Abstract
The normal range of serum cortisol concentrations and the appropriate levels of circulating cortisol in different clinical situations in preterm infants are not well defined. This study aimed to evaluate the impact of perinatal factors on circulating cortisol levels in preterm infants and to create a quantitative model that could estimate the “adjusted cortisol percentile.” Serial serum cortisol concentrations were measured in 209 infants ≤32 wk gestation on d 1, 4, 7, 14, and 21 of life. Seven perinatal factors or conditions that could affect circulating cortisol level were identified. Serum cortisol levels were higher on d 4 (p = 0.007) and d 7 (p = 0.007) but lower on d 21 (p = 0.001) compared with d 1. Serum cortisol was also higher in infants on nasal continuous positive airway pressure (p = 0.003); requiring a second vasopressor (p < 0.001); with intraventricular hemorrhage (≥ grade 3; p < 0.001); with histologic chorioamnionitis (p = 0.007); with severe lung disease (p = 0.046); and with decreasing GA (p < 0.001). A mathematical equation was proposed based on factors derived in this preliminary study for estimating the adjusted cortisol percentile. Frontline neonatologists could now access the equation on our Web site (http://www.sta.cuhk.edu.hk/pswong/ACortP.html) to calculate the adjusted cortisol percentile, which could potentially improve the interpretation of circulating cortisol in different clinical situations.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- AIC:
-
Akaike information criterion
- BIC:
-
Bayesian information criterion
- BPD:
-
bronchopulmonary dysplasia
- HFOV:
-
high-frequency oscillatory ventilation
- HPA:
-
hypothalamic-pituitary-adrenal
- IPPV:
-
intermittent positive pressure ventilation
- IVH:
-
intraventricular hemorrhage
- nCPAP:
-
nasal continuous positive airway pressure
- PE:
-
prediction errors
- VLBW:
-
very LBW
REFERENCES
Ng PC 2000 The fetal and neonatal hypothalamic-pituitary-adrenal axis. Arch Dis Child Fetal Neonatal Ed 82: F250–F254
Mesiano S, Jaffe RB 1997 Developmental and functional biology of the primate fetal adrenal cortex. Endocr Rev 18: 378–403
Helbock HJ, Insoft RM, Conte FA 1993 Glucocorticoid-responsive hypotension in extremely low birth weight newborns. Pediatrics 92: 715–717
Ng PC, Lam CW, Fok TF, Lee CH, Ma KC, Chan IH 2001 Refractory hypotension in preterm infants with adrenocortical insufficiency. Arch Dis Child Fetal Neonatal Ed 84: F122–F124
Ng PC, Lee CH, Lam CW, Ma KC, Fok TF, Chan IH, Wong E 2004 Transient adrenocortical insufficiency of prematurity (TAP) and systemic hypotension in very low birth weight infants. Arch Dis Child Fetal Neonatal Ed 89: F119–F126
Watterberg KL, Gerdes JS, Cook KL 2001 Impaired glucocorticoid synthesis in premature infants developing chronic lung disease. Pediatr Res 50: 190–195
Huysman MW, Hokken-Koelega AC, De Ridder MA, Sauer PJ 2000 Adrenal function in sick very preterm infants. Pediatr Res 48: 629–633
Watterberg KL, Gerdes JS, Cole CH, Aucott SW, Thilo EH, Mammel MC, Couser RJ, Garland JS, Rozycki HJ, Leach CL, Backstrom C, Shaffer ML 2004 Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: a multicenter trial. Pediatrics 114: 1649–1657
Aucott SW, Watterberg KL, Shaffer ML, Donohue PK, PROPHET Study Group 2008 Do cortisol concentrations predict short-term outcomes in extremely low birth weight infants?. Pediatrics 122: 775–781
Ng PC, Lam CW, Lee CH, Ma KC, Fok TF, Chan IH, Wong E 2002 Reference ranges and factors affecting the hCRH test in preterm, very low birth weight infants. J Clin Endocrinol Metab 87: 4621–4628
Heckmann M, Hartmann MF, Kampschulte B, Gack H, Bödeker RH, Gortner L, Wudy SA 2005 Cortisol production rates in preterm infants in relation to growth and illness: a noninvasive prospective study using gas chromatography-mass spectrometry. J Clin Endocrinol Metab 90: 5737–5742
Lee MM, Rajagopalan L, Berg GJ, Moshang T Jr 1989 Serum adrenal steroid concentrations in premature infants. J Clin Endocrinol Metab 69: 1133–1136
Hingre RV, Gross SJ, Hingre KS, Mayes DM, Richman RA 1994 Adrenal steroidogenesis in very low birth weight preterm infants. J Clin Endocrinol Metab 78: 266–270
Ng PC 2008 Is there a ‘normal' range of serum cortisol concentration for preterm infants?. Pediatrics 122: 873–875
Howie RN, Liggins G 1982 The New Zealand study of antepartum glucocorticoid treatment. In: Farrell PM (ed) Lung Development: Biological and Clinical Perspectives, Vol II. Academic Press, New York, pp 255–265
Ment LR, Oh W, Ehrenkranz RA, Philip AG, Vohr B, Allan W, Duncan CC, Scott DT, Taylor KJ, Katz KH, Schneider KC, Makuch RW, Philip AG 1994 Low-dose indomethacin and prevention of intraventricular hemorrhage: a multicenter randomized trial. Pediatrics 93: 543–550
Ballard JL, Khoury JC, Wedig K, Wang L, Eilers-Walsman BL, Lipp R 1991 New Ballard score, expanded to include extremely premature infants. J Pediatr 119: 417–423
Ng PC, Lee CH, Lam CW, Fok TF, Chan IH, Ma KC, Wong E 2004 Early pituitary-adrenal response and respiratory outcomes in preterm infants. Arch Dis Child Fetal Neonatal Ed 89: F127–F130
Goldstein H 1995 Multilevel statistical models. In: Goldstein H (ed) Kendalls Library of Statistics 3. Edward Arnold, London, pp 87–94
Lai TL, Shih MC, Wong SP 2006 A new approach to modeling covariate effects and individualization in population pharmacokinetic. J Pharmacokinet Pharmacodyn 33: 49–74
Lai TL, Shih MC, Wong SP 2006 Flexible modeling of fixed and random effects in generalized mixed models for longitudinal data. Biometrics 62: 159–167
Akaike H 1974 A new look at the statistical model identification. IEEE Trans Automat Contr 19: 716–723
Heckmann M, Wudy SA, Haack D, Pohlandt F 1999 Reference range for serum cortisol in well preterm infants. Arch Dis Child Fetal Neonatal Ed 81: F171–F174
Konishi S, Kitagawa G 2008 Bayesian information criteria. In: Konishi S and Kitagawa G (eds) Information criteria and statistical modeling. Springer, New York, pp 211–236
Watterberg KL, Scott SM, Naeye RL 1997 Chorioamnioitis, cortisol, and acute lung disease in very low birth weight infants. Pediatrics 99: E6
Quinn MW, Wild J, Dean HG, Hartley R, Rushforth JA, Puntis JW, Levene MI 1993 Randomised double-blind controlled trial of effect of morphine on catecholamine concentrations in ventilated pre-term babies. Lancet 342: 324–327
Aloisi AM, Aurilio C, Bachiocco V, Biasi G, Fiorenzani P, Pace MC, Paci V, Pari G, Passavanti G, Ravaioli L, Sindaco G, Vellucci R, Ceccarelli L 2009 Endocrine consequences of opioid therapy. Psychoneuroendocrinology 34: S162–S168
Ng PC, Fok TF, Wong GW, Lam CW, Lee CH, Wong MY, Lam K, Ma KC 1998 Pituitary-adrenal suppression in preterm, very low birth weight infants after inhaled fluticasone propionate treatment. J Clin Endocrinol Metab 83: 2390–2393
Author information
Authors and Affiliations
Additional information
Supported by the Research Fund of the Department of Pediatrics, The Chinese University of Hong Kong.Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.pedresearch.org).
Rights and permissions
About this article
Cite this article
Ng, P., Wong, S., Chan, I. et al. A Prospective Longitudinal Study to Estimate the “Adjusted Cortisol Percentile” in Preterm Infants. Pediatr Res 69, 511–516 (2011). https://doi.org/10.1203/PDR.0b013e31821764b1
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/PDR.0b013e31821764b1
This article is cited by
-
Plasma cortisol and ACTH levels in 416 VLBW preterm infants during the first month of life: distribution in the AGA/SGA population
Journal of Perinatology (2019)
-
Late-onset Circulatory Collapse and Continuous Positive Airway Pressure are Useful Predictors of Treatment-requiring Retinopathy of Prematurity: A 9-year Retrospective Analysis
Scientific Reports (2017)
-
Prenatal and postnatal inflammation in relation to cortisol levels in preterm infants at 18 months corrected age
Journal of Perinatology (2013)
