PEDIATRICS Vol. 115 No. 5 May 2005, pp. 1447 (doi:10.1542/peds.2005-0118)
Weighing Statistical Certainty Against Ethical, Clinical, and Biologic Expediency: The Contributions of the Watterberg Trial Tip the Scales in the Right Direction: In Reply
Kristi Watterberg, MD for the PROPHET Study GroupDivision of Pediatrics/Neonatology
University of New Mexico School of Medicine
Albuquerque, NM 87131-0001
We thank Dr Gordon for his comments on our study.1 He asks whether antenatal glucocorticoids might also act synergistically to increase the risk for gastrointestinal perforation and whether late administration of betamethasone might have contributed to "supraphysiologic cortisol levels." We take this opportunity to present additional data regarding these 2 issues. First, those infants exposed to prenatal steroids were less likely, rather than more likely, to experience gastrointestinal perforation (4.6% vs 10.5%). The result was not statistically significant in our cohort of 360 infants (P = .06), and prenatal steroid administration was not randomized; however, these data make it unlikely that prenatal glucocorticoids act synergistically in the clinical setting to promote perforation.
Regarding the relationship of prenatal glucocorticoid dosing to cortisol concentrations, we found that infants exposed to prenatal glucocorticoids had significantly lower baseline cortisol values (P = .001). For those infants exposed to prenatal steroids, we found that as the time interval between the last dose of prenatal steroid and birth lengthened, the baseline cortisol increased (P < .0001; r = 0.26). These findings are consistent with previous work showing that administration of prenatal glucocorticoids suppresses endogenous cortisol production in the fetus in a time- and dose-dependent manner.2,3
It is problematic to call the cortisol concentrations measured at study baseline supraphysiologic, because they all resulted from endogenous production. The wide range of cortisol values seen in this population illustrates the variability of cortisol production in sick, stressed individuals. We do not know yet whether hydrocortisone in the absence of indomethacin would produce perforation in the premature infant, whatever the cortisol concentration. However, as stated in the article, considering the extremely high levels that some infants showed, monitoring cortisol concentrations in infants in whom hydrocortisone therapy is considered seems prudent.
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- Watterberg KL, Gerdes JS, Cole CH, et al. Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: a multicenter trial.
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[Abstract/Free Full Text] - Ballard PL, Gluckman PD, Liggins GC, Kaplan SL, Grumbach MM. Steroid and growth hormone levels in premature infants after prenatal betamethasone therapy to prevent respiratory distress syndrome. Pediatr Res. 1980;14 :122 –127[Web of Science][Medline]
- Ng PC, Lam CW, Lee CH, et al. Reference ranges and factors affecting the human corticotropin-releasing hormone test in preterm very low birth weight infants.
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[Abstract/Free Full Text]
PEDIATRICS (ISSN 1098-4275). ©2005 by the American Academy of Pediatrics
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