Abstract
BACKGROUND: Despite major advances in neonatal intensive care, mortality in neonatal intensive care units (NICUs) remains a persistent reality. Most deaths now occur after withholding or withdrawing life-sustaining therapies (WWLST), yet some remain sudden or unanticipated. Understanding how and under which circumstances infants die is essential to improving anticipatory communication, ethical consistency, and family-centered support in neonatal end-of-life (EOL) care. METHODS: We conducted a retrospective study including all infants who died in the tertiary NICU of Montpellier University Hospital, France, between May 2022 and May 2025. Demographic, perinatal, clinical, and end-of-life data were extracted from medical records. Deaths were classified as anticipated (following WWLST) or unanticipated (without WWLST). Statistical comparisons explored factors associated with unanticipated deaths. RESULTS: Among 870 NICU admissions, 105 infants (12%) died. Mortality was concentrated in three groups: very premature infants (< 29 weeks' gestation, 55%), infants with severe congenital or early-onset conditions (26%), and those with hypoxic-ischemic encephalopathy (19%). Seventy-six infants (72%) died after a WWLST decision-most often for poor neurological prognosis or perceived futility of care-whereas 23 (22%) died without a prior WWLST decision. Unanticipated deaths were mainly associated with multi-organ failure (≥ 3 organs 65% vs 40%; p=0.02), predominantly cardiovascular or respiratory failure, shorter illness trajectories (1 vs 6.5 days from complication to death; p<0.01), and reduced parental presence during EOL care (52% vs 80%; p<0.01), including fewer opportunities for parents to be present and to hold their infant at the time of death. CONCLUSIONS: In this tertiary NICU, most deaths were anticipated and occurred following structured WWLST processes. Unanticipated deaths primarily reflected rapid clinical deterioration and were associated with more abrupt and less family-centered end-of-life circumstances. These findings underscore the importance of early recognition of dying trajectories and timely multidisciplinary discussions to support anticipatory, compassionate, and parent-centered end-of-life care in the NICU. Strengthening education in neonatal ethics and palliative care may foster more consistent, compassionate, and anticipatory EOL practices.