BACKGROUND In endemic areas, pregnant women are highly susceptible to Plasmodium falciparum malaria characterized by the accumulation of parasitized red blood cells (pRBC) in the placenta. In subsequent pregnancies, women develop protective immunity to pregnancy-associated malaria and this has been hypothesized to be due to the acquisition of antibodies to the parasite variant surface antigen VAR2CSA. In this systematic review we provide the first synthesis of the association between antibodies to pregnancy-specific P. falciparum antigens and pregnancy and birth outcomes. METHODS We conducted a systematic review and meta-analysis of population-based studies (published up to 07 June 2019) of pregnant women living in P. falciparum endemic areas that examined antibody responses to pregnancy-specific P. falciparum antigens and outcomes including placental malaria, low birthweight, preterm birth, peripheral parasitaemia, maternal anaemia, and severe malaria. RESULTS We searched 6 databases and identified 33 studies (30 from Africa) that met predetermined inclusion and quality criteria: 16 studies contributed estimates in a format enabling inclusion in meta-analysis and 17 were included in narrative form only. Estimates were mostly from cross-sectional data (10 studies) and were heterogeneous in terms of magnitude and direction of effect. Included studies varied in terms of antigens tested, methodology used to measure antibody responses, and epidemiological setting. Antibody responses to pregnancy-specific pRBC and VAR2CSA antigens, measured at delivery, were associated with placental malaria (9 studies) and may therefore represent markers of infection, rather than correlates of protection. Antibody responses to pregnancy-specific pRBC, but not recombinant VAR2CSA antigens, were associated with trends towards protection from low birthweight (5 studies). CONCLUSIONS Whilst antibody responses to several antigens were positively associated with the presence of placental and peripheral infections, this review did not identify evidence that any specific antibody response is associated with protection from pregnancy-associated malaria across multiple populations. Further prospective cohort studies using standardized laboratory methods to examine responses to a broad range of antigens in different epidemiological settings and throughout the gestational period, will be necessary to identify and prioritize pregnancy-specific P. falciparum antigens to advance the development of vaccines and serosurveillance tools targeting pregnant women.

中文翻译：

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特定于妊娠的疟疾免疫力和妊娠疟疾风险及不良分娩结果：系统评价。

背景技术在流行地区，孕妇对恶性疟原虫疟疾高度敏感，其特征在于胎盘中寄生红细胞（pRBC）的积累。在随后的怀孕中，妇女对妊娠相关的疟疾产生保护性免疫力，据推测这是由于获得了针对寄生虫变异体表面抗原VAR2CSA的抗体。在这项系统的综述中，我们提供了妊娠特异性恶性疟原虫抗原抗体与妊娠和分娩结局之间关联的首次合成。方法我们对居住在恶性疟原虫流行地区的孕妇进行了基于人群的研究（发表至2019年6月7日）的系统评价和荟萃分析，这些研究检查了针对妊娠特异性P的抗体反应。恶性疟原虫的抗原和结局包括胎盘疟疾，低出生体重，早产，外周寄生性贫血，母亲贫血和严重疟疾。结果我们搜索了6个数据库，确定了33项符合预定纳入和质量标准的研究（非洲30项）：16项研究以能够纳入荟萃分析的格式提供了估计，而17项仅以叙述形式被纳入。估计值主要来自横截面数据（10项研究），并且在影响的大小和方向上均不相同。包括的研究在测试的抗原，用于测量抗体反应的方法以及流行病学设置方面有所不同。在分娩时测得的对妊娠特异性pRBC和VAR2CSA抗原的抗体反应，与胎盘疟疾相关（9项研究），因此可能是感染的标志，而不是保护因素。对妊娠特异性pRBC的抗体反应，而非对重组VAR2CSA抗原的反应，与防止低出生体重的趋势相关（5个研究）。结论虽然对几种抗原的抗体反应与胎盘和周围感染的存在呈正相关，但本综述未发现证据表明任何特异性抗体反应均与跨多个人群的妊娠相关疟疾的预防相关。使用标准化实验室方法进行的进一步前瞻性队列研究，以检验在不同的流行病学环境中以及整个妊娠期对多种抗原的反应，