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Meta-Analysis
. 2020 Jun 1;20(1):827.
doi: 10.1186/s12889-020-08946-5.

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

Luciana Guerra Gallo  1   2 , Jorge Martinez-Cajas  3 , Henry Maia Peixoto  1 , Ana Carolina Esteves da Silva Pereira  4 , Jillian E Carter  2 , Sandra McKeown  5 , Bruno Schaub  6 , Camila V Ventura  7 , Giovanny Vinícius Araújo de França  8 , Léo Pomar  9   10 , Liana O Ventura  11 , Vivek R Nerurkar  12 , Wildo Navegantes de Araújo  1 , Maria P Velez  13
Affiliations
Meta-Analysis

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

Luciana Guerra Gallo et al. BMC Public Health. .

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.

Protocol registration: This systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration no. CRD 42018088075.

Keywords: Congenital Zika syndrome; Congenital disease; Microcephaly; Pregnancy; Risk factors; Systematic review; Zika virus.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram of Selection of studies for the systematic review and meta-analysis
Fig. 2
Fig. 2
Meta-analysis forest plot for prospective studies. 2a. Sex of the newborns/fetuses. 2b. Trimester of pregnancy when ZIKV infection occurred. 2c. Symptoms of ZIKV infection during pregnancy
See this image and copyright information in PMC

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