Spontaneous Achievers, Responders and Non‐Responders: Aligning Treatment With the Natural History of Bronchopulmonary Dysplasia in Preterm Infants

AIM: To examine how early pulmonary phenotype influences treatment response and the interpretation of trial outcomes in bronchopulmonary dysplasia (BPD). METHODS: A narrative review of early respiratory patterns in very preterm infants and their relationship to treatment response, using published trials of postnatal corticosteroids as the primary example. RESULTS: BPD is defined at 36 weeks' postmenstrual age by treatment requirements, reflecting clinical practice rather than the underlying disease biology. The clinical phenotype is evident much earlier. Some infants stabilise with supportive care alone, while others develop persistent pulmonary disease consistent with emerging BPD, with variable responses to treatment. When therapies are applied to broad early populations, spontaneous achievers dilute the apparent treatment effect. As postnatal age increases and populations are enriched for persistent disease, treatment effects become larger and more consistent. Findings from postnatal corticosteroid trials follow this pattern. CONCLUSION: Thus, the effect of disease-modifying therapy in infants at risk of BPD reflects both the intervention and the interaction between population risk and cohort phenotype and is best understood when treatment and trial design align with the early clinical phenotype.