Abstract:
Congenital microcephaly is caused by a multitude of drivers affecting maternal−fetal health during pregnancy. It is a rare outcome in high-income industrial countries where microcephaly rates are in the range of 0.3−0.9 per 1000 newborns. Prevalence of microcephaly varies considerably across developing countries and can go as high as 58 cases per 1000 live births in pregnancies exposed to infection by Zika virus (ZIKV). Not only ZIKV-infected pregnancies, but other drivers can modulate the occurrence and severity of this outcome. Here, we sought to test the ZIKV−microcephaly association vs. competing hypotheses using a meta-analysis with 8341 microcephaly cases pooled from 10,250,994 newborns in the Americas, Africa, and Asia. Analysis of risk ratios (RR) showed teratogens the most likely microcephaly-associated risk factor (RR = 3.43; 95%-CI 2.69−4.38; p-value < 0.0001), while the statistical significance of the ZIKV−microcephaly association was marginal (RR = 2.12; 95%-CI 1.01−4.48; p-value = 0.048). Other congenital infections showed strong but variable associations with microcephaly (RR = 15.24; 95%-CI 1.74−133.70; p-value = 0.014). Microcephaly cases were associated with impoverished socioeconomic settings, but this association was statistically non-significant (RR = 2.75; 95%-CI 0.55−13.78; p-value = 0.22). The marginal ZIKV−microcephaly association and statistical significance of the competing hypotheses suggest maternal ZIKV infection might not be a cause of microcephaly alone.
摘要:
先天性小头畸形是由许多驾驶员在怀孕期间影响母胎健康引起的。在高收入工业国家中,这是罕见的结果,那里的小头畸形发生率在每1000名新生儿0.3-0.9的范围内。在发展中国家,小头症的患病率差异很大,在暴露于寨卡病毒(ZIKV)感染的怀孕中,每1000名活产婴儿中可能高达58例。不仅仅是ZIKV感染的怀孕,但是其他驱动因素可以调节这种结果的发生和严重程度。这里,我们试图测试ZIKV-小头畸形与使用荟萃分析的竞争假设,对来自美洲10,250,994名新生儿的8341例小头畸形病例进行了荟萃分析,非洲,和亚洲。风险比(RR)分析显示致畸剂是最可能的小头畸形相关危险因素(RR=3.43;95%-CI2.69-4.38;p值0.0001),而ZIKV-小头畸形相关性的统计学意义是边缘的(RR=2.12;95%-CI1.01-4.48;p值=0.048)。其他先天性感染与小头畸形有强烈但可变的关联(RR=15.24;95%-CI1.74-133.70;p值=0.014)。小头畸形病例与贫困的社会经济环境有关,但这种关联在统计学上无显著意义(RR=2.75;95%-CI0.55-13.78;p值=0.22).边缘ZIKV-小头畸形关联和竞争假设的统计意义表明,母体ZIKV感染可能不是小头畸形的单独原因。