Born early, age fast: Consequences of premature birth on chronic disease and accelerated ageing.

Recent advances in prenatal and neonatal care have significantly improved the survival rates of extremely low gestational age new-borns (ELGANs), born at ≤28 weeks of gestation. Exposure to low oxygen levels in the intrauterine environment during the last trimester is crucial for normal organ development. The extrauterine environment is highly toxic to ELGANs. Exposure to ambient and supplemental oxygen, intermittent hypoxia, excessive glucocorticoids, hyperalimentation, infections and mechanical ventilation, elevated ROS levels, coupled with insufficient antioxidant defences, lead to oxidative stress. Oxidative stress leads to damages in cell membranes, mitochondria and DNA, negatively impacting developing cells and tissues in all organs. ELGANs are at increased risk of developing acute prematurity-related diseases such as bronchopulmonary dysplasia, pulmonary hypertension and acute kidney injury. As ELGANs age, they face a higher risk of chronic diseases such as chronic obstructive pulmonary disease, cardiovascular disease, chronic kidney disease, type 2 diabetes. and other metabolic diseases later in life. Collectively, these chronic diseases are associated with accelerated ageing and increased mortality in former ELGANs. This review presents the epidemiology of clinical disorders affecting the respiratory, cardiovascular, renal and metabolic systems across the lifespan in ELGANs. It explores the roles of early oxidative stress during the last trimester of organ development in activating signalling pathways that promote cellular senescence and epigenetic reprogramming, leading to acute and chronic disease.