Mothers’ Prenatal Diet has Long-Lasting Effect on Brain Development

Maternal low-folate in early pregnancy has been associated with smaller total brain volume (TBV). Together with higher levels of total homocysteine (tHcy), there is also a link between poorer language and visuospatial performance in children aged between six and eight years.

 

Lead authors of the study Charlotte Ars and Ilse Nijs state: “Our findings suggest that folate insufficiency in early pregnancy has a long-lasting, global effect on brain development and is, together with homocysteine levels, associated with poorer cognitive performance.”

 

The study was carried out at the Erasmus University Medical Center, Rotterdam in The Netherlands, and is part of the Generation R Study, which looked at approximately 10,000 pregnant Dutch women in a period between 2002 and 2006.

 

Maternal folate (active form 5-methyltetrahydrofolate) concentration was measured in plasma and considered to provide a more objective and reliable index of folate status.

Results showed that 35.5% of the mothers with low folate levels used folic acid supplements. Reaching the right level of active folate in the blood is not easy as several factors may intervene. Humans cannot synthesize folate and because of its water soluble nature, the body only stores folate to a limited extent. Low-folate in the blood may occur due to inadequate dietary intake, but also some people have limited ability to metabolize folic acid to the active form.

 

The enzymatic conversion of folate/folic acid to the active 5-MTHF is a multi-step process where the enzyme methylenetetrahydrofolate reductase (MTHFR) owns a key role.

Some individuals, due to their unique genetic patterns and expression, have polymorphic forms of this enzyme and do not produce adequate or effective MTHFR. Although MTHFR gene mutations affect over 40 percent of the world population, sadly this is largely ignored.

 

Homocysteine is a chemical in the blood that is produced when an amino acid (a building block of protein) called methionine is broken down in the body.  Deficiencies in vitamin B12, folic acid and vitamin B6 are associated with raised homocysteine levels.

 

Details of the study
The primary aim of the study was to investigate the association between maternal folate status during early pregnancy and child’s brain development, as indexed by brain volume of six- to eight-year-old children. 256 structural MRI brain scans were collected from a subgroup of 608 children.

 

The secondary aim was to explore whether brain volume accounted for any association between prenatal folate status and the occurrence of cognitive performance or emotional and behavioral problems in the same study sample.

 

Brain volume, cognitive and psychological outcomes were additionally examined in relation to maternal plasma vitamin B12 and total homocysteine (tHcy) levels, owing to the interrelatedness between folate, vitamin B12 and tHcy levels and the associations between vitamin B12 and tHcy and cognitive outcomes in children. 
However, neither prenatal plasma B12 nor homocysteine levels predicted any brain volume outcomes.

 

Child intelligence at age 6 years was found to be substantially lower (7 points) in children of mothers with high plasma tHcy concentrations during early pregnancy, compared with children of mothers with normal tHcy concentrations. Furthermore, high prenatal plasma tHcy levels were associated with poorer language, learning/memory and visuo-spatial performance.

 

“The ‘low folate’ children did not have more emotional or behavioural problems than the ‘normal folate’ children at age 6 years. This finding suggests that effects of prenatal folate insufficiency on the psychological
functioning of children might disappear in the course of development, possibly because of compensating environmental factors, such as adequate nutrition and family functioning, or social stimulation and support from their fairly well educated mothers,” the authors conclude.

 

In conclusion, this work supports the recommendations for prenatal use of folate, that even in the absence of neural tube defects, subtle differences can be seen related to brain growth.

 

Source of folate
Quatrefolic is a source of the active form of folate, the (6S)-5-methyltetrahydrofolate (5-MTHF). Quatrefolic maximizes the benefit of folate supplementation, protecting mothers in pregnancy and, according to this study, young children.

 

Most folate in the diet is from manufactured folic acid in supplements and that added to foods. Folic acid (like food folate) is inactive and needs to be metabolized to 5-methyltetrahydrofolate (5-MTHF) to become metabolically effective. Because folic acid has a complex metabolization process, people consuming folic acid may still be gravely folate deficient because of the big variations in how efficiently folic acid is converted to the bioactive form in different people.

 

Quatrefolic can reach the systemic circulation in the biologically active form of 5-MTHF, without any kind of metabolization.  5-MTHF is the main folate form in blood and cord serum, and can directly enter the folate cycle.
Clinical evidence suggests that supplementation of the natural form of 5-MTHF, such as Quatrefolic, is a better alternative to supplementation of folic acid, and this can effectively improve folate biomarkers in young women in early pregnancy. As Quatrefolic provides the metabolic reduced folate form utilized and stored in the human body, it may also benefit certain genetic defects that influence folate metabolism.

 

It remains to be investigated whether this effect is permanent, hence still visible in adolescence and adulthood.