Clinical validation of the Neonatal Infant Stressor Scale with preterm infant salivary cortisol

Pediatr Res. 2020 Jun;87(7):1237-1243. doi: 10.1038/s41390-019-0713-0. Epub 2019 Dec 17.


Background: Preterm infants face unique stress states in early life. Early-life stress has been associated with changes in cortisol reactivity and behavioral abnormalities later in childhood in non-preterm populations. The Neonatal Infant Stressor Scale (NISS) has been used to estimate infant stress in the neonatal intensive care unit (NICU) but has not been biomarker validated. The relationship between NISS scores and salivary cortisol is unknown. The aim of this study is to test the association between NISS scores and salivary cortisol in the NICU Hospital Exposures and Long-Term Health (NICU-HEALTH) preterm birth cohort.

Methods: Three hundred and eighty-six salivary cortisol specimens were collected from 125 NICU-HEALTH participants during the NICU hospitalization. NISS scores were calculated to represent the infant's experience in the 6 hours prior to specimen collection. Adjusted mixed-effect regression models were used to assess the association between each NISS score and salivary cortisol.

Results: Acute and total NISS scores were significantly associated with salivary cortisol level (P = 0.002 and 0.05, respectively). The chronic NISS score was not associated with salivary cortisol levels. Caffeine treatment and postmenstrual age of the infant were important covariates in all models.

Conclusion: Acute and total NISS score are associated with salivary cortisol level in hospitalized moderately preterm infants.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Biomarkers / metabolism
  • Caffeine / administration & dosage
  • Cohort Studies
  • Female
  • Humans
  • Hydrocortisone / metabolism*
  • Infant, Newborn
  • Intensive Care Units, Neonatal
  • Male
  • Saliva / metabolism*
  • Stress, Psychological / metabolism*


  • Biomarkers
  • Caffeine
  • Hydrocortisone