Abstract

Aims/hypothesisIn an Indian birth cohort, higher maternal homocysteine concentration in pregnancy was associated with lower birthweight of the offspring. Lower maternal vitamin B12 and higher folate concentrations were associated with higher offspring insulin resistance. Disordered one-carbon metabolism during early development may increase later metabolic risk. We explored these associations in another birth cohort in India at three age points.MethodsWe measured plasma vitamin B12, folate and homocysteine concentrations at 30 ± 2 weeks’ gestation in 654 women who delivered at one hospital. Neonatal anthropometry was recorded, and the children’s glucose and insulin concentrations were measured at 5, 9.5 and 13.5 years of age. Insulin resistance was estimated using HOMA of insulin resistance (HOMA-IR).ResultsMaternal homocysteine concentrations were inversely associated with all neonatal anthropometric measurements (p < 0.05), and positively associated with glucose concentrations in the children at 5 (30 min; p = 0.007) and 9.5 years of age (120 min; p = 0.02). Higher maternal folate concentrations were associated with higher HOMA-IR in the children at 9.5 (p = 0.03) and 13.5 years of age (p = 0.03). Maternal vitamin B12 concentrations were unrelated to offspring outcomes.Conclusions/interpretationMaternal vitamin B12 status did not predict insulin resistance in our cohort. However, associations of maternal homocysteine and folate concentrations with birth size, and with childhood insulin resistance and glycaemia in the offspring, suggest a role for nutritionally driven disturbances in one-carbon metabolism in fetal programming of diabetes.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-013-3086-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Highlights

  • Nutrition during fetal development has long-term health consequences [1]

  • All associations remained unchanged after excluding the offspring of gestational diabetes mellitus (GDM) mothers. In this well-characterised cohort of urban Indian children, higher maternal homocysteine concentration was associated with smaller size at birth, and higher postload glucose concentrations at 5 and 9.5 years

  • Higher maternal folate concentration was associated with higher insulin resistance (HOMAIR) at 9.5 and 13.5 years

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Summary

Introduction

Nutrition during fetal development has long-term health consequences [1]. Fetal nutrition is influenced by maternal nutritional status, and experiments in animal models have shown that both maternal undernutrition and overnutrition can cause obesity, insulin resistance and diabetes in the adult offspring [2, 3]. Vitamin B12 and folate are important nutrients required for nucleic acid synthesis, DNA methylation and cellular growth and differentiation. Several studies have reported that low maternal folate and vitamin B12 concentrations and high homocysteine concentrations (a marker of deranged onecarbon metabolism) predict smaller newborn size [4,5,6,7]. Data linking maternal diet and nutrient status to long-term offspring outcomes in humans are limited

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