Another piece of the Zika puzzle: Assessing the associated factors to microcephaly in a systematic review and meta-analysis.

Abstract

Background: Although it is known that Zika virus (ZIKV) infection during pregnancy may lead to microcephaly in the fetus, the prognostic factors associated with this tragic disorder remain unclear. We conducted a systematic review and meta-analysis to assess the prognostic factors associated with the incidence of microcephaly in congenital ZIKV infection. Methods: We conducted a comprehensive search in Ovid MEDLINE, Ovid MEDLINE (R) Epub ahead of print, Embase, Embase Classic, Web of Science, CINAHL, Cochrane CENTRAL, LILACS, and various thesis databases to identify human studies reporting microcephaly associated with congenital ZIKV infection. We requested primary data from the authors of the included studies to calculate summary estimates and conduct the meta-analysis of the most prevalent factors.Results: We screened 4106 titles and abstracts, and identified 12 studies for inclusion in the systematic review. The assessment of ZIKV infection and the definition of microcephaly varied among studies. A total of 6154 newborns/fetuses were enrolled; of those, 1120 (18.20%) had a diagnostic of ZIKV infection, of which 509 (45.45%) were diagnosed with microcephaly. Nine studies addressed the link between congenital ZIKV infection and neurological findings in newborns/fetuses. Half of the studies provided primary data. Three out of 11 factors of interest seem to be prognostic factors of microcephaly: infant’s sex – males compared to females: Relative Risk (RR) 1.30, 95% Confidence Interval (95% CI) 1.14 to 1.49; the stage of pregnancy when infection occurred – infection in the first trimester of pregnancy compared to infection at other stages of pregnancy: RR 1.41, 95% CI 1.09 to 1.82; and asymptomatic infection compared to symptomatic infection during pregnancy: RR 0.68; 95% CI 0.60 to 0.77.Conclusion: Our findings support the female-biased resistance hypothesis and reinforce the risk associated with the stage of pregnancy when ZIKV infection occurs. Continued surveillance of ZIKV infection during pregnancy is needed to identify additional factors that could contribute to developing microcephaly in affected fetuses.

Perinatal characteristics and longer-term outcomes in Brazilian children with confirmed or suspected congenital Zika infection: ZIKAction Paediatric Registry

“…There are multiple reasons for the lack of laboratory-confirmation, which is a common feature of studies of CZS. 9,11,16 Firstly, a proportion of these children were born before ZIKV was first detected in Brazil (in October 2015). 1 Although there were reports of an unknown 'dengue-like' illness in North-Eastern Brazil in 2014 , phylogenetic and molecular clock analyses suggest that ZIKV was introduced into the Americas in the second half of 2013.…”

“…A recent meta-analysis of six studies found a relative risk of microcephaly of 0•68 (95% CI 0•60, 0•77) for asymptomatic versus symptomatic maternal ZIKV infection. 16…”

Zika Virus: A Systematic Review of Teratogenesis, Congenital Anomalies, and Child Mortality

“…The teratogenicity and neuropathology associated with ZIKV might affect fetal growth across the placenta, selective to the central neural system [7]. Consequently, Gallo et al noticed that most severe brain anomalies, likely microcephaly, were linked with the rash during the first trimester of pregnancy [10]. França et al said the rash occurred earlier during pregnancy and the head size was smaller at birth [11].…”

The Ablation of Envelope Protein Glycosylation Enhances the Neurovirulence of ZIKV and Cell Apoptosis in Newborn Mice

“…Phylogenetic analyses have revealed two main ZIKV lineages, African and Asian, and the contemporary epidemics have been traced to the Asian lineage [2]. Currently, ZIKV has been causally linked to microcephaly during pregnancy and thus evolved into a new public health threat [3]. The genome of ZIKV is a positive-sense RNA that contains one open reading frame encoding a polyprotein, which can be cleaved into three structural proteins, including capsid (C), precursor membrane (PrM), and envelope (E), and seven nonstructural (NS) proteins [4,5].…”