Malaria in Pregnancy: Nutrition and Immunologic Effects

描述（由申请人提供）：孕期疟疾是坦桑尼亚和撒哈拉以南非洲许多其他国家的一个主要公共卫生问题。疟疾与母亲的高发病率（包括严重贫血）和胎儿的低出生体重和胎儿丢失有关。维生素A和锌缺乏是可调节疟疾临床病程并加剧相关并发症的特定因素。已发表的文献表明，这两种微量营养素有助于降低胎盘疟疾和相关临床结果的风险，包括妇女的疟疾和贫血，以及低出生体重。我们建议研究补充锌和/或维生素A在降低胎盘疟疾和其他孕产妇/胎儿结局的风险方面的功效。我们将招募9000名育龄妇女，每月对其妊娠情况进行随访，并对2500名孕妇的目标样本进行识别和随机化。符合随机分组条件的受试者为妊娠8周或之前的hiv阴性妇女。妇女将采用因子设计入组，并被分配单独接受锌、单独接受维生素a、同时接受锌和维生素a或安慰剂。所有妇女将按照标准产前护理每天补充叶酸和铁。孕妇及产后婴儿，将被随访至产后6周。补充剂使用的依从性将通过在每月的诊所访问中直接询问妇女和药片数量来评估。还将对依从性的生化评估进行评估，测量400名妇女在随机分组、妊娠30周和分娩时的血浆维生素A和锌浓度。主要终点是胎盘疟疾，次要终点包括孕产妇疟疾、孕产妇贫血和低出生体重。我们建议检查疟疾的体液和细胞介导的免疫反应的关键方面在一个子研究。该方案将由哈佛大学公共卫生学院与坦桑尼亚达累斯萨拉姆的Muhimbili卫生与相关科学大学合作实施。公共卫生相关性：怀孕期间补充维生素A和锌有可能增强免疫反应，以预防胎盘疟疾和/或避免与之相关的临床并发症，如产妇贫血和婴儿出生体重低。然而，这种补充剂对孕妇的安全性和有效性尚未得到检验。拟议的研究将解决这一研究问题，并将提供证据，可能导致孕妇补充维生素A和锌的国际准则的优化，这将对每年在非洲疟疾流行地区怀孕的2500多万妇女很重要。

DESCRIPTION (provided by applicant): Malaria in pregnancy is a major public health problem in Tanzania and many other countries in sub-Saharan Africa. Malaria is associated with tremendous morbidity in the mother including severe anemia, and in the fetus in the form of low birth weight and fetal loss. Vitamin A and zinc deficiencies are specific factors which can modulate the clinical course of malaria and exacerbate associated complications. The published literature suggests that these two micronutrients favor a reduction in risk of placental malaria and related clinical outcomes including malaria and anemia among women, and low birth weight. We propose to study the efficacy of zinc and/or vitamin A supplementation in reducing the risk of placental malaria and other maternal/fetal outcomes. We will recruit 9,000 women of reproductive age and follow them up on monthly basis for pregnancy status, and identify and randomize our target sample of 2500 pregnant women. Subjects eligible for randomization will be HIV-negative women who are at or before 8 weeks of gestation. Women will be enrolled using a factorial design and assigned to receive zinc alone, vitamin A alone, both zinc and vitamin A, or placebo. All women will receive daily folate and iron supplements as per standard prenatal care. Women, and after delivery babies, will be followed up until 6 weeks after delivery. Compliance with supplement use will be assessed by direct questioning of women and pill count at monthly clinic visits. Biochemical assessment of compliance will also be assessed measuring the plasma concentration of vitamin A and zinc in a random subsample of 400 women at randomization, at 30 weeks of gestation, and at delivery. The primary endpoint is placental malaria, and secondary endpoints include maternal malaria, maternal anemia, and low birth weight. We propose to examine key aspects of the humoral and cell-mediated immune response to malaria in a sub-study. The program will be carried out by Harvard School of Public Health in collaboration with Muhimbili University of Health and Allied Sciences in Dar es Salaam, Tanzania. PUBLIC HEALTH RELEVANCE: Vitamin A and zinc supplementation during pregnancy have the potential to boost the immune response to prevent placental malaria and/or avoid clinical complications associated with it such as maternal anemia and low birth weight in the infants. However, the safety and efficacy of such supplements in pregnant women has not been examined. The proposed study will address this research question and will provide evidence that may lead to an optimization of international guidelines on vitamin A and zinc supplementation in pregnant women that will be important for more than 25 million women becoming pregnant in malaria-endemic regions in Africa every year.