Congenital heart defects (CHDs) belong to the most common group of major congenital malformations in newborns. Most CHDs are considered complex diseases with a multifactorial aetiology, which are thought to result from interactions between genetic and environmental factors. This thesis presents the results of the ongoing HAVEN study, in which human congenital heart anomalies and homocysteine related genetic and nutritional factors are investigated. We demonstrate that maternal hyperhomocysteinaemia more than three-fold increases the risk of CHD offspring. Moreover, a low maternal dietary vitamin B12 intake is associated with a nearly two-fold higher CHD risk. With regard to genetic factors, the 5,10-methylenetetrahydrofolate reductase (MHTFR) 1298 AA genotype in fathers and children showed a small but significantly increased CHD risk. Periconceptional folic acid supplementation is beneficial, particularly in children carrying the MTHFR 1298 AA genotype. Con! cerning vitamin B12 related polymorphisms, methionine synthase reductase 66 GG and transcobalamin 776 GG genotypes in mothers and children may contribute to CHD risk, especially combined with the maternal vitamin B12 status. These findings indicate that the maternal nutritional status and gene-nutrient interactions are involved in the pathogenesis of CHDs. Therefore, it might be favourable to advise women to use a diet rich in vitamin B12 and maybe a vitamin B12 supplement in addition to the daily folic acid supplement intake in the periconceptional period. These results can be directly implemented in the preconception care. Preconceptional screening is important for future risk assessment and counselling of parents to be and it may cause a reduced prevalence of CHDs.

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E.A.P. Steegers (Eric)
Erasmus University Rotterdam
Steegers, Prof. Dr. E.A.P. (promotor)
Erasmus MC: University Medical Center Rotterdam

Verkleij-Hagoort , A.C. (2007, April 25). Homocysteine related Nutritional and Genetic Risk Factors for Human Congenital Heart Defects. Erasmus University Rotterdam. Retrieved from