Congenital Zika virus infection: Clinical features, evaluation, and management of the neonate
- Karin Nielsen-Saines, MD, MPH
Karin Nielsen-Saines, MD, MPH
- Professor of Clinical Pediatrics
- Division of Infectious Diseases
- UCLA Mattel Children's Hospital
- David Geffen School of Medicine at UCLA
- Section Editors
- Morven S Edwards, MD
Morven S Edwards, MD
- Section Editor — Pediatric Infectious Diseases
- Professor of Pediatrics
- Baylor College of Medicine
- Leonard E Weisman, MD
Leonard E Weisman, MD
- Section Editor — Neonatology
- Professor of Pediatrics
- Baylor College of Medicine
Zika virus is an arthropod-borne flavivirus transmitted by mosquitoes. Congenital Zika virus infection is associated with severe congenital anomalies. This topic will discuss issues related to newborns congenitally infected with Zika virus. Zika virus infection in pregnant women and other issues related to Zika virus infection, including epidemiology, travel advisories, and infection in older children and adults are reviewed separately. (See "Zika virus infection: Evaluation and management of pregnant women" and "Zika virus infection: An overview".)
Zika virus is a neurotropic virus that particularly targets neural progenitor cells . Murine and human placental studies support the hypothesis that maternal infection leads to placental infection and injury, followed by transmission of the virus to the fetal brain, where it kills neuronal progenitor cells and disrupts neuronal proliferation, migration, and differentiation, which slows brain growth and reduces viability of neural cells [1-7]. Zika virus is also associated with a higher rate of fetal loss throughout pregnancy, including stillbirths. Placental insufficiency is the mechanism postulated to induce fetal loss later in pregnancy; however, significant placental inflammation has not been described to date [3,8-10]. (See "Zika virus infection: Evaluation and management of pregnant women", section on 'Adverse pregnancy outcomes'.)
A series from Brazil described histopathological findings in tissue from two newborns with microcephaly and severe arthrogryposis who died shortly after birth and tissue from a microcephalic infant who died at age two months . In all cases, the mothers lived in Brazil and had symptoms consistent with Zika virus infection in the first trimester. The infants were born at 36, 38, and 38 weeks of gestation. Multiple congenital malformations were noted, including a wide range of brain abnormalities, craniofacial malformations, craniosynostosis, pulmonary hypoplasia, and multiple congenital contractures, consistent with fetal akinesia deformation sequence or severe arthrogryposis. In these three cases, there was immunohistochemical and molecular evidence of virus persistence in the brain. The range of neuropathology included ventriculomegaly, lissencephaly (which commonly aligns with microcephaly), and cerebellar hypoplasia, all of which have been observed in other cases studied . Brains also showed evidence of tissue destruction, including calcifications, gliosis, and necrosis. The presence of necrosis suggests ongoing cellular injury, consistent with the demonstrated continued viral presence. Thus, the patterns of injury are likely to follow from both cellular injury at the time of infection as well as subsequent damage as the brain develops. Evidence from cell culture systems places the neuronal precursor cell as a crucial target for Zika virus infection resulting in cell death . Loss of these cells early in development has been reported to substantially reduce the number of neurons generated and result in small brains without cortical gyration .
Updates regarding the geographic distribution of Zika virus may be viewed at the United States Centers for Disease Control and Prevention website and the Pan American Health Organization/World Health Organization website.
The epidemiology of Zika virus infection is reviewed in detail separately. (See "Zika virus infection: An overview", section on 'Epidemiology'.)
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- GEOGRAPHIC DISTRIBUTION
- RISK OF VERTICAL TRANSMISSION
- CLINICAL FEATURES OF CONGENITAL ZIKA SYNDROME
- In utero
- Findings in the newborn
- - Clinical findings
- - Radiologic findings
- Assessment for microcephaly
- Laboratory evaluation
- - Whom to test
- - Tests to obtain
- - Interpretation
- Additional evaluation
- DIFFERENTIAL DIAGNOSIS
- Symptomatic infants
- Asymptomatic infants
- PERINATAL AND POSTNATAL INFECTION
- Perinatal exposure
- Postnatal infection
- ONLINE RESOURCES
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS