Risk Factors in the Origin of Congenital Left-Ventricular Outflow-Tract Obstruction Defects of the Heart: A Population-Based Case–Control Study

Abstract

The aim of our project was to study possible etiological factors in the origin of congenital heart defects (CHDs) because in the majority of patients the underlying causes are unclear. Cases with different CHD entities as homogeneously as possible were planned for evaluation in the population-based large data set of the Hungarian Case Control Surveillance of Congenital Abnormalities. Dead or surgically corrected 302 live-born cases with different types of left-ventricular outflow tract obstructive defects (LVOT, i.e., valvular aortic stenosis 76, hypoplastic left heart syndrome 76, coarctation of the aorta 113, and other congenital anomalies of aorta 32) were compared with 469 matched controls, 38,151 controls without any defects, and 20,750 malformed controls with other isolated defects. Medically recorded pregnancy complications and chronic diseases were evaluated based on prenatal maternity logbooks, whereas acute diseases, drug treatments, and folic acid/multivitamin supplementation were analyzed both on the basis of retrospective maternal information and medical records. The results of the study showed the role of maternal diabetes in the origin of LVOT in general, while panic disorder was associated with a higher risk of hypoplastic left heart syndrome and ampicillin treatment with a higher risk of coarctation of the aorta (COA). High doses of folic acid had a protective effect regarding the manifestation of LVOT, particularly COA. In conclusion, only a minor portion of causes was shown in our study; thus, further studies are needed to understand better the underlying causal factors in the origin of LVOT.

Maternal Folic Acid Supplementation and the Risk of Congenital Heart Defects in Offspring: A Meta-Analysis of Epidemiological Observational Studies

“…All of the studies were published between 1995 and 2013. These studies included 1 randomized controlled trial 8 , 1 cohort study 9 , and 16 case-control studies 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 . The main characteristics of the included studies are presented in Table 1 .…”

Maternal folic acid supplementation and dietary folate intake and congenital heart defects

“…Epidemiological studies that investigated the association between folic acid intake and the risk of CHDs have reached conflicting results. Twelve studies found that folic acid supplementation before and/or during pregnancy reduced the risk of CHDs [ 8 – 19 ], six studies reported no association between folic acid supplements and CHD risk [ 20 – 25 ], while one study found a significantly increased risk of CHDs associated with folic acid supplement use[ 26 ]. Three studies investigated dietary folate intake and risk of CHDs and found no association [ 27 – 29 ].…”

Genome-Wide DNA Methylation Analysis and Epigenetic Variations Associated with Congenital Aortic Valve Stenosis (AVS)

“…Sites of obstruction are sub-classified as valvular, subvalvular and supravalvular [ 14 ]. About half of infants with severe AVS require surgery [ 15 ]. Mild aortic stenosis is difficult to detect prenatally; however, critical aortic stenosis can lead to left ventricular myocardial dysfunction with endocardial fibroelastosis, left atrial dilation and narrowing of the aortic root [ 16 ].…”