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

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

doi:10.1001/jamanetworkopen.2019.8124

Abstract

Congenital Zika virus (ZIKV) infection may present with a spectrum of clinical and neuroradiographic findings. To determine whether neuroimaging findings for infants with a history of ZIKV exposure are associated with infant clinical outcomes and gestational age at antenatal ZIKV infection. This cohort study retrospectively reviewed neuroimaging results (computed tomography and/or magnetic resonance imaging scans) of 110 ZIKV-exposed infants from a maternity and children's hospital in Rio de Janeiro, Brazil, following the 2015 to 2016 ZIKV epidemic. Neuroimaging from March 1, 2016, to June 30, 2017, was evaluated to determine whether findings were associated with clinical outcomes and the timing of maternal ZIKV infection. Data were analyzed from July 1, 2017, to August 30, 2018. Neuroimaging (computed tomography and/or magnetic resonance imaging) was performed on ZIKV-exposed infants after birth. Blood and/or urine specimens from mothers and infants were tested for ZIKV by polymerase chain reaction assay. Neuroimaging studies were evaluated for structural abnormalities and other forms of brain injury. A total of 110 infants with a mean (SD) gestational age of 38.4 (2.1) weeks had neuroimaging and clinical outcome data reviewed. Of these, 71 (65%) had abnormal neuroimaging findings, with the majority (96%) classified as having severe ZIKV infection at birth. The most common neuroimaging abnormalities were structural abnormalities including brain calcifications, especially at the cortico-subcortical white matter junction, cortex malformations, ventriculomegaly, and reduced brain volumes, followed by brainstem hypoplasia, cerebellar hypoplasia, and corpus callosum abnormalities. Frequency of abnormal imaging was higher in infants with specific clinical findings as opposed to those without them; these findings included fetal brain disruption sequence (100% vs 35%), microcephaly (100% vs 30%), congenital contractures (100% vs 58%), ophthalmologic abnormalities (95% vs 44%), hearing abnormalities (100% vs 58%), and neurologic symptoms (94% vs 10%). Four of 39 infants (10%) without initial evidence of severe ZIKV infection and normal findings on neurologic evaluation at birth had abnormal neuroimaging findings. Neuroimaging abnormalities differed by trimester of maternal ZIKV infection, with 63% of infants born to mothers infected in the first trimester, 13% of infants born to mothers infected in the second trimester, and 1% of infants born to mothers infected in the third trimester exhibiting neuroimaging abnormalities. The odds of abnormal neuroimaging were 7.9 times greater for infants with first trimester ZIKV exposure compared with other trimesters combined (odds ratio, 7.9; 95% CI, 3.0-20.4; P < .001). Neuroimaging abnormalities of computed tomography and/or magnetic resonance imaging scans were common in ZIKV-exposed infants. While neuroimaging abnormalities were seen in 10% of infants without clinically severe ZIKV, most occurred almost exclusively among those with clinically severe ZIKV, especially among those with a history of ZIKV exposure in the first trimester.

Highlights

Zika virus (ZIKV) infection during pregnancy can cause a spectrum of central nervous system (CNS) abnormalities.[1,2,3] Infants severely affected by ZIKV classically present with microcephaly, other structural brain abnormalities, ocular abnormalities, congenital contractures, and profound neurologic impairment.[2]
Frequency of abnormal imaging was higher in infants with specific clinical findings as opposed to those without them; these findings included fetal brain disruption sequence (100% vs 35%), microcephaly (100% vs 30%), congenital contractures (100% vs 58%), ophthalmologic abnormalities (95% vs 44%), hearing abnormalities (100% vs 58%), and neurologic symptoms (94% vs 10%)
Neuroimaging abnormalities differed by trimester of maternal ZIKV infection, with 63% of infants born to mothers infected in the first trimester, 13% of infants born to mothers infected in the second trimester, and 1% of infants born to mothers infected in the third trimester exhibiting neuroimaging

Summary

Introduction

Zika virus (ZIKV) infection during pregnancy can cause a spectrum of central nervous system (CNS) abnormalities.[1,2,3] Infants severely affected by ZIKV classically present with microcephaly, other structural brain abnormalities, ocular abnormalities, congenital contractures, and profound neurologic impairment.[2] Clinical findings of ZIKV-exposed neonates with severe congenital ZIKV have been well described, including among several neuroimaging reports,[2,3,4,5,6] but the utility of neuroimaging for less severely affected infants is unclear. This study describes neuroimaging (computed tomography [CT] and/or magnetic resonance imaging [MRI]) findings and clinical outcomes in ZIKV-exposed infants with a range of clinical findings at birth. Our primary aims were as follows: (1) to review neuroimaging of infants with antenatal ZIKV exposure and to determine whether neuroimaging (CT and/or MRI) findings were associated with infant clinical outcomes and (2) to determine whether the gestational age at in utero ZIKV infection was associated with neuroimaging findings

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Results

Discussion

Conclusion