Brain sparing in fetal growth restriction: The double-edged sword of fetal hypoxaemia

Fetal hypoxaemia during pregnancy is not uncommon, arising from chronic placental insufficiency or acute stressors. In the case of placental insufficiency and chronic fetal hypoxia, fetal growth is reduced, resulting in fetal growth restriction (FGR). Fetal hypoxaemia initiates an immediate adaptive strategy to preserve brain oxygen delivery - the brain sparing response. Asymmetric FGR, in which head size is relatively larger than body size, is evidence of prolonged brain sparing. The acute physiology of the brain sparing response is well-defined in preclinical studies, involving peripheral vasoconstriction and reduced cerebral resistance to promote cerebral vasodilatation. Yet, the mechanisms that maintain fetal brain sparing during sustained hypoxaemia remain incompletely understood. Furthermore, although brain sparing has historically been interpreted as protective, this concept is being challenged, with its presence linked to increased risk of death or neonatal morbidity and neuropathology. This contradiction reflects that brain sparing is not static but evolves with the severity of fetal hypoxaemia; clinical evidence points to a front-to-back pattern of brain vasodilatation that initially prioritises cortical perfusion for higher-order function, whereas prolonged or severe hypoxaemia drives a shift towards brainstem preservation and survival. Thus, the brain sparing response is initiated by fetal hypoxaemia and is a unique indicator of fetal compromise, but it progresses from a compensatory to a maladaptive response. The mechanisms, multisystem physiology and ontogeny of sustained brain sparing in severe FGR are not well characterised, but advancing this knowledge affords new opportunities to diagnose and manage FGR, and to intervene to prevent adverse consequences.