BACKGROUND AND PURPOSE:

• Folic acid supplementation prior to conception may reduce the risk of congenital heart disease (CHD) in offspring
• Data is limited regarding association between maternal red blood cell (RBC) folate and subsequent CHD risk
• Chen et al. (Annals of Internal Medicine, 2022) quantified the association between periconception maternal RBC folate and offspring CHD risk

METHODS:

• Prospective, nested, case–control study and 1-sample Mendelian randomization
  • Data derived from the SPCC (Shanghai Preconception Cohort)
• Participants
  • All mothers of offspring with CHD and individually matched mothers of unaffected offspring
• Exposures
  • Maternal RBC folate, measured before or at early pregnancy
• Study design
  • Odds ratios (ORs) were estimated using logistic regression after adjustment for covariates
  • Mendelian randomization was done using the MTHFR C677T as the genetic instrument
• Primary outcome
  • Offspring CHD

RESULTS:

• Case patients: 197 mothers | Controls: 788
• Median maternal RBC folate concentrations
  • Cases: 714 (IQR, 482 to 1008) nmol/L
  • Controls: 788 (IQR, 557 to 1094) nmol/L
• Maternal RBC folate concentrations were inversely associated with offspring CHD
  • aOR per 100 nmol/L: 0.93 (95% CI, 0.89 to 0.99)
• Periconception maternal RBC folate of ≥906 nmol/L was associated with lower risk for CHD among offspring
  • aOR 0.61 (95% CI, 0.40 to 0.93)
• Mendelian randomization showed that each 100-nmol increase in maternal RBC folate concentrations was significantly associated with reduced offspring CHD risk
  • OR 0.75 (95C CI, 0.61 to 0.92)

CONCLUSION:

• A higher maternal RBC folate concentration early in pregnancy is associated with a reduced risk for congenital heart disease among offspring
• The authors state

We propose that target RBC folate levels higher than those currently recommended for NTD prevention be considered for primary CHD prevention

For prevention of offspring CHD, the authors argue that target folate supplement levels may need to be higher than they currently are, and this presents an avenue for further study

Learn More – Primary Sources:

Periconception Red Blood Cell Folate and Offspring Congenital Heart Disease

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