Pre-natal dietary imbalance of folic acid and vitamin B12 deficiency adversely impacts placental development and fetal growth

Placenta. 2023 Feb:132:44-54. doi: 10.1016/j.placenta.2023.01.003. Epub 2023 Jan 3.


Introduction: The common practice of supplementing folic acid during pregnancy and the absence of such guidelines for vitamin B12 lead to an imbalance of these vitamins, especially in developing countries like India, where many women are vitamin B12 deficient.

Methods: The present study was designed to explore the effect of low vitamin B12 in combination with different levels of folic acid in the parental diet on fetal growth parameters and maternal reproductive performance in a transgenerational manner. The reversibility of these effects was studied by shifting the mice to a regular diet in the F1 generation in the case of transient groups and continued on the same diet in the sustained groups after the dietary exposure in the F0 generation.

Results: Vitamin B12 deficiency and different levels of folic acid resulted in the decreased placental and fetal weight of the F1 generation. Surprisingly, a decreased placental weight, low fetal weight, and reduced crown-rump length and head circumference were observed in F2 fetuses of vitamin B12 deficient with folate over-supplemented (BDFO) transient group, i.e. when F1 mice were shifted to normal diet conditions. Reduced follicles in ovaries and alteration in placental pathology in all the F0 groups and BDFO of the F1 transient group were also seen.

Discussion: Overall, the study revealed that dietary imbalance of vitamin B12 and folic acid, particularly B12 deficiency with over-supplemented folic acid, negatively affects placental and fetal development and maternal reproductive performance. Such effects are passed on to the next generation too.

Keywords: Corpus luteum; Fetal growth parameters; Folic acid; Homocysteine; Placenta; Vitamin B12.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diet
  • Female
  • Fetal Development
  • Fetal Weight
  • Folic Acid*
  • Homocysteine
  • Mice
  • Placenta
  • Placentation
  • Pregnancy
  • Vitamin B 12
  • Vitamin B 12 Deficiency*


  • Folic Acid
  • Vitamin B 12
  • Homocysteine