Maternal hyperhomocysteinaemia is a risk factor for congenital heart disease

Objective To investigate the inter-relation between mother and infant homocysteine, folate and vitamin B-12 status and the risk of a child with congenital heart disease (CHD). Design Case-control study. Setting Erasmus MC, University Medical Centre, Rotterdam, the Netherlands. Population Participants were 149 case-mothers and their children with CHD (n = 151) and 183 control-mothers with their children (n = 175). Methods Approximately 17 months after the index-pregnancy maternal fasting, children's random venous blood samples were drawn to measure plasma total homocysteine, serum and red blood cell (RBC) folate, and serum vitamin B-12 concentrations. Data were compared between cases and controls using the Mann-Whitney U test. The biochemical parameters were dichotomised according to the cutoff value of the 10th percentile of vitamin concentrations and the 90th percentile of homocysteine concentrations based on control data. Risk estimates for the association between CHD and the biochemical parameters were estimated in a logistic regression model. Main outcome measures Medians (minimum-maximum) and odds ratios (OR) (95% confidence intervals [CI]). Results The OR (95% Cl) of having a child with CHD was 2.9 (1.4-6.0) for maternal hyperhomocysteinaemia (>14.3 mu mol/l). This finding is substantiated by a significant concentration-dependent risk (P-trend = 0.004). Hyperhomocysteinaemic case-mothers showed significantly lower serum folate and vitamin B-12 concentrations than normohomocysteinaemic case-mothers. Serum and RBC folate concentrations were significantly higher in case-children than that in control-children. Conclusions Maternal hyperhomocysteinaemia is associated with an increased risk of CHD, partially due to low folate and vitamin B-12 status. The folate status of children warrants further investigation.