Improving lifelong respiratory health after preterm birth

Abstract

Bronchopulmonary dysplasia (BPD; also known as chronic lung disease of prematurity) is the most common complication of extremely preterm birth. Neonatal respiratory support and a range of antenatal and postnatal factors can contribute to lung injury and impaired lung growth and repair in preterm infants, increasing the risk of BPD and persistent respiratory disease, with potentially lifelong consequences for health and wellbeing. Recent society guidelines provide new recommendations on the management of infants, children, and adolescents with post-prematurity respiratory disease (PPRD). Crucially, they emphasise the pressing need for a stronger evidence base to support clinical decision-making in the care of survivors of preterm birth, from infancy into adulthood. The risk of BPD increases with decreasing gestational age and birthweight; despite the development of less injurious strategies for respiratory support—including surfactant administration and protective ventilation—the prevalence of BPD has remained high as survival rates of extremely preterm infants (<28 weeks’ gestation) have increased. However, variations in the definition and diagnosis of BPD mean that estimates of prevalence vary widely. Recent approaches have defined disease severity according to the need for respiratory support and supplemental oxygen at 36 weeks’ postmenstrual age (PMA). But preterm infants who do not meet current criteria for BPD can have adverse respiratory outcomes that require long-term care and support, and the development of diagnostic criteria to reliably establish disease presence and severity, and to predict death or morbidity in survivors, remains a priority for the field. In 2020, an ERS guideline was published on the long-term management of patients with BPD who were discharged from hospital or older than 36 weeks’ PMA. Given the paucity of evidence—assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach—a multidisciplinary task force provided conditional (weak) recommendations on lung imaging and lung function monitoring, daycare attendance, and treatment with bronchodilators, corticosteroids, diuretics, and oxygen. A 2020 position statement from the Thoracic Society of Australia and New Zealand (TSANZ) provided recommendations on the respiratory management of preterm infants with chronic neonatal lung disease, with an emphasis on supplemental oxygen therapy after the neonatal intensive care unit stay. The ATS guideline, published in December, 2021, focuses on the outpatient management of infants, children, and adolescents with respiratory disease associated with premature birth (<37 weeks’ PMA), including those who did not meet the definition of BPD, addressing treatment with bronchodilators, corticosteroids, and diuretics, and adding recommendations on the use of diagnostic polysomnography, swallow evaluation, airway endoscopy, and diagnostic imaging for tracheobronchomalacia. The need for long-term follow-up of individuals born preterm is increasingly recognised and reflected in the new guidelines, which not only provide welcome guidance for clinicians, but also highlight gaps in understanding that demand urgent attention. Further studies are needed of children, adolescents, and adults born with different degrees of prematurity to allow the development of more precise guidelines on the optimum use and timing of monitoring options, diagnostic evaluations, and available treatments. Goals include the identification of subgroups of patients (eg, those with pulmonary hypertension) who might benefit from targeted therapeutic strategies. Knowledge of the mechanisms underlying impairments in alveolar and microvascular development, the emergence of BPD, and lung development and lung function through infancy, childhood, and adolescence—including genetic and epigenetic factors and the role of the microbiome—could lead to the identification of diagnostic, prognostic, and theragnostic biomarkers, and open up new avenues for treatment and prevention. Approaches to BPD risk prediction in preterm neonates, including novel artificial intelligence tools, and breakthrough therapies such as mesenchymal stem cells offer the hope of early intervention to promote repair and prevent disease. Researchers face considerable challenges in the study of preterm neonates and in the long-term follow-up that is needed to track patterns of injury and repair, the course of lung development, lung function, and disease, and the impact of interventions on meaningful biological, clinical, and health outcomes. We join clinicians, researchers, patients, and their advocates in calling for funding and support for research collaborations and the conduct of well designed studies, with the goal of improving long-term respiratory health and quality of life after preterm birth.