Calcium supplementation to prevent pre-eclampsia in Low- and Middle-Income Countries: IPD meta-analysis, network meta-analysis and economic evaluation

问题出在哪里？妊娠期先兆子痫是一种与高血压和尿蛋白有关的疾病，是母婴本可避免死亡的主要原因，尤其是在低收入和中等收入国家。怀孕期间补充钙可以预防先兆子痫，并有可能使这些国家每年有21,500名母亲免于死亡。尽管钙在这些国家的国家基本药物清单上，世界卫生组织(WHO)建议服用高剂量的钙(每天1.5克)来预防先兆子痫，但妊娠期缺钙仍然是一个重大的可预防的公共卫生挑战。我们可以将这归因于母亲们不愿一天三次服用令人不快的大剂量钙片，这往往与呕吐和便秘等副作用有关。此外，大量笨重的平板电脑给运输和储存带来了后勤困难，限制了它们在农村地区的供应。医疗保健专业人员也担心大剂量的钙会影响治疗贫血所需的铁的吸收。需要做什么？我们迫切需要确定a)谁将从补钙中受益最多(基于个体特征)，b)最有效和可接受的最小剂量的钙，以及c)开始补充以预防先兆子痫和并发症的最佳时间。政策制定者和医疗保健专业人员还需要关于钙摄取和实施的障碍以及在有限的医疗资源中补充钙的成本影响的信息。到目前为止，已经做了什么？到目前为止，尽管有超过30,000名妇女参与了许多关于预防先兆子痫的补钙研究，但由于这些研究中女性的特征、补钙剂量和补钙时间的不同，我们能够回答上述问题。我们的国际合作网络(I-CIP)已经在进行上述研究的低收入、中等收入和高收入国家的研究人员、世卫组织指南制定者和怀孕期间补钙方面的专家之间建立了合作伙伴关系，以弥补研究中的空白。我们计划做什么？在这项建议中，我们计划结合来自参与补钙研究的个人的数据，这种技术被称为“IPD荟萃分析”，以确定钙的影响是否在不同的女性群体中有所不同，以及是否根据钙的剂量和使用时间的不同而不同。我们将通过调查和采访获得母亲和医疗保健专业人员的意见，了解他们认为哪些因素可能会阻碍我们发现最有效的补钙策略的吸收和使用。我们将研究钙补充剂的成本与低收入和中等收入国家通过避免先兆子痫及其并发症而节省的成本。这一经济模型将以其他国家的专家可以使用的格式提供，以确定相关的经济影响。加强我们合作伙伴的研究能力是该项目长期可持续性的关键。我们预计会发生什么？我们预计我们的发现将导致更新世界卫生组织关于怀孕期间补钙的现有指南，向政策制定者通报促进补钙的最佳战略和成本，减少孕妇的缺钙，并通过预防先兆子痫来改善母亲和婴儿的结局。我们与患者和公众参与团体合作计划了这项建议，以便妇女参与研究和传播的共同发展。我们与世卫组织(生殖健康、营养、人类生殖方案HRP联盟)的合作是通过指南和现有网络发展和传播我们的工作的关键。

WHAT IS THE PROBLEM?Pre-eclampsia, a condition in pregnancy associated with high blood pressure and protein in the urine, is a major cause of avoidable deaths in mothers and babies, particularly in low and middle-income countries. Calcium supplements in pregnancy could prevent pre-eclampsia and potentially save 21,500 mothers every year from dying in these countries. Although calcium is on the national essential medicines list of these countries, and the World Health Organization (WHO) recommends high-dose calcium (>1.5g/day) to prevent pre-eclampsia, calcium deficiency in pregnancy continues to be a major preventable public health challenge. We can attribute this to the reluctance of mothers to take large, unpalatable high-dose calcium tablets 3-times a day that is often associated with side effects such as vomiting and constipation. Furthermore, large numbers of bulky tablets pose logistical difficulties with transport and storage, limiting their availability in rural areas. The healthcare professionals also have concerns about the large calcium doses affecting the absorption of iron needed to treat anaemia. WHAT NEEDS TO BE DONE?There is an urgent need for us to identify a) the group of women who will benefit the most from calcium supplementation (based on individual characteristics) b) the most effective and acceptable minimal dose of calcium, and c) the best time to start the supplement to prevent pre-eclampsia and complications. Policymakers and healthcare professionals also need information on the barriers to the uptake of calcium and its implementation, and the cost implications of supplementation within limited healthcare resources.WHAT HAS BEEN DONE SO FAR?To-date, despite over 30,000 women participating in numerous studies on calcium supplementation to prevent pre-eclampsia, we were able to answer the above questions due to differences in the characteristics of women, the dosage and timing of calcium in these studies. Our international collaborative network (i-CIP) has established a partnership between researchers from low, middle- and high-income countries who conducted the above studies, WHO guideline developers, and experts on calcium supplementation in pregnancy to answer the gaps in research.WHAT DO WE PLAN TO DO?In this proposal, we plan to combine the data from individuals who participated in studies on calcium supplementation by a technique called 'IPD meta-analysis' to determine if the effects of calcium differed between different groups of women, and if it varied according to the dose and duration of calcium use. We will obtain the views of mothers and healthcare professionals through surveys and interviews on what they consider may hinder the uptake and use of the calcium supplementation strategy that we find to be most effective. We will study the costs of calcium supplementation against the costs saved in low- and middle-income countries by avoiding pre-eclampsia and its complications. This economic model will be provided in a format that can be used by experts in other countries to determine the relevant economic impact. Research capacity strengthening of our partners is the key to the long-term sustainability of the project. WHAT DO WE EXPECT WILL HAPPEN?We expect our findings to lead to an update of the existing WHO guidelines on calcium supplementation in pregnancy, inform policymakers on optimal strategies and costs to promote calcium supplementation, reduce calcium deficiency in pregnant women, and improve outcomes for mother and baby by preventing pre-eclampsia. We planned this proposal in partnership with the patient and public involvement groups so that women are involved in the co-development of the study and dissemination. Our collaboration with WHO (Reproductive health, Nutrition, Human Reproduction Programme HRP Alliance) is key to the development and dissemination of our work through guidelines and existing networks.