Zika virus infection evaluation of pregnant women
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
According to the CDC, pregnant women suspected to have Zika virus infection may be required to undergo amniocentesis and testing of histopathologic samples of the placenta and umbilical cord, frozen placental tissue and cord tissue for Zika virus RNA, and cord serum for Zika and dengue virus IgM and neutralizing antibodies.
Evaluation of Pregnant Women
- Amniocentesis is associated with an overall 0.1% risk of pregnancy loss when performed at less than 24 weeks of gestation.
- Amniocentesis performed ≥15 weeks of gestation is associated with lower rates of complications than those performed at earlier gestational ages, and early amniocentesis (≤14 weeks of gestation) is not recommended.
- Health care providers should discuss the risks and benefits of amniocentesis with their patients. A positive RT-PCR result on amniotic fluid would be suggestive of intrauterine infection and potentially useful to pregnant women and their health care providers
- For a live birth with evidence of maternal or fetal Zika virus infection, the following tests are recommended:[1]
- Histopathologic examination of the placenta and umbilical cord
- Testing of frozen placental tissue and cord tissue for Zika virus RNA
- Testing of cord serum for Zika and dengue virus IgM and neutralizing antibodies.
- If a pregnancy results in a fetal loss in a woman with history of travel to an area of Zika virus transmission with symptoms consistent with Zika virus disease during or within 2 weeks of travel or findings of fetal microcephaly, Zika virus RT-PCR and immunohistochemical staining should be performed on fetal tissues, including umbilical cord and placenta.
- There is no commercially available test for Zika virus. Testing for Zika virus infection is performed at CDC and several state health departments. Health care providers should contact their state or local health department to facilitate testing and for assistance with interpreting results.
- In a pregnant woman with laboratory evidence of Zika virus in serum or amniotic fluid, serial ultrasounds should be considered to monitor fetal anatomy and growth every 3–4 weeks. Referral to a maternal-fetal medicine or infectious disease specialist with expertise in pregnancy management is recommended.[1]
PCR
- Zika virus testing of maternal serum includes reverse transcription-polymerase chain reaction (RT-PCR) testing for symptomatic patients with onset of symptoms within the previous week.
- Zika virus RT-PCR testing can be performed on amniotic fluid.
- Currently, it is unknown how sensitive or specific this test is for congenital infection. Also, it is unknown if a positive result is predictive of a subsequent fetal abnormality, and if so, what proportion of infants born after infection will have abnormalities.[1]
Serology
- Immunoglobulin M (IgM) and neutralizing antibody testing should be performed on specimens collected ≥4 days after onset of symptoms. Cross-reaction with related flaviviruses (e.g., dengue or yellow fever) is common with antibody testing, and thus it might be difficult to distinguish Zika virus infection from other flavivirus infections.
- Consultation with state or local health departments might be necessary to assist with interpretation of results.
- Testing of asymptomatic pregnant women is not recommended in the absence of fetal microcephaly or intracranial calcifications.
Algorithm for Evaluation of Pregnant Women with History of Travel
- The following algorithm shows the interim guidelines for the evaluation and testing of pregnant women with history of travel to an area with Zika virus transmission, with or without clinical illness* consistent with Zika virus disease:[1]
Pregnant woman with history of travel to an area with Zika virus transmission (see list of areas here) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Pregnant woman reports clinical illness consistent with Zika virus diseasee during or within 2 weeks of travel | Pregnant woman does NOT report clinical illness consistent with Zika virus disease during or within 2 weeks of travel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Test for Zika virus infection | Fetal ultrasound to detect microcephaly or intracranial calcifications | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Positive or inconclusive test for Zika virus infection | Negative test(s) for Zika virus infection | Either finding present | No findings present | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Fetal ultrasound to detect microcephaly or intracranial calcifications Offer amniocentesis for Zika virus testing | Fetal ultrasound to detect microcephaly or intracranial calcifications | Consider serial ultrasounds to detect development of microcephaly or intracranial calcifications | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Either finding present | No findings present | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Consider amniocentesis for Zika virus testing | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Test pregnant woman for Zika virus infection Consider amniocentesis for Zika virus testing | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Note: Availability of Zika virus testing is limited; consult your state or local health department to facilitate testing. Tests include Zika virus reverse transcription–polymerase chain reaction (RT-PCR) and Zika virus immunoglobulin M (IgM) and neutralizing antibodies on serum specimens. Given the overlap of symptoms and endemic areas with other viral illnesses, evaluate for possible dengue or chikungunya virus infection.
Laboratory evidence of maternal Zika virus infection: 1) Zika virus RNA detected by RT-PCR in any clinical specimen; or 2) positive Zika virus IgM with confirmatory neutralizing antibody titers that are ≥4-fold higher than dengue virus neutralizing antibody titers in serum. Testing would be considered inconclusive if Zika virus neutralizing antibody titers are <4-fold higher than dengue virus neutralizing antibody titers.
Amniocentesis is not recommended until after 15 weeks of gestation. Amniotic fluid should be tested for Zika virus RNA by RT-PCR.
*Clinical illness is consistent with Zika virus disease if two or more symptoms (acute onset of fever, maculopapular rash, arthralgia, or conjunctivitis) are present.
Algorithm adapted from the Centers for Disease Control and Prevention [2], Retrieved on February 1st, 2016.[1]
Collection and Submission of Fetal Tissues for Zika Virus Testing
- The following information applies to fetal tissue collection and submission. For cord blood and amniotic fluid analysis, please contact your state or local health department to determine the appropriate guidance for collection, submission, and testing.
- Please make sure that your state or local health department and CDC have been notified and have approved submission and shipment of all specimens before they are collected and sent.
- CDC Form 50.34 is required to be submitted with all specimens. For test order name, enter “Zika virus”.
- Please direct questions to pathology@cdc.gov.
Collection of Fetal or Infant Tissues
- Please notify: zika_adb_epi@cdc.gov prior to any tissue specimen submission.
- Appropriate consent from the parents or guardian must be obtained by the healthcare provider prior to collection and submission of specimens for Zika virus testing.
- Ensure that a portion of the tissue or products of conception is collected and routed for routine evaluation or cytogenetics, as needed.
- To optimize evaluation of possible Zika virus infection on fetal tissues, please provide both formalin fixed and frozen tissues. If it is not possible to provide both types of tissue, prioritize formalin fixed tissues.
- The type of tissues available for evaluation will depend on the gestational age of the fetus and the collection procedure that is performed. Effort should be made to maintain the tissue architecture, and to minimize any dissection or disruption of the tissues.
- Collection of brain tissue is most important to evaluate for possible Zika virus infection. Maintaining the structure of the brain architecture is particularly important to help evaluate viral neuropathology.
- Placenta should be sampled extensively (or submitted intact if early gestation); please include several full thickness pieces, including sections of the placental disk, membranes, umbilical cord, and any pathologic lesions when possible.
- If individual organs or tissue types can be easily identified at autopsy, please provide a 0.5-1.0 cm sample from each major organ, including heart, lungs, liver, kidneys, skeletal muscle, and bone marrow. Sampling of eyes is highly recommended.
- For situations where individual organs or tissue types cannot be identified, please provide any available tissue with minimal disruption.
- CDC Infectious Diseases Pathology Branch (IDPB) can accept microscopic or gross photos from health departments as part of either telediagnosis consultation or routine tissue specimen submission for diagnostic evaluation. Photos should not contain patient names or medical record numbers. Visit the CDC ePathology telediagnosis page for more details.
Formalin Fixed or Paraffin Embedded Tissues
- Histopathology, immunohistochemical staining, and reverse transcription-polymerase chain reaction (RT-PCR) will be performed on fixed tissues, as needed.
- Tissues should be placed into one or more sterile containers containing adequate formalin.
- Fixed tissues should be stored and shipped at room temperature.
- Fixed tissues should not be shipped with frozen samples.
- If paraffin blocks are available, please submit in accordance with shipment guidelines for formalin fixed tissues.
Fixed tissues should be shipped to: Infectious Diseases Pathology Branch Centers for Disease Control and Prevention 1600 Clifton Rd NE, MS G-32 Atlanta, Georgia 30329-4027
Additional instructions for collecting, handling, and shipping formalin fixed tissues are also available. Additional questions should be directed to pathology@cdc.gov or 404-639-3133.
Frozen Tissues
- RT-PCR can be performed on frozen tissues.
- Fresh tissue should be placed into one or more sterile containers.
- If samples are taken from individual organs, please provide at minimum a 0.25 cm square from each organ.
- Frozen tissues should be stored at -70 degrees Centigrade and shipped on dry ice. If dry ice is not available, tissues can be shipped on wet ice but is not optimal.
Frozen tissues should be shipped to: Arboviral Diseases Branch Diagnostic Laboratory Centers for Disease Control and Prevention 3156 Rampart Road Fort Collins, Colorado 80521
More information about collecting, handling, and shipping frozen tissues is available and dditional questions should be directed to the Arboviral Diseases Branch at zika_adb_epi@cdc.gov or 970-221-6400.
Reporting of Results
- Test results will be reported to the state health department and the submitting healthcare provider.
- Turnaround time will vary and depend on testing volume.
References
- ↑ 1.0 1.1 1.2 1.3 1.4 Petersen EE, Staples JE, Meaney-Delman D, Fischer M, Ellington SR, Callaghan WM; et al. (2016). "Interim Guidelines for Pregnant Women During a Zika Virus Outbreak - United States, 2016". MMWR Morb Mortal Wkly Rep. 65 (2): 30–3. doi:10.15585/mmwr.mm6502e1. PMID 26796813.