Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study

Abstract

Aims/hypothesis Raised maternal plasma total homocysteine (tHcy) concentrations predict small size at birth, which is a risk factor for type 2 diabetes mellitus. We studied the association between maternal vitamin B 12 , folate and tHcy status during pregnancy, and offspring adiposity and insulin resistance at 6 years. Methods In the Pune Maternal Nutrition Study we studied 700 consecutive eligible pregnant women in six villages. We measured maternal nutritional intake and circulating concentrations of folate, vitamin B 12 , tHcy and methylmalonic acid (MMA) at 18 and 28 weeks of gestation. These were correlated with offspring anthropometry, body composition (dual-energy X-ray absorptiometry scan) and insulin resistance (homeostatic model assessment of insulin resistance [HOMA-R]) at 6 years. Results Two-thirds of mothers had low vitamin B 12 (<150 pmol/l), 90% had high MMA (>0.26 μmol/l) and 30% had raised tHcy concentrations (>10 μmol/l); only one had a low erythrocyte folate concentration. Although short and thin (BMI), the 6-year-old children were relatively adipose compared with the UK standards (skinfold thicknesses). Higher maternal erythrocyte folate concentrations at 28 weeks predicted higher offspring adiposity and higher HOMA-R (both p <0.01). Low maternal vitamin B 12 (18 weeks; p=0.03) predicted higher HOMA-R in the Diabetologia (2008)

Moderately high intake of folic acid has a negative impact on mouse embryonic development

“…These concerns include increased tumor growth (Cole et al, 2007;Mason et al, 2007;Lawrance et al, 2009), although this has been refuted by other investigations (Gibson et al, 2011;Stevens et al, 2011) and perturbations in immune function (Troen et al, 2006;Halsted, 2008). There is also evidence that high maternal folate concentrations can be associated with greater adiposity and higher insulin resistance in the offspring, which could increase the risk for type 2 diabetes (Yajnik et al, 2008).…”

Nutritional status as assessed by nutrient intakes and biomarkers among women of childbearing age – is the burden of nutrient inadequacies growing in America?

“…Compromised nutrient intakes during the 'critical windows' of preconception and conception can adversely influence pregnancy outcome, increase risk for birth defects, alter the nutrient composition of breast milk, condition infants and children to altered growth trajectories and predispose them to chronic diseases in later life (2)(3)(4)(5)(6) . Carmichael and co-workers showed that adequate periconception intakes of folate, vitamin B 12 , vitamin B 6 and riboflavin were associated with decreased risk of neural tube defects among Californian women (7) .…”

Policy statement on folic acid and neural tube defects

“…30 In addition, a slightly increased risk of wheeze and respiratory tract infections was found in offspring whose mothers took folic acid supplements during pregnancy. 31 Yajnik et al 32 reported that children whose mothers had high folate and low vitamin B12 levels during pregnancy had the highest risk of insulin-resistance, compared with those whose mothers who only had low B12 or high folate (but both of those groups had higher levels than did those whose mothers had normal B12 and folate). Increased folate levels have also been associated with increased lung cancer risk 33 ; reduced natural killer cell cytotoxicity 34 ; and, in the presence of concomitant low B12, anemia and cognitive impairment in the elderly.…”