Congenital Zika Virus Infection

Abstract

IMPORTANCE Recent studies have reported an increase in the number of fetuses and neonates with microcephaly whose mothers were infected with the Zika virus (ZIKV) during pregnancy. To our knowledge, most reports to date have focused on select aspects of the maternal or fetal infection and fetal effects. OBJECTIVE To describe the prenatal evolution and perinatal outcomes of 11 neonates who had developmental abnormalities and neurological damage associated with ZIKV infection in Brazil. DESIGN, SETTING, AND PARTICIPANTS We observed 11 infants with congenital ZIKV infection from gestation to 6 months in the state of Paraíba, Brazil. Ten of 11 women included in this study presented with symptoms of ZIKV infection during the first half of pregnancy, and all 11 had laboratory evidence of the infection in several tissues by serology or polymerase chain reaction. Brain damage was confirmed through intrauterine ultrasonography and was complemented by magnetic resonance imaging. Histopathological analysis was performed on the placenta and brain tissue from infants who died. The ZIKV genome was investigated in several tissues and sequenced for further phylogenetic analysis. MAIN OUTCOMES AND MEASURES Description of the major lesions caused by ZIKV congenital infection. RESULTS Of the 11 infants, 7 (63.6%) were female, and the median (SD) maternal age at delivery was 25 (6) years. Three of 11 neonates died, giving a perinatal mortality rate of 27.3%. The median (SD) cephalic perimeter at birth was 31 (3) cm, a value lower than the limit to consider a microcephaly case. In all patients, neurological impairments were identified, including microcephaly, a reduction in cerebral volume, ventriculomegaly, cerebellar hypoplasia, lissencephaly with hydrocephalus, and fetal akinesia deformation sequence (ie, arthrogryposis). Results of limited testing for other causes of microcephaly, such as genetic disorders and viral and bacterial infections, were negative, and the ZIKV genome was found in both maternal and neonatal tissues (eg, amniotic fluid, cord blood, placenta, and brain). Phylogenetic analyses showed an intrahost virus variation with some polymorphisms in envelope genes associated with different tissues. CONCLUSIONS AND RELEVANCE Combined findings from clinical, laboratory, imaging, and pathological examinations provided a more complete picture of the severe damage and developmental abnormalities caused by ZIKV infection than has been previously reported. The term congenital Zika syndrome is preferable to refer to these cases, as microcephaly is just one of the clinical signs of this congenital malformation disorder.

Is There More to Zika? Complex Cardiac Disease in a Case of Congenital Zika Syndrome

“…Severe central nervous system involvement in congenital Zika syndrome, an increased incidence of Guillain-Barré syndrome in countries where ZIKV is present, animal data showing brain involvement and microcephaly, and relevant pathology studies, support the hypothesis that ZIKV is neurotropic [8,9,10,11,12,13]. However, Melo et al [14] showed intrahost virus variation with evidence for polymorphisms in envelope genes that are associated with different tissue tropism, which implies that the same viral strain can have tropism for different tissues within the same host.…”

New Insights into the Natural History of Congenital Zika Virus Syndrome

“…Although more than 1,500 studies have been published during the last year on this issue, relatively few information is available on the natural history of the fetal disease during its early stages and on the dynamics of brain involvement during pregnancy [1][2][3].…”

Seasonality of birth defects in West Africa: could congenital Zika syndrome be to blame?

“…were collated by month/year. Reporting standards for birth complications varied between years; thus, we focused exclusively on visible neurodevelopmental complications (such as microcephaly) and pregnancy losses (such as stillbirth) that could be attributed to potential CZS 1,2 (Supplementary Table 1 and Supplementary Table 2). To infer the "vulnerability window" of 12 weeks (spanning 10 to 14 weeks) post-conception, we assumed that births that were not reported as premature in the records were full-term, thus enabling us to infer the likely month of conception 29 .…”

“…Since 2015, when an initial link between Zika Virus (ZIKV) and microcephaly was discovered in Brazil, the term congenital Zika syndrome (CZS) has been coined to reflect a broad range of Zika-linked neurodevelopmental damages 1 beyond microcephaly [1][2][3] , including ocular 4,5 and auditory defects 6,7 . The overall risk of Zika-linked birth defects has been estimated at ~10% and 15% for infections during the 1st trimester 8 , potentially impacting thousands of infants in the US and US territories alone.…”