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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 volume 39, pages 934–940 (2019)Cite this article

Subjects

Abstract

Objective

The aim of this study is to establish the serum level distribution of cortisol and ACTH in VLBW preterm newborns and determine which neonates are ideal candidates for the stimulation test for adrenal insufficiency.

Methods

Plasma cortisol and ACTH levels were evaluated in 416 VLBW newborns on days 1, 7, and 30 of life. Gender, gestational age, weight, type of delivery, RDS prophylaxis, and perinatal morbidities were considered as potential variability factors.

Results

Cortisol and ACTH levels significantly decreased between 1, 7, and 30 days. Significantly higher cortisol levels were found at lower gestational ages and in infants born by vaginal delivery, whereas lower levels were observed in those born after maternal corticosteroid treatment. The distribution of cortisol and ACTH levels in healthy infants born by cesarian section is presented.

Conclusion

Even if high or low levels were not frequently linked to illness, the presented distribution data may indicate that the newborns are ideal candidates for the stimulation test.

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References

  1. Beverley E, Murphy BEP. Steroid arteriovenous differences in umbilical cord plasma: evidence of cortisol production by the human fetus in early gestation. J Clin Endocrinol Metab. 1973;36:1036–7.

  2. Economides DL, Nicolaides KH, Linton EA, Perry LA, Chard T. Plasma cortisol and adrenocorticotropin in appropriate and small for gestational age fetuses. Fetal Ther. 1988;3:158–64.

    Article  CAS  Google Scholar 

  3. Donaldson A, Nicolini U, Symes EK, Rodeck CH, Tannirandorn Y. Changes in concentrations of cortisol, dehydroepiandrosterone sulphate and progesterone in fetal and maternal serum during pregnancy. Clin Endocrinol. 1991;35:447–51.

    Article  CAS  Google Scholar 

  4. Iwanaga K, Yamamoto A, Matsukura T, Niwa F, Kawai M. Corticotrophin-releasing hormone stimulation tests for the infants with relative adrenal insufficiency. Clin Endocrinol. 2017;87:660–4.

    Article  CAS  Google Scholar 

  5. Bagnoli F, Mori A, Fommei C, Coriolani G, Badii S, Tomasini B. ACTH and cortisol cord plasma concentrations in preterm and term infants. J Perinatol. 2013;33:520–4.

    Article  CAS  Google Scholar 

  6. Moore TA, Schmid KK, French JA. Comparison of cortisol samples in the first two weeks of life in preterm infants. J Pedia Endocrinol Metab. 2015;28:415–20.

    CAS  Google Scholar 

  7. Finken MJJ, van der Voorn B, Hollanders JJ, Ruys CA, de Waard M, van Goudoever JB, et al. Programming of the hypothalamus-pituitary-adrenal axis by very preterm birth. Ann Nutr Metab. 2017;70:170–4.

    Article  CAS  Google Scholar 

  8. Travers S, Martinerie L, Boileau P, Lombès M, Pussard E. Alterations of adrenal steroidomic profiles in preterm infants at birth. Arch Dis Child Fetal Neonatal Ed. 2018;103:143–51.

    Article  Google Scholar 

  9. Ng PC. Adrenocortical insufficiency and refractory hypotension in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2018. https://doi.org/10.1136/archdischild-2016-311289.

    Article  Google Scholar 

  10. Ng PC. Effect of stress on the hypothalamic-pituitary-adrenal axis in the fetus and newborn. J Pedia. 2011;158(Suppl 2):41–3.

    Article  Google Scholar 

  11. Ng PC, Wong SP, Chan IH, Lam HS, Lee CH, Lam CW. A prospective longitudinal study to estimate the “adjusted cortisol percentile” in preterm infants. Pedia Res. 2011;69:511–6.

    Article  CAS  Google Scholar 

  12. Jett PL, Samuels MH, McDaniel PA. Variability of plasma cortisol levels in extremely low birth weight infants. J Clin Endocrinol Metab. 1997;82:2921–5.

    CAS  PubMed  Google Scholar 

  13. Waffarn F, Davis EP. Effects of antenatal corticosteroids on the hypothalamic-pituitary-adrenocortical axis of the fetus and newborn: experimental findings and clinical considerations. Am J Obstet Gynecol. 2012;207:446–54.

    Article  CAS  Google Scholar 

  14. Ng PC, Wong GWK, Lam CWK. The pituitary-adrenal response to exogenous human corticotropin-releasing hormon in preterm, very low birth weight infants. J Clin Endocrinol Metab. 1997;82:797–9.

    Article  CAS  Google Scholar 

  15. Watterberg KL, Scott SM. Evidence of early adrenal insufficiency in babies who develop bronchopulmonary dysplasia. Pediatrics. 1995;95:120–5.

    CAS  PubMed  Google Scholar 

  16. Watterberg KL, Scott SM, Backstrom C, Gifford KL, Cook KL. Links between early adrenal function and respiratory outcome in preterm infants: airway inflammation and patent ductus arteriosus. Pediatrics. 2000;105:320–4.

    Article  CAS  Google Scholar 

  17. Bolt RJ, van Weissenbruch MM, Popp-Snijders C, Sweep CG, Lafeber HN, Delemarre-van de Waal HA. Fetal growth and the function of the adrenal cortex in preterm infants. J Clin Endocrinol Metab. 2002;87:1194–9.

    Article  CAS  Google Scholar 

  18. Bertino E, Spada E, Occhi L, Coscia A, Giuliani F, Gagliardi L, et al. Neonatal anthropometric charts: the italian neonatal study compared with other European studies. J Pediatr Gastroenterol Nutr. 2010;51:353–61.

    PubMed  Google Scholar 

  19. Watterberg KL, Shaffer ML, Garland JS, Thilo EH, Mammel MC, Couser RJ, et al. Effect of dose on response to adrenocorticotropin in extremely low birth weight infants. J Clin Endocrinol Metab. 2005;90:6380–5.

    Article  CAS  Google Scholar 

  20. Ng PC, Lam CW, Lee CH. Reference ranges and factors affecting the human corticotropin-releasing hormone test in preterm, very low birth weight infants. J Clin Endocrinol Metab. 2002;87:4621–8.

    Article  CAS  Google Scholar 

  21. Grunau RE, Haley DW, Whitfield MF, Weinberg J, Yu W, Thiessen P. Altered basal cortisol levels at 3, 6, 8 and 18 months in infants born at extremely low gestational age. J Pedia. 2007;150:151–6.

    Article  CAS  Google Scholar 

  22. Heckmann M, Wudy SA, Haack D, Pohlandt F. Reference range for serum cortisol in well preterm infants. Arch Dis Child Fetal Neonatal Ed. 1999;81:171–4.

    Article  Google Scholar 

  23. Mears K, Mcauliffe F, Grimes H, Morrison JJ. Fetal cortisol in relation to labour, intrapartum events and mode of delivery. Obstetrics. 2004;24:129–32.

    CAS  Google Scholar 

  24. Vogl SE, Worda C, Egarter C. Mode of delivery is associated with maternal and fetal endocrine stress response. BJOG. 2006;113:441–5.

    Article  CAS  Google Scholar 

  25. Gitau R, Menson E, Pickles V, Fisk NM, Glover V, MacLachlan N. Umbilical cortisol levels as an indicator of the fetal stress response to assisted vaginal delivery. Eur J Obstet Gynecol Reprod Biol. 2001;98:14–7.

    Article  CAS  Google Scholar 

  26. Bagnoli F, Bruchi S, Marosi G, Inaudi P, Massafra C, Bracci R. Progesterone and cortisol plasma levels at birth: influence of labour and fetal distress. IJP. 1991;7:660–4.

    Google Scholar 

  27. Murphy BE. Human fetal serum cortisol levels at delivery: a review. Endocr Rev. 1983;4:150–4.

    Article  CAS  Google Scholar 

  28. Ng PC, Wong GW, Lam CW. Pituitary-adrenal response in preterm very low birth weight infants after treatment with antenatal corticosteroids. J Clin Endocrinol Metab. 1997;82:3548–52.

    Article  CAS  Google Scholar 

  29. Sari FN, Dizdar EA, Oguz SS, Andiran N, Erdeve O, Uras N, et al. Baseline and stimulated cortisol levels in preterm infants: is there any clinical relevance? Horm Res Paediatr. 2012;77:12–8.

    Article  CAS  Google Scholar 

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Acknowledgements

The Journal Club is a collaboration between the American Academy of Pediatrics—Section of Neonatal Perinatal Medicine and the International Society for Evidence-Based Neonatology (EBNEO.org).

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Authors and Affiliations

  1. Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy

    Annalisa Mori & Franco Bagnoli

  2. Department of Paediatric Endocrinology, Regina Margherita Children’s Hospital, Turin, Italy

    Gerdi Tuli, Daniele Tessaris & Luisa de Sanctis

  3. Department of Public Health and Paediatric Sciences, University of Turin, Turin, Italy

    Gerdi Tuli, Daniele Tessaris & Luisa de Sanctis

  4. Neonatology and Neonatal Intensive Care Unit, Riuniti Hospital, Foggia, Italy

    Rosario Magaldi & Matteo Rinaldi

  5. Division of Neonatology and Neonatal Intensive Care Unit (P.G.), Department of Maternal and Child Health, University of Pisa, Pisa, Italy

    Paolo Ghirri

Authors
  1. Annalisa Mori
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  2. Gerdi Tuli
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  3. Rosario Magaldi
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  4. Paolo Ghirri
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  7. Franco Bagnoli
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  8. Luisa de Sanctis
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Corresponding author

Correspondence to Gerdi Tuli.

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The authors declare that they have no conflict of interest.

Ethics

The study protocol was approved by the Ethics Committee of each Institution or University participating in the study.

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Written consent was obtained from the parents. The study protocol was approved by the Ethics Committee of each Institution or University participating in the study.

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Mori, A., Tuli, G., Magaldi, R. et al. Plasma cortisol and ACTH levels in 416 VLBW preterm infants during the first month of life: distribution in the AGA/SGA population. J Perinatol 39, 934–940 (2019). https://doi.org/10.1038/s41372-019-0381-2

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