MaternalMTHFR 677C>Tgenotype and dietary intake of folate and vitamin B₁₂: their impact on child neurodevelopment

Abstract

Using the Bayley test, the mental and psychomotor development in a cohort of 253 children were evaluated. Maternal dietary intake of vitamin B(12) and folate was assessed from a semiquantitative questionnaire administered during the first trimester of pregnancy. Maternal genotypes of MTHFR (677C>T and 1298A>C), were ascertained by PCR-RFLP. The 677T and 1298C variant alleles were present in 59% and 10% of participants, respectively. A dietary deficiency of vitamin B(12) was negatively associated with mental development (beta = -1.6; 95% CI = -2.8 to -0.3). In contrast, dietary intake of folate (< 400 mg/day) reduced the mental development index only among children of mothers who were carriers of the TT genotype (beta = -1.8; 95% CI = -3.6 to -0.04; P for interaction = 0.07). Vitamin B(12) and folate supplementation during pregnancy could have a favorable impact on the mental development of children during their first year of life, mainly in populations that are genetically susceptible.

Vitamin B-12 and Cognition in Children

“…Two studies from India noted that a higher maternal vitamin B-12 status during pregnancy was associated with improved child cognitive outcomes and developmental indexes (43,45). One study from Mexico reported that inadequate maternal dietary intake of vitamin B-12 during pregnancy was associated with poorer developmental outcomes in their infants (50). Four observational studies noted no significant associations between maternal vitamin B-12 status and child cognitive outcomes, although specific cognitive outcomes assessed varied, and the ages of children ranged from 1 to 10 y of age (44,46,47,49).…”

“…These studies used a variety of dietary assessment methods and cutoff points for vitamin B-12 intake, which limits comparability of findings between studies. In other cohort studies (50,54), plasma vitamin B-12 concentrations were measured in either the mother or child only at one time point. The time integration or the relevant etiologic period of vitamin B-12 in the development of cognitive outcomes later in childhood is unknown.…”

“…Maternal vitamin B-12 dietary intake during pregnancy was not significantly associated with child IQ (49). In a prospective cohort study in Mexico, investigators examined the associations between maternal dietary vitamin B-12 intake (with an FFQ) in the first trimester of pregnancy and child development at 1, 3, 6, and 12 mo of age (50). Inadequate maternal vitamin B-12 intake (<2.0 mg/d) was associated with poorer mental development scores (b = 21.6; 95% CI: 22.8, 20.3; P < 0.05) in children at 12 mo of age as measured by the BSID-II (50).…”

Emerging roles for folate and related B-vitamins in brain health across the lifecycle

“…The common 677C T polymorphism in the gene coding for the folate metabolising enzyme MTHFR is an important genetic determinant of plasma homocysteine and individuals homozygous for the polymorphism (MTHFR 677TT genotype), are prone to low folate status and elevated plasma homocysteine concentrations. Recent studies from Mexico, where the frequency of the MTHFR 677TT genotype is reported to be the highest in the world (26) , showed that the maternal MTHFR 677TT genotype is a predictor of poor child neurodevelopment (27) especially in combination with low maternal folate intake (<400 μg/d) during the first trimester of pregnancy (28) . However, research in this area is limited and further studies are required to investigate whether children born to mothers genetically susceptible to impaired folate status are more at risk of impaired neurodevelopment.…”

Epigenetic epidemiology in psychiatry: A translational neuroscience perspective

“…Genetic studies on associations between genetic variants in Mthfr and various major psychiatric disorders such as schizophrenia, bipolar disorder and unipolar depressive disorder, have yielded largely inconclusive and often mixed results [189][190][191][192][193][194][195]. Given the essential role of Mthfr in brain function and neurodevelopment [196,197], and the fact that family and twin studies have established considerable shared genetic variance between psychiatric disorders [198][199][200], a recent meta-analysis (on a total of more than 29,000 subjects) tested whether genetic variation in Mthfr contributes to the shared genetic vulnerability of schizophrenia, bipolar disorder and unipolar depressive disorder [201]. This meta-analysis showed that Mthfr C677T was significantly associated with the combined group of schizophrenia, bipolar disorder and unipolar depressive disorder (odds ratio = [202].…”