The Effects of Maternal Hypoxia on Pregnancy Outcome, Lipid and Glucose Metabolism and Gestational Diabetes

Both increased and decreased birth weight increase maternal and perinatal mortality and morbidity and predispose to metabolic and cardiovascular dysfunctions later in life. Hypoxia is the second most important factor determining fetal growth while duration of gestation is the most important. Maternal overweight and gestational diabetes are the major causes of fetal macrosomia.

In this study we examined the effects of environmental hypoxia on maternal glucose and lipid metabolism in mice. We discovered that improved glucose tolerance, reduced insulin resistance and reduced amount of white adipose tissue led to decreased birth weight. Next, we examined if environmental hypoxia could protect obese dams from development of gestational diabetes. We found out that environmental hypoxia improved maternal metabolism and reduced adiposity but challenged placental health and fetal growth.

The major risk factors for gestational diabetes are overweight, advanced maternal age, previous gestational diabetes, family history of type 2 diabetes and ethnicity. We examined the association of hemoglobin (Hb), the major distributor of oxygen, levels with risk for gestational diabetes in the Finnish Gestational Diabetes Study (FinnGeDi) and observed that higher Hb levels within the normal variation of the Finnish pregnant women increased the risk for gestational diabetes. On the other hand, lower Hb levels were protective against development of gestational diabetes. Within normal variation the lower Hb levels have been found to activate the hypoxia response and associate with improved metabolic health. This could explain the association between Hb levels and the risk for gestational diabetes. As opposed to environmental hypoxia, the lower Hb levels did not lead to decreased birth weight.

Hypoxia response has a marked effect on maternal metabolism, but the environmental hypoxia used in these studies, corresponding to oxygen tension at altitude of 2700 m, was too severe for fetal growth. However, hypoxia response induced by lower Hb levels was beneficial for maternal metabolism without negative effects on the child. On the other hand, higher Hb levels associate with higher risk for gestational diabetes via higher blood pressure levels, increased body weight and poor glucose tolerance. Hypoxia has a high potential for treatment and prevention of metabolic dysfunction during pregnancy but there is a delicate balance between risks and benefits.