The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000, CA, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000, CA, Rotterdam, the Netherlands.
Department of Clinical Chemistry, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000, CA, Rotterdam, the Netherlands.
Clin Nutr. 2021 Sep;40(9):5133-5140. doi: 10.1016/j.clnu.2021.08.001. Epub 2021 Aug 9.
BACKGROUND & AIMS: Suboptimal 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.
This 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.
As 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 distensibility 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.
Circulating 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.
胎儿期循环中维生素 B12、叶酸和同型半胱氨酸浓度不足似乎与学龄期的心脏代谢健康有关。我们研究了胎儿期循环中维生素 B12 和叶酸浓度较低以及同型半胱氨酸浓度较高是否也与学龄期早期动脉粥样硬化的迹象有关。
本研究纳入了 3826 名学龄儿童及其母亲，这些儿童来自“胎儿队列研究”（Generation R Study），这是一项从怀孕早期开始的基于人群的前瞻性队列研究。我们检测了孕早期和脐带血血清总活性 B12 和血浆叶酸及同型半胱氨酸浓度与 10 岁儿童颈总动脉内膜中层厚度和顺应性之间的关系。
与正常孕早期血清总 B12 浓度（≥145 pmol/L）相比，低血清总 B12 浓度（＜145 pmol/L）与学龄儿童的颈动脉内膜中层厚度增加有关（差值 0.09 个标准差评分（SDS）；95%置信区间（CI）：0.01，0.16）。与正常孕早期血浆叶酸浓度（≥8 nmol/L）相比，低血浆叶酸浓度（＜8 nmol/L）与学龄儿童的颈动脉顺应性降低有关（差值-0.16 SDS；95% CI：-0.28，-0.04）。连续测量的孕早期循环总活性 B12、叶酸和同型半胱氨酸浓度与学龄儿童的颈动脉内膜中层厚度或颈动脉顺应性无关。出生时脐带血中同型半胱氨酸浓度每增加一个 SDS，与学龄儿童颈动脉顺应性降低 0.05 SDS（95% CI：-0.09，-0.02）有关。脐带血总活性 B12 和叶酸浓度与学龄儿童的颈动脉内膜中层厚度或颈动脉顺应性无关。
胎儿期循环中总 B12、叶酸和同型半胱氨酸浓度似乎与学龄期亚临床动脉粥样硬化的标志物有关。需要进一步研究来检验这些关联的因果关系和机制。
