Pregestational Diabetes and Congenital Heart Defects

Abstract

Studies have consistently shown a significant increase in the risk of congenital heart defects in the offspring of diabetic mothers compared with those of nondiabetic pregnancies. Evidence points that all types of pregestational diabetes have the capacity of generating cardiac malformations in a more accentuated manner than in gestational diabetes, and there seems to be an increased risk for all congenital heart defects phenotypes in the presence of maternal diabetes. Currently, the application of some therapies is under study in an attempt to reduce the risks inherent to diabetic pregnancies; however, it has not yet been possible to fully prove their effectiveness. The present review aims to better understand the mechanisms that govern the association between pregestational diabetes and congenital heart defects and how maternal diabetes interferes with fetal cardiac development, as there is still a long way to go in the investigation of this complex process.

Fig. 1

. Flow diagram of the literature review.

Fig. 2

Evidence points to an association between pregestational diabetes and a higher propensity of the offspring to develop congenital heart disease (CHD). This correlation seems to be justified, on the one hand, by the presence of fetal hyperglycemia and hyperinsulinemia and, on the other hand, by a deficient placental development. Thus, the teratogenesis of maternal diabetes will reside in the generation of reactive oxygen and nitrogen species (oxidative stress), culminating in epigenetic and cell cycle changes, which condition a defective cardiogenesis. Simultaneously, studies highlight the role of genetic predisposition for abnormal fetal cardiac development, so that this interrelation between fetal environment and genetic background will be at the basis of fetal heart defects.