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]

References

  1. 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.