Low folate levels during pregnancy could lead to children with smaller brains and poorer cognition

February 8, 2016

A new study involving 256 Dutch children aged six to eight years has shown that low pre-natal folate status leads to reduced brain volume and reduced intelligence.

A subset of 256 Dutch children aged six to eight years of the Generation R cohort has been assessed for brain size (using functional magnetic resonance imaging), cognition and emotional development, and correlated with folic acid status of their mothers during pregnancy (1). The study demonstrated that mothers who had insufficient folate plasma levels (i.e., ˂ 8 nmol/l) during their pregnancy produced children with smaller brains and a lower intelligence quotient (IQ) than those mothers who were replete with folate. In the case of the deficient mothers, it was found that all parts of the child’s brain suffered a similar degree of shrinkage. However, unlike similar studies made when the children were 18 months and three years of age, there was no effect on emotional behavior.

Folic acid, also known as vitamin B9, is essential for normal cell division (2). The US Institute of Medicine recommends that pregnant mothers have a daily intake of 600 µg/day. Normal recommended intakes for adults vary from 200 to 400 µg/day. Folate is particularly important for the replication and growth of neural cells. It is involved in the methylation and synthesis of DNA. Folic acid deficiency in pregnant mothers has been shown to be a cause of neural tube defects (e.g., spina bifida) in their offspring (3). It has been shown that folate deficiency, through the epigenetic mechanism of methylation, can modify gene expression leading to adverse changes in brain development (4).

An earlier study from 2012, using a less accurate measure of folate status in pregnancy (a food frequency questionnaire) than the current study, had previously demonstrated that higher maternal folate levels produced three-year-old children with generally higher levels of intelligence (5).

The new study (1) had the advantage of accurately measuring levels of folic acid, homocysteine and vitamin B12 in maternal blood plasma. It also used sophisticated functional magnetic resonance imaging techniques to assess the brain anatomy of the children. Prenatal homocysteine and vitamin B12 levels were not found to be associated with brain volume, cognition or behavior. There may have been some confounding factors in the study, as the members of the folate-deficient group were also more likely to be smokers and less likely to take folate supplements. Also, it cannot be assumed that similar results would be obtained in other populations where the general level of nutrition does not meet the high standards found in the Netherlands. However, the study does produce anatomical and intelligence test evidence that folate deficiency in pregnancy leads to impaired brain development in their children that persists until at least 6 years of age.


  1. Ars CL, Nijs IM, El Marroun HE, Muetzel R et al.; “Prenatal folate, homocysteine and vitamin B12 levels and brain volumes, cognitive development and psychological functioning”.; British Journal of Nutrition 2016 (ahead of print).
  2. NUTRI-FACTS (accessed 27.1.16):
  3. Berti C, Biesalski HK, Gärtner R, et al. (2011) Micronutrients in pregnancy: current knowledge and unresolved questions. Clin Nutr 2011; 30: 689–701.
  4. Nyaradi A, Li J, Hickling S, et al.; “The role of nutrition in children’s neurocognitive development, from pregnancy through childhood”. Front Hum Neurosci 2013: 7: 1–16.
  5. Villamor E, Rifas-Shiman S, Gillmann M, et al.; “Maternal intake of methyl-donor nutrients and child cognition at 3 years of age”. Paediatr Perinat Epidomiol 2012; 26: 328–335.