The peripheral chemoreflex and fetal defenses against intrapartum hypoxic-ischemic brain injury at term gestation

Fetal hypoxemia is ubiquitous during labor and, when severe, is associated with perinatal death and long-term neurodevelopmental disability. Adverse outcomes are highly associated with barriers to care, such that developing countries have a disproportionate burden of perinatal injury. The prevalence of hypoxemia and its link to injury can be obscure, simply because the healthy fetus has robust coordinated defense mechanisms, spearheaded by the peripheral chemoreflex, such that hypoxemia only becomes apparent in the minority of cases associated with stillbirth, severe metabolic acidemia or adverse neurodevelopmental outcomes. This represents only the extreme end of the spectrum, when defense mechanisms have failed due to severe/prolonged hypoxemia, or the fetal defenses are compromised by additional risk factors. Understanding the fetal defenses to hypoxemia and when the fetus begins to decompensate is crucial to understanding perinatal health and disease, by linking antenatal health, intrapartum events, the neonatal trajectory and ultimately life-long neurodevelopmental health.