Respir Physiol Neurobiol. 2026 Jun 19:104610. doi: 10.1016/j.resp.2026.104610. Online ahead of print.
ABSTRACT
Infants born prematurely often develop apnea of prematurity (AOP), characterized by periodic apneas with intermittent hypoxia (IH) and commonly treated with supplemental oxygen. On the other hand, infants born at high altitude experience sustained hypoxia from birth. Thus, during critical developmental period, many infants experience abnormal oxygen environments, including hypoxia or hyperoxia. Emerging evidence indicates that disrupted neonatal oxygen homeostasis can produce long-lasting effects on cardiorespiratory function. Preterm infants also exhibit systemic inflammation, and elevated inflammatory cytokines, which may influence respiratory control. This review summarizes clinical and experimental studies examining how neonatal extreme O2 environment and inflammation affect respiratory control, with an emphasis on underlying mechanisms. Clinical and experimental findings show that IH associated with AOP enhances the hypoxic ventilatory response (HVR) and promotes breathing instability, largely through carotid body chemoreflex sensitization. These changes can persist in adulthood and may increase susceptibility to early-onset cardiorespiratory disease, potentially through epigenetic disruption of redox homeostasis. By contrast, neonatal sustained hypoxia transiently impairs carotid body oxygen sensing and ventilatory responses but typically resolves with maturation. Neonatal hyperoxia, however, causes persistent structural and functional impairment of carotid body function. Whether shared epigenetic mechanisms underlie IH and hyperoxia-induced effects, and how altered carotid body signaling reshapes central respiratory networks, remain important questions for future research.
PMID:42320662 | DOI:10.1016/j.resp.2026.104610