Chronic respiratory morbidity and wheeze after preterm birth: a narrative review

Preterm birth, defined as birth before 37 weeks of gestation, affects approximately 10% of pregnancies worldwide. Premature birth disrupts normal lung development with those born at earlier gestations most affected. Individuals born preterm are at increased risk of lifelong respiratory morbidity, including recurrent wheeze. As a consequence, affected individuals are often given an incorrect diagnosis of asthma. Asthma is considered a clinical description and is defined as a clinical syndrome characterised by wheeze, breathlessness, and chest tightness, sometimes accompanied by excess cough. This narrative review reports wheeze following preterm birth, considers prematurity-associated lung disease as an alternative diagnosis to asthma and discusses early life exposures as modifiable factors. Furthermore, whether prediction of those at highest risk is possible and what is the optimum management and follow up for affected individuals is discussed. Preterm birth is associated with an approximately double the risk of wheezing in childhood and is particularly common in those born extremely prematurely. While type two (T2) asthma is the predominant asthma phenotype in the general paediatric population, non-T2 mechanisms may be more relevant in those born preterm and hence why they are often unresponsive to standard asthma regimens. Potentially modifiable risk factors are antenatal corticosteroids, in utero growth retardation, chorioamnionitis, maternal antenatal smoking, breast feeding, neonatal antibiotic exposure, aspiration lung disease, viral infections, pollution, the microbiome and socio-economic factors. Prematurely born individuals have a lower lung function trajectory than those born at term, predictors of those at higher risk may be possible using either a definition of BPD that emphasises the respiratory support needed at 36 weeks PMA or cluster analysis using clinical data. The heavy burden of chronic respiratory morbidity in this population warrants their lifelong follow-up and a personalised approach to their management.