Epidemiology of cardiovascular malformations: Prevalence and risk factors

Abstract

Epidemiological approaches to the study of cardiovascular malformations (CVMs) face challenges of disease definition, nomenclature, changing diagnostic methodologies, the rarity of the disease in the general population, and the incorporation of current knowledge on genetics and morphogenesis into designing studies to investigate risk factors and implement preventive strategies. Previous studies, especially the population-based Baltimore-Washington Infant Study, have documented variability in the prevalence of specific types of CVM by time, place, and personal characteristics and have highlighted the potential prevention of diabetes-associated heart malformations through timely medical management of pre-conception diabetes. Left-sided obstructive heart defects have been identified as targets for new studies of genetic risk factors. Potential environmental risk factors for CVMs also have been identified, such as organic solvents and pesticides, coincident with the emergence of new strategies to study genetic susceptibility and gene-environment interactions. Increased collaborative, multicenter research on these and other factors, such as nutritional factors in early pregnancy, offers new hope for potentially reducing the burden of CVM in the population.

Integration of a Notch-dependent mesenchymal gene program and Bmp2-driven cell invasiveness regulates murine cardiac valve formation

“…Congenital cardiac valvuloseptal defects are the most frequently diagnosed developmental malformations during the first year of human life (1), and several valvular defects manifest in adult disease (2). Evidence from animal models has linked many genes and signaling pathways to cardiac valve development (3); however, mutations of the human homologs seldom correlate with human valve defects (4).…”

Guest Editorial: Special Issue on Fetal Hemodynamics

“…6,8,12 The clinical relevance of defining the origins of congenital cardiovascular malformations relates to the high incidence of heart defects in humans (approximately 1% of live births and a much higher percentage of the pregnancies that end unsuccessfully in the first trimester), the requirement for medical and surgical intervention in at least 25% of these children in the first year of life, and the life-long impact of congenital heart disease on health, employment, and subsequent generations. 16,19 The broad based and international investigation that integrates comparative and developmental biology, the molecular genetics of invertebrate and vertebrate animal models, multimodal and predictive bioengineering approaches early 10 and expanding data sets from advanced human fetal imaging 20 and intervention 18 has reached the tipping point where observed congenital cardiovascular malformations can now be coupled to unique sequences of spatio-temporal events that trigger predictable altered developmental trajectories. One of the outcomes of this expanding knowledge base will be altered clinical management strategies designed to redirect developing structures towards preferred states that optimize fetal cardiovascular structure and function, 18 postnatal successful interventions, and improved quality of life.…”

Drosophila Model of Congenital Heart Diseases

“…Taking advantage of the Drosophila model we recently performed a study using data obtained from a patient with hypoplastic left heart syndrome (HLHS). HLHS is the most severe type of left-sided heart defect, and occurs in 2-4% of all infants born with congenital heart disease (Loffredo, 2000). We found that this patient had a balanced chromosomal translocation whose breakpoint is in close proximity to a member of the kinesin family (Akasaka, Grosfeld, et al, unpubl.).…”