Both parents’ B12 levels linked to birth defect risk

Clinical takeaway: Consider optimizing vitamin B12 status in both prospective parents before conception, alongside established folate recommendations for women, as higher parental B12 levels and adequate maternal red blood cell (RBC) folate were associated with lower birth defect risk.

Folic acid supplementation is a cornerstone of neural tube defect prevention, but whether broader parental nutritional status influences the risk of other birth defects remains less clear. This study is notable because it evaluated both maternal and paternal biomarkers around conception and focused largely on non-neural tube defects, including congenital heart defects.

In this prospective cohort study from China, investigators analyzed 3,032 couples who provided blood samples within 4 months before conception and 17,765 women tested during early pregnancy. Across the cohorts, 472 birth defects were identified, most of them non-neural tube defects and more than half involving congenital cardiac malformations.

Higher maternal and paternal vitamin B12 levels before conception were associated with progressively lower rates of birth defects. Among mothers, predicted birth defect prevalence fell from about 50 cases per 1,000 pregnancies in the lowest vitamin B12 category to 16 per 1,000 in the highest category, a relative reduction of roughly two-thirds. A similar pattern was seen among fathers, with rates declining from 56 to 24 cases per 1,000 pregnancies.

Maternal RBC folate measured during early pregnancy was also linked to lower risk. Predicted prevalence decreased from 26 cases per 1,000 pregnancies in women with the lowest folate levels to about 17 per 1,000 among those with RBC folate concentrations between 906 and 1,131 nmol/L, with little additional benefit observed at higher levels. Associations between preconception RBC folate and birth defects were less consistent.

“These findings extend work focused primarily on maternal folate and suggest that broader consideration of periconception nutritional status, including paternal vitamin B12, may inform birth defect prevention,” the authors wrote.

Source: Chen H, et al. (2026 Sep 1) Ann Intern Med. Periconception Parental Red Blood Cell Folate, Vitamin B12, and Birth Defects in Offspring: A Prospective Cohort Study