Higher parental vitamin B12 associated with fewer birth defects

1. In this prospective cohort study, higher parental preconception and maternal postconception vitamin B12 levels were associated with lower odds and prevalence of birth defects.

2. Higher folate levels were also associated with fewer birth defects, although preconception estimates were imprecise and postconception benefits plateaued at higher levels.

Evidence Rating Level: 2 (Good)

Study Rundown: Folic acid is well established to reduce the risk of neural tube defects (NTDs), prompting interest in whether improved folate status may also prevent other birth defects. However, evidence regarding folate and non-NTDs remains inconclusive. Paternal functional vitamin B12 deficiency may also be associated with congenital heart defects. This study assessed whether parental vitamin B12 and red blood cell (RBC) folate concentrations around conception were associated with the overall risk of birth defects. In an analysis of more than 30,000 pregnancies, higher parental preconception vitamin B12 concentrations were associated with lower odds of birth defects. Higher preconception RBC folate concentrations were also inversely associated with birth defects, although estimates were imprecise. Higher maternal vitamin B12 concentrations after conception were associated with a lower prevalence and reduced odds of birth defects, particularly at higher concentrations. Higher postconception maternal RBC folate concentrations were similarly associated with reduced prevalence and odds, although the association was less pronounced at higher concentrations. Sensitivity analyses were largely consistent with the primary findings. Generalizability was limited by potential residual confounding, the absence of data on folate-related genetic polymorphisms, and the predominantly Han Chinese population living in a setting without mandatory folic acid fortification. Nevertheless, these findings suggest that higher parental periconceptional vitamin B12 concentrations may be associated with a reduced risk of birth defects, highlighting the potential role of non-folate biomarkers in birth defect prevention.

Click to read this study in AIM

Relevant Reading: Maternal use of folic acid and multivitamin supplements and infant risk of birth defects in Norway, 1999–2013

In-Depth [prospective cohort]: This prospective cohort study evaluated associations between parental periconceptional vitamin B12 and red blood cell (RBC) folate concentrations and the overall risk of birth defects. Participants planning pregnancy within 1 year were recruited from 29 sites across Greater Shanghai, China. Birth defects were identified through prenatal ultrasound, neonatal congenital heart disease screening, delivery records, and confirmatory imaging. The primary outcome was clinically confirmed birth defects among live births, stillbirths, and pregnancy terminations for fetal anomalies. Of 30,052 completed pregnancies, 27,260 with maternal biomarker measurements obtained before conception or within 4 months of gestation were eligible. Overall, 472 birth defects occurred, corresponding to a prevalence of 1.73%. Primary analyses included a preconception parental cohort (n = 3,032; 73 cases) and a postconception maternal cohort (n = 17,765; 327 cases). Low vitamin B12 concentrations (<221 pmol/L) occurred in 9.4% of preconception women, 24.0% of preconception men, and 30.6% of postconception women. Higher preconception maternal vitamin B12 concentrations were associated with lower odds of birth defects (295 vs 221 pmol/L: odds ratio [OR], 0.81 [95% confidence interval [CI], 0.69-0.95]; 443 vs 221 pmol/L: OR, 0.62 [95% CI, 0.44-0.88]). Paternal vitamin B12 showed a similar but attenuated association (295 vs 221 pmol/L: OR, 0.78 [95% CI, 0.68-0.91]). Predicted prevalence decreased from 49.6 to 16.2 cases per 1,000 pregnancies across the lowest and highest maternal vitamin B12 categories and from 55.5 to 24.0 cases per 1,000 across paternal categories. Higher postconception maternal RBC folate was also associated with lower odds of birth defects (906 vs 340 nmol/L: OR, 0.63 [95% CI, 0.55-0.72]), although the association plateaued at higher concentrations. Higher postconception vitamin B12 was modestly associated with lower odds, particularly at 443 versus 221 pmol/L (OR, 0.79 [95% CI, 0.64-0.97]). Sensitivity analyses were consistent with the primary findings. Overall, higher parental periconceptional vitamin B12 concentrations were associated with a lower risk of birth defects.

Image: PD

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