Malaria in Pregnancy: Nutrition and Immunologic Effects

描述（由申请人提供）：在坦桑尼亚和撒哈拉以南非洲的许多其他国家，妊娠期疟疾是一个主要的公共卫生问题。疟疾与母亲的巨大发病率（包括严重贫血）以及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具体因素。已发表的文献表明，这两种微量营养素有利于降低胎盘疟疾的风险和相关的临床结果，包括妇女疟疾和贫血，以及低出生体重。我们建议研究锌和/或维生素A补充剂在降低胎盘疟疾和其他母婴结局风险方面的疗效。我们将招募9，000名育龄妇女，每月随访她们的妊娠状况，并确定和随机分配我们的目标样本2，500名孕妇。有资格接受随机化的受试者为妊娠8周或8周前的HIV阴性女性。将使用析因设计招募女性，并分配接受单独的锌，单独的维生素A，锌和维生素A，或安慰剂。所有妇女将按照标准产前护理接受每日叶酸和铁补充剂。妇女和分娩后的婴儿将被随访至分娩后6周。通过直接询问妇女和每月门诊访视时的药丸计数来评估补充剂使用的依从性。还将通过测量随机分组、妊娠30周和分娩时400名女性的随机子样本中维生素A和锌的血浆浓度来评估依从性的生化评估。主要终点是胎盘疟疾，次要终点包括母体疟疾、母体贫血和低出生体重。我们建议在子研究中检查体液和细胞介导的疟疾免疫应答的关键方面。该计划将由哈佛公共卫生学院与坦桑尼亚达累斯萨拉姆的Muhimbili卫生和联合科学大学合作实施。

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.