Maternal Effects of Repeat-Dose Steroids
abstract & Commentary
Synopsis: Repeated doses of betamethasone markedly reduce maternal basal cortisol levels and the response to low-dose corticotropin stimulation, findings consistent with secondary adrenal insufficiency.
Source: McKenna DS, et al. Am J Obstet Gynecol 2000;183:669-673.
To determine whether repeated doses of corticosteroids administered to accelerate fetal pulmonary maturation would suppress the maternal hypothalamic-pituitary-adrenal axis, McKenna and colleagues performed a prospective case-controlled study including 18 pregnant women who received at least two weekly courses of antenatal betamethasone, two doses of 12 mg 24 hours apart, and six control women matched for gestational age. The study group included 16 women admitted for preterm labor, including two women with twin gestations and two with placenta previa. The mean gestational age in the study group was 31.4 weeks, and in the control group, 30.2 weeks. Patients in the study group received, on average, three courses of steroids with a range of 2-6. Both groups underwent a low-dose corticotropin stimulation test to detect maternal adrenal insufficiency. The test was performed at least 48 hours after the second dose of the weekly cortiosteroid course.
Basal cortisol levels at 8 a.m. were markedly reduced in the corticosteroid group, 1.9 µg/dL vs. 26.5 µg/dL in the controls. The corticotropin stimulation test in the controls revealed a peak value of 44.4 µg/dL reached at 27.4 minutes. However, in the steroid treated group, none of the patients reached the lower 99% limit value of 30 µg/dL. The average peak value was only 10.8 µg/dL, at 37 minutes. Baseline corticotropin levels were also significantly lower in the steroid treated group.
McKenna et al concluded that repeated doses of betamethasone markedly reduce maternal basal cortisol levels and the response to low-dose corticotropin stimulation, findings consistent with secondary adrenal insufficiency.
Comment by Steven G. Gabbe, MD
Recent studies have focused on the risks associated with repeated doses of antenatal corticosteroids administered to accelerate fetal lung maturity. McKenna et al demonstrate that this therapy may produce secondary maternal adrenal suppression, an effect that could be of concern during the stress of labor and delivery. They advise that repeated doses of steroids be used only in those pregnancies at the highest risk for preterm delivery.
It is well known that the maximum perinatal benefit of corticosteroid treatment occurs 24 hours after the therapy has been initiated and lasts for seven days. In patients considered to be at risk for preterm birth, many obstetricians have adopted the practice of repeating the steroid dose at weekly intervals. To examine the risks and benefits of repetitive steroid treatment, the National Institute of Child Health and Human Development convened a Consensus Panel in August 2000. Because of concerns raised by studies in animals and humans that showed adverse effects on neurologic development and growth without clear evidence of benefit, the Panel concluded that repeated doses of steroids should now be used only in research studies.
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