The effect of bubble nasal continuous positive airway pressure application on saliva cortisol levels in full-term neonates

  • Noor Fadli Idrus
  • Andi Dwi Bahagia Febriani Hasanuddin University
  • Ema Alasiry
Keywords: salivary cortisol, nCPAP, term neonates


Background Neonates with respiratory distress are commonly treated with bubble nasal continuous positive airway pressure (nCPAP) and undergo many procedures that cause stress-induced pain. Salivary cortisol is a biomarker of alteration in the hypothalamic-pituitary-adrenal axis caused by repeated and long-term exposure to stress.

Objective To analyze the effect of bubble nCPAP use on salivary cortisol levels in full-term infants.

Methods This study used a one-group pre-test­–post-test design to compare salivary cortisol levels before and 30 minutes after bubble nCPAP application. Salivary cortisol was measured using an ELISA method. Pain was also assessed at the same time points using the Neonatal Infant Pain Scale (NIPS) score. We included infants of 37 0/7 to 42 6/7 weeks’ gestational age with respiratory distress necessitating bubble nCPAP application. Infants with birth weight of <2,500 grams, major congenital anomalies, an APGAR score of <5 at 5 minutes, shock, and infants who had undergone surgery were excluded.

Results A total of 38 subjects participated in this study. Prior to bubble nCPAP application, median cortisol levels were significantly lower (1.65 ng/mL) than after bubble nCPAP application (6.8 ng/mL) (p value?). There were no significant differences in cortisol increase based on gender, type of birth, or salivary cortisol sampling time. There were significant differences in pain level after the 30-minute nCPAP  application.

Conclusion An increase in cortisol levels and pain scale scores during administration of bubble  nCPAP  indicates a pain response in full-term neonates; therefore, this procedure should be accompanied by pain or stress management.


1. Guay JM, Carvi D, Raines DA, Luce WA. Care of the neonate on nasal continuous positive airway pressure: a bedside guide. Neonatal Netw. 2018;37:24–32. DOI:
2. Jacob J, Kamitsuka M, Clark RH, Kelleher AS, Spitzer AR. Etiologies of NICU deaths. Pediatrics. 2015;135:e59-65. DOI:
3. Marfuah M, Barlianto W, Susmarini D. Faktor risiko kegawatan nafas pada neonatus di rsd. dr. haryoto kabupaten lumajang tahun 2013. JNSU. 2013;1:119-27. [cited 2023 April 26]. Available from:
4. Vitaliti SM, Costantino G, Li Puma L, Re MP, Vergara B, Pinello G. Painful procedures in the NICU. J Matern Fetal Neonatal Med. 2012;25 Suppl 4:146–7. DOI:
5. Dunn MS, Kaempf J, de Klerk A, de Klerk R, Reilly M, Howard D, et al. Randomized trial comparing 3 approaches to the initial respiratory management of preterm neonates. Pediatrics. 2011;128:e1069-76. DOI: Epub 2011 Oct 24.
6. Fischer C, Bertelle V, Hohlfeld J, Forcada-Guex M, Stadelmann-Diaw C, Tolsa JF. Nasal trauma due to continuous positive airway pressure in neonates. Arch Dis Child Fetal Neonatal Ed. 2010;95:F447-51. DOI:
7. Osman M, Elsharkawy A, Abdel-Hady H. Assessment of pain during application of nasal-continuous positive airway pressure and heated, humidified high-flow nasal cannulae in preterm infants. J Perinatol. 2015;35:263–7. DOI:
8. Relland LM, Gehred A, Maitre NL. Behavioral and physiological signs for pain assessment in preterm and term neonates during a nociception-specific response: a systematic review. Pediatr Neurol. 2019;90:13–23. DOI:
9. Provenzi L, Giusti L, Fumagalli M, Tasca H, Ciceri F, Menozzi G, et al. Pain-related stress in the neonatal intensive care unit and salivary cortisol reactivity to socio-emotional stress in 3-month-old very preterm infants. Psychoneuroendocrinology. 2016;72:161–5. DOI:
10. Cabral DM, Antonini SRR, Custódio RJ, Martinelli CEJ, da Silva CAB. Measurement of salivary cortisol as a marker of stress in newborns in a neonatal intensive care unit. Horm Res Paediatr. 2013;79:373–8. DOI:
11. Ivars K, Nelson N, Theodorsson A, Theodorsson E, Ström JO, Mörelius E. Development of salivary cortisol circadian rhythm in preterm infants. PLoS One. 2017;12:e0182685. DOI:
12. D’Agata AL, Roberts MB, Ashmeade T, Dutra SVO, Kane B, Groer MW. Novel method of measuring chronic stress for preterm infants: skin cortisol. Psychoneuroendocrinology. 2019;102:204–11. DOI:
13. Rebelato C, Fernandes Stumm E. Analysis of pain and free cortisol of newborns in intensive therapy with therapeutic procedures. Brazilian J Pain. 2019;2:159-65. DOI:
14. Donia AES, Tolba OA. Effect of early procedural pain experience on subsequent pain responses among premature infants. Egypt Pediatr Assn Gazette. 2016;64:74–80. DOI:
15. Osman M, Elsharkawy A, Abdel-Hady H. Assessment of pain during application of nasal-continuous positive airway pressure and heated, humidified high-flow nasal cannulae in preterm infants. J Perinatol. 2015;35:263–7. DOI:
16. Sarapuk I, Pavlyshyn H. Assessment and correction of stress in preterm infants and their mothers. Turkish Arch Pediatr. 2022;57:146–50. DOI:
17. Arafa A, ELMeneza S, Hafeez S, Arafa A. The relation between role of serum cortisol level and response to various respiratory support strategies among preterm infants. Open J Pediatr. 2020;10:504–14. DOI:
18. 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 Pediatr. 2007;150:151–6. DOI:
19. Sobas EM, Reinoso R, Cuadrado-Asensio R, Fernández I, Maldonado MJ, Pastor JC. Reliability of potential pain biomarkers in the saliva of healthy subjects: inter-individual differences and intersession variability. PLoS One. 2016;11:e0166976. DOI:
20. Trevisanuto D, Grazzina N, Doglioni N, Ferrarese P, Marzari F, Zanardo V. A new device for administration of continuous positive airway pressure in preterm infants: comparison with a standard nasal CPAP continuous positive airway pressure system. Intensive Care Med. 2005;31:859–64. DOI: Epub 2005 Apr 19.
21. American Academy of Pediatrics – Committee on Fetus and Newborn and Section on Surgery and Canadian Paediatric Society – Fetus and Newborn Committee: Prevention and management of pain and stress in the neonate. Pediatrics 2006;118:2231–2241. PMID: 10654977.
22. Yamada J, Stevens B, De Silva N, Gibbins S, Beyene J, Taddio A, Newman C, Koren G: Hair cortisol as a potential biologic marker of chronic stress in hospitalized neonates. Neonatology 2007;92:42–49. DOI:
23. Kim SS. Prevention and management of pain in the neonatal intensive care unit. Clin Exp Pediatr. 2020;63:16–7. DOI:
How to Cite
Idrus NF, Febriani ADB, Alasiry E. The effect of bubble nasal continuous positive airway pressure application on saliva cortisol levels in full-term neonates. PI [Internet]. 21Feb.2024 [cited 18Apr.2024];64(1):22-. Available from:
Received 2022-12-22
Accepted 2024-02-21
Published 2024-02-21