UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Congenital Zika virus infection: Clinical features, evaluation, and management of the neonate

Author
Karin Nielsen-Saines, MD, MPH
Section Editors
Morven S Edwards, MD
Leonard E Weisman, MD
Deputy Editor
Carrie Armsby, MD, MPH

INTRODUCTION

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".)

PATHOGENESIS

Zika virus is a neurotropic virus that particularly targets neural progenitor cells [1]. 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'.)

HISTOPATHOLOGY

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 [11]. 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 [12]. 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 [13]. 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 [14].

GEOGRAPHIC DISTRIBUTION

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'.)

                             

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Mon Nov 21 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Costello A, Dua T, Duran P, et al. Defining the syndrome associated with congenital Zika virus infection. Bull World Health Organ 2016; 94:406.
  2. Miner JJ, Cao B, Govero J, et al. Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise. Cell 2016; 165:1081.
  3. Tabata T, Petitt M, Puerta-Guardo H, et al. Zika Virus Targets Different Primary Human Placental Cells, Suggesting Two Routes for Vertical Transmission. Cell Host Microbe 2016; 20:155.
  4. Cugola FR, Fernandes IR, Russo FB, et al. The Brazilian Zika virus strain causes birth defects in experimental models. Nature 2016; 534:267.
  5. Vouga M, Baud D. Imaging of congenital Zika virus infection: the route to identification of prognostic factors. Prenat Diagn 2016; 36:799.
  6. Jurado KA, Simoni MK, Tang Z, et al. Zika virus productively infects primary human placenta-specific macrophages. JCI Insight 2016; 1.
  7. Garcez PP, Loiola EC, Madeiro da Costa R, et al. Zika virus impairs growth in human neurospheres and brain organoids. Science 2016; 352:816.
  8. Brasil P, Pereira JP Jr, Raja Gabaglia C, et al. Zika Virus Infection in Pregnant Women in Rio de Janeiro - Preliminary Report. N Engl J Med 2016.
  9. Quicke KM, Bowen JR, Johnson EL, et al. Zika Virus Infects Human Placental Macrophages. Cell Host Microbe 2016; 20:83.
  10. Rosenberg AZ, Yu W, Hill DA, et al. Placental Pathology of Zika Virus: Viral Infection of the Placenta Induces Villous Stromal Macrophage (Hofbauer Cell) Proliferation and Hyperplasia. Arch Pathol Lab Med 2016.
  11. Martines RB, Bhatnagar J, de Oliveira Ramos AM, et al. Pathology of congenital Zika syndrome in Brazil: a case series. Lancet 2016; 388:898.
  12. Hazin AN, Poretti A, Turchi Martelli CM, et al. Computed Tomographic Findings in Microcephaly Associated with Zika Virus. N Engl J Med 2016; 374:2193.
  13. Tang H, Hammack C, Ogden SC, et al. Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth. Cell Stem Cell 2016; 18:587.
  14. Gilmore EC, Walsh CA. Genetic causes of microcephaly and lessons for neuronal development. Wiley Interdiscip Rev Dev Biol 2013; 2:461.
  15. Driggers RW, Ho CY, Korhonen EM, et al. Zika Virus Infection with Prolonged Maternal Viremia and Fetal Brain Abnormalities. N Engl J Med 2016; 374:2142.
  16. Mlakar J, Korva M, Tul N, et al. Zika Virus Associated with Microcephaly. N Engl J Med 2016; 374:951.
  17. Schuler-Faccini L, Ribeiro EM, Feitosa IM, et al. Possible Association Between Zika Virus Infection and Microcephaly - Brazil, 2015. MMWR Morb Mortal Wkly Rep 2016; 65:59.
  18. Martines RB, Bhatnagar J, Keating MK, et al. Notes from the Field: Evidence of Zika Virus Infection in Brain and Placental Tissues from Two Congenitally Infected Newborns and Two Fetal Losses--Brazil, 2015. MMWR Morb Mortal Wkly Rep 2016; 65:159.
  19. Calvet G, Aguiar RS, Melo AS, et al. Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study. Lancet Infect Dis 2016; 16:653.
  20. Microcephaly Epidemic Research Group1. Microcephaly in Infants, Pernambuco State, Brazil, 2015. Emerg Infect Dis 2016; 22:1090.
  21. Sarno M, Sacramento GA, Khouri R, et al. Zika Virus Infection and Stillbirths: A Case of Hydrops Fetalis, Hydranencephaly and Fetal Demise. PLoS Negl Trop Dis 2016; 10:e0004517.
  22. de Fatima Vasco Aragao M, van der Linden V, Brainer-Lima AM, et al. Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study. BMJ 2016; 353:i1901.
  23. Miranda-Filho Dde B, Martelli CM, Ximenes RA, et al. Initial Description of the Presumed Congenital Zika Syndrome. Am J Public Health 2016; 106:598.
  24. Moore CA, Staples JE, Dobyns WB, et al. Characterizing the Pattern of Anomalies in Congenital Zika Syndrome for Pediatric Clinicians. JAMA Pediatr 2016.
  25. Ventura CV, Maia M, Dias N, et al. Zika: neurological and ocular findings in infant without microcephaly. Lancet 2016; 387:2502.
  26. Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR. Zika Virus and Birth Defects--Reviewing the Evidence for Causality. N Engl J Med 2016; 374:1981.
  27. World Health Organization. Zika virus and complications: Questions and answers. http://www.who.int/features/qa/zika/en/ (Accessed on April 19, 2016).
  28. Cordeiro MT, Pena LJ, Brito C, et al. Positive IgM for Zika virus in the cerebrospinal fluid of 30 neonates with microcephaly in Brazil. Lancet 2016.
  29. Araujo TVB, Rodrigues LC, Ximenes RAA. Association between Zika virus infection and microcephaly in Brazil, January to May, 2016: preliminary report of a case-control study. Lancet Infect Dis 2016.
  30. Karin Nielsen-Saines, personal communication.
  31. Cauchemez S, Besnard M, Bompard P, et al. Association between Zika virus and microcephaly in French Polynesia, 2013-15: a retrospective study. Lancet 2016; 387:2125.
  32. Johansson MA, Mier-y-Teran-Romero L, Reefhuis J, et al. Zika and the Risk of Microcephaly. N Engl J Med 2016; 375:1.
  33. de Paula Freitas B, de Oliveira Dias JR, Prazeres J, et al. Ocular Findings in Infants With Microcephaly Associated With Presumed Zika Virus Congenital Infection in Salvador, Brazil. JAMA Ophthalmol 2016.
  34. Moshfeghi DM, de Miranda HA 2nd, Costa MC. Zika Virus, Microcephaly, and Ocular Findings. JAMA Ophthalmol 2016; 134:945.
  35. Ventura CV, Maia M, Travassos SB, et al. Risk Factors Associated With the Ophthalmoscopic Findings Identified in Infants With Presumed Zika Virus Congenital Infection. JAMA Ophthalmol 2016; 134:912.
  36. Ventura CV, Maia M, Bravo-Filho V, et al. Zika virus in Brazil and macular atrophy in a child with microcephaly. Lancet 2016; 387:228.
  37. Ventura CV, Maia M, Ventura BV, et al. Ophthalmological findings in infants with microcephaly and presumable intra-uterus Zika virus infection. Arq Bras Oftalmol 2016; 79:1.
  38. Leal MC, Muniz LF, Ferreira TS, et al. Hearing Loss in Infants with Microcephaly and Evidence of Congenital Zika Virus Infection - Brazil, November 2015-May 2016. MMWR Morb Mortal Wkly Rep 2016; 65:917.
  39. van der Linden V, Filho EL, Lins OG, et al. Congenital Zika syndrome with arthrogryposis: retrospective case series study. BMJ 2016; 354:i3899.
  40. França GV, Schuler-Faccini L, Oliveira WK, et al. Congenital Zika virus syndrome in Brazil: a case series of the first 1501 livebirths with complete investigation. Lancet 2016; 388:891.
  41. Update: Interim Guidance for Health Care Providers Caring for Pregnant Women with Possible Zika Virus Exposure — United States, July 2016 http://www.cdc.gov/mmwr/volumes/65/wr/mm6529e1.htm?s_cid=mm6529e1_e (Accessed on July 25, 2016).
  42. Besnard M, Eyrolle-Guignot D, Guillemette-Artur P, et al. Congenital cerebral malformations and dysfunction in fetuses and newborns following the 2013 to 2014 Zika virus epidemic in French Polynesia. Euro Surveill 2016; 21.
  43. Soares de Oliveira-Szejnfeld P, Levine D, Melo AS, et al. Congenital Brain Abnormalities and Zika Virus: What the Radiologist Can Expect to See Prenatally and Postnatally. Radiology 2016; 281:203.
  44. Russell K, Oliver SE, Lewis L, et al. Update: Interim Guidance for the Evaluation and Management of Infants with Possible Congenital Zika Virus Infection — United States, August 2016. MMWR Morb Mortal Wkly Rep 2016; 65.
  45. World Health Organization. WHO child growth standards: Length/height-for-age, weight-for-age, weight-for-height and body mass index-for-age: Methods and development. WHO, Geneva 2006. http://www.who.int/childgrowth/publications/technical_report_pub/en/ (Accessed on January 26, 2016).
  46. Victora CG, Schuler-Faccini L, Matijasevich A, et al. Microcephaly in Brazil: how to interpret reported numbers? Lancet 2016; 387:621.
  47. World Health Organization. Assessment of infants with microcephaly in the context of Zika virus: Interim guidance, 25 February 2016. http://apps.who.int/iris/bitstream/10665/204475/1/WHO_ZIKV_MOC_16.3_eng.pdf (Accessed on February 25, 2016).
  48. Villar J, Cheikh Ismail L, Victora CG, et al. International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project. Lancet 2014; 384:857.
  49. Centers for Disease Control and Prevention. Congenital Microcephaly Case Definitions. http://www.cdc.gov/zika/public-health-partners/microcephaly-case-definitions.html (Accessed on April 04, 2016).
  50. Petersen LR, Jamieson DJ, Honein MA. Zika Virus. N Engl J Med 2016; 375:294.
  51. World Health Organization. Pregnancy management in the context of Zika virus: Interim guidance, 2 March 2016. http://apps.who.int/iris/bitstream/10665/204520/1/WHO_ZIKV_MOC_16.2_eng.pdf (Accessed on March 03, 2016).
  52. Oliveira DB, Almeida FJ, Durigon EL, et al. Prolonged Shedding of Zika Virus Associated with Congenital Infection. N Engl J Med 2016.
  53. Rabe IB, Staples JE, Villanueva J, et al. Interim Guidance for Interpretation of Zika Virus Antibody Test Results. MMWR Morb Mortal Wkly Rep 2016; 65:543.
  54. Besnard M, Lastere S, Teissier A, et al. Evidence of perinatal transmission of Zika virus, French Polynesia, December 2013 and February 2014. Euro Surveill 2014; 19.
  55. Fleming-Dutra KE, Nelson JM, Fischer M, et al. Update: Interim Guidelines for Health Care Providers Caring for Infants and Children with Possible Zika Virus Infection--United States, February 2016. MMWR Morb Mortal Wkly Rep 2016; 65:182.
  56. Centers for Disease Control and Prevention. Questions and Answers for Healthcare Providers Caring for Infants and Children with Possible Zika Virus Infection. http://www.cdc.gov/zika/hc-providers/qa-pediatrician.html (Accessed on February 22, 2016).
  57. Colt S, Garcia-Casal MN, Peña-Rosas JP, et al. Transmission of Zika virus through breast milk and other breastfeeding-related bodily-fluids: A systematic review. Bull World Health Organ 2016.