Maternal Obesity and Diabetes Mellitus as Risk Factors for Congenital Heart Disease in the Offspring

Abstract

Congenital heart disease (CHD) is the most common anatomical malformation occurring live-born infants and an increasing cause of morbidity and mortality across the lifespan and throughout the world. Population-based observations have long described associations between maternal cardiometabolic disorders and the risk of CHD in the offspring. Here we review the epidemiological evidence and clinical observations relating maternal obesity and diabetes mellitus to the risk of CHD offspring with particular attention to mechanistic models of maternal-fetal risk transmission and first trimester disturbances of fetal cardiac development. A deeper understanding of maternal risk factors holds the potential to improve both prenatal detection of CHD by identifying at-risk pregnancies, along with primary prevention of disease by improving preconception and prenatal treatment of at-risk mothers.

Keywords: cardiometabolic; congenital heart disease; maternal diabetes mellitus; maternal obesity.

Figure 1

Potential mechanisms for transmission of maternal metabolic risk for congenital heart disease (CHD) in the fetus. Illustration of potential mechanisms of transmission of maternal factors during pregnancy influencing risk for CHD in offspring. Maternal diabetes mellitus and obesity share a variety of intermediate phenotypes (bidirectional gray arrow), which could be transmissible from mother to fetus in the blood across the placenta (red arrow) or transmitted genetically at the time of conception by pleiotropic variants, conferring risk for both metabolic phenotypes and CHD (green arrow). Specific differences in placental function related to maternal obesity may also contribute to risk (purple arrow). Experimental models have suggested a variety of potential mechanisms by which maternal metabolic factors may disturb development of the heart, which occurs early in pregnancy during the first trimester.