Oxidative stress and birth defects in infants of women with pregestational diabetes

Hyperglycemia characteristic of diabetes mellitus triggers pathological processes in fetal development of various structures such as the retina, peripheral nerves, renal glomerulus, and arterial and venous beds. Women with diabetes prior to conception have children with birth defects three to five times more frequently than women without diabetes. There is no specific pattern of birth defects, but the central nervous and cardiovascular systems are the most affected. Hyperglycemia leads to mitochrondrial superoxide radical production, which activates five metabolic pathways that mediate damage leading to diabetic embryopathy. Once oxidative stress is established, there is modification of gene expression controlling embryonic development in critical periods. Vitamin E application in animal models has greatly lowered occurrence of birth defects in embryonic and fetal stages, consistent with an etiologic role for oxidative stress in dysmorphogenesis. Effective metabolic control before and during pregnancy, achieved in Cuba by implementing programs for control of birth defects in children of diabetic pregnant women, has been found effective.