Association between exposure to stress and experienced discomfort in preterm infants

BACKGROUND: Extremely (<26 weeks) and very (26-30 weeks) preterm infants are frequently exposed to stressors in the neonatal intensive care unit (NICU). This study investigated whether cumulative stress exposure, gestational age, postnatal age, or medication use influences discomfort during the first week after birth. METHODS: We retrospectively studied 41 extremely and 41 very preterm infants matched for clinical factors. Stress exposure was assessed using the Neonatal Infant Stressor Scale (NISS), and discomfort with the COMFORTneo scale. Associations were examined adjusting for gestational age, postnatal age, and sedative/analgesic use. RESULTS: Cumulative stress exposure was not associated with discomfort in any model (β -0.0046 to 0.0006; all p > 0.4). Gestational age and sedative/analgesic use were also not significant. COMFORTneo scores were higher on postnatal Day 3 (β = 0.91, p < 0.001) and Day 5 (β = 0.75, p = 0.004). CONCLUSION: Stress exposure, as measured by the NISS, does not directly correspond to discomfort in preterm infants. Postnatal age emerged as a key determinant during the first week of life. These findings highlight the complexity of discomfort assessment in very and extremely preterm infants and suggest that factors beyond stress exposure contribute to early-life distress. IMPACT STATEMENT: Cumulative stress exposure in the NICU does not directly predict experienced discomfort in preterm infants, indicating that behavioral responses may not solely reflect stress. Postnatal age is a key determinant, with the highest COMFORTneo scores on Days 3 and 5, highlighting critical timing effects in early neonatal care. These findings emphasize that developmental stage and care routines influence early-life distress, informing optimized pain and stress management strategies in preterm infants.