Malaria in Pregnancy: Nutrition and Immunologic Effects

描述(申请人提供)：妊娠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。疟疾在母亲中的发病率很高，包括严重的贫血，在胎儿中表现为低出生体重和胎儿丧失。维生素A和锌缺乏是影响疟疾临床进程并加剧相关并发症的具体因素。已发表的文献表明，这两种微量营养素有助于降低患胎盘性疟疾的风险和相关的临床结果，包括妇女中的疟疾和贫血，以及低出生体重。我们建议研究补充锌和/或维生素A在降低胎盘疟疾风险和其他母婴结局方面的效果。我们将招募9000名育龄妇女，每月跟踪她们的怀孕状况，并确定并随机抽取2500名孕妇作为目标样本。符合随机抽样条件的受试者将是怀孕8周或之前的艾滋病毒阴性妇女。女性将采用析因设计进行登记，并被分配为单独服用锌、单独服用维生素A、同时服用锌和维生素A，或服用安慰剂。根据标准的产前护理，所有妇女每天都将获得叶酸和铁质补充剂。妇女和分娩后的婴儿将被跟踪，直到分娩后6周。将通过直接询问妇女和每月就诊时的药片计数来评估补充剂使用的依从性。还将对依从性的生化评估进行评估，测量随机抽样的400名妇女在随机、怀孕30周和分娩时的血浆维生素A和锌浓度。主要终点是胎盘性疟疾，次要终点包括产妇疟疾、产妇贫血和低出生体重。我们建议在一项子研究中检查疟疾体液免疫和细胞免疫反应的关键方面。该项目将由哈佛公共卫生学院与坦桑尼亚达累斯萨拉姆的穆亨比利健康与联合科学大学合作实施。公共卫生相关性：孕期补充维生素A和锌有可能增强免疫反应，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过低。然而，此类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，可能导致对孕妇补充维生素A和锌的国际指南进行优化，这对非洲疟疾流行地区每年2500多万怀孕妇女来说将是重要的。

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.