Influences of maternal diabetes on fetal heart development

Introduction

High blood sugar is linked to congenital heart defects during pregnancy. Congenital heart disease (CHD) is a well-known and very common birth defect. And even with significant progress in care, it remains the leading cause of non-communicable death in infants.

Full Story

Congenital heart disease (CHD) is the result of a complex interaction between genetic and non-genetic, or "environmental factors working on the fetus. The environmental factors are a very vital area of investigations. One of those environmental factors is maternal hyperglycemia. On the development of the fetal heart, potential gene-environmental influences in that context are effective. Whereas genetic contributors have become increasingly defined, as was recently summarized in an American Heart Association Scientific Statement published in “Circulation”, which was co-authored by Vidu Garg, MD, the director of the center at nationwide children's hospital for cardiovascular research in the research institute.

Many epidemiological studies have demonstrated a strong link between the increased risk of maternal diabetes and CHD among infants born to affected mothers. And many factors, which include diabetes type, other environmental impacts, and potentially some genetic predictions can affect the chances of developing the CHD subtypes. We believe that maternal diabetes can eventually be affected by the diseases that are expressed in the genes during fetal development.
During hyperglycemic conditions, it is possible to combine cellular and molecular changes in the developing heart with new high-throughput genomic technologies. By doing this we can be mechanically defined to these perils and even single-cell levels. Opening these cellular mysteries opens the door to potential intervention to reduce the risk of developing embryos that develop CHD", said Dr. Vidu Garg in a statement.

Type 1 and type 2 diabetes are associated with specific CHD subtypes. Babies born with Type 1 diabetes were more concerned with congenital malformations and atrioventricular septal defects. Those who are born with Type 2 diabetes have the highest risk of hepatotoxicity and there are blocking distortions in the ventricular outflow path. Both types of maternal diabetes also increased the risk of other types of CHD in infants, in which the right ventricular outflow path barrier blocking distortions and ventricular septal defects are at lower levels.

The gestational age at which the fetus is exposed to maternal diabetes is also very important. During pregnancy and during the first trimester, maternal diabetes is associated with diabetic embryopathy in the fetus, which affects the heart, neural tube, and the great vessel. When maternal diabetes develops in the second half of pregnancy, then it is associated with fetal macrosomia, cardiomyopathy, the increasing incidence of perinatal complications and the mortality rate.

Diabetes is a complicated disease, which occurs in metabolism with abnormal homeostasis of many components, which eventually leads to the overall metabolic syndrome. Despite this complexity, hyperglycemia has been defined as the primary teratogen in all forms of diabetes. In fact, birth defects in maternal hyperglycemia due to infants are still unknown.

“The underlying molecular mechanism, by which changes in the level of maternal glucose causes congenital heart defects, is actively under investigation in our laboratory and others. We suspect that this gene-environmental interaction is related to the deformation of specific epigenetic processes in the fetal heart. Ultimately, we hope that these risks can be translated into genetically tested mothers for environmental risk factors and their children's cardiac regulatory genes. We estimate that these genetic changes will work as a risk factor for the development of CHD in high-risk populations, such as those with diabetes, said Dr. Basu, a research assistant professor in the Garg lab at the Center for Cardiovascular Research.

According to the study report, the current evidence shows the following processes and pathways:

Reactive oxygen species (ROS)-mediated influences on cardiac morphogenesis
Potential alternations in the cell-type specific epigenetic landscape in order to maternal diabetes.
Changes in the signaling pathways are critical for cardiac development, including Wnt, Hif1? and Tgf? and Notch at the translational and transcriptional levels in response to maternal-fetal hyperglycemia and associated oxidative stress.

Journal References:

Birth Defects Research, 2018; DOI: 10.1002/bdr2.1416

Circulation, 2018; 1 DOI: 10.1161/CIR.0000000000000606

Influences of maternal diabetes on fetal heart development