Long-term Respiratory Outcomes of Extreme Preterm Birth. A regional cohort study

Background: Survival after extremely preterm (EP) birth has increased considerably during the last three decades. The lifetime respiratory prospects for survivors are unknown. Aim: To study long-term respiratory health following EP birth, here defined as being born before or at 28 weeks of pregnancy, or with a birth weight less than 1001 gram. Methods: Three population-based cohorts born EP (EPB) in 1982-1985, 1991-1992, or 1999-2000, and individually matched term-born control subjects (TB) underwent clinical examinations, comprehensive tests of pulmonary function (PF) and surveys of respiratory symptoms. The first cohort was examined at 18 and 25 years of age, the second at 11 and 18 years of age, and the third at 11 years of age. Results: Symptoms of lung disease resolved during the age span studied, but variables of bronchial airflow were lower in the EPB than the TB group, and most marked in subgroups with neonatal bronchopulmonary dysplasia (BPD). Airflow limitations tracked in parallel in EPB and TB groups through puberty (11-18 years) and into early adult life (18-25 years), with no relative improvement or deterioration. At 25 years of age, significant bronchial obstruction, resistance, and hyperresponsiveness were observed, and subgroups had pulmonary hyperinflation. Children born EP in 1999- 2000 had less airflow limitation and less pulmonary hyperinflation compared to children born similarly preterm in 1991-1992, particularly those with a history of BPD. Improvements were statistically related to increased use of antenatal corticosteroids and treatment with surfactant in the 1999-2000 cohort. Conclusions and implications: EP birth was associated with persistent bronchial obstruction and hyperresponsiveness from childhood to adulthood, with no indications of catch-up growth or early onset deterioration compared to TB subjects. Failing to reach peak predicted PF at early adulthood, combined with possible prospects of steeper age-related declines, suggest a potential for early onset chronic obstructive pulmonary disease (COPD) in subgroups. Less impairment among the most recently born 1999-2000 cohort indicates that better treatment not only improves survival but also respiratory outcome. Studies of these issues are few, hampering our understanding of long-term outcomes and ability to propose explanatory mechanisms.