Eryilmaz H, et al. - Researchers assessed the links between fetal folic acid exposure, cortical maturation, and psychiatric risk in youths. In relation to gestational exposure to folic acid-fortified grain products, altered cortical development was observed, resulting in an attenuated risk of psychosis in youths.

Methods

• Researchers performed this retrospective, observational clinical cohort study at Massachusetts General Hospital (MGH).
• Study participants were 292 youths 8 to 18 years of age born between January 1993 and December 2001 (inclusive of folic acid fortification rollout ±3.5 years) with normative results of clinical magnetic resonance imaging, divided into three age-matched groups based on birthdate and related level of prenatal folic acid fortification exposure (none, partial, or full).
• Participants underwent magnetic resonance imaging between January 2005 and March 2015.
• For replication, clinical extension, and specificity, they studied two independent, observational, community-based cohorts (Philadelphia Neurodevelopmental Cohort [PNC] and National Institutes of Health Magnetic Resonance Imaging Study of Normal Brain Development [NIH]) comprising 1,078 youths 8 to 18 years of age born throughout (PNC, 1992-2003) or before (NIH, 1983-1995) the rollout of folic acid fortification.
• They also performed statistical analysis from 2015 to 2018.
• Exposures included US–mandated grain product fortification with folic acid, introduced in late 1996 and fully in effect by mid-1997.
• They assessed differences in cortical thickness among nonexposed, partially exposed, and fully exposed youths (MGH) and underlying associations between age and cortical thickness (all cohorts).
• They carried out analysis of the PNC cohort, wherein the association of age–cortical thickness slopes with the odds of psychotic symptoms was also assessed.

Results

• They found exposure-related cortical thickness increases in bilateral frontal and temporal regions (9.9% to 11.6%; corrected P < .001 to P=.03) and emergence of quadratic (delayed) age-associated thinning in temporal and parietal regions (β = -11.1 to -13.9; corrected P=.002) in the MGH cohort (139 girls and 153 boys; mean [SD] age, 13.3 [2.3] years).
• They also observed exposure-associated delays of cortical thinning (β = -1.59 to -1.73; corrected P < .001 to P=.02) in the contemporaneous PNC cohort (417 girls and 444 boys; mean [SD] age, 13.5 [2.7] years); these were found to be located in similar regions and with similar durations of delay as in the MGH cohort.
• In the PNC cohort, flatter thinning profiles in frontal, temporal, and parietal regions were found to be related to lower odds of psychosis spectrum symptoms (odds ratio, 0.37-0.59; corrected P < .05).
• In the nonexposed NIH cohort (118 girls and 99 boys; mean [SD] age, 13.3 [2.6] years), earlier thinning was observed in all identified regions.