Maternal choline concentrations during pregnancy and choline-related genetic variants as risk factors for neural tube defects

Am J Clin Nutr. 2014 Oct;100(4):1069-74. doi: 10.3945/ajcn.113.079319. Epub 2014 Aug 13.


Background: Low maternal choline intake and blood concentration may be risk factors for having a child with a neural tube defect (NTD); however, the data are inconsistent. This is an important question to resolve because choline, if taken periconceptionally, might add to the protective effect currently being achieved by folic acid.

Objective: We examined the relation between NTDs, choline status, and genetic polymorphisms reported to influence de novo choline synthesis to investigate claims that taking choline periconceptionally could reduce NTD rates.

Design: Two study groups of pregnant women were investigated: women who had a current NTD-affected pregnancy (AP; n = 71) and unaffected controls (n = 214) and women who had an NTD in another pregnancy but not in the current pregnancy [nonaffected pregnancy (NAP); n = 98] and unaffected controls (n = 386). Blood samples to measure betaine and total choline concentrations and single nucleotide polymorphisms related to choline metabolism were collected at their first prenatal visit.

Results: Mean (±SD) plasma total choline concentrations in the AP (2.8 ± 1.0 mmol/L) and control (2.9 ± 0.9 mmol/L) groups did not differ significantly. Betaine concentrations were not significantly different between the 2 groups. Total choline and betaine in the NAP group did not differ from controls. Cases were significantly more likely to have the G allele of phosphatidylethanolamine-N-methyltransferase (PEMT; V175M, +5465 G>A) rs7946 (P = 0.02).

Conclusions: Our results indicate that maternal betaine and choline concentrations are not strongly associated with NTD risk. The association between PEMT rs7946 and NTDs requires confirmation. The addition of choline to folic acid supplements may not further reduce NTD risk.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Betaine / blood
  • Case-Control Studies
  • Choline / blood*
  • Dietary Supplements
  • Female
  • Folic Acid / blood
  • Genome, Human
  • Genotype
  • Humans
  • Logistic Models
  • Neural Tube Defects / genetics*
  • Phosphatidylethanolamine N-Methyltransferase / blood
  • Phosphatidylethanolamine N-Methyltransferase / genetics
  • Polymorphism, Single Nucleotide*
  • Pregnancy
  • Risk Factors
  • Selection, Genetic
  • Young Adult


  • Betaine
  • Folic Acid
  • Phosphatidylethanolamine N-Methyltransferase
  • Choline