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. 2018 Jul 1;75(7):747-748.
doi: 10.1001/jamapsychiatry.2018.0378.

Neuroprotective Effects of Prenatal Folic Acid Supplementation: Why Timing Matters

Joshua L Roffman  1   2
Affiliations

Neuroprotective Effects of Prenatal Folic Acid Supplementation: Why Timing Matters

Joshua L Roffman. JAMA Psychiatry. .
No abstract available

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Figures

Figure.
Figure.. Maternal folate levels and risk for pre- versus postnatal-onset CNS disorders.
Rapidly dividing fetal and placental cells, and their related demand for one-carbon moieties to support DNA synthesis and DNA/histone methylation, cause maternal blood folate levels to decline throughout pregnancy. In the setting of low periconceptional maternal folate levels, this decline can have adverse consequences on CNS development. Epidemiologic evidence suggests that risk for neural tube defects (NTD) and, potentially, for more subtle neurodevelopmental disorders (NDD) such as autism and schizophrenia can be mitigated by maternal intake of food-based folic acid (fortification) or prenatal vitamins containing folic acid (supplements). However, the type and timing of this exposure may have different implications for NTD versus NDD risk. The curves in this figure represent four different levels of exposure, their effects on circulating folate levels throughout pregnancy, and their potential relevance to prevention. Exposure to fortification alone (orange arrow) may be sufficient to ameliorate NTD risk, even in the absence of prenatal vitamin supplements during neural tube closure in the first month of pregnancy. However, even on the background of fortification exposure (red arrow), delay of supplements until after the periconceptional period (yellow arrow) may not sufficiently restore depleted maternal folate stores in time for optimal epigenetic priming later in gestation, when specialized brain systems develop. As DNA and histone methylation marks established in fetal life persist well after birth, periconceptional folate deficits potentially predispose to altered cortical development throughout childhood and adolescence, and increased risk for NDD.
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