Q&A: Zika testing guidance for pregnant women

The CDC recently updated guidance on the interpretation of Zika testing results for women who plan on becoming pregnant and live in or frequently travel to areas where Zika is circulating.

Because Zika antibodies can remain in the body for months after infection, the CDC cautioned that Zika virus immunoglobulin M (IgM) ELISA assays may not be able to determine the timing of the onset of the infection. Therefore, they recommend that health care professionals consider testing women who plan on becoming pregnant and may have been exposed to Zika for antibodies before pregnancy, using the results to establish baseline IgM results and to help determine whether a woman became infected during pregnancy.

Photo of Margaret Honein
Margaret Honein

Infectious Disease News spoke with Margaret Honein, PhD, MPH, lead for the CDC’s Pregnancy and Birth Defects Task Force, to discuss how the CDC’s guidance can ensure that clinicians have the latest information for counseling patients who are infected with Zika during pregnancy.

After determining that a pregnant patient may have been exposed to Zika virus, what should clinicians do next?

The CDC recommends testing for Zika virus infection for pregnant women who have possible exposure to an area with risk of Zika virus infection with a CDC Zika travel notice, even if they do not have symptoms. Possible exposure includes living in or recently traveling to one of these areas or having sex (vaginal, anal or oral or the sharing of sex toys) without a condom with someone who lives in or has recently traveled to an area with risk of Zika during pregnancy. The CDC also recommends testing for pregnant women with possible exposure to an area with risk of Zika but without a CDC Zika travel notice if they develop symptoms of Zika or if their fetus has abnormalities on an ultrasound that may be related to Zika infection.

What kind of testing is recommended to confirm whether a pregnant patient has Zika virus infection?

The type of testing recommended varies according to when a woman visits a provider relative to when her symptoms began or, if she is asymptomatic, the date of her last possible exposure to Zika virus. During the first 2 weeks after the start of illness (or exposure), Zika virus disease can be diagnosed by performing nucleic acid testing (NAT). Serology assays can also be used to detect Zika virus-specific IgM and neutralizing antibodies, which typically develop toward the end of the first week of illness. Plaque-reduction neutralization testing (PRNT) can be performed to measure virus-specific neutralizing antibodies to confirm primary flavivirus infections and differentiate from other viral illnesses.

On May 5, 2017, the CDC issued a Health Alert Notice (HAN) to share emerging data suggesting that Zika virus infection may result in prolonged detection of Zika antibodies for some individuals. Some areas with a CDC Zika travel notice are moving into a second season where local mosquitoes may be spreading Zika. Women living in or frequently (eg, daily, weekly) traveling to areas with Zika virus transmission, who are currently pregnant, may have been infected before conception, and for these women, it may be difficult to determine when the infection occurred. Given these new data, the CDC issued the recommendation that for asymptomatic pregnant women with ongoing risk of Zika virus exposure (ie, those currently living in or frequently traveling to areas with Zika virus transmission), in addition to previously recommended IgM testing, health care providers can consider concurrent Zika virus NAT testing at least once per trimester to provide additional clinical information to determine whether the positive IgM test results indicate a recent infection.

Each clinical scenario is unique, and health care 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. The CDC offers many tools and resources for health care providers, including a Zika Pregnancy Testing Algorithm.

Because the proportion of pregnancies among women with confirmed Zika virus infection that resulted in a fetus or baby with birth defects was higher in women who were infected during the first trimester, h ow can clinicians manage these patients and does this care plan differ for those who were infected during the second or third trimester?

The available data indicate that infection in the first and second trimester causes birth defects, but it remains to be seen if third trimester infections pose lesser or perhaps different risks, such as growth restriction or stillbirth. Based on the current information available, the CDC’s clinical management guidance does not differ by trimester for prenatal care. If a pregnant patient tests positive for Zika in any trimester, health care providers should watch the pregnancy more closely. It may be necessary to conduct more ultrasound examinations or other tests to check the fetus’ growth and development. In the case of a recent Zika virus infection or flavivirus infection (where the specific virus cannot be identified), health care providers should consider serial ultrasound examinations every 3 to 4 weeks to assess fetal anatomy and growth. Decisions regarding amniocentesis should be made on an individual basis.

What tests should infants with congenital Zika virus exposure receive and when?

Zika virus testing is recommended for infants born to mothers with laboratory evidence of Zika virus infection during pregnancy, and for infants who have abnormal clinical findings suggestive of congenital Zika virus syndrome and a maternal epidemiologic link suggesting possible exposure during pregnancy, regardless of maternal Zika virus test results. Testing infants for congenital Zika virus infection should be performed within the first 2 days after birth, particularly in areas where Zika virus is currently circulating.

Of note, health care providers should consider testing of infants if there is concern about infant follow-up care or if maternal testing was not performed or was negative in a setting of an exposure that occurred more than 12 weeks earlier.

All infants born to mothers with laboratory evidence of Zika virus infection during pregnancy should receive a comprehensive physical exam, head ultrasound to assess the brain’s structure, standard newborn hearing assessment and lab testing for Zika virus, even if no abnormalities are apparent at birth. For infants without laboratory evidence of Zika virus infection but for whom suspicion for congenital Zika virus infection remains, health care providers should evaluate for other causes of congenital infection and consider an ophthalmology exam and auditory brainstem response (ABR) hearing test before hospital discharge or within 1 month of birth.

CDC also offers guidance and resources for the evaluation and management of infants with possible congenital Zika virus infection. Resources include an Infant Testing Algorithm; a pocket guide on the Evaluation and Management for Infants with Possible Congenital Zika Infection; and an Infant Testing Tool.

What precautions regarding Zika should clinicians be sharing with their patients who are planning to becom e pregnant?

For women planning to become pregnant, health care providers should discuss the potential risk of Zika virus infection in pregnancy, the signs and symptoms associated with Zika virus disease and when to seek care if the patient develops symptoms of Zika virus disease. They should also emphasize strategies to prevent mosquito bites. Preconception counseling guides are available on the CDC’s website.

What is the CDC currently doing to combat Zika virus infection in the United States?

The CDC continues to work 24/7 with our partners to respond to this public health emergency. The U.S. Zika Pregnancy Registry, Zika Active Pregnancy Surveillance System in Puerto Rico and rapid Zika Birth Defects Surveillance continue to collect information about Zika and help guide our nation’s response. Preventing Zika virus infection during pregnancy, remains the priority. Pregnant women should:

  • avoid travel to areas with risk of Zika. Pregnant women who must travel to an area with risk of Zika should talk to their health care provider before traveling to understand the risks;
  • follow steps to prevent mosquito bites if they live in or travel to an area with risk of Zika; and
  • avoid getting Zika through sex by using condoms or not having sex if their sex partner lives in or travels to an area with risk of Zika.

References:

https://www.cdc.gov/zika/pdfs/zika_peds.pdf

https://www.cdc.gov/zika/pdfs/pediatric-evaluation-follow-up-tool.pdf

https://www.cdc.gov/zika/pdfs/placental-testing-guidance.pdf

Disclosures: Honein reports no relevant financial disclosures.

The CDC recently updated guidance on the interpretation of Zika testing results for women who plan on becoming pregnant and live in or frequently travel to areas where Zika is circulating.

Because Zika antibodies can remain in the body for months after infection, the CDC cautioned that Zika virus immunoglobulin M (IgM) ELISA assays may not be able to determine the timing of the onset of the infection. Therefore, they recommend that health care professionals consider testing women who plan on becoming pregnant and may have been exposed to Zika for antibodies before pregnancy, using the results to establish baseline IgM results and to help determine whether a woman became infected during pregnancy.

Photo of Margaret Honein
Margaret Honein

Infectious Disease News spoke with Margaret Honein, PhD, MPH, lead for the CDC’s Pregnancy and Birth Defects Task Force, to discuss how the CDC’s guidance can ensure that clinicians have the latest information for counseling patients who are infected with Zika during pregnancy.

After determining that a pregnant patient may have been exposed to Zika virus, what should clinicians do next?

The CDC recommends testing for Zika virus infection for pregnant women who have possible exposure to an area with risk of Zika virus infection with a CDC Zika travel notice, even if they do not have symptoms. Possible exposure includes living in or recently traveling to one of these areas or having sex (vaginal, anal or oral or the sharing of sex toys) without a condom with someone who lives in or has recently traveled to an area with risk of Zika during pregnancy. The CDC also recommends testing for pregnant women with possible exposure to an area with risk of Zika but without a CDC Zika travel notice if they develop symptoms of Zika or if their fetus has abnormalities on an ultrasound that may be related to Zika infection.

What kind of testing is recommended to confirm whether a pregnant patient has Zika virus infection?

The type of testing recommended varies according to when a woman visits a provider relative to when her symptoms began or, if she is asymptomatic, the date of her last possible exposure to Zika virus. During the first 2 weeks after the start of illness (or exposure), Zika virus disease can be diagnosed by performing nucleic acid testing (NAT). Serology assays can also be used to detect Zika virus-specific IgM and neutralizing antibodies, which typically develop toward the end of the first week of illness. Plaque-reduction neutralization testing (PRNT) can be performed to measure virus-specific neutralizing antibodies to confirm primary flavivirus infections and differentiate from other viral illnesses.

PAGE BREAK

On May 5, 2017, the CDC issued a Health Alert Notice (HAN) to share emerging data suggesting that Zika virus infection may result in prolonged detection of Zika antibodies for some individuals. Some areas with a CDC Zika travel notice are moving into a second season where local mosquitoes may be spreading Zika. Women living in or frequently (eg, daily, weekly) traveling to areas with Zika virus transmission, who are currently pregnant, may have been infected before conception, and for these women, it may be difficult to determine when the infection occurred. Given these new data, the CDC issued the recommendation that for asymptomatic pregnant women with ongoing risk of Zika virus exposure (ie, those currently living in or frequently traveling to areas with Zika virus transmission), in addition to previously recommended IgM testing, health care providers can consider concurrent Zika virus NAT testing at least once per trimester to provide additional clinical information to determine whether the positive IgM test results indicate a recent infection.

Each clinical scenario is unique, and health care 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. The CDC offers many tools and resources for health care providers, including a Zika Pregnancy Testing Algorithm.

Because the proportion of pregnancies among women with confirmed Zika virus infection that resulted in a fetus or baby with birth defects was higher in women who were infected during the first trimester, h ow can clinicians manage these patients and does this care plan differ for those who were infected during the second or third trimester?

The available data indicate that infection in the first and second trimester causes birth defects, but it remains to be seen if third trimester infections pose lesser or perhaps different risks, such as growth restriction or stillbirth. Based on the current information available, the CDC’s clinical management guidance does not differ by trimester for prenatal care. If a pregnant patient tests positive for Zika in any trimester, health care providers should watch the pregnancy more closely. It may be necessary to conduct more ultrasound examinations or other tests to check the fetus’ growth and development. In the case of a recent Zika virus infection or flavivirus infection (where the specific virus cannot be identified), health care providers should consider serial ultrasound examinations every 3 to 4 weeks to assess fetal anatomy and growth. Decisions regarding amniocentesis should be made on an individual basis.

What tests should infants with congenital Zika virus exposure receive and when?

Zika virus testing is recommended for infants born to mothers with laboratory evidence of Zika virus infection during pregnancy, and for infants who have abnormal clinical findings suggestive of congenital Zika virus syndrome and a maternal epidemiologic link suggesting possible exposure during pregnancy, regardless of maternal Zika virus test results. Testing infants for congenital Zika virus infection should be performed within the first 2 days after birth, particularly in areas where Zika virus is currently circulating.

PAGE BREAK

Of note, health care providers should consider testing of infants if there is concern about infant follow-up care or if maternal testing was not performed or was negative in a setting of an exposure that occurred more than 12 weeks earlier.

All infants born to mothers with laboratory evidence of Zika virus infection during pregnancy should receive a comprehensive physical exam, head ultrasound to assess the brain’s structure, standard newborn hearing assessment and lab testing for Zika virus, even if no abnormalities are apparent at birth. For infants without laboratory evidence of Zika virus infection but for whom suspicion for congenital Zika virus infection remains, health care providers should evaluate for other causes of congenital infection and consider an ophthalmology exam and auditory brainstem response (ABR) hearing test before hospital discharge or within 1 month of birth.

CDC also offers guidance and resources for the evaluation and management of infants with possible congenital Zika virus infection. Resources include an Infant Testing Algorithm; a pocket guide on the Evaluation and Management for Infants with Possible Congenital Zika Infection; and an Infant Testing Tool.

What precautions regarding Zika should clinicians be sharing with their patients who are planning to becom e pregnant?

For women planning to become pregnant, health care providers should discuss the potential risk of Zika virus infection in pregnancy, the signs and symptoms associated with Zika virus disease and when to seek care if the patient develops symptoms of Zika virus disease. They should also emphasize strategies to prevent mosquito bites. Preconception counseling guides are available on the CDC’s website.

What is the CDC currently doing to combat Zika virus infection in the United States?

The CDC continues to work 24/7 with our partners to respond to this public health emergency. The U.S. Zika Pregnancy Registry, Zika Active Pregnancy Surveillance System in Puerto Rico and rapid Zika Birth Defects Surveillance continue to collect information about Zika and help guide our nation’s response. Preventing Zika virus infection during pregnancy, remains the priority. Pregnant women should:

  • avoid travel to areas with risk of Zika. Pregnant women who must travel to an area with risk of Zika should talk to their health care provider before traveling to understand the risks;
  • follow steps to prevent mosquito bites if they live in or travel to an area with risk of Zika; and
  • avoid getting Zika through sex by using condoms or not having sex if their sex partner lives in or travels to an area with risk of Zika.

References:

https://www.cdc.gov/zika/pdfs/zika_peds.pdf

https://www.cdc.gov/zika/pdfs/pediatric-evaluation-follow-up-tool.pdf

https://www.cdc.gov/zika/pdfs/placental-testing-guidance.pdf

Disclosures: Honein reports no relevant financial disclosures.

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