Higher periconception RBC folate tied to lower offspring CHD risk

Greater maternal red blood cell (RBC) folate, the gold-standard biomarker of folate exposure, appears to lower the risk of offspring congenital heart disease (CHD), reveals a study.

This prospective, nested, case-control study and 1-sample Mendelian randomization were conducted in 29 maternity institutions in 12 districts of Greater Shanghai, China. A total of 197 mothers of offspring with CHD and 788 individually matched mothers of unaffected offspring from the Shanghai Preconception Cohort were included.

The researchers measured maternal RBC folate before or at early pregnancy. They estimated odds ratios (ORs) using conditional logistic regression after adjustment for covariates. Mendelian randomization was carried out using the methylenetetrahydrofolate reductase (MTHFR) C677T as the genetic instrument.

Median maternal RBC folate concentrations were lower among case patients than control participants (714 vs 788 nmol/L). In addition, maternal RBC folate concentrations inversely correlated with offspring CHD (adjusted OR per 100 nmol/L, 0.93, 95 percent confidence interval [CI], 0.89‒0.99).

For mothers with periconception RBC folate ≥906 nmol/L, the adjusted OR was 0.61 (95 percent CI, 0.40‒0.93) relative to those with RBC folate <906 nmol/L.

In Mendelian randomization, each 100-nmol increment in maternal RBC folate concentrations significantly correlated with lower offspring CHD risk (OR, 0.75, 95 percent CI, 0.61‒0.92).

“For primary CHD prevention, higher target RBC folate levels than currently recommended for neural tube defect prevention may be needed and warrant further study,” the researchers said.

The study was limited by potential confounding due to unmeasured covariates in the nested case-control study.