Risk and Protective Factors in the Origin of Atrial Septal Defect Secundum - National Population-Based Case-Control Study

Abstract

The aim of this study was to assess the risk factors in the origin of lethal or surgically corrected isolated atrial septal defect secundum. The population-based Hungarian Case-Control Surveillance of Congenital Abnormalities (conducted between 1980 and 1996) comprised 472 atrial septal defect secundum cases, 678 matched controls and 38,151 available controls without any defects; in addition, 21,022 malformed controls with other isolated defects. Medically recorded chronic disorders in the prenatal maternity logbook were evaluated, while acute maternal diseases, drug treatments and pregnancy supplements were analyzed on the basis of both prospective medically recorded data and retrospective maternal information. Acute pelvic inflammatory disease, paroxysmal supraventricular tachycardia and phenolphthalein treatment due to severe constipation of mothers were shown to contribute to the development of atrial septal defect secundum of their children. High doses of folic acid in early pregnancy had positively influenced a minor part of isolated atrial septal defect secundum in foetuses. In conclusion, the obvious genetic predisposition for atrial septal defect secundum is connected with maternal paroxysmal supraventricular tachycardia and triggered by acute pelvic inflammatory diseases and phenolphthalein treatment, while the manifestation of atrial septal defect secundum can be reduced by high doses of folic acid supplementation in early pregnancy.

A Common Polymorphism in the MTHFD1 Gene Is a Modulator of Risk of Congenital Heart Disease

“…In addition to the genetic polymorphisms investigated, known environmental risk factors were also taken into account in the data analysis, to avoid bias. All of the environmental CHD risk factors that were identified in the present study (i.e., child gender, maternal smoking, higher parity, positive family anamnesis of CHD, maternal chronic disease, and a lack of folate supplementation during early pregnancy) had already been detected in previous studies [ 8 , 9 , 21 , 22 , 23 ]. We investigated the association of 10 common polymorphisms in nine genes that code for the enzymes and transporters in the folate-methionine metabolic pathways with CHD and its subtypes.…”

The association between folic acid supplementation and congenital heart defects: Systematic review and meta-analysis

“…Specifically, 9 studies were obtained from the United States, 13 – 21 and another 9 studies were from Hungary. 22 – 30 The remaining 7 studies were from China; 31 – 37 3 studies from Netherlands; 38 – 40 2 studies from the United States and Canada; 41 , 42 2 studies from Norway; 43 , 44 1 study from Denmark and Norway; 45 1 study from Russia; 46 1 study from Northern Ireland; 47 1 study from Australia 48 and 1 study from India. 49 Regarding the study design of included studies, 27 (72.97%) are case–control studies.…”

“…49 Regarding the study design of included studies, 27 (72.97%) are case-control studies. [13][14][15][16][17][18][19][20][21][22][23][24][25]28,29,31,[33][34][35][38][39][40][41][42][46][47][48] The remaining 8 are cohort studies 27,32,36,37,[43][44][45]49 and 2 randomized controlled trial (RCT) studies. 26,30 The sample size of included studies ranged from 407 with the use of case-control study design in the United States and Canada to 894,927 participants with the use of cohort study design in Norway.…”