechanism of protection because both intraventricular hemorrhage and necrotizing enterocolitis may be associated with disturbances in organ perfusion. We hypothesized that postnatal changes in Doppler BFV and cardiac function would differ between infants whose mothers did and did not receive antenatal glucocorticoids.…”

“…Infants whose mothers received antenatal steroids have higher blood pressures (15) and less need for blood pressure support (15,24) than do those whose mothers did not receive steroids. In preterm lambs, antenatal glucocorticoid treatment increases both blood pressure and cardiac output (28). The effect of antenatal steroid therapy on cardiac output and regional hemodynamics in newborn premature infants has not been examined previously.…”

Hemodynamic Disturbances in Premature Infants Born after Chorioamnionitis: Association with Cord Blood Cytokine Concentrations

“…Although we found no differences in hemodynamic measures among infants who received single versus multiple doses of antenatal steroid [current study (data not shown) and (40)], it remains possible that the glucocorticoid lessens hemodynamic disturbances in the newborn by reducing the production of inflammatory mediators. Additional studies performed on infants born to mothers with acutely symptomatic chorioamnionitis, who did not benefit from the positive effects of antenatal steroid administration on cardiac function (41,42), might better distinguish the hemodynamic effects of chorioamnionitis.…”

Skeletal muscle glucose transporter protein responses to antenatal glucocorticoids in the ovine fetus

“…A single course of corticosteroids administered to women at risk of delivering prematurely decreases the incidence of respiratory distress syndrome, and of morbidity and mortality in neonates (Doyle et al 1986, Crowley 1995, National Institutes of Health Consensus Development Panel 1995. In animal studies, antenatal corticosteroids have been shown to exert extra-pulmonary effects (Padbury et al 1995, Berry et al 1997) including a negative impact on fetal growth (Ikegami et al 1997, Jobe et al 1998. Recent evidence in animal studies suggests that when antenatal corticosteroids disrupt the fetal hormonal/metabolic milieu, there can be far-reaching implications into the postnatal period (Nyirenda et al 1998, Gatford et al 2000, Moss et al 2001, Dodic et al 2002.…”