Brustad Nicklas, Garland Juri, Thorsen Jonathan, Sevelsted Astrid, Krakauer Martin, Vinding Rebecca K, Stokholm Jakob, Bønnelykke Klaus, Bisgaard Hans, Chawes Bo L
Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Physiology and Nuclear Medicine, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
JAMA Pediatr. 2020 May 1;174(5):419-427. doi: 10.1001/jamapediatrics.2019.6083.
Studies suggest an association between maternal vitamin D status during pregnancy and offspring anthropometry and bone mineralization, but investigations are few and with mixed results.
To investigate the effect of a high dose vs standard dose of vitamin D supplementation in pregnancy on anthropometric and bone outcomes until age 6 years in the offspring.
DESIGN, SETTING, AND PARTICIPANTS: A prespecified analysis of a double-blinded, randomized clinical trial in the Copenhagen Prospective Studies on Asthma in Childhood 2010 mother-child cohort that included 623 pregnant mothers and their 584 children. Data were analyzed between January 2019 and September 2019.
Vitamin D supplementation of 2800 IU/d (high-dose) vs 400 IU/d (standard-dose) from pregnancy week 24 until 1 week after birth.
Longitudinal anthropometry assessments including length/height, weight, and body mass index until age 6 years and bone mineral content (BMC) and bone mineral density (BMD) at age 3 years and 6 years from dual-energy radiography absorptiometry scans.
At age 6 years, 517 children (89%) completed the clinical follow-up. All participants were Danish and white; 261 were boys and 256 were girls. A mixed-effects model analysis of dual-energy radiography absorptiometry scan outcomes from ages 3 years and 6 years showed that children in the vitamin D vs placebo group had higher whole-body BMC: mean difference adjusted (aMD) for age, sex, height, and weight was 11.5 g (95% CI, 2.3-20.7; P = .01); higher whole-body-less-head BMC aMD was 7.5 g (95% CI, 1.5-13.5; P = .01); and higher head BMD aMD was 0.023 g/cm2 (95% CI, 0.003-0.004; P = .03). The largest effect was in children from vitamin D-insufficient mothers (<30 ng/mL; to convert to nanomoles per liter, multiply by 2.496) and among winter births. In a post hoc analysis, we found borderline lower incidence of fractures in the vitamin D group (n = 23 vs n = 36; incidence rate ratio, 0.62 [95% CI, 0.37-1.05]; P = .08), but no differences in any anthropometric outcomes. Adjustment for a concomitant ω-3 polyunsaturated fatty acids intervention did not change the results.
High-dose vitamin D supplementation in pregnancy improved offspring bone mineralization through age 6 years compared with the standard dose, suggesting an increased recommended gestational intake, which may influence peak bone mass, fracture risk, and risk of osteoporosis later in life. We found no supplementation effect on anthropometric outcomes.
ClinicalTrials.gov Identifier: NCT00856947.
研究表明孕期母亲的维生素D状态与后代人体测量指标及骨矿化之间存在关联，但相关研究较少且结果不一。
探讨孕期补充高剂量与标准剂量维生素D对后代6岁前人体测量指标及骨骼结局的影响。
设计、地点和参与者：对哥本哈根儿童哮喘前瞻性研究2010母婴队列中的一项双盲、随机临床试验进行预先设定的分析，该队列包括623名孕妇及其584名子女。于2019年1月至2019年9月期间进行数据分析。
从妊娠第24周直至出生后1周，补充2800 IU/d（高剂量）维生素D与400 IU/d（标准剂量）维生素D。
纵向人体测量评估，包括直至6岁的身长/身高、体重和体重指数，以及通过双能X线吸收测定扫描得出的3岁和6岁时的骨矿物质含量（BMC）和骨矿物质密度（BMD）。
6岁时，517名儿童（89%）完成了临床随访。所有参与者均为丹麦白人；261名是男孩，256名是女孩。对3岁和6岁时双能X线吸收测定扫描结果进行的混合效应模型分析显示，维生素D组儿童与安慰剂组相比，全身BMC更高：经年龄、性别、身高和体重调整后的平均差异（aMD）为11.5 g（95%CI，2.3 - 20.7；P = 0.01）；全身（不包括头部）BMC的aMD更高，为7.5 g（95%CI，1.5 - 13.5；P = 0.01）；头部BMD的aMD更高，为0.023 g/cm²（95%CI，0.003 - 0.004；P = 0.03）。最大的效应出现在母亲维生素D水平不足（<30 ng/mL；换算为每升纳摩尔数时，乘以2.496）的儿童以及冬季出生的儿童中。在一项事后分析中，我们发现维生素D组骨折发生率略低（n = 23 vs n = 36；发病率比，0.62 [95%CI，0.37 - 1.05]；P = 0.08），但在任何人体测量指标方面均无差异。对同时进行的ω-3多不饱和脂肪酸干预进行调整后，结果未改变。
与标准剂量相比，孕期补充高剂量维生素D可改善后代至6岁时的骨矿化，提示应增加孕期推荐摄入量，这可能会影响峰值骨量、骨折风险以及晚年骨质疏松症风险。我们未发现补充维生素D对人体测量指标有影响。
ClinicalTrials.gov标识符：NCT00856947。
