Neonatal cushingoid syndrome resulting from serial courses of antenatal betamethasone.

BACKGROUND: Antenatal steroid therapy has been shown to induce accelerated pulmonary maturation in preterm fetuses when delivery is imminent. Although this form of therapy has been used for 20 years, few studies or case reports have discussed the indications for or complications of retreatment, especially when more than two courses of steroids have already been given. We report a case of neonatal cushingoid syndrome with hypothalamic-pituitary-adrenal axis suppression following maternal treatment with seven courses of betamethasone. CASE: A 31-year-old white woman, gravida 3, para 1, spontaneous abortion 1, presented with a single intrauterine pregnancy at 24 weeks' gestation, a bulging amniotic sac, and repeated cerclage failure. Antenatal betamethasone therapy was begun at 12.5 mg intramuscularly every 12 hours for two doses. Because of cervical dilatation, bulging membranes, and intermittent contractions, the expectation of imminent premature delivery did not diminish over the next 42 days. As the effect of antenatal steroids wanes after 7 days, a course of therapy was administered each week for as long as the threat of preterm delivery remained. Seven courses of betamethasone were given before delivery at 34.5 weeks post-conception age. The 2625-g male neonate appeared cushingoid on physical examination, with basal serum cortisol levels less than 3.3 micrograms/dL. CONCLUSION: Physical findings of the neonate and laboratory investigation of both infant and mother suggested combined hypothalamic-pituitary-adrenal axis suppression. The cushingoid features of the infant demonstrate an undesired and previously unreported complication of an effective antenatal therapy. The unusual variant in this case was that the initial indication for steroid therapy (risk of premature delivery) persisted for 8 weeks after the first dose of betamethasone. It remains unknown how many weekly antenatal steroid courses can be administered before marked fetal adrenal suppression becomes evident. Risk-benefit ratios should be carefully considered before each retreatment.

Dissociation between the effects of theophylline and caffeine on premature airway smooth muscles.

Xanthine derivatives relax adult airway smooth muscle (ASM). To determine whether caffeine and theophylline relax preterm ASM contracted by acetylcholine, 27 tracheal rings obtained from seven preterm lambs (120-135 d gestation) were studied. ASM was contracted using 10(-5) M acetylcholine (control) after the muscle was stretched to the length at which maximum active tension was developed isometrically. Concentration-effect curves for each xanthine were obtained by cumulative addition of the drug. Theophylline produced a significant decrease (p less than 0.001) in active tension at each dose, whereas caffeine significantly increased (p less than 0.001) active tension at 10(-4) and 10(-3) M concentrations. Addition of caffeine and theophylline to previously uncontracted ASM did not alter tension. Thus, it appears that, in contrast to their effect on adult ASM, the xanthine derivatives caffeine and theophylline have differential effects on prestimulated ASM in preterm lambs. These findings raise important questions about various aspects of the current therapeutic use of caffeine and theophylline.