Long-Term Lung Function in Extremely Preterm Infants: Evidence, Trajectories, and Clinical Implications

Advances in perinatal and neonatal care have markedly improved the survival of extremely preterm infants; however, long-term respiratory outcomes remain a major clinical concern. Preterm birth is increasingly recognized as an early-life determinant of long-term respiratory health, with several individuals exhibiting persistent lung function impairment beyond childhood. We synthesized current evidence on long-term respiratory outcomes across the prematurity spectrum, primarily focusing on spirometric outcomes in extremely preterm infants, while distinguishing these physiological deficits from clinical respiratory morbidities. Longitudinal cohort studies generally demonstrate persistent airflow limitation, with extremely preterm survivors frequently exhibiting forced expiratory volume in 1 s (FEV₁) values 1.0 to 1.5 z-scores below term-born peers. These physiological deficits are greater in individuals with bronchopulmonary dysplasia (BPD) history, where FEV₁ and FEV₁/forced vital capacity z-scores often remain persistently low, ranging between -1.5 and -2.0 by early adulthood, with evidence of progressive worsening in some cohorts. Evidence regarding temporal trends in lung function is heterogeneous. However, secular trend analysis indicates that although advances in perinatal care have coincided with significant FEV₁ z-score improvements for infants born at 26-27 weeks' gestation (e.g., from -0.90 to -0.39 over a 20-year period), outcomes for those at the limits of viability (22-25 weeks) have shown little improvement. Despite substantial progress in neonatal care, long-term respiratory impairment remains common following preterm birth. Establishing risk-stratified, long-term surveillance systems targeting high-risk groups-such as those with extreme prematurity, severe BPD, recurrent infections, or impaired fetal growth-may help characterize trajectories and optimize long-term respiratory health.