Low prenatal folate levels may be associated with a smaller total brain volume and poorer language and visuo-spatial performance in children at six to eight years, research suggests.
The research carried out at Erasmus University Medical Center in the Netherlands and published in the British Journal of Nutrition, was part of the Generation R Study, which looked at nearly 10,000 pregnant Dutch women.
The current study analysed a sample subgroup of 256 children. The researchers’ primary aim was to examine the association between prenatal folate status and children’s brain anatomy and volume at age six to eight years.
Their secondary aim was to explore the associations between brain volume, cognitive performance and emotional or behavioural problems.
Higher homocysteine levels in the mother also predicted poorer language performance. No associations were found with psychological problems however.
Asked about the health implications of these results for expectant mothers, author Professor Tonya White told us: “I believe our works supports the recommendations for prenatal use of folate and that even in the absence of neural tube defects, subtle differences can be seen related to brain growth.
"Thus, we believe that there is an important public health message.”
Maternal folate levels in early pregnancy were assessed by blood samples against laboratory-determined ‘low’ levels (plasma folate less than 8 nanomolels per litre) and ‘normal’ levels (8nmol/l and above). Further analysis was also carried out using stricter cut-offs.
Emotional and behavioural problems in the children were reported by the mother using a checklist, and intelligence tests were also carried out. MRI brain scans were used to assess total brain volume and other brain variables.
Factors that may affect the results such as gestational age, mothers pre-pregnancy BMI and educational levels and breastfeeding were also considered in the statistical analysis.
There was 48% data missing for breast feeding duration but White said this would not affect the results as they co-varied for other maternal factors related to breastfeeding.
The researchers found brain volumes were smaller in the low folate group compared to the normal folate group.
When they evaluated the brain’s sub-structures they found that “it appears to be a global effect, effecting regions of the brain about the same,” said White.
Mothers with adequate folate levels were more likely to use folic acid supplements and lower folate mothers were more likely to smoke during early pregnancy.
Homocysteine and vitamin B12 levels were not associated with brain volume or behavioural problems, but higher prenatal homocysteine levels were associated with lower IQ in children at age six.
Future studies should examine the mechanisms and effects of prenatal homocysteine on child cognition, said the authors.
Previous results from the Generation R study had associated lower folate with emotional and behavioural problems at age one to five years. The authors said the reason this might not have continued to age six may be due to compensating environmental factors.
Adequate nutrition and family and social support may cause the effects of prenatal folate insufficiency to ‘disappear’ during development, they suggested. This might be more probable with the well-educated Dutch parents used in the sample.