Abnormal Maternal Biomarkers of Homocysteine and Methionine Metabolism and the Risk of Congenital Heart Defects

Abstract

Cardiac malformations present at birth are an important component of pediatric cardiovascular disease and constitute a major percentage of clinically significant birth defects. Moreover, congenital heart disease is an important cause of mortality and morbidity in the young. A child with congenital heart disease is an economical and social burden for both parents and the community. Not all types of CHD behave the same. Some types may be lethal to the newborn shortly after birth, or even intrauterine. Others may be tolerated for varying periods of time, but leaving an inverse impact on the patient's health status and might end in early deaths. Knowledge about the epidemiology of CHD is important in determining the cause, allocating appropriate resources and planning effective prevention and management. In most cases, the cause of Congenital Heart Disease is unknown but associated conditions are noted to increase the risk for having CHD. The association between folic acid deficiency and congenital malformation is especially well-known. Several studies have proposed that maternal periconceptional use of folic acid protects against the occurrence of congenital anomalies, including CHD. Few studies reported altered concentrations of biomarkers associated with homocysteine metabolism among women with pregnancies affected by heart defects. Evidence demonstrates that homocysteine is elevated among women with a history of adverse pregnancy outcomes including pereclampsia , recurrent early pregnancy losses ,NTD, orofacial cleft and congenital heart defect disorders. Our study was planned using Case - Control design, we aimed to determine whether biomarkers of the folic acid pathway, including homocysteine and methionine metabolism are altered among non pregnant women who have had a pregnancy affected by congenital heart defects, the results was compared with those of women without such a history. Twenty Five subjects was contacted to participate in the study, as well as twenty five control Subjects was chosen to participate. Fasting blood samples were withdrawn by normal venipuncture at The Medical Genetic Center , Faculty of Medicine, Ain Shams University to measure plasma concentration of : • Vitamin B-12 and folic acid. • Homocysteine. • Methionine. • S-adenosylmethionine (SAM) • S- adenosylhomocysteine (SAH). and the work was carried out at the Medical Research Center, Faculty of Medicine, Ain Shams University. The results of our study show that the age of mothers ages in cases ranged between 20 and 39 years with mean of ± 30.64 years and in controls ranged between 19 and 38 years with mean of ± 25.36 years with high significant difference between them (P <0.01). There was no significant difference between cases and control as regards the time between the end of pregnancy of index and date of blood draw for study participation. Vitamin supplementation before and during pregnancy of index was significantly different between cases and control.(60%) of control group was giving history of taking vitamins during pregnancy versus (28%) only of cases. The obstetric history as regarding abortion and still birth was relatively high in cases with no significant difference between cases and control. While the results as regard early neonatal death was significantly different between cases and control(28% of cases show positive history while only 4%of control show positive history). The history of smoking or exposure to environmental tobacco smoke was positive in(28%) of cases and(12%)of control with no significant difference between them. Dietary caffeine intake did not vary significantly between cases and control In our study the majority of cases were Low educated (52%),while the majority of control group were highly educated (40%). Congenital acyanotic heart disease represented the majority of our studied cases accounting for (76%) of the total cases while congenital cyanotic heart disease accounting for (24%) of the total cases. As regarding the acyanotic group, VSD was the most common lesion being present in 32% of our patients and the next most common lesion was ASD being present in 20% of these patients. As regard the acyanotic group, the other frequent defects were present in the following order: PS (8%), PDA (8%). As regard cyanotic heart defects, tetralogy of fallot was the most frequent type recorded 12%, followed by transposition of great arteries (8%),and double outlet right ventricle (4%). The results of our study shows that plasma concentrations of homocysteine(48.028 nmol/L), SAH (21.578 nmol/L ) and SAM (14.283 nmol/L) were elevated among case subjects while plasma concentration of vitamin B12 (882.5 pg/mL) and folic acid (10.654 ng/mL) were elevated among control subjects. There was no significant difference in plasma concentration of methionine between case and control subjects.