Fetoplacental oxygen homeostasis in pregnancies with maternal diabetes mellitus and obesity

Diabetes mellitus or obesity during pregnancy can cause fetal hypoxia, resulting in reduced fetal growth. This Review discusses the metabolic causes of fetal hypoxia in pregnancies with diabetes mellitus and/or obesity and the fetal adaptations to this oxygen deficit. Despite improvements in clinical management, pregnancies complicated by pre-existing diabetes mellitus, gestational diabetes mellitus or obesity carry substantial risks for parent and offspring. Some of the endocrine and metabolic changes in parent and fetus in diabetes mellitus and obesity lead to fetal oxygen deficit, mostly due to insulin-induced accelerated fetal metabolism. The human fetus deals with reduced oxygenation through a wide range of adaptive responses that act at various levels in the placenta as well as the fetus. These responses ensure adequate oxygen delivery to the fetus, increase the oxygen transport capacity of fetal blood and redistribute oxygen-rich blood to vital organs such as the brain and heart. The liver has a central role in adapting to reduced oxygenation by increasing its oxygen extraction and stimulating erythropoietin synthesis to increase haematocrit. The type of adaptive response depends on the onset and duration of hypoxia and the severity of the metabolic disturbance. In pregnancies characterized by diabetes mellitus or obesity, these adaptive systems come under additional strain owing to the increased maternal supply of glucose and resultant fetal hyperinsulinaemia, both of which stimulate oxidative metabolism. In the rare situation that the adaptive responses are overwhelmed, stillbirth can ensue.

Automated summary

Diabetes mellitus or obesity during pregnancy can lead to fetal hypoxia, which affects fetal growth. The metabolic and endocrine changes caused by diabetes mellitus and obesity result in fetal oxygen deficit, but the fetus adapts through various responses to ensure sufficient oxygen supply.