This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ng, P. C. Articles by Wong, E. Search for Related Content PubMed PubMed Citation Articles by Ng, P. C. Articles by Wong, E.

Reference Ranges and Factors Affecting the Human Corticotropin-Releasing Hormone Test in Preterm, Very Low Birth Weight Infants

Department of Pediatrics (P.C.N., C.H.L., K.C.M., T.F.F.), Department of Chemical Pathology (C.W.K.L., I.H.S.C.), and Center for Clinical Trials and Epidemiological Research (E.W.), Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, N.T., Hong Kong

Address all correspondence and requests for reprints to: Prof. P. C. Ng, Department of Pediatrics, Level 6, Clinical Sciences Building, Prince of Wales Hospital, Shatin, N.T., Hong Kong. E-mail: pakcheungng{at}cuhk.edu.hk.

Abstract

This prospective study aims to investigate the factors that influence the human CRH (hCRH) test and to provide reference ranges for plasma corticotropin (ACTH) and serum cortisol concentrations of the stimulation test in preterm, very low birth weight (VLBW) infants.

Two hundred twenty-six hCRH tests were performed on 137 VLBW infants at d 7 and 14 of life. Plasma ACTH did not differ significantly between infants whose mothers did not receive antenatal corticosteroids (group 1) and those whose mothers received one or two doses (group 2) or more than two doses (group 3) of the drug. However, plasma ACTH levels at d 7 were found to be significantly higher in infants with severe lung disease who required intermittent positive-pressure ventilation (IPPV) or high-frequency oscillation ventilation (HFOV), compared with those who had milder pulmonary disease and did not require mechanical ventilation or needed only continuous positive airway pressure (CPAP) support (P < 0.011). A significantly higher rate of increase in plasma ACTH concentration at d 7 was also observed in infants whose mothers suffered from antepartum hemorrhage (P < 0.016).

In contrast, infants in group 2 had significantly lower serum cortisol, compared with group 1 infants (P < 0.05), whereas group 3 infants did not have serum cortisol levels significantly different from those of patients in group 1 or 2. Significant positive correlation between serum cortisol at d 7 and the time interval between the last dose of antenatal dexamethasone and delivery was also observed in group 3 infants (r > 0.33, P < 0.045). In addition, infants who required IPPV or HFOV had significantly lower serum cortisol at d 7 (P < 0.0001), but this pattern of cortisol response was reversed on d 14, with infants requiring IPPV or HFOV having significantly higher serum cortisol (P < 0.036). The reference ranges for plasma ACTH and serum cortisol concentrations of the hCRH test at d 7 and 14 were also provided for group 1 and group 2 infants.

This study demonstrates that even one or two doses of antenatal corticosteroids cause adrenal suppression in VLBW infants. Maternal antepartum hemorrhage also influences the pituitary response of preterm newborns in the first week of life. The change in the pattern of cortisol response in sick ventilated (IPPV or HFOV) infants during the first 2 wk of life suggests that a proportion of preterm infants may have inadequate adrenal response to stress in early postnatal life, but it is likely that rapid adaptation of the hypothalamic-pituitary-adrenal axis results in enhanced and more appropriate cortisol response by d 14. The percentile distribution of plasma ACTH and serum cortisol responses provides useful statistical reference data for interpretation of the hCRH test in VLBW infants and may also assist in facilitating the use of corticosteroids replacement therapy in cases with clinical manifestations suggestive of adrenal insufficiency.

This article has been cited by other articles:

				P. Nykanen, T. Raivio, K. Heinonen, O. A Janne, and R. Voutilainen Circulating glucocorticoid bioactivity and serum cortisol concentrations in premature infants: the influence of exogenous glucocorticoids and clinical factors Eur. J. Endocrinol., May 1, 2007; 156(5): 577 - 583. [Abstract] [Full Text] [PDF]

				P. C. Ng, C. H. Lee, F. L. Bnur, I. H.S. Chan, A. W.Y. Lee, E. Wong, H. B. Chan, C. W.K. Lam, B. S.C. Lee, and T. F. Fok A Double-Blind, Randomized, Controlled Study of a "Stress Dose" of Hydrocortisone for Rescue Treatment of Refractory Hypotension in Preterm Infants Pediatrics, February 1, 2006; 117(2): 367 - 375. [Abstract] [Full Text] [PDF]

				K. L. Watterberg, M. L. Shaffer, J. S. Garland, E. H. Thilo, M. C. Mammel, R. J. Couser, S. W. Aucott, C. L. Leach, C. H. Cole, J. S. Gerdes, et al. Effect of Dose on Response to Adrenocorticotropin in Extremely Low Birth Weight Infants J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6380 - 6385. [Abstract] [Full Text] [PDF]

				K. Watterberg and for the PROPHET Study Group Weighing Statistical Certainty Against Ethical, Clinical, and Biologic Expediency: The Contributions of the Watterberg Trial Tip the Scales in the Right Direction: In Reply Pediatrics, May 1, 2005; 115(5): 1447 - 1447. [Full Text] [PDF]

				R. E. Grunau, J. Weinberg, and M. F. Whitfield Neonatal Procedural Pain and Preterm Infant Cortisol Response to Novelty at 8 Months Pediatrics, July 1, 2004; 114(1): e77 - e84. [Abstract] [Full Text] [PDF]

				P C Ng, C H Lee, C W K Lam, K C Ma, T F Fok, I H S Chan, and E Wong Transient adrenocortical insufficiency of prematurity and systemic hypotension in very low birthweight infants Arch. Dis. Child. Fetal Neonatal Ed., March 1, 2004; 89(2): F119 - F126. [Abstract] [Full Text] [PDF]

				P C Ng, C H Lee, C W K Lam, K C Ma, I H S Chan, E Wong, and T F Fok Early pituitary-adrenal response and respiratory outcomes in preterm infants Arch. Dis. Child. Fetal Neonatal Ed., March 1, 2004; 89(2): F127 - F130. [Abstract] [Full Text] [PDF]

				K Hussain and A Aynsley-Green Hyperinsulinaemic hypoglycaemia in preterm neonates Arch. Dis. Child. Fetal Neonatal Ed., January 1, 2004; 89(1): F65 - F67. [Abstract] [Full Text] [PDF]