The role of maternal folic acid supplementation on offspring neurodevelopment

Folic acid is a B-vitamin and is well known for its role during early neurodevelopment. It promotes the closure of the neural tube in utero. The neural tube in the developing embryo is the first step to forming the brain and spinal cord. If the neural tube does not close, it can lead to neural tube defects (NTDs), such as spina bifida. Women of child bearing age are recommended to supplement their diet with 0.4 -1 mg of folic acid daily. Additionally, to reduce the number of NTDs mandatory folic acid fortification laws were put into place in 1998 in the US and Canada, as well as other countries around the world. In response to mandatory fortification, there has been a reduction in the number of NTDs in both Canada and the US.
 
 
Recently, maternal over supplementation of folic acid has raised some concerns.  Over supplementation is defined as ingesting over 1 mg of folic acid daily. There has been an increase in over supplementation of folic acid in the US and Canada where mandatory folic acid fortification laws are in place and supplement use is high. Epidemiological studies have reported that too much folic acid has been associated with increased risk of cancer. Interestingly, too much maternal folic acid intake has been associated with autism spectrum disorder, but the data is not clear as other studies have reported the protective effects. Furthermore, too much maternal folic acid has been reported to change neurodevelopment in animals.
 
A recent published study investigated whether too much maternal folic acid is associated with changes in the neurodevelopment of offspring. Using a mouse model of maternal over supplementation of folic acid the authors report that male offspring from mothers that were fed high levels of folic acid had impaired memory and brain development.  The amount of folic acid in the diet of mothers was 20mg/kg to model over supplementation in humans. Animals from mothers with over supplementation of folic acid did not remember seeing a familiar object as well as control animals did. Furthermore, they had reduced levels of a neurotransmitter that is important in learning and memory called acetylcholine.
 
These are some of the first results showing how maternal over supplementation with folic acid may affect early neurodevelopment. We recently published an up-to-date review of how maternal over supplementation of folic acid impacts offspring neurodevelopment.  Our comprehensive analysis includes studies from human populations as well as basic science studies to understand how things in the brain as well as behaviors are changing when mothers are supplementing with too much folic acid.  More studies are required to understand the full impact of how maternal over supplementation studies affect offspring neurological development. As someone wise once said, everything in moderation.