Using a series of small public data sets, researchers found a positive association of prenatal exposure to folic acid fortification with subsequent cortical development in the brain—considered key for cognitive and mental health—through adolescence.
The finding suggests that increased prenatal exposure to folic acid through food fortification may protect against psychosis through altered postnatal cortical development.
When folic acid fortification
was put in place in the United States in 1998, it was to prevent neural tube defects. Eighty-one countries now require folic acid, noted the study, published Tuesday in JAMA
Previous epidemiologic data regarding mental illness suggested potentially broader effects of prenatal folate exposure on postnatal brain development, but until now the link was unsubstantiated.
Adolescence directly precedes the period of greatest risk for psychiatric disorders, some of which are characterized by reductions in cortical thickness present at the onset of illness. In addition, some of the most severe child-onset psychiatric disorders, including autism and early-onset schizophrenia, are linked with marked accelerations in loss of gray matter.
In this study, researchers looked at 3 separate, independent groups of youths, ages 8 to 18, who had brain magnetic resonance imaging (MRI) done during 3 different time periods.
One retrospective, observational clinical cohort study was conducted at the Massachusetts General Hospital (MGH) among 292 youths born between January 1993 and December 2001 (inclusive of folic acid fortification rollout ± 3.5 years) with normative MRI results.
They were split into 3 age-matched groups based on birthdate and related level of prenatal folic acid fortification exposure (none, partial, or full). MRIs were performed between January 2005 and March 2015.
Those groups were compared with 2 independent, observational, community-based cohorts (Philadelphia Neurodevelopmental Cohort [PNC] and National Institutes of Health Magnetic Resonance Imaging Study of Normal Brain Development [NIH]).
The PNC group was made up of 1078 youths born throughout the rollout of the folic acid implementation between 1992 to 2003. The NIH group was born before the rollout between 1983 to 1995.
Researchers found widespread increases in frontal and temporal cortical thickness among groups of youths who were born just after, compared with just before, the rollout of folic acid fortification.
Youths who were born during the rollout, and who therefore had partial exposure, demonstrated intermediate increases, consistent with a dose association.
The NIH cohort, made up only of individuals who were not exposed to fortification, showed earlier cortical thinning in the same regions.
The MGH cohort (139 girls and 153 boys; mean [SD] age, 13.3 [2.3] years) demonstrated increases in exposure-associated cortical thickness in the 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 (beta = –11.1 to –13.9; corrected P
The contemporaneous PNC cohort (417 girls and 444 boys; mean [SD] age, 13.5 [2.7] years) also exhibited exposure-associated delays of cortical thinning (beta = –1.59 to –1.73; corrected P
<.001 to P
= .02), located in similar regions and with similar durations of delay as in the MGH cohort. Flatter thinning profiles in frontal, temporal, and parietal regions were associated with lower odds of psychosis spectrum symptoms in the PNC cohort (odds ratio [OR], 0.37-0.59; corrected P
All identified regions displayed earlier thinning in the nonexposed NIH cohort (118 girls and 99 boys; mean [SD] age, 13.3 [2.6] years).
Collectively, the study suggests an association of prenatal exposure to folic acid fortification with increased cortical thickness through early adolescence, accompanied by delayed onset of cortical thinning and reduced risk of mental illness.
The researchers said although they believe their study is the first to link prenatal exposure to folic acid fortification to changes in subsequent cortical development, how exactly that happens has yet to be determined.
Eryilmaz H, Dowling KF, Huntington FC, et al. Association of prenatal exposure to population-wide folic acid fortification with altered cerebral cortex maturation in youths [published online July 3, 2018]. JAMA Psychiatry