Bah Amat, Wegmuller Rita, Cerami Carla, Kendall Lindsay, Pasricha Sant-Rayn, Moore Sophie E, Prentice Andrew M
MRC Unit The Gambia & MRC International Nutrition Group, PO Box 273, Banjul, The Gambia.
MRC Unit The Gambia, PO Box 273, Banjul, The Gambia.
BMC Pregnancy Childbirth. 2016 Jul 13;16(1):157. doi: 10.1186/s12884-016-0934-8.
Until recently, WHO recommended daily iron supplementation for all pregnant women (60 mg/d iron combined with 400ug/d folic acid) where anaemia rates exceeded 40 %. Recent studies indicate that this may pose a risk to pregnant women. Therefore, there is a need to explore screen-and-treat options to minimise iron exposure during pregnancy using an overall lower dosage of iron that would achieve equivalent results as being currently recommended by the WHO. However, there is a lack of agreement on how to best assess iron deficiency when infections are prevalent. Here, we test the use of hepcidin a peptide hormone and key regulator of iron metabolism, as a potential index for 'safe and ready to receive' iron.
DESIGN/METHODS: This is a 3-arm randomised-controlled proof-of-concept trial. We will test the hypothesis that a screen-and-treat approach to iron supplementation using a pre-determined hepcidin cut-off value of <2.5 ng/ml will achieve similar efficacy in preventing iron deficiency and anaemia at a lower iron dose and hence will improve safety. A sample of 462 pregnant women in rural Gambia will be randomly assigned to receive: a) UNU/UNICEF/WHO international multiple micronutrient preparation (UNIMMAP) containing 60 mg/d iron (reference arm); b) UNIMMAP containing 60 mg/d iron but based on a weekly hepcidin screening indicating if iron can be given for the next 7 days or not; c) or UNIMMAP containing 30 mg/d iron as in (b) for 12 weeks in rural Gambia. The study will test if the screen-and-treat approach is non-inferior to the reference arm using the primary endpoint of haemoglobin levels at a non-inferiority margin of 0.5 g/dl. Secondary outcomes of adverse effects, compliance and the impact of iron supplementation on susceptibility to infections will also be assessed.
This trial is expected to contribute towards minimising the exposure of pregnant women to iron that may not be needed and therefore potentially harmful. If the evidence in this study shows that the overall lower dosage of iron is non-inferior to 60 mg/day iron, this may help decrease side-effects, improve compliance and increase safety. The potential for the use of hepcidin for a simple point-of-care (PoC) diagnostic for when it is most safe and effective to give iron may improve maternal health outcomes.
ISRCTN21955180.
直到最近，世界卫生组织还建议，在贫血率超过40%的地区，对所有孕妇进行每日铁补充（60毫克/天的铁与400微克/天的叶酸联合使用）。最近的研究表明，这可能会给孕妇带来风险。因此，有必要探索筛查和治疗方案，以在孕期使用总体较低剂量的铁来尽量减少铁暴露，同时达到与世界卫生组织目前建议相当的效果。然而，在感染流行时如何最好地评估缺铁，尚无定论。在此，我们测试使用铁调素（一种肽类激素和铁代谢的关键调节因子）作为 “安全且适宜补铁” 的潜在指标。
设计/方法：这是一项三臂随机对照概念验证试验。我们将检验以下假设：使用预先确定的铁调素临界值<2.5纳克/毫升进行补铁的筛查和治疗方法，在较低铁剂量下预防缺铁和贫血的疗效相似，从而提高安全性。462名冈比亚农村孕妇的样本将被随机分配接受：a）联合国大学/联合国儿童基金会/世界卫生组织国际多种微量营养素制剂（UNIMMAP），含60毫克/天的铁（参照组）；b）含60毫克/天铁的UNIMMAP，但基于每周一次的铁调素筛查，以确定接下来7天是否可补铁；c）或如b组那样含30毫克/天铁的UNIMMAP，在冈比亚农村使用12周。该研究将以血红蛋白水平作为主要终点，非劣效边际为0.5克/分升，检验筛查和治疗方法是否不劣于参照组。还将评估不良反应、依从性以及补铁对感染易感性的影响等次要结果。
该试验有望有助于尽量减少孕妇接触可能不需要因而可能有害的铁。如果本研究的证据表明总体较低剂量的铁不劣于60毫克/天的铁，这可能有助于减少副作用、提高依从性并增加安全性。使用铁调素进行简单的即时护理（PoC）诊断，以确定何时补铁最安全有效，这有可能改善孕产妇健康结局。
ISRCTN21955180
