Omotayo Moshood O, Dickin Katherine L, Pelletier David L, Mwanga Erick O, Kung'u Jacqueline K, Stoltzfus Rebecca J
Program in International Nutrition, Cornell University, Ithaca, NY;
Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY; and.
J Nutr. 2017 Oct;147(10):1986-1991. doi: 10.3945/jn.117.251926. Epub 2017 Sep 6.
To prevent preeclampsia, the WHO recommends antenatal calcium supplementation in populations with inadequate habitual intake. The WHO recommends 1500-2000 mg Ca/d with iron-folic acid (IFA) taken separately, a complex pill-taking regimen. The objective of this study was to test the hypothesis that simpler regimens with lower daily dosages would lead to higher adherence and similar supplement intake. In the Micronutrient Initiative Calcium Supplementation study, we compared the mean daily supplement intake associated with 2 dosing regimens with the use of a parallel, cluster-randomized noninferiority trial implemented in 16 primary health care facilities in rural Kenya. The standard regimen was 3 × 500 mg Ca/d in 3 pill-taking events, and the low-dose regimen was 2 × 500 mg Ca/d in 2 pill-taking events; both regimens included a 200 IU cholecalciferol and calcium pill and a separate IFA pill. We enrolled 990 pregnant women between 16 and 30 wk of gestation. The primary outcome was supplemental calcium intake measured by pill counts 4 and 8 wk after recruitment. We carried out intention-to-treat analyses with the use of mixed-effect models, with regimen as the fixed effect and health care facilities as a random effect, by using a noninferiority margin of 125 mg Ca/d. Women in facilities assigned to the standard regimen consumed a mean of 1198 mg Ca/d, whereas those assigned to the low-dose regimen consumed 810 mg Ca/d. The difference in intake was 388 mg Ca/d (95% CI = 341, 434 mg Ca/d), exceeding the prespecified margin of 125 mg Ca/d. The overall adherence rate was 80% and did not differ between study arms. Contrary to our expectation, a simpler, lower-dose regimen led to significantly lower supplement intake than the regimen recommended by the WHO. Further studies are needed to precisely characterize the dose-response relation of calcium supplementation and preeclampsia risk and to examine cost effectiveness of lower and simpler regimens in program settings. This trial was registered at clinicaltrials.gov as NCT02238704.
为预防子痫前期，世界卫生组织建议在习惯性摄入量不足的人群中进行产前补钙。世界卫生组织建议每日补充1500 - 2000毫克钙，并单独服用铁叶酸（IFA），这是一种复杂的服药方案。本研究的目的是检验以下假设：每日剂量较低的更简单方案会导致更高的依从性和相似的补充剂摄入量。在微量营养素倡议补钙研究中，我们在肯尼亚农村的16个初级卫生保健机构中，采用平行整群随机非劣效性试验，比较了两种给药方案的平均每日补充剂摄入量。标准方案是每日分3次服用3×500毫克钙，低剂量方案是每日分2次服用2×500毫克钙；两种方案均包括一粒200国际单位胆钙化醇和钙片以及一粒单独的铁叶酸片。我们纳入了990名孕周在16至30周之间的孕妇。主要结局是在招募后4周和8周通过药片计数测量的补钙摄入量。我们使用混合效应模型进行意向性分析，将方案作为固定效应，卫生保健机构作为随机效应，非劣效性界值为每日125毫克钙。分配到标准方案的机构中的女性平均每日摄入1198毫克钙，而分配到低剂量方案的女性平均每日摄入810毫克钙。摄入量差异为每日388毫克钙（95%置信区间 = 341, 434毫克钙/天），超过了预先设定的125毫克钙/天的界值。总体依从率为80%，研究组之间无差异。与我们的预期相反，一种更简单、低剂量的方案导致的补充剂摄入量显著低于世界卫生组织推荐的方案。需要进一步研究以精确描述补钙与子痫前期风险的剂量反应关系，并在项目环境中检验更低、更简单方案的成本效益。该试验在clinicaltrials.gov上注册，注册号为NCT02238704。
