The Impact of Maternal Obesity and Diabetes on the Development of Congenital Heart Defects (CHDs) in Offspring: A Narrative Review

Congenital heart disease (CHD) is the most common anatomical malformation occurring in live-born infants and an increasing cause of morbidity and mortality all over the world. Population-based observations have described associations between maternal cardiometabolic disorders and the risk of CHD in offspring. The present article is a narrative review. The aim of this study was to review the epidemiological evidence and clinical observations relating maternal obesity and diabetes mellitus to the risk of CHD in offspring, with particular attention paid to first trimester disturbances of fetal cardiac development and the influence of genetic, epigenetic and environmental factors. Studies have shown that maternal diabetes is a risk factor associated with nearly all subtypes of CHDs in offspring, while obesity and overweight are associated with increased risk for complex defects and outflow tract obstruction and decreased risk for ventricular septal defects. Diabetes and obesity share several phenotypes, which could be transmissible from mother to fetus via the placenta. This means that an increase in maternal glucose could be responsible for the prevalence of CHD in newborns of obese women. On the other hand, maternal diabetes may induce epigenetic modifications in the developing fetus. DNA methylation changes can impact gene expression patterns relevant to heart development. The abovementioned studies are heterogenous, express different opinions and are often difficult to compare. Therefore, the results from these meta-analyses must be interpreted with caution. Optimal diabetes control is responsible for the prevention of oxidative stress in diabetic pregnancies, and a deeper understanding of maternal risk factors holds the potential to improve both prenatal detection of CHDs by identifying at-risk pregnancies and primary prevention of diseases by improving preconception management.