Congenital heart disease (CHD) is the most common birth defect. And even with remarkable advances in care, it remains the leading cause of non-infectious death in infants.
CHD is the result of a complicated interplay between genetic and non-genetic, or “environmental,” factors acting on the fetus.
While the genetic contributors have become increasingly defined as was recently summarized in an American Heart Association Scientific Statement published in Circulation that was co-authored by Dr. Vidu Garg, the environmental factors are an important area of investigation.
One of those environmental factors is maternal hyperglycemia.
In a comprehensive review, Garg and Dr. Madhumita Basu looked at the impact of maternal diabetes, and potential gene-environmental influences in that context, on fetal heart development.
“Many studies have demonstrated a strong correlation between maternal diabetes and increased risk of CHD in babies born to affected mothers,” says Garg, who is the director of the Center for Cardiovascular Research in The Research Institute at Nationwide Children’s Hospital.
“And many factors, including the type of diabetes, other environmental influences, and potentially certain genetic predispositions can influence which CHD subtypes are likely to develop.”
For example, the researchers say type 1 and type 2 diabetes are linked with specific CHD subtypes.
The researchers found that babies born to mothers with type 1 diabetes had a greater association with conotruncal malformations and atrioventricular septal defects.
Those born to mothers with type 2 diabetes had the highest risk of heterotaxy and left ventricular outflow tract obstructive malformations.
Both types of maternal diabetes also increased the risk of other types of CHD in the infants.
The researchers also found the gestational age at which the fetus is exposed to maternal diabetes is also important.
Maternal diabetes before conception and during the first trimester is associated with diabetic embryopathy in the fetus, which affects the heart, great vessels, and neural tube.
When maternal diabetes develops in the latter half of pregnancy, it is associated with fetal macrosomia, cardiomyopathy, increased incidence of perinatal complications and mortality.
Diabetes is a complex disease, with abnormal homeostasis of multiple components in metabolism that ultimately leads to the overall metabolic syndrome.
Despite this complexity, hyperglycemia has been determined to be the primary factor in all forms of diabetes. How exactly maternal hyperglycemia causes birth defects in infants is still unknown, according to researchers.
More Research Needed
“Teasing out the cellular and molecular changes in the developing heart during hyperglycemic conditions is possible with newer high throughput genomic technologies,” Garg adds. “Doing so will enable us to define these perturbations mechanistically, and even down to a single-cell level.”
Unlocking these cellular secrets opens the door to potential interventions to reduce the risk of the fetus developing CHD.
“Ultimately, our hope is to translate these findings by screening mothers with environmental risk factors and their children for genetic variants in cardiac regulatory genes,” says Basu. “We predict that these genetic variants will serve as risk factors for the development of CHD in high-risk populations, such as those with maternal diabetes.”
The research was recently published in Birth Defects Research.
Published with permission from Nationwide Children’s Hospital.
Influences of maternal diabetes on fetal heart development. 2018, December 21. EurekAlert! Retrieved: https://www.eurekalert.org/pub_releases/2018-12/nch-iom122118.php