BACKGROUND AND PURPOSE:

• In several countries, food is fortified with folic acid (synthetic, more highly bioavailable form compared to naturally occurring folate)
  • Folate levels in women of reproductive age have doubled with a concomitant reduction in neural tube defects
  • Studies show lower risk of language delay and autism in offspring exposed to prenatal folic acid (see ‘Related ObG Topics’ below)
• Ervilmaz et al. (JAMA Psychiatry 2018) examined the associations between fetal folic acid exposure, cortical maturation and psychiatric risk in youths

METHODS:

• Retrospective, observational clinical cohort study (1993-2001)
  • Two additional independent, observational, community-based cohorts were also used
    • One of these cohorts assessed the association of age–cortical thickness slopes with the odds of psychotic symptoms
  • Participants were between the ages of 8-18 years
  • Children were born before or during the United States-mandated grain product fortification with folic acid, which was introduced in late 1996 and fully in effect by mid-1997
  • Youths were separated into 3 age-matched groups
    • Nonexposed
    • Partially exposed
    • Fully exposed
  • All subjects received magnetic resonance imaging (MRI) to determine the association between age and cortical thickness

RESULTS:

• 292 youths were included in the retrospective study and 1,078 from the community-based cohorts
• The retrospective cohort (139 girls and 153 boys; mean [SD] age, 13.3 [2.3] years) demonstrated the following in the folic acid group
  • Increased Cortical thickness in bilateral frontal and temporal regions (9.9%-11.6%; corrected P < .001 to P = .03)
  • Emergence of quadratic (delayed) age-associated thinning in temporal and parietal regions (β = –11.1 to –13.9; corrected P = .002)
• Flatter thinning profiles in frontal, temporal, and parietal regions were associated with lower odds of psychosis spectrum symptoms (odds ratio, 0.37-0.59; corrected P < .05)
• All identified regions displayed earlier thinning in a nonexposed cohort (118 girls and 99 boys; mean [SD] age, 13.3 [2.6] years)

CONCLUSION:

• Folic acid supplementation is associated with delayed onset of cortical thinning, which in one study was linked with lower odds of psychosis spectrum symptoms

Learn More – Primary Sources:

Association of Prenatal Exposure to Population-Wide Folic Acid Fortification With Altered Cerebral Cortex Maturation in Youths

Related ObG Topics:

NTDs and Pregnancy – Folic Acid Recommendations

Reduced Risk of Autism in Offspring Exposed to Folic Acid During Pregnancy

Cleft Lip and Palate – Considerations and Discussion Points

Do Maternal Multivitamin Supplements Decrease Risk for Autism in Offspring?