Zhao Z and Tan C
Diabetes mellitus in early pregnancy is the most severe maternal disease that can cause congenital birth defects in newborn infants, a complication known as diabetic embryopathy. Even in the developed countries where aggressive glycemic control and perinatal care are available, the birth defect rate in diabetic pregnancies is still three times higher than the background rate. With the rapid increases in the number of diabetic women in childbearing age, the birth defect rate is projected to elevate dramatically in the near future. Thus, prevention of embryonic malformations becomes an urgent task. Basic research using animal models has uncovered the involvement of major cellular activities, including proliferation and apoptosis, and associated intracellular metabolic conditions, including nitrosative, oxidative, and endoplasmic reticulum stresses in diabetic embryopathy. Basic research has also demonstrated the effectiveness of treatments via targeting the intracellular stress conditions to reduce embryonic malformations. However, translation of the basic findings into human application requires high standards of safety to the embryos and mothers. Recent identification and clinical investigation of bioactive substances from plants have advanced the exploration for safe and effective naturally occurring phytochemicals, including flavonoids, stilbenoids, and curcuminoids, as candidate agents to prevent birth defects in diabetic pregnancies.