During 2015, the rates of microcephaly reported in Northeast Brazil were high, but rates in other Zika-affected areas were significantly lower. The authors were interested in whether these were due to alternate causes or the involvement of arboviral co-factors. They combined data from multiple national reporting databases in Brazil to estimate the exposure to nine known or hypothesised causes of microcephaly for every pregnancy nationwide since the beginning of the ZIKV outbreak (3.6–5.4 million cases 2015–2017). The authors could find no evidence for alternative non-ZIKV causes of the 2015–2017 microcephaly outbreak, nor evidence that concurrent exposure to arbovirus infection or vaccination had modified the risk. The absolute risk of microcephaly was estimated to be 40.8 per 10,000 births, with 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 between ZIKV and other birth defects were also detected, albeit at lower relative risks than that of microcephaly (relative risk <1.5). Therefore it is likely that congenital ZIKV infection, particularly in the first two trimesters of pregnancy, is associated with microcephaly, and less frequently with other birth defects. The geographic differences in microcephaly rate may have been due to the Northeast region being disproportionately affected by this Zika virus outbreak, with 94% of an estimated 8.5 million total cases occurring in this region.
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