An ad-hoc session was held at the Society for Maternal-Fetal Medicine (SMFM) 36th Annual Pregnancy Meeting to share knowledge and discuss clinical best practices for optimizing maternal and perinatal health in the face of the recent Zika virusepidemic. Dr Laura Riley, SMFM’s immediate past president, Director of Labor and Delivery at the Massachusetts General Hospital, and an obstetrical infectious diseases expert, organized a panel of leaders, including William Callaghan, MD, MPH, Chief of the Maternal and Infant Health Branch of CDC’s Division of Reproductive Health; Brenna Hughes, MD, MSCR, Associate Professor at Alpert Medical School of Brown University; and R Phillips Heine, MD, Professor and Division Chief of MFM at Duke University. This panel was tasked with relaying the released interim guidelines on the management of pregnant women with possible Zika virus exposure.
Zika is a mosquito-borne single-stranded RNA Flavivirus, related to dengue virus. According to the CDC, only 1 in 5 people infected with Zika virus will become symptomatic. Characteristic clinical findings are an acute onset of fever with maculopapular rash, arthralgias, or conjunctivitis, usually within 1-2 weeks of infection.1 Other reported symptoms include a headache or myalgias. The illness is usually mild, with symptoms lasting for several days to a week. The actual Zika viral infection rate, incidence of maternal-fetal transmission, immune response, and any causal relationship to fetal microcephaly, abnormal brain development, or other adverse pregnancy outcome, are not currently known. Moreover, the CDC is uncertain on the sensitivity and specificity of currently available serologic testing (IgM, no IgG testing available). Current countries with reported active Zika virus transmission are shown in Figure 1, although CDC cautions that this map is routinely updated and should be rechecked frequently.
Current guidelines call for at least baseline sonographic screening for fetal anomalies in general and for head and brain development specifically for pregnant women with exposure in Zika-endemic areas. Along with the potential need to discuss alternative differential diagnoses to explain any reported symptoms or findings, it is prudent and recommended to refer patients with concerns about Zika exposure or Zika-associated fetal issues to an MFM subspecialist with specific knowledge in this area whenever feasible. Subspecialists will then work directly with local and state health departments to coordinate testing and interpretation of results. A listing of state and territorial health departments can be found at http://www.cdc.gov/mmwr/international/relres.html. Zika testing currently is being performed almost exclusively at the CDC, but with the approval of a local health authority, many states are actively developing programs for screening and testing exposed pregnant women on a more local level.
Appropriate clinical scenarios requiring serum testing are listed below in the case studies. When sent, Zika serology IgM testing will be the most commonly run assay, with results reported as a titer, interpreted as “likely positive,” “inconclusive,” or “likely negative.” If a patient has been symptomatic in the preceding week (and only then), Zika RNA testing by reverse-transcriptase PCR (RT-PCR) will be performed. This emphasizes the importance of taking and providing a detailed travel and symptom history to the lab performing the testing. The sensitivity of the IgM assay is currently unknown and is being evaluated. This serum sample should also be tested for other common flaviviruses endemic to the area, such as dengue and chikungunya, but these tests must be ordered separately by the provider through commercial labs. A history should be obtained for prior exposure (vaccination or infection) to dengue, yellow fever, Japanese encephalitis or West Nile viruses, as these antibodies may cross-react with Zika testing. A positive Zika virus IgM should have a confirmatory neutralizing antibody titer ≥4-fold higher than dengue virus-neutralizing antibody titers in serum by plaque-reduction neutralization testing. Testing would be considered inconclusive if Zika virus-neutralizing antibody titers are < 4-fold higher than dengue virus-neutralizing antibody titers.