Congenital Zika infection: neurology can occur without microcephaly

Cardoso, Taíssa Ferreira; Santos, Rosana Silva dos; Corrêa, Raquel Miranda; Campos, Juliana Vieira; Silva, Ricardo de Bastos; Tobias, Christine Castinheiras; Prata‐Barbosa, Arnaldo; Cunha, Antônio José Lêdo Alves da; Ferreira, Halina Cidrini

doi:10.1136/archdischild-2018-314782

Cited by 34 publications

(46 citation statements)

References 4 publications

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“…All the children evaluated were full term with normal weight, similar to the findings of the study by Cardoso et al (2018) 7 .…”

Section: Discussionsupporting

confidence: 87%

“…Studies suggest that children exposed to ZIKV during gestation, but born without microcephaly or other noticeable changes, may develop late CZS-related manifestations and present with developmental abnormalities such as hypotonia, hypertonia, signs of ataxia, dyskinesia, and irritability 7 . ZIKV has been reported in children born with CZS, although few studies have reported on newborns who were asymptomatic at birth but whose mothers had ZIKV during pregnancy.…”

Section: Introductionmentioning

confidence: 99%

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Neurological growth and development of children asymptomatic at birth whose mothers had Zika during pregnancy

Maia

Azevedo

Oliveira

et al. 2021

Rev. Soc. Bras. Med. Trop.

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Introduction: Newborn who had Zika vírus but did not show microcephaly at birth may have neuropsychomotor development problems. We aimed to evaluate the developmental and anthropometric milestones of asymptomatic children whose mothers had Zika during pregnancy in Northeastern Brazil in 2015 and 2016. Methods: We conducted a descriptive cross-sectional case series study of children in Fortaleza born without microcephaly whose mothers had Zika during pregnancy. Home visits were undertaken to evaluate the developmental milestones and gather anthropometric data of the children and to conduct semi-structured interviews with the mothers to identify their socioeconomic and gestational profiles and assess the newborns after birth. Results: In total, 30 cases were identified. Of these, 17 children and their mothers participated in the study. The median age of the mothers at the time of delivery was 26 years. All were symptomatic, and TORCH was negative. At the time of the home visit, all had growth profiles suitable for their age. However, nearly all children (15/17, 88.2%) presented at least one developmental delay, considering their age group. Conclusions: There were late changes in the neuropsychomotor development of children born to mothers who had Zika during pregnancy, suggesting the need for specialized medical follow-ups.

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“…All the children evaluated were full term with normal weight, similar to the findings of the study by Cardoso et al (2018) 7 .…”

Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Neurological growth and development of children asymptomatic at birth whose mothers had Zika during pregnancy

Maia

Azevedo

Oliveira

et al. 2021

Rev. Soc. Bras. Med. Trop.

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“…Traveller/non-traveller populations: In this update, we found further evidence that congenital abnormalities occurred in infants born to women travellers returning from ZIKV-affected areas and women remaining in those areas. In total, 25 publications report on 272 congenital abnormalities due to ZIKV infection in travellers 27, 29, 30, 32, 34, 36, 38, 42, 45, 56, 58, 61, 89, 94, 98, 109, 117, 122, 123, 137, 140, 151, 153, 166, 173 , with 109 publications reporting congenital abnormalities due to ZIKV in 2652 non travellers 24– 26, 28, 31, 33, 35, 37, 39– 41, 43, 44, 46– 48, 50, 51, 54, 57, 60, 62– 79, 81, 83– 85, 87, 88, 90– 93, 95– 97, 100, 101, 104– 106, 110– 113, 115, 116, 118, 119, 121, 124– 135, 142– 147, 149, 152, 154, 156– 164, 167, 168, 171, 172, 175– 180, 182, …”

Section: Resultsmentioning

confidence: 99%

Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: A living systematic review

et al. 2019

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Background: The Zika virus (ZIKV) caused a large outbreak in the Americas leading to the declaration of a Public Health Emergency of International Concern in February 2016. A causal relation between infection and adverse congenital outcomes such as microcephaly was declared by the World Health Organization (WHO) informed by a systematic review structured according to a framework of ten dimensions of causality, based on the work of Bradford Hill. Subsequently, the evidence has continued to accumulate, which we incorporate in regular updates of the original work, rendering it a living systematic review. Methods: We present an update of our living systematic review on the causal relation between ZIKV infection and adverse congenital outcomes and between ZIKV and GBS for four dimensions of causality: strength of association, dose-response, specificity, and consistency. We assess the evidence published between January 18, 2017 and July 1, 2019. Results: We found that the strength of association between ZIKV infection and adverse outcomes from case-control studies differs according to whether exposure to ZIKV is assessed in the mother (OR 3.8, 95% CI: 1.7-8.7, I2=19.8%) or the foetus/infant (OR 37.4, 95% CI: 11.0-127.1, I2=0%). In cohort studies, the risk of congenital abnormalities was 3.5 times higher after ZIKV infection (95% CI: 0.9-13.5, I2=0%). The strength of association between ZIKV infection and GBS was higher in studies that enrolled controls from hospital (OR: 55.8, 95% CI: 17.2-181.7, I2=0%) than in studies that enrolled controls at random from the same community or household (OR: 2.0, 95% CI: 0.8-5.4, I2=74.6%). In case-control studies, selection of controls from hospitals could have biased results. Conclusions: The conclusions that ZIKV infection causes adverse congenital outcomes and GBS are reinforced with the evidence published between January 18, 2017 and July 1, 2019.

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“…These results suggest that infants infected with ZIKV during fetal development and born with normal sized brains may have neurodevelopmental abnormalities that only become apparent later in development. This finding is of particular importance because most infants born during the 2015-2016 ZIKV epidemic in the ZIKV hotspots were born with normal sized heads and microcephaly, while an extreme phenotype, is thought to be relatively low frequency (7,56,57).…”

Section: -D) Thementioning

confidence: 99%

“…Importantly, the neuroanatomical abnormalities that we observed in all three ZIKV-infected fetal brains, but not in control brains, occurred even in the absence of the extreme ZIKV infection phenotype documented in human infants, microcephaly. These findings may help explain why some infants born with normal sized heads during the ZIKV epidemic have developed significant sensory, motor, and sociocognitive challenges as they grow up (6)(7)(8)(9)(10)(11).…”

Section: -D) Thementioning

confidence: 99%

Neuroanatomical abnormalities in a nonhuman primate model of congenital Zika virus infection

Amh

Beckman

Bennett

et al. 2020

Preprint

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Zika virus (ZIKV) infection of pregnant women can cause major congenital neuronal abnormalities. In the present study, we evaluated neuropathological consequences of fetal ZIKV exposure in rhesus macaques, a highly translatable animal model for human neural development. Quantitative neuroanatomical analyses of the nearly full-term brains of fetuses infected with ZIKV at gestational days 50, 64, and 90, and three procedure-matched sham-inoculated controls were carried out. Whole tissue sections across a complete cerebral hemisphere were evaluated using immunohistochemical and neuroanatomical staining techniques to detect virus localization, identify affected cell types and evaluate gross neuroanatomical abnormalities. None of the subjects were microcephalic. Immunohistochemical staining revealed the presence of ZIKV in the frontal lobe, which contained activated microglia and showed increased apoptosis of immature neurons. ZIKV-infected animals exhibited macrostructural changes within the occipital lobe, including a reduction in gyrification as well as a higher proportion of white matter. Finally, the ZIKV-infected subjects had abnormalities throughout the visual pathway, including disorganization within the lateral geniculate nucleus (LGN) and primary visual cortex (V1). Regional differences tracked with the temporal patterns of the developing brain and likely reflect the neural progenitor cell tropism ZIKV exhibits – painting a picture of inflammatory processes related to viral infiltration sweeping through the cortex, followed by a wave of cell death resulting in morphological changes. These findings may help explain why some infants born with normal sized heads during the ZIKV epidemic manifest developmental challenges as they age, and ultimately may contribute to developing effective treatments and interventions.One sentence summaryMacaque fetuses infected with Zika virus show both macro- and micro-scale neuropathological abnormalities, including decreased gyrencephality, relative increases in cortical white matter, activation of glia, and increased apoptosis.

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Congenital Zika infection: neurology can occur without microcephaly

Cited by 34 publications

References 4 publications

Neurological growth and development of children asymptomatic at birth whose mothers had Zika during pregnancy

Neurological growth and development of children asymptomatic at birth whose mothers had Zika during pregnancy

Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: A living systematic review

Neuroanatomical abnormalities in a nonhuman primate model of congenital Zika virus infection

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