Sequential Neuroimaging of the Fetus and Newborn With In Utero Zika Virus Exposure

Abstract

Importance: The evolution of fetal brain injury by Zika virus (ZIKV) infection is not well described.

Objectives: To perform longitudinal neuroimaging of fetuses and infants exposed to in utero maternal ZIKV infection using concomitant magnetic resonance imaging (MRI) and ultrasonography (US), as well as to determine the duration of viremia in pregnant women with ZIKV infection and whether the duration of viremia correlated with fetal and/or infant brain abnormalities.

Design, setting, and participants: A cohort of 82 pregnant women with clinical criteria for probable ZIKV infection in Barranquilla, Colombia, and Washington, DC, were enrolled from June 15, 2016, through June 27, 2017, with Colombian women identified by community recruitment and physician referral and travel-related cases of American women recruited from a Congenital Zika Program.

Interventions and exposures: Women received 1 or more MRI and US examinations during the second and/or third trimesters. Postnatally, infants underwent brain MRI and cranial US. Blood samples were tested for ZIKV.

Main outcomes and measures: The neuroimaging studies were evaluated for brain injury and cerebral biometry.

Results: Of the 82 women, 80 were from Colombia and 2 were from the United States. In 3 of 82 cases (4%), fetal MRI demonstrated abnormalities consistent with congenital ZIKV infection. Two cases had heterotopias and malformations in cortical development and 1 case had a parietal encephalocele, Chiari II malformation, and microcephaly. In 1 case, US results remained normal despite fetal abnormalities detected on MRI. Prolonged maternal polymerase chain reaction positivity was present in 1 case. Of the remaining 79 cases with normal results of prenatal imaging, postnatal brain MRI was acquired in 53 infants and demonstrated mild abnormalities in 7 (13%). Fifty-seven infants underwent postnatal cranial US, which detected changes of lenticulostriate vasculopathy, choroid plexus cysts, germinolytic/subependymal cysts, and/or calcification in 21 infants (37%).

Conclusions and relevance: In a cohort of pregnant women with ZIKV infection, prenatal US examination appeared to detect all but 1 abnormal fetal case. Postnatal neuroimaging in infants who had normal prenatal imaging revealed new mild abnormalities. For most patients, prenatal and postnatal US may identify ZIKV-related brain injury.

Figure 1.. Fetal Magnetic Resonance Imaging Performed at 18 and 22 Weeks’ Gestational Age

A, Axial image at 18 weeks’ gestational age demonstrates a prominent heterotopia in the right occipital horn (arrowhead). B, Coronal image at 18 weeks’ gestational age shows multiple small irregularities in the left posterior atrium consistent with heterotopias (arrowheads). C, Axial image at 22 weeks’ gestational age shows bilateral atrial and occipital heterotopias (arrowheads). D, Axial image at 22 weeks’ gestational age at a higher level shows an abnormal indentation of the left lower parietal cortex (arrowhead) consistent with a developing cortical dysplasia.

Figure 2.. Fetal Magnetic Resonance Imaging Performed at 32 Weeks’ Gestational Age

A, Coronal image at 32 weeks’ gestational age reveals small irregularities in the body of the right lateral ventricle (black arrowheads) consistent with heterotopias. There is a relative lack of sulcation of the posterior frontal lobes (white arrowheads) consistent with cortical dysplasia or polymicrogyria. B, Off midline sagittal image shows additional heterotopias in the right frontal horn (black arrowhead) and abnormal sulcation of the anterior right frontal cortex (white arrowheads) consistent with additional areas of cortical dysplasia or polymicrogyria.

Figure 3.. Fetal Magnetic Resonance Imaging Performed at 28 and 37 Weeks’ Gestational Age

A, Sagittal image at 28 weeks’ gestational age shows a broad posterior calvarial defect through which the posterior cerebral hemisphere herniates (black arrowhead), consistent with an encephalocele. Extracerebral and posterior fossa subarachnoid fluid spaces are absent; the fourth ventricle is not visualized, typical of stigmata of a Chiari II malformation (white arrowhead). Severe microcephaly is evident. B, Axial image at 28 weeks’ gestational age near the vertex shows the posterior protrusion of cerebral hemisphere through the calvarial defect (arrowheads) and lack of cerebrospinal fluid around the cerebral hemispheres. C, Sagittal midline image at 37 weeks’ gestational age demonstrates similar findings of a posterior encephalocele (arrowheads) and stigmata of a Chiari II malformation as evident in panel A.