The association between Zika virus infection and microcephaly in Brazil 2015-2017: An observational analysis of over 4 million births
The association between Zika virus infection and microcephaly in Brazil 2015-2017: An observational analysis of over 4 million births
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DOI：
10.1371/journal.pmed.1002755
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发表时间：
2019-03-01
期刊：
影响因子：
15.8
通讯作者：
Marinho, Fatima
中科院分区：
文献类型：
--
作者：
Brady, Oliver J.;Osgood-Zimmerman, Aaron;Marinho, Fatima
2015年，在首次南美寨卡病毒（ZIKV）暴发后，巴西东北部报告了小头症的高发率。在其他寨卡疫区报告的小头畸形率明显较低，提示其他原因或虫媒病毒辅助因子参与加剧小头畸形率。方法和发现我们合并了来自巴西多个国家报告数据库的数据，以估计自寨卡病毒暴发开始以来，全国每次妊娠暴露于9种已知或假设的小头症原因；这在2015年1月1日至2017年5月23日期间产生了360万至540万例病例（取决于分析情况）。寨卡病毒与小头畸形之间的关联通过具有替代原因或效应修饰因子的模型进行了统计检验。我们没有发现2015-2017年小头症暴发的其他非寨卡病毒原因的证据，也没有发现同时暴露于虫媒病毒感染或接种疫苗会改变风险。我们估计，在妊娠早期或中期感染寨卡病毒的情况下，小头畸形的绝对风险为每1万例分娩40.8例（95% CI 34.2-49.3），相对风险为16.8例（95% CI 3.2-369.1）；然而，由于寨卡病毒感染率变化很大，在寨卡病毒爆发期间，巴西的大多数孕妇面临的风险水平较低。寨卡病毒与其他出生缺陷的关联也有统计学意义，但相对风险低于小头畸形（相对风险< 1.5）。我们的分析受到在建立全国寨卡病毒监测之前缺少数据的限制，并且其结果可能受到常规收集的监测数据中无法获得的小头畸形的未测量混杂原因的影响。结论：本研究进一步证实，先天性寨卡病毒感染，特别是在妊娠头2个月，与小头畸形有关，而与其他出生缺陷的关联较少。由于没有发现导致小头症发病率地域差异的其他原因，我们假设东北地区受到寨卡疫情的影响不成比例，估计850万例病例中有94%发生在该地区，这表明需要进行血清患病率调查以确定潜在原因。
Background In 2015, high rates of microcephaly were reported in Northeast Brazil following the first South American Zika virus (ZIKV) outbreak. Reported microcephaly rates in other Zika-affected areas were significantly lower, suggesting alternate causes or the involvement of arboviral cofactors in exacerbating microcephaly rates.Methods and findings We merged data from multiple national reporting databases in Brazil to estimate exposure to 9 known or hypothesized causes of microcephaly for every pregnancy nationwide since the beginning of the ZIKV outbreak; this generated between 3.6 and 5.4 million cases (depending on analysis) over the time period 1 January 2015-23 May 2017. The association between ZIKV and microcephaly was statistically tested against models with alternative causes or with effect modifiers. We found no evidence for alternative non-ZIKV causes of the 2015-2017 microcephaly outbreak, nor that concurrent exposure to arbovirus infection or vaccination modified risk. We estimate an absolute risk of microcephaly of 40.8 (95% CI 34.2-49.3) per 10,000 births and a relative risk of 16.8 (95% CI 3.2-369.1) given ZIKV infection in the first or second trimester of pregnancy; however, because ZIKV infection rates were highly variable, most pregnant women in Brazil during the ZIKV outbreak will have been subject to lower risk levels. Statistically significant associations of ZIKV with other birth defects were also detected, but at lower relative risks than that of microcephaly (relative risk < 1.5). Our analysis was limited by missing data prior to the establishment of nationwide ZIKV surveillance, and its findings may be affected by unmeasured confounding causes of microcephaly not available in routinely collected surveillance data.Conclusions This study strengthens the evidence that congenital ZIKV infection, particularly in the first 2 trimesters of pregnancy, is associated with microcephaly and less frequently with other birth defects. The finding of no alternative causes for geographic differences in microcephaly rate leads us to hypothesize that the Northeast region was disproportionately affected by this Zika outbreak, with 94% of an estimated 8.5 million total cases occurring in this region, suggesting a need for seroprevalence surveys to determine the underlying reason.