High Maternal RBC Folate reduces risk of congenital heart disease in Newborns, finds study

Higher levels of RBC Folate in pregnant women are linked to decreased risk of congenital heart disease in newborns as per a new study that was published in the journal Annals of Internal Medicine. Higher RBC folate levels than currently recommended for neural tube defects may be necessary for preventing CHD in newborns. 

Periconceptional folic acid supplementation is generally recommended for the prevention of neural tube defects, but it has also been suggested to protect against congenital heart disease (CHD). Maternal red blood cell (RBC) folate is the gold standard biomarker for folate exposure but the association between the RBC folate and CHD risk is lacking. Hence researchers from Shanghai, China province conducted a Prospective, nested, case-control study to investigate the association between periconceptional maternal RBC folate and offspring CHD risk at 29 maternity institutions in 12 districts of Greater Shanghai, China. 

The participants included 197 mothers of offspring with CHD and 788 individually matched mothers of unaffected offspring from the Shanghai Preconception Cohort (SPCC) and were randomized by 1-sample Mendelian randomization using the methylenetetrahydrofolate reductase (MTHFR) C677T as the genetic instrument. Maternal RBC folate was measured before or at early pregnancy and conditional logistic regression after adjustment for covariates was used to estimate the odds ratio. 

Key findings from the study: 

• Case patients had lower median maternal RBC folate concentrations than control participants (714 nmol/L vs. 788 nmol/L).
• Maternal RBC folate concentrations and offspring CHD were inversely associated.  
  
• The adjusted OR for mothers with periconception RBC folate of 906 nmol/L or more was 0.61.
• As per the Mendelian randomization, each 100-nmol increase in maternal RBC folate concentrations was significantly associated with reduced offspring CHD risk. 

Thus, the researchers concluded that CHD risk in the offspring reduces with higher maternal RBC folate levels. They suggested further studies to check if higher target RBC folate levels than currently recommended for neural tube defect prevention may be needed to prevent primary CHD. 

for further reading, click here: 10.7326/M22-0741

Chen H, Zhang Y, Wang D, et al. Periconception Red Blood Cell Folate and Offspring Congenital Heart Disease: Nested Case-Control and Mendelian Randomization Studies [published online ahead of print, 2022 Aug 23]. Ann Intern Med. 2022;10.7326/M22-0741.