Antenatal steroid treatment: suppression with no impairment of the adaptive function of the HPA-axis in newborns at birth

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To the Editors:

In a recent article, Battin et al¹ analyzed the effects of single and repeat courses of antenatal steroids on the function of neonatal hypothalamic-pituitary-adrenal (HPA) axis. To evaluate HPA axis function, the authors used metyrapone challenge test. They demonstrated that exposure to multiple courses of betamethasone did not significantly alter the function of HPA axis in newborns at age 2-3 days of life.

We strongly agree with the authors stating that multiple administration of antenatal steroids is a safe method with regard to the ability of the HPA axis playing a key role in the adaptation of the newborn. However, the authors did not provide data on how the steroid treatment affected HPA axis at all, whether they found decrease in the overall function of the adrenal gland or did not, and whether there was any difference between the ability of the HPA axis in newborns of treated and nontreated mothers to respond to stress or methyrapone challenge.

More than 20 years ago, we published data on the effect of antenatal steroid treatment given 24-48 hours prior to labor.² We compared data from infants of steroid-treated and nontreated mothers, with focus on the actual stress status of the newborns determined by actual pH, negative base excess, and pCO₂ values as indicators of asphyxia. We considered the asphyxia group as the 1 exposed to higher-than-normal stress. Thus, we could analyze the reactivity of the HPA axis in “real” stress situation, following antenatal steroid administration.

We measured plasma cortisol levels on days 1, 3, and 7 of life. We found that antenatal steroid treatment did in fact significantly decrease plasma cortisol levels on day 1 of life. Furthermore, asphyxia (ie, “real” stress) resulted in significantly higher plasma cortisol values on day 1, as compared with the nonasphyxia groups, in newborns of both treated and nontreated mothers. On days 3 and 7, no statistical difference of plasma cortisol levels between steroid-treated and nontreated as well as asphyxia and nonasphyxia groups was observed.

These data prove that antenatal steroids cause a transient, reversible suppression of the HPA axis. However, our data prove that the HPA axis remains responsive to stress, even if it is suppressed. In addition, adrenal function returns to normal in a few days after birth. Because, in our setting, antenatal steroid was given 1-2 days prior to delivery, we are confident that antenatal steroid prophylaxis is a safe method in preventing lung complications of premature newborns.

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References 

1. Battin MR, Bevan C, Harding J. Repeat doses of antenatal steroids and hypothalamic-pituitary-adrenal axis function. Am J Obstet Gynecol. 2007;197:40–42
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2. Bodis J, Szabo I, Ertl T, et al. The effect of glucocorticoid treatment during pregnancy on adrenocortical activity in premature newborns. Magyar Noorv Lapja. 1984;47:335–339
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