Antenatal betamethasone dose effects in preterm rabbits studied at 27 days gestation

Abstract

Pregnant rabbits received bethamethasone (0.05, 0.2, 0.4, or 0.5 mg.kg-1.day-1) or vehicle control for 2 days before delivery of fetuses at 27 days gestation to evaluate dose-related effects on surfactant pool sizes with and without ventilation, pressure-volume measurements, lung protein leaks, and precursor incorporation into lung saturated phosphatidylcholine (PC). Alveolar wash-saturated PC pool sizes in betamethasone-exposed fetuses were less than in controls (P less than 0.01). At higher doses, total lung saturated PC also decreased (P less than 0.01). Maximal lung volumes on pressure-volume loops were larger than controls only at the 0.4 mg.kg-1.day-1 dose (P less than 0.05). The larger maximal volumes, despite decreased saturated PC pools, indicated increased responsiveness of the steroid-treated lungs to the smaller saturated PC pool sizes. Vascular-to-alveolar iodinated albumin leak decreased with steroid treatment independently of dose (P less than 0.01). No consistent pattern of increased precursor incorporation into saturated PC by lung slices was seen. Our results indicate that, in preterm rabbits exposed to a range of maternal corticosteroid doses, the beneficial lung maturational effect of structural alterations with increased responses to endogenous saturated PC pools was maximal even at the lowest dose.

Antenatal Betamethasone Administration Decreases the Lung Hyaluronan Concentration in Preterm Rabbit Pups

“…In fetal rats, Schellenberg et al (30) found an increase in lung water content after antenatal exposure to dexamethasone. In other studies the lung water content was found to be unaffected by antenatal steroid exposure, both in fetal rabbits (14,31) and in preterm lambs (27). The lack of effect on the lung water content in most groups in the present study is also in accordance with our previous finding that changes in the hyaluronan concentration per dry lung weight are not paralleled by changes in the lung water content at birth (20).…”

“…An additional finding in the present study was the absence of an effect of steroid exposure on the mean birth weight in pups delivered at GA 27 d. Retarded fetal growth after antenatal exposure of fetal rabbits to different doses of corticosteroids has been reported previously (13)(14)(15), but the effects described have varied. Rider et al (14), for instance, found that in rabbit pups delivered at GA 27 d, the highest betamethasone dose studied (0.5 mg/kg, given daily for 2 d before delivery) had the smallest effect on the birth weight.…”

“…Either or both of these two effects could in turn constitute one part of the general acceleration of lung maturation that can be induced by antenatal administration of a corticosteroid (4,6). The lack of effect on pups delivered at GA 28 and 29 d might be explained by a hypothetical GA-related time window of corticosteroid sensitivity (14), or by the almost complete lung maturation at 28 d of gestation. After direct corticosteroid administration to fetal rabbits 2 or 3 d before delivery at GA 21-28 d, Kikkawa et al (7) found that the pulmonary maturation in each GA group was accelerated by 1-1.5 d, up to GA 28 d, when the maturation was almost complete as assessed by microscopic examination.…”

“…After direct corticosteroid administration to fetal rabbits 2 or 3 d before delivery at GA 21-28 d, Kikkawa et al (7) found that the pulmonary maturation in each GA group was accelerated by 1-1.5 d, up to GA 28 d, when the maturation was almost complete as assessed by microscopic examination. Furthermore, in a study of the effects of maternal administration of betamethasone, Rider et al (14) noted that the maturational effect on the lung structure was maximal even at the lowest dose of betamethasone used (0.05 mg/kg, given daily for 2 d before delivery). These findings could possibly explain why no additional effect was observed in the present study in pups delivered at GA 25 d whose mothers were given two doses of betamethasone, compared with the effect in corresponding pups exposed to only one dose.…”

“…The effects of antenatal glucocorticoid administration on fetal lung morphology and function have been most extensively studied in the rabbit and sheep. In preterm rabbits, improved postnatal lung function after maternal corticosteroid administration has been observed even without an increase in the surfactant content of lung tissue or alveoli (13)(14)(15).…”