Association of Altered Ratio of Maternal Folic Acid and Vitamin B12 during Pregnancy with Newborn Birth Weight, Head Circumference, and Chest Circumference

Abstract

Objective

This study evaluated the effect of an altered ratio of maternal RBC folate (MRF) to serum vitamin B12 (MB12) on pregnancy and newborn outcomes.

Methods

Blood samples were collected from pregnant women and the umbilical cord at the time of delivery. Estimations of RBC folate and serum vitamin B12 from maternal and cord blood samples and total homocysteine (HCY) were performed. Maternal and newborn anthropometric parameters like placental weight (PW), head circumference (HC), chest circumference (CC), and body weight (BW) were measured in offsprings after birth. We stratified the pregnant women into six groups (a) vitamin B12 normal and folic acid normal (BNFN)-control group, (b) vitamin B12 normal and folic acid elevated (BNFE), (c) vitamin B12 normal and folic acid deficient (BNFD), (d) vitamin B12 deficient and folic acid normal (BDFN), (e) vitamin B12 deficient and folic acid elevated (BDFE) and (f) vitamin B12 deficient and folic acid deficient (BDFD) based on their levels of RBC folate (MRF) and vitamin B12 (MB12). The expression of the one-carbon metabolism genes (methionine synthase (MS), glycine N-methyltransferase (GNMT), and cystathionine β-synthase (CBS) was also studied in placental tissue by using real-time PCR.

Results

Cord blood RBC folate was significantly reduced in groups BDFE and BDFD as compared to the control group (BNFN). The cord blood vitamin B12 levels were also reduced in the BDFE group as compared to the BDFD. All the newborn parameters viz. PW, HC, CC, and BW, were reduced in the altered MRF/MB12 ratio (low & high vs. normal ratio). Total HCY was significantly elevated in the groups with (BDFE & BDFN) an imbalance of maternal RBC folate and serum vitamin B12 as compared to the control group. Downregulation of one-carbon metabolism genes like MS (p < 0.001), GNMT (p < 0.05), and CBS (p < 0.01) in placental tissue was observed in the high MRF/MB12 ratio group as compared to the normal ratio group. A strong positive correlation was also observed between MRF, MB12, and newborn parameters.

Conclusions

The altered ratio of folate to vitamin B12 in the maternal blood is associated with adverse growth and development of the newborn.

Keywords:

• Vitamin B12
• Folic acid
• Pregnancy
• Birth weight
• Homocysteine
• Placental genes

Author contributions

RR, AM, DS and JK designed the study and analyzed the data. DS and VS helped in analyzing folate and vitamin B12 levels. RR, DS, PS performed the experiments. RR, AM and JK prepared the manuscript, and all authors critically revised and approved the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data will be made available upon direct request to the authors of this paper. No datasets were generated or analyzed during the current study.

Additional information

Funding

We thank the women and their infants who participated in this study. Research funding played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.