What Does Zika Virus Mean for the Children of the Americas?

Hotez, Peter J.

doi:10.1001/jamapediatrics.2016.1465

Cited by 18 publications

(16 citation statements)

References 18 publications

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“…Prior studies have highlighted both the urgent need for further investigation of neurodevelopmental outcomes in children with prenatal ZIKV exposure and the challenge of identifying instruments appropriated for evaluating children across the spectrum of CZS, especially those with severe microcephaly. [17][18][19] In this investigation, we applied the SWYC screening test to assess the neurodevelopment and behavior of prenatally ZIKV-exposed children with and without microcephaly who were born during the ZIKV microcephaly epidemic (2015-2017) in Pernambuco in the Northeast of Brazil. 20 According to the SWYC screening, virtually all participants with severe microcephaly (Group 1) and approximately two-thirds of participants with moderate microcephaly (Group 2) were considered 'at risk of development delay.'…”

Section: Discussionmentioning

confidence: 99%

Pediatric neurodevelopment by prenatal Zika virus exposure: A cross-sectional study of the Microcephaly Epidemic Research Group Cohort

Silva

Eickmann

Ximenes

et al. 2020

Preprint

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Background: The implications of congenital Zika Virus (ZIKV) infections for pediatric neurodevelopment and behavior remain inadequately studied. The aim of this study is to investigate patterns of neurodevelopment and behavior in groups of children with differening severities of ZIKV-related microcephaly and children with prenatal ZIKV exposure in the absence of microcephaly.Methods: We conducted a cross-sectional study, nested in a cohort, of 274 children (aged 10-45 months) who were born during the peak and decline of the microcephaly epidemic in Northeast Brazil. Participants were evaluated between February 2017 and August 2019 at two tertiary care hospitals in Recife, Pernambuco, Brazil. We analyzed the children in four groups assigned based on clinical and laboratory criteria: Group 1 had severe microcephaly; Group 2 had moderate microcephaly; Group 3 had prenatal ZIKVexposure confirmed by maternal RT-PCR testing but no microcephaly; and Group 4 was a neurotypical control group. Groups were evaluated clinically for neurological abnormalities and compared using the Survey of Wellbeing of Young Children (SWYC), a neurodevelopment and behavior screening instrument validated for use in Brazil. Children with severe delays underwent further evaluation with an adapted version of the SWYC.Results: Based on the SWYC screening, we observed differences between the groups for developmental milestones but not behavior. Among the 114 children with severe microcephaly of whom 98.2% presented with neurological abnormalities, 99.1% were ‘at risk of development delay’ according to the SWYC instrument. Among the 20 children with moderate microcephaly of whom 60% presented with neurological abnormalities, 65% were ‘at risk of development delay’. For children without microcephaly, the percentages found to be ‘at risk of developmental delay’ were markedly lower and did not differ by prenatal ZIKV exposure status: Group 3 (N=94), 13.8%; Group 4 (N=46), 21.7%.Conclusions: Among children with prenatal ZIKV exposure, we found a gradient of risk of development delay according to head circumference. Children with severe microcephaly were at highest risk for delays, while normocephalic ZIKV-exposed children had similar risks to unexposed control children. We propose that ZIKV-exposed children should undergo first-line screening for neurodevelopment and behavior using the SWYC instrument. Early assessment and follow-up will enable at-risk children to be referred to a more comprehensive developmental evaluation and to multidisciplinary care management.

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Section: Discussionmentioning

confidence: 99%

Pediatric neurodevelopment by prenatal Zika virus exposure: A cross-sectional study of the Microcephaly Epidemic Research Group Cohort

Silva

Eickmann

Ximenes

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Pediatric neurodevelopment by prenatal Zika virus exposure: a cross-sectional study of the Microcephaly Epidemic Research Group Cohort

et al. 2020

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Background The implications of congenital Zika Virus (ZIKV) infections for pediatric neurodevelopment and behavior remain inadequately studied. The aim of this study is to investigate patterns of neurodevelopment and behavior in groups of children with differening severities of ZIKV-related microcephaly and children with prenatal ZIKV exposure in the absence of microcephaly. Methods We conducted a cross-sectional study, nested in a cohort, of 274 children (aged 10–45 months) who were born during the peak and decline of the microcephaly epidemic in Northeast Brazil. Participants were evaluated between February 2017 and August 2019 at two tertiary care hospitals in Recife, Pernambuco, Brazil. We analyzed the children in four groups assigned based on clinical and laboratory criteria: Group 1 had severe microcephaly; Group 2 had moderate microcephaly; Group 3 had prenatal ZIKVexposure confirmed by maternal RT-PCR testing but no microcephaly; and Group 4 was a neurotypical control group. Groups were evaluated clinically for neurological abnormalities and compared using the Survey of Wellbeing of Young Children (SWYC), a neurodevelopment and behavior screening instrument validated for use in Brazil. Children with severe delays underwent further evaluation with an adapted version of the SWYC. Results Based on the SWYC screening, we observed differences between the groups for developmental milestones but not behavior. Among the 114 children with severe microcephaly of whom 98.2% presented with neurological abnormalities, 99.1% were ‘at risk of development delay’ according to the SWYC instrument. Among the 20 children with moderate microcephaly of whom 60% presented with neurological abnormalities, 65% were ‘at risk of development delay’. For children without microcephaly, the percentages found to be ‘at risk of developmental delay’ were markedly lower and did not differ by prenatal ZIKV exposure status: Group 3 (N = 94), 13.8%; Group 4 (N = 46), 21.7%. Conclusions Among children with prenatal ZIKV exposure, we found a gradient of risk of development delay according to head circumference. Children with severe microcephaly were at highest risk for delays, while normocephalic ZIKV-exposed children had similar risks to unexposed control children. We propose that ZIKV-exposed children should undergo first-line screening for neurodevelopment and behavior using the SWYC instrument. Early assessment and follow-up will enable at-risk children to be referred to a more comprehensive developmental evaluation and to multidisciplinary care management.

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“…During pregnancy, ZIKV poses a substantial risk of fetal neurodevelopmental defects, resulting in profound long-term disability and immense costs of future care, influencing individuals and communities [21,25] . The full spectrum of CZS is still being elucidated, coupled with concerns that ZIKV-related outcomes are underreported, particularly when ZIKV infections result in later onset of developmental delays and learning disabilities without visible microcephaly [26] , or includes other systemic abnormalities that manifest postnatally, such as dysphagia [27] , seizures [28] , and hearing loss [29] . For example, recent evidence suggests that ZIKV infection in pregnancy may have been linked with microcephaly and other neurodevelopmental defects in the US (Hawaii) as early as 2007, with several (likely travel-related) births in 2009 and 2011 being definitively linked to maternal ZIKV-positive antibodies [30] .…”

Section: Zikv-mediated Pathogenesis?mentioning

confidence: 99%

Dysregulation of RNA editing may help explain pathogenicity mechanisms of congenital Zika syndrome and Guillain-Barre syndrome

Piontkivska

Miyamoto

Wayne

2018

Preprint

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Many Zika virus (ZIKV) pathogenesis-related studies have focused primarily on virus-driven pathology and neurotoxicity, instead of considering the possibility of pathogenesis as an (unintended) consequence of host innate immunity: specifically, as the side-effect of an otherwise well-functioning machine. The hypothesis presented here suggests a new way of thinking about the role of host immune mechanisms in disease pathogenesis, focusing on dysregulation of post-transcriptional RNA editing as a candidate driver of a broad range of observed neurodevelopmental defects and neurodegenerative clinical symptoms in both infants and adults linked with ZIKV infections. We collect and synthesize existing evidence of ZIKV-mediated changes in expression of adenosine deaminases that act on RNA (ADARs), known links between abnormal RNA editing and pathogenesis, as well as ideas for potential translational applications, including genomic profile-based molecular diagnostic tools and/or treatment strategies.

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What Does Zika Virus Mean for the Children of the Americas?

Cited by 18 publications

References 18 publications

Pediatric neurodevelopment by prenatal Zika virus exposure: A cross-sectional study of the Microcephaly Epidemic Research Group Cohort

Pediatric neurodevelopment by prenatal Zika virus exposure: A cross-sectional study of the Microcephaly Epidemic Research Group Cohort

Pediatric neurodevelopment by prenatal Zika virus exposure: a cross-sectional study of the Microcephaly Epidemic Research Group Cohort

Dysregulation of RNA editing may help explain pathogenicity mechanisms of congenital Zika syndrome and Guillain-Barre syndrome

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