The Importance of Maternal Folate Status for Brain Development and Function of Offspring

Eva F.G. Naninck, Pascalle C. Stijger, Elske M. Brouwer-Brolsma*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

65 Citations (Scopus)


The importance of an adequate periconceptional maternal folate status to prevent fetal neural tube defects has been well demonstrated and resulted in the recommendation for women to use folic acid supplements during the periconception period. The importance of maternal folate status for offspring neurodevelopment and brain health is less well described. We reviewed the current evidence linking maternal folate status before conception and during pregnancy with neurodevelopment and cognition of the offspring. We discuss both animal and human studies. Preclinical research revealed the importance of maternal folate status for several key processes required for normal neurodevelopment and brain functioning in the offspring, including DNA synthesis, regulation of gene expression, synthesis of phospholipids and neurotransmitters, and maintenance of healthy plasma homocysteine concentrations. Human observational studies are inconclusive; about half have shown a positive association between maternal folate status and cognitive performance of offspring. Whereas some studies suggest a positive association between maternal folate intake and cognition of offspring during childhood, data from interventional studies are too limited to conclude that there is a direct effect. Future preclinical studies are needed to help us characterize the behavioral effects, understand the underlying mechanisms, and to establish an optimal dosage and time window of folate supplementation. Moreover, more conclusive data from well-designed human observational studies and randomized controlled trials are needed to determine whether current recommendations for folic acid supplementation during pregnancy cover the needs for normal cognitive development in the offspring.

Original languageEnglish
Pages (from-to)502-519
Number of pages18
JournalAdvances in Nutrition
Issue number3
Publication statusPublished - 1 May 2019


  • brain
  • cognition
  • developmental
  • folate
  • folic acid
  • maternal
  • neuropsychological
  • prenatal


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