Effects of Antenatal Glucocorticoids on Circulatory Adaptation at Birth in the Ovine Fetus

Abstract

Objective: Adaptation to extra-uterine life requires dramatic increase in pulmonary blood flow. Mechanisms that induce pulmonary vasodilatation at birth are incompletely understood but include alveolar ventilation, increase in PaO₂, and production of vasoactive mediators. We hypothesized that antenatal glucocorticoids (GC) increase pulmonary vasodilatation to birth-related stimuli. Study Design: To test this hypothesis, we studied the pulmonary hemodynamic response at birth to mechanical ventilation with low (<10%) and then with high (100%) FiO₂ in chronically prepared late-gestation fetal lambs treated or not by antenatal maternal steroids. Results: Basal mean aortic and pulmonary artery pressure (PAP), left pulmonary blood flow, pulmonary vascular resistance (PVR), and blood gas were similar between control and dexamethasone-treated animals (GC group). During mechanical ventilation with low FiO₂, mean PVR decreased by 40% in the control group (from 0.44 ± 0.01 to 0.25 ± 0.01 mm Hg/ml/min) and by 60% in the GC group (from 0.44 ± 0.02 to 0.19 ± 0.02 mm Hg/ml/min) (p < 0.01). When subsequently ventilated with 100% O₂, there was no difference in PVR decrease between groups (0.15 ± 0.02 mm Hg/ml/min in the GC group vs. 0.14 ± 0.01 mm Hg/ml/min in the control group). Conclusion: Antenatal GC enhance pulmonary vasodilatation induced by alveolar ventilation at birth but do not alter the pulmonary vascular response to O₂. We speculate that antenatal steroids exposure improve adaptation at birth through acceleration of both parenchymal and vascular lung maturation.

Antenatal Corticosteroids Increase Fetal, But Not Postnatal, Pulmonary Blood Flow in Sheep

“…These data contrast with our findings of a marked increase in fetal PBF in response to antenatal corticosteroids, with little or no beneficial effect on the transition of the pulmonary circulation at birth. The difference between our findings and those of previous studies (25,27) is likely because of the maturity of the fetus when exposed to corticosteroids. In previous studies, fetuses were treated at 135-138 d of gestation (25,27), whereas in our study, fetuses were treated at ϳ125 d; term is ϳ147 d.…”

“…In particular, corticosteroids can increase pulmonary vascular reactivity in response to vasodilatory stimuli, including catecholamines (24,25) prostaglandins, and NO (24,26). However, previous studies found that antenatal corticosteroids have no effect on basal PBF in fetal sheep (25,27) and were considered to enhance pulmonary vasodilation induced by alveolar ventilation at birth; this effect was independent of oxygen-mediated changes. These data contrast with our findings of a marked increase in fetal PBF in response to antenatal corticosteroids, with little or no beneficial effect on the transition of the pulmonary circulation at birth.…”

“…This may explain why PBF was found to increase only 1.5-fold, in corticosteroid-treated fetuses compared with a 4-fold increase in control fetuses. However, a previous study found that antenatal corticosteroids only had a positive affect on postnatal PBF and PVR when the fraction of inspired oxygen (FiO 2 ) was Ͻ1.0 (27). As all fetuses were initially ventilated with 100% oxygen, which was then reduced as required to maintain oxygenation, it is possible that a significant effect of antenatal corticosteroids on postnatal PBF will have been observed if the lambs were initially ventilated in air.…”

Effects of Antenatal Betamethasone on Human Fetal Branch Pulmonary Artery Flow Velocity Waveforms

“…As catecholamines, especially norepinephrine, may play a significant role in the maintenance of the fetal pulmonary circulation and during the transitional circulation at birth, the authors speculated that corticosteroids could have a role in perinatal cardiovascular adaptation by enhancing the norepinephrine-mediated pulmonary vasodilatation. Recently, the same authors have reported that antenatal dexamethasone enhances pulmonary vasodilatation induced by alveolar ventilation at birth [9] . Similarly, it has been reported that a single dose of antenatal betamethasone enhanced relaxation of pulmonary arteries of preterm lambs induced by ␤ -adrenergic agonists and prostaglandin E 2 [10] .…”

Prise en charge médicale per- et postnatale de la hernie congénitale diaphragmatique

“…Cette chute rapide des RVP est la conséquence d'une vasodilatation [7]. De multiples mécanismes contribuent à cette adaptation circulatoire à la vie extra-utérine, comme la ventilation alvéolaire, l'augmentation des pressions partielles en O 2 , les contraintes vasculaires de cisaillement (shear stress) et la libération de médiateurs vasodilatateurs [8][9][10].…”