Periconception Parental Red Blood Cell Folate, Vitamin B₁₂, and Birth Defects in Offspring : A Prospective Cohort...

Maternal folic acid prevents neural tube defects, but associations of parental folate and vitamin B₁₂ with birth defects remain unclear.

To quantify associations of parental vitamin B₁₂ and red blood cell (RBC) folate with offspring birth defects.

Prospective cohort study.

Shanghai Preconception Cohort, China.

3032 couples (73 birth defect cases) with biomarkers sampled within 4 months before conception, and 17 765 women (327 birth defect cases) sampled at 4 months' gestation or earlier.

Standardized predicted prevalences of birth defects ascertained among live births, stillbirths, and abortions due to fetal abnormalities were estimated using weighted logistic regression.

Higher preconception parental levels of vitamin B₁₂ were associated with lower predicted prevalences of birth defects in dose-response analyses. For preconception maternal vitamin B₁₂ from the lowest (<148 pmol/L) to highest (≥590 pmol/L) categories, predicted prevalence decreased from 49.6 to 16.2 cases per 1000 pregnancies; paternal vitamin B₁₂ showed a similar but attenuated pattern (55.5 to 24.0 cases per 1000 pregnancies). Preconception parental RBC folate showed imprecise patterns of lower predicted prevalence. For postconception maternal RBC folate, predicted prevalence was lower at levels of 906 to 1131 nmol/L than at levels below 453 nmol/L (16.5 vs. 25.7 cases per 1000 pregnancies), with little further reduction at higher levels. For postconception maternal vitamin B₁₂, predicted prevalence changed little across lower categories but was lower at higher levels (11.8 vs. 20.4 cases per 1000 pregnancies at ≥590 vs. 148 to 294 pmol/L, respectively).

Residual confounding.

Periconception parental vitamin B₁₂ and postconception maternal RBC folate were associated with lower predicted prevalences of birth defects.

National Key Research and Development Program of China, National Natural Science Foundation of China, and Chinese Academy of Medical Sciences.