Update: Interim Guidance for Health Care Providers Caring for Pregnant Women with Possible Zika Virus Exposure - United States (Including U.S. Territories), July 2017

Abstract

CDC has updated the interim guidance for U.S. health care providers caring for pregnant women with possible Zika virus exposure in response to 1) declining prevalence of Zika virus disease in the World Health Organization's Region of the Americas (Americas) and 2) emerging evidence indicating prolonged detection of Zika virus immunoglobulin M (IgM) antibodies. Zika virus cases were first reported in the Americas during 2015-2016; however, the incidence of Zika virus disease has since declined. As the prevalence of Zika virus disease declines, the likelihood of false-positive test results increases. In addition, emerging epidemiologic and laboratory data indicate that, as is the case with other flaviviruses, Zika virus IgM antibodies can persist beyond 12 weeks after infection. Therefore, IgM test results cannot always reliably distinguish between an infection that occurred during the current pregnancy and one that occurred before the current pregnancy, particularly for women with possible Zika virus exposure before the current pregnancy. These limitations should be considered when counseling pregnant women about the risks and benefits of testing for Zika virus infection during pregnancy. This updated guidance emphasizes a shared decision-making model for testing and screening pregnant women, one in which patients and providers work together to make decisions about testing and care plans based on patient preferences and values, clinical judgment, and a balanced assessment of risks and expected outcomes.

FIGURE 1

Updated interim testing recommendations^,,,,,, and interpretation of results for symptomatic pregnant women with possible Zika virus exposure^, — United States (including U.S. territories), July 2017 Abbreviations: IgM = immunoglobulin M; NAT = nucleic acid test; PRNT = plaque reduction neutralization test. * Ask about type and duration of Zika virus exposure before and during current pregnancy. Exposure before the current pregnancy might limit interpretation of Zika virus IgM results; pretest counseling can help inform testing decisions. Some patients may choose not to receive Zika virus IgM testing. ^† Zika virus testing is not routinely recommended for pregnant women with a previous diagnosis of laboratory-confirmed Zika virus infection by either NAT or serology (positive/equivocal Zika virus or dengue virus IgM and Zika virus PRNT ≥10 and dengue virus PRNT <10 results). ^§ This algorithm also applies to pregnant women with possible Zika virus exposure who have a fetus with prenatal ultrasound findings consistent with congenital Zika virus syndrome. ^¶ The duration of detectable Zika virus RNA in pregnant women following infection is not known. Preliminary data suggest that NAT might remain positive for several weeks after symptom onset in some pregnant women. Zika virus IgM antibodies are most likely to be detected within 12 weeks after infection; however, IgM antibodies might be detected for months after infection, limiting the ability to determine whether infection occurred before or during the current pregnancy. ** Dengue virus IgM antibody testing is recommended for symptomatic pregnant women. For laboratory interpretation in the presence of dengue virus IgM results, refer to https://www.cdc.gov/dengue/clinicallab/laboratory.html. ^†† Nonnegative results include “positive,” “equivocal,” “presumptive positive,” or “possible positive.” These are examples of assay interpretation that might accompany test results; nonnegative serology terminology varies by assay. For explanation of a specific interpretation, refer to the instructions for use for the specific assay performed. Information on each assay can be found at https://www.fda.gov/MedicalDevices/Safety/EmergencySituations/ucm161496.htm#zika under the “Labeling” tab for the specific assay. ^§§ Currently, PRNT confirmation is not routinely recommended for persons living in Puerto Rico. For laboratory interpretation in the absence of PRNT testing, refer to https://www.cdc.gov/zika/pdfs/lab-table.pdf. ^¶¶ Despite the high specificity of NAT, false-positive NAT results have been reported. If both serum and urine specimens are NAT-positive, regardless of IgM antibody results, results should be interpreted as evidence of acute Zika virus infection. If either serum or urine specimen is NAT-positive in conjunction with a positive Zika virus IgM, results should be interpreted as evidence of acute Zika virus infection. If NAT is only positive on serum or urine and IgM testing is negative, repeat testing on the original NAT-positive specimen. If repeat NAT is positive, results should be interpreted as evidence of acute Zika virus infection. If repeat NAT testing is negative, results are indeterminate and health care providers should repeat Zika virus IgM antibody testing on a serum specimen collected ≥2 weeks after symptom onset. If subsequent IgM antibody test is positive, interpret as evidence of acute Zika virus infection, but if negative, interpret as no evidence of Zika virus infection. *** Possible Zika virus exposure includes travel to or residence in an area with risk for Zika virus transmission (https://wwwnc.cdc.gov/travel/page/zika-travel-information) during pregnancy or the periconceptional period (8 weeks before conception [6 weeks before the last menstrual period]), or sex without a condom during pregnancy or the periconceptional period, with a partner who traveled to, or resides in an area with risk for Zika virus transmission. ^††† For the purposes of this guidance, recent possible Zika virus exposure or Zika virus/flavivirus infection is defined as a possible exposure or infection during the current pregnancy or periconceptional period.

FIGURE 2

Updated interim testing recommendations^,, and interpretation of results^, for asymptomatic pregnant women with possible Zika virus exposure^,, — United States (including U.S. territories), July 2017 Abbreviations: IgM = immunoglobulin M; NAT = nucleic acid test; PRNT = plaque reduction neutralization test. * Ask about type and duration of Zika virus exposure before and during the current pregnancy. Exposure before the current pregnancy might limit interpretation of Zika virus IgM results; pretest counseling can help inform testing decisions. ^† Zika virus testing is not routinely recommended for pregnant women with a previous diagnosis of laboratory-confirmed Zika virus infection by either NAT or serology (positive/equivocal Zika virus or dengue virus IgM and Zika virus PRNT ≥10 and dengue virus PRNT <10 results). ^§ The interval for Zika virus NAT testing during pregnancy is unknown. Preliminary data suggest that NAT might remain positive for several weeks after infection in some pregnant women. For women without a prior laboratory-confirmed diagnosis of Zika virus, NAT testing should be offered at the initiation of prenatal care, and if Zika virus RNA is not detected on clinical specimens, two additional tests should be offered during the course of the pregnancy coinciding with prenatal visits. The proportion of fetuses and infants with Zika virus–associated birth defects is highest among women with first and early second trimester infections; therefore, conducting all NAT testing during the first and second trimesters might be considered to help identify infections early in pregnancy. However, adverse outcomes have been associated with infection diagnosed in the third trimester; therefore, testing every trimester might be considered. ^¶ Despite the high specificity of NAT, false-positive NAT results have been reported. If both serum and urine specimens are NAT-positive, interpretation should be acute Zika virus infection. If NAT is only positive on serum or urine, testing should be repeated on the original NAT-positive specimen. If repeat NAT is positive, results should be interpreted as evidence of acute Zika virus infection. If repeat NAT testing is negative, results are indeterminate and health care providers should perform IgM testing on a specimen collected ≥2 weeks after initial specimen collection. For laboratory interpretation, refer to https://www.cdc.gov/zika/pdfs/lab-table.pdf. ** A negative Zika virus NAT result does not exclude infection during pregnancy because it represents a single point in time. Zika virus RNA levels decline over time, and the duration of the presence of Zika virus RNA in serum and urine following infection varies among pregnant women. Despite Zika virus IgM antibody test limitations (e.g., cross-reactivity with other flaviviruses and prolonged detection for months, presenting challenges in determining the timing of infection), which should be discussed as part of pretest counseling, patients may still choose to receive Zika virus IgM testing. ^†† Possible Zika virus exposure includes travel to or residence in an area with risk for Zika virus transmission (https://www.cdc.gov/zika/geo/index.html) during pregnancy or the periconceptional period (8 weeks before conception [6 weeks before the last menstrual period]), or sex without a condom, during pregnancy or the periconceptional period, with a partner who traveled to, or resides in an area with risk for Zika virus transmission. ^§§ Persons with ongoing possible Zika virus exposure include those who reside in or frequently travel (e.g., daily or weekly) to an area with risk for Zika virus transmission. ^¶¶ For the purposes of this guidance, recent possible Zika virus exposure or Zika virus/flavivirus infection is defined as a possible exposure or infection during the current pregnancy or periconceptional period.