Neuroprognostication in infants born preterm at the limits of viability: assessment under uncertainty

Infants born extremely preterm at the limits of viability (LoV) represent a relatively small population but account for a disproportionate share of long-term neurodevelopmental impairment. Clinical decision-making at the LoV is often guided by expectations of neurodevelopmental outcome, yet during these early days prognostic uncertainty is high. This review proposes a structured approach to neuroprognostication based on longitudinal clinical reasoning rather than single-timepoint prognostication. Being born at the LoV establishes baseline vulnerability through global brain dysmaturation. Subsequent prematurity-related clinical events, including major systemic morbidities such as bronchopulmonary dysplasia, necrotizing enterocolitis, and sepsis, progressively modify potential outcomes over time. Neonatal intensive care exposures, growth trajectory, environmental factors, and sex further influence developmental pathways. The presence of preterm brain injury, including germinal-matrix and intraventricular hemorrhage, white matter injury, and cerebellar hemorrhage is also an important predictor of neurodevelopmental outcome. Prognostic confidence emerges from integrating these data as new information becomes available. The proposed framework for neuroprognostication in infants born at the LoV integrates clinical, neuroimaging and environmental risk factors to form a prognostic opinion. Emphasis is placed on probabilistic outcomes, where the initial prognostic opinion serves as a baseline that can be updated as new clinical and neuroimaging information emerges. IMPACT: Neuroprognostication for infants born at the limits of viability should integrate clinical, neuroimaging and environmental risk factors to form a baseline prognostic opinion. This initial prognostic opinion can be refined as new findings emerge during the prolonged NICU admission. Major neonatal morbidities and everyday NICU exposures modify the developmental trajectory, while preterm brain injury adds more specificity to the possible range of outcomes. Counseling should avoid binary predictions, frame prognosis as a spectrum of probabilities, acknowledge uncertainty, and update expectations as the clinical course evolves. A structured counseling framework supports transparent risk communication, shared decision-making, and early developmental intervention.