Survival of infants with neural tube defects in the presence of folic acid fortification

Pediatrics. 2006 Mar;117(3):803-13. doi: 10.1542/peds.2005-1364.


Objective: Neural tube defects (NTDs) are preventable through preconceptional and periconceptional folic acid intake. Although decreases in the prevalence of NTDs have been reported since folic acid fortification of United States grain products began, it is not known whether folic acid plays a role in reducing the severity of occurring NTDs. Our aim was to determine whether survival among infants born with spina bifida and encephalocele has improved since folic acid fortification and to measure the effects of selected maternal, pregnancy, and birth characteristics on first-year (infant) survival rates.

Methods: A retrospective cohort study was conducted and included 2841 infants with spina bifida and 638 infants with encephalocele who were born between 1995 and 2001 and were registered in any of 16 participating birth defects monitoring programs in the United States. First-year survival rates for both spina bifida and encephalocele cohorts were measured with Kaplan-Meier estimation; factors associated with improved chances of first-year survival, including birth before or during folic acid fortification, were measured with Cox proportional-hazards regression analysis.

Results: Infants with spina bifida experienced a significantly improved first-year survival rate of 92.1% (adjusted hazard ratio: 0.68; 95% confidence interval: 0.50-0.91) during the period of mandatory folic acid fortification, compared with a 90.3% survival rate for those born before fortification. Infants with encephalocele had a statistically nonsignificant increase in survival rates, ie, 79.1% (adjusted hazard ratio: 0.76; 95% confidence interval: 0.51-1.13) with folic acid fortification, compared with 75.7% for earlier births.

Conclusions: Folic acid may play a role in reducing the severity of NTDs in addition to preventing the occurrence of NTDs. This phenomenon contributes to our understanding of the efficacy of folic acid. Additionally, as survival of NTD-affected infants improves, health care, education, and family support must expand to meet their needs.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Dietary Supplements
  • Encephalocele / mortality
  • Encephalocele / prevention & control
  • Female
  • Flour*
  • Folic Acid / administration & dosage*
  • Food, Fortified*
  • Humans
  • Infant
  • Infant, Newborn
  • Neural Tube Defects / mortality*
  • Neural Tube Defects / prevention & control*
  • Pregnancy
  • Prenatal Care*
  • Spinal Dysraphism / mortality
  • Spinal Dysraphism / prevention & control
  • Survival Rate
  • Vitamin B Complex / administration & dosage*


  • Vitamin B Complex
  • Folic Acid