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Meta-Analysis
. 2021 Feb 19;16(2):e0246643.
doi: 10.1371/journal.pone.0246643. eCollection 2021.

Fetal, neonatal, and infant outcomes associated with maternal Zika virus infection during pregnancy: A systematic review and meta-analysis

Marlos Melo Martins  1 , Antonio José Ledo Alves da Cunha  2 , Jaqueline Rodrigues Robaina  3 , Carlos Eduardo Raymundo  3 , Arnaldo Prata Barbosa  3 , Roberto de Andrade Medronho  4
Affiliations
Meta-Analysis

Fetal, neonatal, and infant outcomes associated with maternal Zika virus infection during pregnancy: A systematic review and meta-analysis

Marlos Melo Martins et al. PLoS One. .

Abstract

The occurrence of fetal and neonatal disorders in pregnant women with Zika virus infection in the literature is not consistent. This study aims to estimate the prevalence rate of these disorders in fetuses/neonates of pregnant women with confirmed or probable infection by Zika virus. A systematic review with meta-analysis was conducted in November 2020. Cohort studies that contained primary data on the prevalence of unfavorable outcomes in fetuses or neonates of women with confirmed or probable Zika virus infection during pregnancy were included. A total of 21 cohort studies were included, with a total of 35,568 pregnant women. The meta-analysis showed that central nervous system abnormalities had the highest prevalence ratio of 0.06 (95% CI 0.03-0.09). Intracranial calcifications had a prevalence ratio of 0.01 (95% CI 0.01-0.02), and ventriculomegaly 0.01 (95% CI 0.01-0.02). The prevalence ratio of microcephaly was 0.03 (95% CI 0.02-0.05), fetal loss (miscarriage and stillbirth) was 0.04 (95% CI 0.02-0.06), Small for Gestational Age was 0.04 (95% CI 0.00-0,09), Low Birth Weight was 0.05 (95% CI 0.03-0.08) and Prematurity was 0.07 (95% CI 0.04-0.10). The positivity in RT-PCR for ZIKV performed in neonates born to infected mothers during pregnancy was 0.25 (95% CI 0.06-0.44). We also performed the meta-analysis of meta-analysis for microcephaly with the prevalence ratios from other two previously systematic reviews: 0.03 (95% CI 0.00-0.25). Our results contribute to measuring the impact of Zika virus infection during pregnancy on children's health. The continuous knowledge of this magnitude is essential for the implementation development of health initiatives and programs, in addition to promoting disease prevention, especially in the development of a vaccine for Zika virus. PROSPERO protocol registration: http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42019125543.

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Conflict of interest statement

NO authors have competing interests.

Figures

Fig 1
Fig 1. Articles selection flow in the systematic review.
Fig 2
Fig 2. Meta-analysis of the prevalence rate of microcephaly in neonates born to ZIKV infected mothers.
Random-Effects/Values represent proportions with 95% confidence intervals. Model. I2 (total heterogeneity/total variability): 95.21%. Test for Heterogeneity: Q(df = 15) = 530.1468, p value < 0.0001.
Fig 3
Fig 3. Meta-analysis of the prevalence rate of CNS abnormalities in neonates born to ZIKV infected mothers.
Random-Effects/Values represent proportions with 95% confidence intervals. Model. I2 (total heterogeneity/total variability): 98.66%. Test for Heterogeneity: Q(df = 12) = 347.6898, p value < 0.0001.
Fig 4
Fig 4. Meta-analysis of the prevalence rate of intracranial calcifications in neonates born to ZIKV infected mothers.
Random-Effects/Values represent proportions with 95% confidence intervals. Model. I2 (total heterogeneity/total variability): 0.51%. Test for Heterogeneity: Q(df = 5) = 4.0328, p value = 0.5447.
Fig 5
Fig 5. Meta-analysis of the prevalence rate of ventriculomegaly in neonates born to ZIKV infected mothers.
Random-Effects/Values represent proportions with 95% confidence intervals. Model. I2 (total heterogeneity/total variability): 0.00%. Test for Heterogeneity: Q(df = 4) = 0.9991, p value = 0.9099.
Fig 6
Fig 6. Meta-analysis of the prevalence rate of fetal loss in ZIKV infected mothers.
Random-Effects/Values represent proportions with 95% confidence intervals. Model. I2 (total heterogeneity/total variability): 97.11%. Test for Heterogeneity: Q(df = 15) = 306.0131, p value < 0.0001.
Fig 7
Fig 7. Meta-analysis of the prevalence rate of SGA in neonates born to ZIKV infected mothers.
Random-Effects/Values represent proportions with 95% confidence intervals. Model. I2 (total heterogeneity/total variability): 43.97%. Test for Heterogeneity: Q(df = 2) = 3.4191, p value = 0.1810.
Fig 8
Fig 8. Meta-analysis of the prevalence rate of LBW in neonates born to ZIKV infected mothers.
Random-Effects/Values represent proportions with 95% confidence intervals. Model. I2 (total heterogeneity/total variability): 90.04%. Test for Heterogeneity: Q(df = 4) = 19.8976, p value = 0.0005.
Fig 9
Fig 9. Meta-analysis of the prevalence rate of prematurity in neonates born to ZIKV infected mothers.
Random-Effects/Values represent proportions with 95% confidence intervals. Model. I2 (total heterogeneity/total variability): 92.39%. Test for Heterogeneity: Q(df = 6) = 70.1163, p value < 0.0001.
Fig 10
Fig 10. Meta-analysis of the prevalence rate of positivity in RT-PCR for ZIKV in neonates born to ZIKV infected mothers.
Random-Effects/Values represent proportions with 95% confidence intervals. Model. I2 (total heterogeneity/total variability): 98.89%. Test for Heterogeneity: Q(df = 5) = 257.0044, p value < 0.0001.
Fig 11
Fig 11. Meta-analysis of the prevalence rate of microcephaly in neonates born to ZIKV infected mothers.
Random-Effects/Values represent proportions with 95% confidence intervals. Model. I2 (total heterogeneity/total variability): 98.89%. Test for Heterogeneity: Q(df = 5) = 257.0044, p value < 0.0001.
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