Association Between Neonatal Neuroimaging and Clinical Outcomes in Zika-Exposed Infants From Rio de Janeiro, Brazil

Pool, Kara‐Lee; Adachi, Kristina; Karnezis, Stellios; Salamon, Noriko; Romero, Tahmineh; Nielsen‐Saines, Karin; Pone, Sheila Moura; Boechat, M. Ines; Aibe, Mitsue Senra; Silva, Tallita Gomes da; Ribeiro, Carla Trevisan Martins; Brasil, Patrícia; Zin, Andréa; Tsui, Irena; Gaw, Stephanie L.; Daltro, Pedro; Ribeiro, Bianca Guedes; Fazecas, Tatiana; Cruz, Luiz Celso Hygino da; Nogueira, Rosete; Vasconcelos, Zilton; Pereira, José Paulo; Salles, Tania Saad; Barbosa, Claudia N.; Chen, Weiqiang; Foo, Suan-Sin; Jung, Jae U.; Moreira, Maria Elisabeth Lopes; Pone, Marcos Vinícius da Silva

doi:10.1001/jamanetworkopen.2019.8124

Cited by 59 publications

(70 citation statements)

References 29 publications

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“…disorders altering normal brain morphology). 2,3,20 Later neurodevelopmental findings: Defined as abnormal based on the presence of any of the following beyond 6 months of life: (1) Severe developmental delay with a Bayley-III Score 21 under -2SD (less than 70) in any functional domain (cognitive, language or motor) as previously All rights reserved. No reuse allowed without permission.…”

Section: Pediatric Outcomesmentioning

confidence: 99%

Zika Virus Vertical Transmission in Children With Confirmed Antenatal Exposure

Brasil

Vasconcelos

Kerin³

et al. 2020

Preprint

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Background: In utero transmission of Zika virus (ZIKV) can lead to adverse infant outcomes, but vertical transmission rates are unknown.Methods: Antenatally ZIKV-exposed children were followed prospectively since the time of the Rio de Janeiro epidemic in 2015-16. Serum and urine specimens were collected from infants from birth throughout the first year of life. Specimens were tested by quantitative reverse transcriptase polymerase chain reaction (PCR) and/or IgM antibody capture Zika MAC-ELISA.Infants had neurodevelopmental evaluations, brain imaging, eye examinations, and hearing assessments.Results: Over time 130 in utero ZIKV-exposed (mothers PCR+) children were tested with 407 specimens evaluated: 161 sera were tested by PCR and IgM assays, 85 urines by PCR; 84 children (65%) were positive in at least one assay. Among 94 children tested within 3 months of age, 70% were positive (39% serum PCR, 48% urine PCR, 39% IgM). After 3 months, 33%were positive by any laboratory method. Five children were intermittently PCR+ beyond 200 days of life. Concordance between IgM and PCR results was 52%, sensitivity 65%, specificity 40% (with any positive PCR result as the gold standard); IgM and serum PCR were 61% concordant; serum and urine PCR 55%. Most children (65%) were clinically normal. Positive results were seen in 29 of 45 children (64%) with abnormal findings and 55 of 85 normal children (65%), p=0٠98. Earlier maternal trimester of infection was associated with positive infant laboratory results but not infant clinical disease (p=0٠04).Conclusions: ZIKV has a high in utero transmission rate. Laboratory confirmed infection is not necessarily associated with abnormal infant findings.

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Section: Pediatric Outcomesmentioning

confidence: 99%

Zika Virus Vertical Transmission in Children With Confirmed Antenatal Exposure

Brasil

Vasconcelos

Kerin³

et al. 2020

Preprint

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“…5 The cerebral mantle can be severely thin, and infection may even result in fetal brain disruption sequence, a finding that is unusual for other congenital infections that cause microcephaly. 2,5 The abnormal neuroimaging findings reported in the study by Pool et al 1 include the full range of brain abnormalities that are more uniquely seen in ZIKV, and this may be associated with the spectrum of clinical findings seen in affected infants.…”

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confidence: 96%

“…2 The comprehensive infant evaluations were similar to the proposed guidelines set forth by the US Centers for Disease Control and Prevention for the diagnosis and evaluation of ZIKV-exposed infants. 3 In the study by Pool et al, 1 71 of 110 infants (65%) had abnormal head CT or brain MRI findings, with most having clinical classification at birth of the severe phenotype of congenital Zika syndrome.…”

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confidence: 97%

“…Conversely, among the 39 infants with a normal-to-mild clinical phenotype and normal neurologic examination findings, only 4 (10%) had abnormal neuroimaging findings. 1 Among the 4 infants who did not have findings of congenital Zika syndrome at birth, neuroimaging findings may be associated with other noninfectious causes. It is important to point out that the infants included in the study by Pool et al 1 underwent neuroimaging with either head CT or brain MRI after either abnormal findings on cranial US or because cranial US was not feasible owing to a small fontanelle, which was the result of either older infant age or microcephaly.…”

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confidence: 98%

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Importance of Neuroimaging in the Evaluation of Zika Virus–Exposed Infants

Mulkey

2019

JAMA Netw Open

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A little more than 3 years ago, Zika virus (ZIKV) emerged as a newly recognized congenital infection associated with substantial risk to the developing fetal brain after infection during pregnancy. Although the virus had been circulating in French Polynesia and other regions before the epidemic in Central and South America in 2015 and 2016, its devastating effects on the developing brain were previously unrecognized. The study by Pool and colleagues 1 highlights the neuroimaging findings of a large number of ZIKV-exposed infants at a high-risk obstetric and pediatric referral center in Rio de Janeiro, Brazil, from March 2016 to June 2017. The medical team at the Fernandes Figueira Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, rapidly established clinical care protocols for the evaluation of a large number of ZIKV-exposed infants. Infant evaluations included laboratory testing for ZIKV, neuroimaging with cranial ultrasonography (US), head computed tomography (CT), and brain magnetic resonance imaging (MRI). Infants were also evaluated by a multidisciplinary team including specialists in pediatric infectious disease and ophthalmology and had their hearing assessed by brainstem auditory evoked response. The phenotype of Zika syndrome was described at

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“…1,2,[23][24][25] Consistent with our ndings, a 2019 Brazilian investigation assessing children with cerebral palsy and probable CZS, of whom 97.5% had microcephaly, using the Bayley Scale of Infant and Toddler Development III (Bayley-III) reported scores below 70 (i.e., suggesting severe developmental delays) for almost all participants across all three scales: cognitive, 95.1%; language, 97.6%; motor, 97.6% 23. A case series study assessing 24 children with ZIKV-related microcephaly in Northeast Brazil using the Denver Developmental Screening Test II also found a high degree of impairment for neuropsychomotor development.…”

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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

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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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Association Between Neonatal Neuroimaging and Clinical Outcomes in Zika-Exposed Infants From Rio de Janeiro, Brazil

Cited by 59 publications

References 29 publications

Zika Virus Vertical Transmission in Children With Confirmed Antenatal Exposure

Zika Virus Vertical Transmission in Children With Confirmed Antenatal Exposure

Importance of Neuroimaging in the Evaluation of Zika Virus–Exposed Infants

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

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