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.

Developmental Biology in Central America, the northern region of South America and the Caribbean

“…(Krauer et al 2017, Yepez et al 2017, Medina and Medina-Montoya 2017, Peña et al 2019. Findings from these studies described some of the developmental abnormalities in children born to mothers that were infected with Zika during pregnancy (Sebastian et al 2017, Rice et al 2018, Gely-Rojas et al 2018, Ochoa et al 2019, Mulkey et al 2019, Santos-Antonio et al 2019. Most important, patient cohorts that were born during this epidemic are being followed in longitudinal studies to determine the long-term effects of Zika infection (Cortes et al 2018, Wilder-Smith et al 2019.…”

Long-term alterations in brain and behavior after postnatal Zika virus infections in infant macaques

“…Infants born with this syndrome can develop seizures, hearing and vision problems, feeding difficulties, and gross motor abnormalities 17 . Importantly, recent reports have documented the postnatal onset of microcephaly, neurologic dysfunction, and neurodevelopmental abnormalities in infants infected prenatally but without overt symptoms at birth [18][19][20][21][22] , highlighting the potential of ZIKV to cause ongoing damage in the postnatal period.…”

Ultrasound prediction of Zika virus-associated congenital injury using the profile of fetal growth

“…[7,14] Although ultrasound remains the most available method for prenatal diagnosis of ZIKV-associated birth defects, studies suggest it is insufficient to predict the widening array of congenital ZIKV injury. [15][16][17][18] The lack of a prenatal diagnostic test to either predict or rule out ZIKV-associated anomalies represents a major clinical challenge in ZIKVendemic areas.…”