Beneficial effects on psychosocial and cognitive development observed in children following in utero folic acid supplementation track with changes in their DNA methylation.

Increasingly accurate surveys of human health throughout the life course has led experts to propose that stresses on the developing child whilst in the mother’s womb can affect the individual’s health later in life. Such long-term effects on health are thought to be mediated by a semi-permanent trace on the genes called an epigenetic mark, mediated by processes such as DNA methylation. DNA methylation patterns may be altered by the mother’s diet, particularly folate – a key component in the DNA methylation cycle. Currently, mothers are recommended to supplement their diet with 400μg folic acid/day as a preventative measure against neural tube defects prior to/during the first trimester. However, there remains no clinical recommendation as to whether mothers should continue supplementation during the latter two trimesters and the potentially heritable effects. Thus, we analysed cord blood samples (n=93) from the Folic Acid Supplementation in the Second and Third Trimesters (FASSTT) randomised control trial for genome-wide DNA methylation. Offspring exposed to folic acid in later pregnancy had fewer highly methylated genomic regions and more intermediately methylated sites. Upon further interrogation, gene ontology analysis revealed these sites are enriched for genes associated with cognition and neurological system processes, and tissue analysis revealed enrichment of affected genes associated with the brain. Cognitive and psychosocial testing of the children at age 7 years, using standardised tests (WPPSI, TEIQue-CSF, RASP), showed that the children supplemented during pregnancy scored significantly higher for emotional intelligence, resilience and verbal IQ. Thus, this study offers a potential biological mechanism linking maternal folate levels with childhood cognition.