Abstract
SummaryBackground & aimsSuboptimal circulating vitamin B12, folate and homocysteine concentrations during fetal life seem to be associated with cardiometabolic health at school-age. We examined whether fetal exposure to lower circulating vitamin B12 and folate concentrations and higher circulating homocysteine concentrations is also associated with early signs of atherosclerosis at school-age.MethodsThis study among 3826 school-age children and their mothers was embedded in the Generation R Study, a population-based prospective cohort study from early pregnancy onwards. We examined the associations of early-pregnancy and cord blood serum total and active B12 and plasma folate and homocysteine concentrations with common carotid artery intima-media thickness and distensibility in the children aged ten years.ResultsAs compared to normal early-pregnancy serum total B12 concentrations (≥145 pmol/L), low serum total B12 concentrations (<145 pmol/L) were associated with higher carotid intima-media thickness in the children at school-age (difference 0.09 standard deviations score (SDS); 95% confidence interval (CI): 0.01, 0.16). As compared to normal early-pregnancy plasma folate concentrations (≥8 nmol/L), low plasma folate concentrations (<8 nmol/L) were associated with lower carotid disten-sibility in the children at school-age (difference −0.16 SDS; 95% CI: −0.28, −0.04). Early-pregnancy circulating total and active B12, folate and homocysteine concentrations measured continuously were not associated with carotid intima-media thickness or carotid distensibility in the children at school-age. One SDS higher plasma homocysteine concentrations measured in cord blood at birth was associated with a −0.05 SDS (95% CI: −0.09, −0.02) lower carotid distensibility at school-age. Cord blood total and active B12 and folate concentrations were not associated with carotid intima-media thickness or carotid distensibility at school-age.ConclusionsCirculating total B12, folate and homocysteine concentrations during fetal life seem to be associated with markers of subclinical atherosclerosis at school-age. Further studies need to examine the causality and mechanisms underlying these associations.
Highlights
Atherosclerosis and related cardiovascular disease seems to originate at least partly from the earliest phase of life [1e3].Autopsy studies have shown that the formation of intimal thickening and fatty streaks, both involved in the pathogenesis of atherosclerosis, already begins in childhood and has even been observed in fetuses [4,5]
In a population-based study among 3826 motherechild pairs, we examined the associations of these one-carbon metabolism markers, sampled in early pregnancy and in cord blood at birth, with common carotid artery intima-media thickness and distensibility in children aged ten years
The same circulating one-carbon metabolism markers correlated moderately between maternal blood and cord blood (r 1⁄4 0.37e0.60) (Supplementary Table 2)
Summary
Atherosclerosis and related cardiovascular disease seems to originate at least partly from the earliest phase of life [1e3].Autopsy studies have shown that the formation of intimal thickening and fatty streaks, both involved in the pathogenesis of atherosclerosis, already begins in childhood and has even been observed in fetuses [4,5]. We examined whether fetal exposure to lower circulating vitamin B12 and folate concentrations and higher circulating homocysteine concentrations is associated with early signs of atherosclerosis at school-age. We examined the associations of early-pregnancy and cord blood serum total and active B12 and plasma folate and homocysteine concentrations with common carotid artery intima-media thickness and distensibility in the children aged ten years. Results: As compared to normal early-pregnancy serum total B12 concentrations (!145 pmol/L), low serum total B12 concentrations (
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