Sauer Cassandra, Hoang Mai-Anh, Kroeun Hou, Gupta Aman Sen, Ngik Rem, Sokchea Meng, Labonté Jocelyne M, Chea Mary, Klemm Rolf, Mishra Ashutosh, Panicker Aishwarya, Sokhal Vin, Karakochuk Crystal D
Food, Nutrition & Health, The University of British Columbia, Vancouver, BC, Canada; Healthy Starts, BC Children's Hospital Research Institute, Vancouver, BC, Canada.
Helen Keller International, New York, NY, United States.
Am J Clin Nutr. 2025 Jul;122(1):166-173. doi: 10.1016/j.ajcnut.2025.04.033. Epub 2025 May 5.
The Cambodian Ministry of Health is exploring transitioning from iron and folic acid (IFA) to multiple micronutrient supplements (MMS) during pregnancy and is seeking rigorous evidence to inform this policy change.
We aimed to assess the adherence and acceptability of MMS compared with IFA supplementation during pregnancy.
We conducted an open-label cluster-randomized noninferiority trial across 48 health centers in Cambodia. A total of 1546 healthy pregnant individuals (18-45 y) were recruited at their first antenatal care (ANC) visit (<14 weeks of gestation) and randomized to 1 of 3 arms at the health center level: 1) IFA for 90 d (IFA-90, n = 515), the current standard of care; 2) MMS for 180 d via 1 180-tablet bottle (MMS-180, n = 516); or 3) MMS for 180 d via 2 90-tablet bottles (MMS-90, n = 515). Our primary outcome was the noninferiority of adherence rates of MMS-180 compared with IFA-90, assessed by tablet counts and compared against a predefined noninferiority margin of -15%. Mixed-effects linear regression models were used to estimate the mean difference (95% confidence interval [95% CI]) in adherence rates. Our secondary outcomes included the mean difference in ANC attendance between the MMS groups and the acceptability of MMS across 6 domains.
Overall, 88% of participants completed the trial, with high mean adherence rates across arms (91% for IFA-90, 95% for MMS-180, and 95% for MMS-90). The adjusted mean (95% CI) difference in adherence rates between MMS-180 and IFA-90 groups was 3.9% (1.7, 6.2). The adjusted mean (95% CI) difference in ANC visits for MMS-180 and MMS-90 groups was 0.0 (-0.1, 0.2) visits. The acceptability of MMS was positive (90%-100% "agreement" across 6 domains).
Both IFA and MMS were highly acceptable, yet adherence to MMS was superior to IFA. These findings support the transition from IFA to MMS in Cambodia. This trial was registered at Clinicaltrials.gov as NCT05867836.
柬埔寨卫生部正在探索在孕期从铁和叶酸（IFA）补充剂过渡到多种微量营养素补充剂（MMS），并寻求有力证据以指导这一政策变化。
我们旨在评估孕期MMS与IFA补充剂相比的依从性和可接受性。
我们在柬埔寨的48个健康中心开展了一项开放标签整群随机非劣效性试验。共有1546名健康孕妇（18 - 45岁）在首次产前检查（ANC，妊娠<14周）时被招募，并在健康中心层面随机分为3组中的1组：1）服用IFA 90天（IFA - 90组，n = 515），这是当前的标准治疗方案；2）通过1瓶180片的MMS服用180天（MMS - 180组，n = 516）；或3）通过2瓶90片的MMS服用180天（MMS - 90组，n = 515）。我们的主要结局是MMS - 180组与IFA - 90组依从率的非劣效性，通过药片计数评估，并与预先定义的 - 15%的非劣效性界值进行比较。使用混合效应线性回归模型估计依从率的平均差异（95%置信区间[95%CI]）。我们的次要结局包括MMS组之间ANC就诊次数的平均差异以及MMS在6个领域的可接受性。
总体而言，88%的参与者完成了试验，各组的平均依从率都很高（IFA - 90组为91%，MMS - 180组为95%，MMS - 90组为95%）。MMS - 180组与IFA - 90组之间依从率的调整后平均（95%CI）差异为3.9%（1.7，6.2）。MMS - 180组和MMS - 90组ANC就诊次数的调整后平均（95%CI）差异为0.0（ - 0.1，0.2）次就诊。MMS的可接受性是积极的（6个领域的“同意”率为90% - 100%）。
IFA和MMS都具有很高的可接受性，但MMS的依从性优于IFA。这些发现支持柬埔寨从IFA向MMS的转变。该试验已在Clinicaltrials.gov注册，注册号为NCT05867836。
