Higher Maternal Plasma Folate but Not Vitamin B-12 Concentrations during Pregnancy Are Associated with Better Cognitive Function Scores in 9- to 10- Year-Old Children in South India

Abstract

Folate and vitamin B-12 are essential for normal brain development. Few studies have examined the relationship of maternal folate and vitamin B-12 status during pregnancy and offspring cognitive function. To test the hypothesis that lower maternal plasma folate and vitamin B-12 concentrations and higher plasma homocysteine concentrations during pregnancy are associated with poorer neurodevelopment, 536 children (aged 9-10 y) from the Mysore Parthenon birth cohort underwent cognitive function assessment during 2007-2008 using 3 core tests from the Kaufman Assessment Battery, and additional tests measuring learning, long-term storage/retrieval, attention and concentration, and visuo-spatial and verbal abilities. Maternal folate, vitamin B-12, and homocysteine concentrations were measured at 30 +/- 2 wk gestation. During pregnancy, 4% of mothers had low folate concentrations (<7 nmol/L), 42.5% had low vitamin B-12 concentrations (<150 pmol/L), and 3% had hyperhomocysteinemia (>10 micromol/L). The children's cognitive test scores increased by 0.1-0.2 SD per SD increase across the entire range of maternal folate concentrations (P < 0.001 for all), with no apparent associations at the deficiency level. The associations with learning, long-term storage/retrieval, visuo-spatial ability, attention, and concentration were independent of the parents' education, socioeconomic status, religion, and the child's sex, age, current size, and folate and vitamin B-12 concentrations. There were no consistent associations of maternal vitamin B-12 and homocysteine concentrations with childhood cognitive performance. In this Indian population, higher maternal folate, but not vitamin B-12, concentrations during pregnancy predicted better childhood cognitive ability. It also suggests that, in terms of neurodevelopment, the concentration used to define folate deficiency may be set too low.

Erythrocyte folate concentrations, CpG methylation at genomically imprinted domains, and birth weight in a multiethnic newborn cohort

“…Our findings that moderate folate levels in early pregnancy are associated with higher birth weight regardless of race/ethnicity are consistent with previous studies, [14][15][16][17][18][19][20][21][22][23][24]50 although an equally large number of studies from Europe, Asia and the US [25][26][27][28][29][30][31] have not confirmed these associations. Reasons for discordant findings are unclear.…”

“…13 In humans, evidence of associations between maternal folate concentrations and fetal growth is conflicting, as high levels have been linked to both low and high birth weight, [14][15][16][17][18][19][20][21][22][23][24] while other studies found no associations. [25][26][27][28][29][30][31] Extremes of the birth weight distribution have been associated with a wide range of childhood and adultonset chronic diseases and conditions including obesity, impaired glucose tolerance, type 2 diabetes, coronary artery disease, congestive heart failure and some cancers.…”

The vulnerable developing brain

“…What has been comparatively ignored is the contribution of adverse conditions during pregnancy, such as moderate maternal undernutrition during early pregnancy, on the developmental programming of neurodegenerative diseases. Of related interest is a study that has linked inappropriate maternal nutrition with cognitive impairment in children (20) and preliminary reports associating adverse pregnancy with an increased prevalence of depression and schizophrenia in later life (21).…”

Foetal Programming and Consequences

“…This suggests a need for balanced nutrition. These two vitamins also influence the offspring neurodevelopment (Veena et al, 2010;Godbole et al, 2009;Bhate et al, 2008). Higher maternal homocysteine concentration (caused by vitamin B 12 and folate deficiency) is associated with foetal growth restriction.…”

“…However, if they face overnutrition in postnatal life (urban migration), they are likely to develop obesity and hyperglycaemia at a young age, and gestational diabetes in girls that propagates the obesity and diabetes phenotype ("fuel-mediated teratogenesis") (Freinkel, 1980). Rapidly transitioning countries like India seem to have both cycles running simultaneously, feeding into an explosive epidemic of NCDs (Silverman et al, 1995;Yajnik, 2009;Krishnaveni et al, 2010).…”