The Human Fetus and Metabolic Adaptations to Hypoxia

Abstract

Mammalian fetuses and neonates are equipped with a number of adaptations that prevent them from the risk of hypoxia connected to perinatal life. Due to the overall size relationship of metabolic rate, along with the metabolic cost of thermoregulation, small endotherms have high energetic demands, limiting their tolerance to undersupply. Hence a reduction in metabolic rate is a common feature of all perinatal adaptations. These include (I) an “inappropriately” low (size-related) metabolic rate, favoring tissue oxygenation despite the intrauterine low-oxygen environment; (II) a gatekeeper role of the placenta, capable of reducing its own O2 consumption in favor of the fetus, who in turn refrains from growth in favor of maintenance metabolism; and (III) the diving response combining a slow heart beat with a redistribution of blood flow in favor of central organs. The latter is complemented postnatally by the suppression of heat production and the onset of autoresuscitative gasps. The self-protective responses are arranged in cascading manner and offer a resistance to O2 deficiency rather than a true hypoxia tolerance. In clinical practice, the “oxyconforming” ability to actively reduce metabolic demand in response to hypoxia (hypoxic hypometabolism) is hard to distinguish from the passive metabolic breakdown caused by hypoxia.