This case-control study was undertaken with the primary objective to compare serum homocysteine levels in cases of CHD and age-gender-matched healthy controls. The secondary objective to compare serum homocysteine levels in cases which were positive or negative for rubella infection in the serum by ELISA. In this study, the serum homocysteine levels were significantly higher in cases of CHD as compared to healthy controls. In addition to this, the serum homocysteine levels in rubella positive cases were significantly higher as compared to rubella negative cases.
Our study demonstrated that a total of 7.75% of CHD cases of aged 0-11 months in the studied population were found to have rubella infection. A similar study was available in India (2021), where 80 infant-mother pairs were investigated for congenital rubella as Etiology for causation of CHD, showed the prevalence of rubella infection was 8.75% in infants, which is close similar to our finding [12].
Among socio-demographic characteristics, birth weight, weight and body length, rural residence, joint families were also significantly associated with CHD cases. Similar findings were reported by B. Vaidyanathan et al.. that birth weight and height were significantly associated with congenital heart disease. [13-17] A population-based retrospective cohort study conducted in Canada found that infants born to mothers living in low-income neighbourhoods were more at risk for developing CHD compared to infants born to mothers living in higher-income neighbourhoods [18]. In rural areas most of the families were joint and due to lack of awareness and low education status, children are at higher risk.
According to hooshmand et al.., high levels of homocysteine amino acid are often associated with a wide variety of diseases, including CHD and neuro degenerative disorders like neural tube defects (NTD). In our study we found 5 times higher serum homocysteine levels in CHD cases as compared to controls, which is closely similar to the levels of serum homocysteine in the Turkish population as reported by C. Sanli et al. [11] This indicates an enhanced risk of CHD.
Few studies suggested that the novel and traditional cardiovascular risk factor, including endothelial dysfunction may interact with infectious agents to influence the inflammatory and procoagulant environ of atherosclerosis.[19] According to Persian Gulf study Chlamydia. pneumonia and cytomegalovirus showed significant association with increased serum Hcy levels (hyperhomocysteinemia) and several other studies also investigated the association of serum homocysteine levels and viral infections. [20-25] In the current study, we found significant higher levels of serum homocysteine in rubella seropositive cases as compared to rubella seronegative cases among CHD cases.
CHD is the result of incomplete development of heart during the first six weeks of pregnancy. According to Thomas et al. homocysteine amino acid acts as teratogenic agent which leads the dysmorphogenesis of the heart and neural tube as well as ventral wall.[26]
Malik R showed in their study that the increased levels of maternal serum homocysteine (Hyperhomocysteinemia) are statically significantly associated with increased risk of CHD [27]. Some other studies suggested that various maternal biomarkers of homocysteine pathway disturbing homocysteine metabolism as lower folate and cobalamin levels were noticed mother of CHD children with elevated levels of homocysteine. Similar Study was conducted by Huhta JC. [26, 28, 29]. KE Elizabeth analyses the nutrient- gene interaction, they found significant association between low serum folate, high serum homocysteine and the presence of genetic polymorphism among children and their mothers were noted as a risk of CHD. [30] Based on their study’s results consumption of peri-conceptional folate supplementation with vitamin B12 is the best primary prevention of CHD.
Our study has some limitations. We should also measure serum folate levels as folate plays very important role in this pathway and expected to decrease in cases with increase in homocysteine. Genetic analysis could be performed to understand the best knowledge of developmental mechanism of CHD.
Strength of the study was we have recruited age and gender matched healthy controls. The methodology was robust with adequate sample size and power of the study.