Elevated homocysteine levels in mothers with neural tube defects: a systematic review and meta-analysis

J Matern Fetal Neonatal Med. 2017 Sep;30(17):2051-2057. doi: 10.1080/14767058.2016.1236248. Epub 2016 Oct 3.


Purpose: To find the real relationship between maternal total homocysteine (tHcy) level and risk of neural tube defects (NTDs).

Materials and methods: A systematic review and meta-analysis were conducted. The literature search was conducted with the use of PubMed and EMBASE databases and weighted mean difference (WMD) with 95% confidence interval (CI) was applied to measure the difference in tHcy level between case and control group. Seventeen articles involving 3237 subjects were included according to the inclusion criteria.

Results: Pooled result showed that mothers with NTDs offspring demonstrated significantly a higher mean log plasma tHcy level than mothers with normal offspring (log WMD: 0.06; 95%CI: 0.02-0.09, p = 0.001), corresponding to an increase of 6% (2-9%) in the geometric mean. Subgroup analyses also displayed this difference in subjects who were detected during pregnancy or without folate supplementation before sampling. However, in the mandatory folate fortification countries, we did not find this association.

Conclusions: A slightly higher tHcy level in mothers with NTDs was indicated, but potential confounders could not be ruled out completely. Further larger or cohort studies are needed to confirm this association.

Keywords: Neural tube defects; folate supplementation; homocysteine; meta; prenatal care.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Case-Control Studies
  • Female
  • Folic Acid / therapeutic use*
  • Hematinics / therapeutic use*
  • Homocysteine / blood*
  • Humans
  • Neural Tube Defects / blood*
  • Neural Tube Defects / etiology*
  • Neural Tube Defects / prevention & control
  • Pregnancy


  • Hematinics
  • Homocysteine
  • Folic Acid