Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Research Institute, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada;
Research Institute, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; School of Medicine, Trinity College, Dublin, Ireland;
Pediatrics. 2015 Jan;135(1):e152-66. doi: 10.1542/peds.2014-1703. Epub 2014 Dec 15.
Vitamin D deficiency may represent a modifiable risk factor to improve outcome in severe illness. The efficacy of high-dose regimens in rapid normalization of vitamin D levels is uncertain.
We conducted a systematic review of pediatric clinical trials administering high-dose vitamin D to evaluate 25-hydroxyvitamin D (25[OH]D) response and characteristics associated with final 25(OH)D levels by using Medline, Embase, and the Cochrane Central Register of Controlled Trials, including reference lists of systematic reviews and eligible publications. Uncontrolled and controlled trials reporting 25(OH)D levels after high-dose (≥1000 IU) ergocalciferol or cholecalciferol were selected. Two reviewers independently extracted and verified predefined data fields.
We identified 88 eligible full-text articles. Two of 6 studies that administered daily doses approximating the Institute of Medicine's Tolerable Upper Intake Level (1000-4000 IU) to vitamin D-deficient populations achieved group 25(OH)D levels >75 nmol/L within 1 month. Nine of 10 studies evaluating loading therapy (>50 000 IU) achieved group 25(OH)D levels >75 nmol/L. In meta-regression, baseline 25(OH)D, regimen type, dose, age, and time factors were associated with final 25(OH)D levels. Adverse event analysis identified increased hypercalcemia risk with doses >400 000 IU, but no increased hypercalcemia or hypercalciuria with loading doses <400 000 IU (or 10 000 IU/kg). Few studies in adolescents evaluated loading dose regimens >300 000 IU.
Rapid normalization of vitamin D levels is best achieved by using loading therapy that considers disease status, baseline 25(OH)D, and age (or weight). Loading doses >300 000 IU should be avoided until trials are conducted to better evaluate risk and benefit.
维生素 D 缺乏可能是改善重病患者预后的一个可改变的危险因素。大剂量方案能否快速使维生素 D 水平正常化尚不确定。
我们对儿科临床试验进行了系统评价，评估了给予大剂量维生素 D 治疗后 25-羟维生素 D（25[OH]D）的反应以及与最终 25（OH）D 水平相关的特征，检索了 Medline、Embase 和 Cochrane 对照试验中心注册库，包括系统评价和合格文献的参考文献列表。选择了报告大剂量（≥1000IU）麦角钙化醇或胆钙化醇后 25（OH）D 水平的未对照和对照试验。两名评审员独立提取和验证了预定义的数据字段。
我们确定了 88 篇符合条件的全文文章。6 项研究中的 2 项，给予接近医学研究所可耐受上限摄入量（1000-4000IU）的每日剂量，使维生素 D 缺乏人群在 1 个月内达到 25（OH）D 水平＞75nmol/L。10 项评估负荷治疗（＞50000IU）的研究中有 9 项达到了＞75nmol/L 的组 25（OH）D 水平。在元回归中，基线 25（OH）D、方案类型、剂量、年龄和时间因素与最终 25（OH）D 水平相关。不良事件分析发现，剂量＞400000IU 时发生高钙血症的风险增加，但负荷剂量＜400000IU（或 10000IU/kg）时未增加高钙血症或高钙尿症。很少有研究评估青少年的负荷剂量方案＞300000IU。
通过使用考虑疾病状态、基线 25（OH）D 和年龄（或体重）的负荷治疗，可以最好地实现维生素 D 水平的快速正常化。在进行更好地评估风险和获益的试验之前，应避免使用＞300000IU 的负荷剂量。
