Novel method of measuring chronic stress for preterm infants: Skin cortisol

Infants who begin life in the medicalized environment of the neonatal intensive care unit (NICU) do so under stressful conditions. Environmental exposures are often abrasive to vulnerable infants, while invasive and noninvasive lifesaving interventions provide additional pain and/or stress. The most commonly selected biomarker to measure stress is cortisol. The skin is the barrier between the external environment and communicates with our neurological, endocrine and immune regulatory networks. To examine if skin cortisol may be a reliable biomarker of stress, NICU stress exposure and repeated measurements of skin cortisol in very preterm infants were examined retrospectively during the first 6 weeks of life. The temporal relationship between skin cortisol and NICU stress exposure was also analyzed.

Participants included 82 preterm infants born weighing less than 1500 g, admitted to a level III NICU, with a mean gestational age of 28.5 weeks. Infants were studied from birth through 6 weeks of life. NICU stress data was collected using the Neonatal Infant Stressor Scale. Skin samples were collected using d-squame tape as soon after birth as possible and every two weeks thereafter.

On average, infants experienced approximately 43 stressful events per day during the first 6 weeks of life in the NICU. Stress level and cortisol reactivity varied by gestation age. Higher stress resulted in higher cortisol for infant >28 weeks; lower stress scores were associated with higher stress for infants <28 weeks. Stress exposure during 7 days prior to cortisol sampling yielded the highest AUC for the 2 groups. A statistically significant interaction was identified between gestational age and stress exposure during the previous 7 days (p < 0.01).

This is the first study to demonstrate skin cortisol as a preterm infant biomarker of chronic stress exposure. For infants with appropriate skin maturation, this non-invasive sampling method provides several benefits. Importantly, this method may be less intrusive and disruptive for preterm infants.