Brustad Nicklas, Chawes Bo L, Thorsen Jonathan, Krakauer Martin, Lasky-Su Jessica, Weiss Scott T, Stokholm Jakob, Bønnelykke Klaus, Bisgaard Hans
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
EClinicalMedicine. 2021 Dec 24;43:101254. doi: 10.1016/j.eclinm.2021.101254. eCollection 2022 Jan.
Exposure to vitamin D in early life has been associated with improved bone mineralization, but no studies have investigated the combined effect of pregnancy supplementation and childhood 25(OH)D concentrations on bone health.
We analyzed the effect of serum 25(OH)D concentrations at age 6 months and 6 years and the combined effect with prenatal high-dose vitamin D (2800 vs. 400 IU/day) on bone mineral density (BMD) and content (BMC) assessed by dual-energy X-ray absorptiometry (DXA) scans at age 3 and 6 years and longitudinal risk of fractures in a double-blinded, randomized clinical trial in the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC) mother-child cohort with enrollment from March 4, 2009, to November 17, 2010, and clinical follow-up until January 31, 2019 (NCT00856947). All participants randomized to intervention and with complete data were included in the analyses.
At age 6 months, serum 25(OH)D concentration was measured in 93% ( = 541) of 584 children. Children with sufficient (≥ 75 nmol/l) vs. insufficient (< 75 nmol/l) concentrations did not have lower risk of fractures: incidence rate ratio (95% CI); 0.64 (0.37;1.11), = 0.11. However, vitamin D sufficient children from mothers receiving high-dose supplementation during pregnancy had a 60% reduced incidence of fractures compared with vitamin D insufficient children from mothers receiving standard-dose: 0.40 (0.19;0.84), = 0.02.At age 6 years, serum 25(OH)D concentration was measured in 83% ( = 318) of 383 children with available DXA data. Whole-body bone mineralization was higher in vitamin D sufficient children at age 6 years; BMD, adjusted mean difference (aMD) (95% CI): 0.011 g/cm (0.001;0.021), = 0.03, and BMC, aMD: 12.3 g (-0.8;25.4), = 0.07, with the largest effect in vitamin D sufficient children from mothers receiving high-dose vitamin D supplementation; BMD, aMD: 0.016 g/cm (0.002;0.030), = 0.03, and BMC, aMD: 23.5 g (5.5;41.5), = 0.01.
Childhood vitamin D sufficiency improved bone mineralization and in combination with prenatal high-dose vitamin D supplementation reduced the risk of fractures.
The study was supported by The Lundbeck Foundation R16-A1694, The Danish Ministry of Health 903,516, The Danish Council for Strategic Research 0603-00280B and The European Research Council 946,228.
生命早期接触维生素D与改善骨矿化有关，但尚无研究调查孕期补充维生素D和儿童25(OH)D浓度对骨骼健康的联合作用。
在哥本哈根儿童哮喘前瞻性研究2010（COPSAC）母婴队列中进行了一项双盲、随机临床试验，纳入时间为2009年3月4日至2010年11月17日，临床随访至2019年1月31日（NCT00856947）。我们分析了6个月和6岁时血清25(OH)D浓度的影响，以及产前高剂量维生素D（2800 vs. 400 IU/天）与3岁和6岁时通过双能X线吸收测定（DXA）扫描评估的骨密度（BMD）和骨量（BMC）的联合作用，以及骨折的纵向风险。所有随机分配至干预组且有完整数据的参与者均纳入分析。
6个月时，在584名儿童中的93%（n = 541）测量了血清25(OH)D浓度。25(OH)D浓度充足（≥75 nmol/l）与不足（<75 nmol/l）的儿童骨折风险无差异：发病率比（95% CI）为0.64（0.37；1.11），P = 0.11。然而，孕期接受高剂量补充的母亲所生的维生素D充足儿童与接受标准剂量的母亲所生的维生素D不足儿童相比，骨折发生率降低了60%：0.40（0.19；0.84），P = 0.02。6岁时，在有可用DXA数据的383名儿童中的83%（n = 318）测量了血清25(OH)D浓度。6岁时维生素D充足的儿童全身骨矿化更高；BMD，调整后平均差异（aMD）（95% CI）：0.011 g/cm²（0.001；0.021），P = 0.03，BMC，aMD：12.3 g（-0.8；25.4），P = 0.07，在孕期接受高剂量维生素D补充的母亲所生的维生素D充足儿童中效果最为显著；BMD，aMD：0.016 g/cm²（0.002；0.030），P = 0.03，BMC，aMD：23.5 g（5.5；41.5），P = 0.01。
儿童期维生素D充足可改善骨矿化，并与产前高剂量维生素D补充联合使用可降低骨折风险。
该研究由伦贝克基金会R16 - A1694、丹麦卫生部903,516、丹麦战略研究理事会0603 - 00280B和欧洲研究理事会946,228资助。
