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Testing Pregnant Women

When should pregnant women be tested?

CDC has designed an algorithm based on current recommendations to assist in clinical decision making about testing for Zika virus infection. Testing recommendations by area of travel are outlined below.

CDC Zika Testing Recommendations for Pregnant Women

	 	 CDC Zika Testing Recommendations for Pregnant Women

	pink rectangleAreas with a CDC Zika travel notice: Areas where the virus has been newly introduced or reintroduced and mosquitoes in the area are infected with Zika virus and are spreading it to people.

	orange rectangleAreas with Zika risk but no CDC Zika travel notice: Areas where the virus was present before 2015 and there is no evidence transmission has stopped and areas where the virus is likely to be circulating but has not been documented. Travel notices would be considered if the number of cases rises to the level of an outbreak.

	blue rectangleFor exposure* in the United States, please visit this webpage for current maps and guidance.

*Exposure means living in or traveling to this area or having sex without a condom with someone who lives in or has traveled to this area.

If your patient… When to be tested
Traveled to an area with Zika virus infection risk that has a CDC Zika travel notice Pregnant women who traveled to an area with a Zika travel notice should be tested for Zika after their return from travel, regardless of whether or not they have symptoms.
Traveled to an area with Zika virus infection risk but no CDC Zika travel notice Pregnant women who traveled to an area with Zika risk should be tested if they develop symptoms of Zika or if their fetus has abnormalities on an ultrasound that may be related to Zika infection. Because the level of risk of Zika virus infection is unknown in areas with Zika risk but without travel notices, routine testing is not recommended for pregnant women who have traveled to those areas but who do not have symptoms. However, testing may be offered on a case-by-case basis.  
Lives in an area with Zika virus infection risk that has a CDC Zika travel notice

Pregnant women who live in an area with a Zika travel notice are at risk of getting Zika throughout pregnancy. For this reason, testing should be offered

  • At the first prenatal care visit and
  • A second test in the second trimester.

If a pregnant woman has symptoms of Zika at any time during her pregnancy, she should be tested for Zika.

What types of testing for Zika virus are available to diagnose pregnant women?

The type of testing recommended varies depending on the time of evaluation relative to symptom onset or last date of possible exposure.

  • Testing of serum and urine by RNA NAT (nucleic acid testing) is recommended for pregnant women who seek care up to 2 weeks after symptom onset or last date of possible exposure. A positive RNA NAT test confirms the diagnosis of recent maternal Zika virus infection.
  • For pregnant women who seek care 2-12 weeks after symptom onset or last date of possible exposure, serologic assays can be offered to detect Zika virus-specific IgM antibodies. 
  • Immediate RNA NAT testing is recommended for women who have a positive or equivocal Zika virus IgM result, because it provides the potential for a definitive diagnosis of Zika virus infection.
  • Within the United States and most US territories, a negative RNA NAT result should be followed up with plaque reduction neutralization testing to measure virus specific neutralizing antibodies to confirm the presence of an immune response to a flavivirus infection and to differentiate Zika infection from other similar illnesses. Interpretation of serologic results has been described and published elsewhere.

Is an immunoglobulin G (IgG) test for Zika virus commercially available?

No. There is currently no commercially available, FDA-cleared test.

How is Zika virus infection diagnosed in pregnant women?

Laboratory evidence of a confirmed recent Zika virus infection includes:

 1) Detection of Zika virus or Zika virus RNA or antigen in any body fluid or tissue specimen; or

 2) Positive or equivocal Zika virus or dengue virus IgM test on serum or cerebrospinal fluid (CSF) with a positive titer for Zika virus (≥10) from plaque reduction neutralization testing (PRNT) together with negative PRNT titer (i.e., <10) for dengue virus.  Interpretation of serologic results has been described and published elsewhere.  

What are the challenges in interpreting Zika virus testing?

RT-PCR test may not demonstrate Zika virus RNA in a woman with Zika virus infection if the period of viremia has passed. Serum serologic testing can be performed, however, cross-reactivity with related flaviviruses (e.g., dengue and yellow fever viruses) is common. Plaque-reduction neutralization testing (PRNT) can be performed to measure virus-specific neutralizing antibodies to Zika virus, but neutralizing antibodies may still yield cross-reactive results in persons who were previously infected with another flavivirus, such as dengue, or has been vaccinated against yellow fever or Japanese encephalitis. It is important to work closely with your state or local health department to ensure the appropriate test is ordered and interpreted correctly.

Does a positive Zika virus IgM always indicate Zika virus infection?

No; a positive IgM result can be difficult to interpret since cross-reactivity can occur with related flaviviruses (e.g., dengue, Japanese encephalitis, West Nile, yellow fever). A positive Zika virus IgM result may reflect: previous vaccination against a flavivirus (e.g., yellow fever); previous infection with a related flavivirus; or recent or current infection with a flavivirus, including Zika virus.

What does a negative Zika virus IgM mean?

A negative IgM result suggests that infection did not occur and could obviate the need for serial ultrasounds during pregnancy when testing is performed 2-12 weeks after possible exposure to Zika virus. However, data on the performance of IgM serologic testing in asymptomatic people is limited.  This information is based on experience with other flaviviruses.

Does a negative Zika virus RNA NAT always rule out Zika virus infection?

No. Up to 2 weeks after symptom onset, viral RNA can often be identified in serum and/or urine, and RNA NAT is the preferred test. However, viral RNA decreases over time, and a negative RNA NAT on serum collected during this testing window does not preclude Zika virus infection. Serologic testing should be performed.

What specimens can be tested for Zika virus?

Zika virus RNA NAT and serology assays can be performed on maternal serum or cerebrospinal fluid. Zika virus RNA NAT can also be performed on maternal whole blood, amniotic fluid, plasma, and urine. Other testing that can be performed includes the following: 1) histopathologic examination and immunohistochemical staining of the placenta and umbilical cord, 2) Zika virus testing of frozen placental tissue and cord tissue, and 3) IgM and neutralizing antibody testing of cord blood. For a number of reasons, the use of cord blood to diagnose other congenital viral infections such as HIV and syphilis has yielded inaccurate results.

  • For example, maternal blood can contaminate cord blood specimens leading to a false positive result, while Wharton’s jelly in the umbilical cord can yield a false negative result.
  • Cord blood samples can become clotted, which does not allow for appropriate serologic testing. 
  • While collection and testing of cord blood for Zika virus testing can be performed, these results should be interpreted in conjunction with results of testing of infant serum.

What should providers consider when ordering a test for Zika virus infection?

Each clinical scenario is unique, and healthcare providers should consider all available information when ordering a test for Zika virus infection, including patient travel history or possible exposure through sexual contact, history of flavivirus infection, vaccination history, ultrasound findings, and the presence of symptoms. Providers should work with their state, local, and territorial health departments for assistance obtaining and interpreting test results.

What are the recommendations for Zika virus testing of men or women attempting conception?

Testing for Zika virus infection should be performed on persons with possible exposure to Zika virus with one or more of the following symptoms during travel or within 2 weeks of possible exposure: acute onset of fever, rash, arthralgia, or conjunctivitis.

Routine testing is not currently recommended for non-pregnant women or men with possible Zika virus exposure who do not have clinical illness, even if the couple is attempting conception. For more information on diagnostic testing for Zika, see Testing for Zika.

Is testing the semen of men with possible exposure to Zika virus recommended?

No, testing the semen of men with possible exposure to Zika virus is not currently recommended. Testing of semen has not yet been validated and interpretation of the test results is not yet understood. Intermittent shedding in semen can occur with other viruses and the pattern of Zika virus shedding in semen is unknown. In addition, the detection of Zika virus RNA in semen might not indicate the presence of infectious virus in semen. Studies are underway to better understand the performance of these tests, the persistence of Zika virus in semen, and how best to interpret the results.

How can pregnant women be prioritized for laboratory testing?

All laboratory testing requests and results reports for pregnant women should clearly indicate pregnancy status. This will facilitate prioritization of testing, ascertainment of pregnancies affected by Zika, and consistent interpretation of laboratory results.

When should testing be offered to pregnant women who have had sex without a condom (or other barriers to prevent sexual transmission) with a partner who traveled to or resided in an area of active Zika virus transmission?

Pregnant women who have had sex without a condom (or other barriers to prevent sexual transmission) with a partner who has traveled to or resides in an area with active Zika virus transmission should be tested for Zika virus infection, according to the updated algorithm [PDF - 2 pages].

How can clinicians get help with testing?

Healthcare providers should work closely with the state, local, or territorial health department to ensure that the appropriate test is ordered and interpreted correctly. In addition, CDC maintains a 24/7 Zika consultation service for health officials and healthcare providers caring for pregnant women. To contact the service, call 770-488-7100 and ask for the Zika Pregnancy Hotline or email ZIKAMCH@cdc.gov.

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