Folate fortification and supplementation in prevention of folate-sensitive neural tube defects: A systematic review of policy

Nathan A. Shlobin, Melissa A. LoPresti, Rebecca Y. Du, Sandi Lam*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Objective: Neural tube defects (NTDs) are common congenital neurological defects, resulting in mortality, morbidity, and impaired quality of life for patients and caregivers. While public health interventions that increase folate consumption among women who are or plan to become pregnant are shown to reduce folate-sensitive NTDs, public health policy reflecting the scientific evidence lags behind. The authors aimed to identify the types of policies applied, associated outcomes, and impact of folate fortification and supplementation on NTDs worldwide. By identifying effective legislation, the authors aim to focus advocacy efforts to more broadly effect change, reducing the burden of NTDs in neurosurgery. Methods: A systematic review was conducted exploring folate fortification and supplementation policies using the PubMed and Scopus databases. Titles and abstracts from articles identified were read and selected for full-text review. Studies meeting inclusion criteria were reviewed in full and analyzed for study design, aim, population, interventions, and outcomes. Results: Of 1637 resultant articles, 54 were included. Mandatory folate fortification was effective at reducing folatesensitive NTDs. Mandatory fortification also decreased hospitalization rates and deaths after discharge and increased 1st-year survival for infants with NTDs. Recommended folate supplementation also resulted in decreased NTDs; however, issues with compliance and adherence were a concern and impacted effectiveness. Folate fortification and/or supplementation resulted in decreased NTD prevalence, although more change was attributed to fortification. Dual policies may hold the most promise. Furthermore, reductions in NTDs were associated with significant cost savings over time. Conclusions: Both mandatory folate fortification and recommended supplementation policies were found to effectively decrease folate-sensitive NTD rates when applied. A comprehensive approach incorporating mandatory folate fortification, appropriate folate supplementation, and improved infrastructure and access to prenatal care may lead to decreased NTDs worldwide. This approach should be context-specific, emphasize education, and account for regional access to healthcare and social determinants of health. With wide implications for NTDs, associated health outcomes, quality of life of patients and caregivers, and economic impacts, policy changes can drastically improve global NTD outcomes. As caretakers of children with NTDs, the authors as neurosurgeons advocate for a comprehensive policy, the engagement of stakeholders, and a broader global impact.

Original languageEnglish (US)
Pages (from-to)294-310
Number of pages17
JournalJournal of Neurosurgery: Pediatrics
Issue number3
StatePublished - Mar 2021


  • Congenital
  • Folate
  • Folic acid
  • Fortification
  • Neural tube defects
  • Policy
  • Public health
  • Spina bifida
  • Supplementation

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology


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