Premature birth, homeostatic plasticity and respiratory consequences of inflammation

Infants who are born premature can have persistent apnea beyond term gestation, reemergence of apnea associated with inflammation during infancy, increased risk of sudden unexplained death, and sleep disorder breathing during infancy and childhood. The autonomic nervous system, particularly the central neural networks that control breathing and peripheral and central chemoreceptors and mechanoreceptors that modulate the activity of the central respiratory network, are rapidly developing during the last trimester (22–37 weeks gestation) of fetal life. With advances in neonatology, in well-resourced, developed countries, infants born as young as 23 weeks gestation can survive. Thus, a substantial part of maturation of central and peripheral systems that control breathing occurs ex-utero in infants born at the limit of viability. The balance of excitatory and inhibitory influences dictates the ultimate output from the central respiratory network. We propose in this review that simply being born early in the last trimester can trigger homeostatic plasticity within the respiratory network tipping the balance toward inhibition that persists in infancy. We discuss the intersection of premature birth, homeostatic plasticity and biological mechanisms leading to respiratory depression during inflammation in former premature infants.