UNLABELLED: This study aims to quantify stress exposure related to clinical stressors in preterm infants during NICU admission and identify risk factors for high stress exposure. In this national cohort study, preterm infants (gestational age <
29 weeks) were prospectively followed during the first 28 days of their admission to one of the 10 NICUs in the Netherlands. The NeO-stress score, consisting of 38 clinical stressors graded with a severity index, was applied to describe stress exposure. We assessed the impact of infant characteristics at birth and postnatal age on NeO-stress scores using linear mixed modelling. In total, 446 infants were included with a median gestational age of 27 CONCLUSION: Stress exposure in preterm infants during NICU admission varies over time with infants with the lowest gestational age at risk for experiencing the highest levels of stress throughout NICU admission. This highlights the importance stress reduction and provides opportunities for future interventions aimed at reducing stress exposure. WHAT IS KNOWN: • Preterm birth and admission to a Neonatal Intensive Care Unit is very stressful. • High stress exposure in neonatal life is associated with adverse long term outcome. WHAT IS NEW: • Stress exposure is highest in infants with the youngest gestational ages where it remains high or even increases during the first month of life. • Lower gestational age, no antenatal administration of corticosteroids and lower 5-min Apgar score were significantly related with higher daily NeO-stress scores.