Cerebral injuries associated with Zika virus in utero exposure in children without birth defects in French Guiana

Félix, Arthur; Hallet, Edouard; Favre, A.; Kom-Tchameni, Rémi; Defo, Antoine; Fléchelles, Olivier; Rosenthal, Jean-Marc; Douine, Maylis; Elenga, Narcisse

doi:10.1097/md.0000000000009178

Cited by 9 publications

(6 citation statements)

References 7 publications

(6 reference statements)

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“…Congenital ZIKV infection in humans causes severe microcephaly at birth only in a small percent of babies ( Cauchemez et al, 2016 ; Johansson et al, 2016 ; Reynolds et al, 2017 ), while some apparently healthy newborn babies can still develop postnatal congenital ZIKV syndromes including head growth restrictions and behavioral deficits, before 1 year of age ( Bilbo and Schwarz, 2009 ; Felix et al, 2017 ). Consistent with our findings in mice, some human infants, without apparent microcephaly at birth, displayed postnatal syndromes of disproportionate head growth, while one baby developed difficulties moving its left hand months after birth.…”

Section: Resultsmentioning

confidence: 99%

“…This also holds true for other congenital viral infections, such as cytomegalovirus (CMV) and rubella, which can both cause postnatal manifestations in infants, such as seizures, hearing loss and neurodevelopmental delays, with no obvious abnormalities noticed at birth ( Sever et al, 1985 ; Fowler et al, 1992 ). Furthermore, the contribution and/or degree of maternal and fetal inflammation triggering neurodegeneration in utero must also be considered in order to better understand the mechanisms involved neuropathological progression post birth ( Bilbo and Schwarz, 2009 ; Felix et al, 2017 ; Vermillion et al, 2017 ; Hirsch et al, 2018 ). Most importantly, recent evidence has surfaced that some normal appearing neonates born to ZIKV-infected pregnant women have developed postnatal microcephaly symptoms including brain neuroimaging abnormalities, head growth restrictions, and behavioral deficits months after birth ( Licon, 2016 ; van der Linden et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

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Congenital Zika Virus Infection in Immunocompetent Mice Causes Postnatal Growth Impediment and Neurobehavioral Deficits

et al. 2018

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A small percentage of babies born to Zika virus (ZIKV)-infected mothers manifest severe defects at birth, including microcephaly. Among those who appeared healthy at birth, there are increasing reports of postnatal growth or developmental defects. However, the impact of congenital ZIKV infection in postnatal development is poorly understood. Here, we report that a mild congenital ZIKV-infection in pups born to immunocompetent pregnant mice did not display apparent defects at birth, but manifested postnatal growth impediments and neurobehavioral deficits, which include reduced locomotor and cognitive deficits that persisted into adulthood. We found that the brains of these pups were smaller, had a thinner cortical layer 1, displayed increased astrogliosis, decreased expression of microcephaly- and neuron development- related genes, and increased pathology as compared to mock-infected controls. In summary, our results showed that even a mild congenital ZIKV infection in immunocompetent mice could lead to postnatal deficits, providing definitive experimental evidence for a necessity to closely monitor postnatal growth and development of presumably healthy human infants, whose mothers were exposed to ZIKV infection during pregnancy.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Congenital Zika Virus Infection in Immunocompetent Mice Causes Postnatal Growth Impediment and Neurobehavioral Deficits

et al. 2018

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“…Although the incidence of ocular and subtle brain injuries first detected after birth is unknown, it can be inferred from large case series. (16, 29, 41) In a Brazilian cohort of 116 pregnant women with laboratory evidence of ZIKV infection and a rash, 42% of fetuses had abnormal clinical or brain imaging findings. (42) The variety of neurologic findings included epilepsy, dysphagia with feeding difficulties, visual and hearing deficits, spasticity and hypertonicity.…”

Section: Broadening Spectrum Of Zikv-associated Fetal Injurymentioning

confidence: 99%

Zika virus and the nonmicrocephalic fetus: why we should still worry

Walker

Little²,

Roby

et al. 2019

American Journal of Obstetrics and Gynecology

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Zika virus (ZIKV) is a mosquito-transmitted flavivirus and was first linked to congenital microcephaly due to a large outbreak in Northeastern Brazil. Although the ZIKV epidemic is now in decline, pregnancies in large parts of the Americas remain at risk due to ongoing transmission and the potential for new outbreaks. This review presents why Zika virus is still a complex and worrisome public health problem with an expanding spectrum of birth defects and why ZIKV and related viruses may evade the immune response to injure the fetus. Recent reports indicate that the spectrum of fetal brain and other anomalies associated with ZIKV exposure is broader and more complex than microcephaly alone and includes subtle fetal brain and ocular injuries; thus, the ability to prenatally diagnose fetal injury associated with ZIKV infection remains limited. New studies indicate that ZIKV imparts disproportionate effects on fetal growth with an unusual femur-sparing profile, potentially providing a new approach to identify viral injury to the fetus. Studies to determine the limitations of prenatal and postnatal testing for detection of ZIKV-associated birth defects and long-term neurocognitive deficits are needed to better guide counseling for women with a possible infectious exposure. It is also imperative that we investigate why ZIKV is so adept at infecting the placenta and the fetal brain to better predict other viruses with similar capabilities that may give rise to new epidemics. The efficiency with which ZIKV evades the early immune response to enable infection of the mother, placenta and fetus is likely critical for understanding why the infection may either be fulminant or limited. Furthermore, studies suggest that several emerging and related viruses may also cause birth defects, including West Nile virus, which is endemic in many parts of the United States. With mosquito-borne diseases increasing worldwide, there remains an urgent need to better understand the pathogenesis of ZIKV and related viruses to protect pregnancies and child health.

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“…All the papers that evaluated the central nervous system found neurological alterations, and the main ones were seizure, epilepsy, irritability, pyramidal syndrome, sleep disorders, and hyperexcitability ( 5 , 12 , 18 , 19 , 27 , 31 , 35 , 36 , 42 , 45 , 46 , 48 , 50 , 51 , 54 , 56 , 61 , 62 , 66 , 69 – 71 , 74 , 77 ). Regarding neuro-psychomotor development, all 15 papers reported motor, cognitive, or language delay ( 10 , 11 , 15 , 17 , 18 , 24 , 32 , 33 , 44 , 47 , 52 , 58 , 61 , 62 , 65 ).…”

Section: Resultsmentioning

confidence: 99%

“…19,27,31,35,36,42,45,46,48,50,51,FIGURE 2 | Zika studies reviewed by year of publication and country of origin. 54, 56, 61, 62, 66, 69-71, 74, 77).…”

mentioning

confidence: 99%

Time to Evaluate the Clinical Repercussions of Zika Virus Vertical Transmission? A Systematic Review

Amaral¹,

Malacarne²,

Brandão³

et al. 2021

Front. Psychiatry

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Background: Vertical transmission of Zika Virus (ZIKV) can be associated with several clinical features in newborn infants. The goal of the present review was to analyze the current state of knowledge regarding clinical repercussions following perinatal exposure to ZIKV in children up to 3 years of age.Methods: A systematic review of published studies was carried out, without the restriction of language or date of publication, identified in the databases PubMed, Virtual Health Library (BVS), Scopus, and Web of Science and the catalog for CAPES theses and dissertations. According to the proposed flowchart, the bibliographic search resulted in 1,563 papers. Of these, according to the eligibility criteria, 70 were selected for systematic review; all were published between 2016 and 2021.Results: Regarding clinical findings, 19 papers evaluated clinical imaging alterations, 21 ophthalmic manifestations, and 39 evaluated the central nervous system; of these, 15 analyzed neuro-psychomotor development. The remainder evaluated audiological (n = 14), nutritional (n = 14), orthopedic (n = 7), cardiorespiratory (n = 5), genitourinary (n = 3) or endocrinological (n = 1) manifestations.Conclusion: It is critical for studies to continue monitoring children with antenatal ZIKV exposure as they grow, given the unknown long-term repercussions of ZIKV and the recognized postnatal complications of this infection during pregnancy. Broader descriptions of observed clinical findings are also important in order to characterize the entire spectrum of disease in children.Systematic Review Registration: PROSPERO REGISTER: CRD42020205947.

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Cerebral injuries associated with Zika virus in utero exposure in children without birth defects in French Guiana

Cited by 9 publications

References 7 publications

Congenital Zika Virus Infection in Immunocompetent Mice Causes Postnatal Growth Impediment and Neurobehavioral Deficits

Congenital Zika Virus Infection in Immunocompetent Mice Causes Postnatal Growth Impediment and Neurobehavioral Deficits

Zika virus and the nonmicrocephalic fetus: why we should still worry

Time to Evaluate the Clinical Repercussions of Zika Virus Vertical Transmission? A Systematic Review

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