Clinical Guidance

Interim Guidelines for the Evaluation of Infants Born to Mothers Infected With West Nile Virus During Pregnancy

Published in MMWR Vol.53, No. 7; Feb 27, 2004

West Nile virus (WNV) is a single-stranded RNA flavivirus with antigenic similarities to Japanese encephalitis and St. Louis encephalitis viruses. It is transmitted to humans primarily through the bites of infected mosquitoes. Flavivirus infection during pregnancy has been associated rarely with both spontaneous abortion and neonatal illness but has not been known to cause birth defects in humans (1--4). During 2002, a total of 4,156 cases of WNV illness in humans, including 2,946 cases of neuroinvasive disease, were reported to CDC by state health departments. In 2002, a woman who had WNV encephalitis during the 27th week of her pregnancy delivered a full-term infant with chorioretinitis, cystic destruction of cerebral tissue, and laboratory evidence of congenitally acquired WNV infection (5,6). Although this case demonstrated intrauterine WNV infection in an infant with congenital abnormalities, it did not prove a causal relation between WNV infection and these abnormalities. During 2002, CDC investigated three other instances of maternal WNV infection. In all three cases, the infants were born at full term with normal appearance and negative laboratory tests for WNV infection; cranial imaging studies and ophthalmologic examinations were not performed. During 2003, CDC received reports of approximately 9,100 cases of WNV illness, including approximately 2,600 cases of neuroinvasive disease*. CDC is gathering data on pregnancy outcomes for approximately 70 women with WNV illness during pregnancy (CDC, unpublished data, 2003).

To develop guidelines for evaluating infants born to mothers who acquire WNV infection during pregnancy, on December 2, 2003, CDC convened a meeting of specialists in the evaluation of congenital infections. This report summarizes the interim guidelines established during that meeting.

Screening for WNV During Pregnancy

No specific treatment for WNV infection exists, and the consequences of WNV infection during pregnancy have not been well defined. For these reasons, screening of asymptomatic pregnant women for WNV infection is not recommended.

Diagnosis of WNV Infection During Pregnancy

Pregnant women who have meningitis, encephalitis, acute flaccid paralysis, or unexplained fever in an area of ongoing WNV transmission should have serum (and cerebrospinal fluid [CSF], if clinically indicated) tested for antibody to WNV. If serologic or other laboratory tests indicate recent infection with WNV, these infections should be reported to the local or state health department, and the women should be followed to determine the outcomes of their pregnancies.

Evaluation of the Fetus in Pregnant Women with WNV Infection

If WNV illness is diagnosed during pregnancy, a detailed ultrasound examination of the fetus to evaluate for structural abnormalities should be considered no sooner than 2--4 weeks after onset of WNV illness in the mother, unless earlier examination is otherwise indicated. Amniotic fluid, chorionic villi, or fetal serum can be tested for evidence of WNV infection. However, the sensitivity, specificity, and predictive value of tests that might be used to evaluate fetal WNV infection are not known, and the clinical consequences of fetal infection have not been determined. In case of miscarriage or induced abortion, testing of all products of conception (e.g., the placenta and umbilical cord) for evidence of WNV infection is advised to document the effects of WNV infection on pregnancy outcome.

Evaluation of Infants Born to Mothers Infected with WNV During Pregnancy

When an infant is born to a mother who was known or suspected to have WNV infection during pregnancy, clinical evaluation is recommended (Box 1). Further evaluation should be considered if any clinical abnormality is identified or if laboratory testing indicates that an infant might have congenital WNV infection (Box 2).

Prevention of WNV Infection During Pregnancy

Pregnant women who live in areas with WNV-infected mosquitoes should apply insect repellent to skin and clothes when exposed to mosquitoes and wear clothing that will help protect against mosquito bites. In addition, whenever possible, pregnant women should avoid being outdoors during peak mosquito-feeding times (i.e., usually dawn and dusk).

Reported by: West Nile Virus Intrauterine Infection Working Group. E Hayes, MD, D O'Leary, DVM, Div of Vector-Borne Infectious Diseases, National Center for Infectious Diseases; SA Rasmussen, MD, Div of Birth Defects and Developmental Disabilities, National Center on Birth Defects and Developmental Disabilities, CDC.

Editorial Note: Neither the proportion of WNV infections during pregnancy that result in congenital infection nor the spectrum of clinical abnormalities associated with congenital WNV infection is known. However, the case reported in 2002 suggests that intrauterine transmission of WNV in some instances might affect the newborn adversely. To evaluate the possible effects of WNV infection during pregnancy, CDC is gathering clinical and laboratory data on outcomes of pregnancies of women who were known or suspected to be infected with WNV during pregnancy. Clinicians who are aware of WNV infections of pregnant women are encouraged to report such cases to CDC by calling their state or local health departments or by contacting CDC, telephone 970-221-6400.

Acknowledgements
Members of the West Nile Intrauterine Infection Working Group: JM Friedman, PhD, Univ of British Columbia. K Jones, MD, Univ of California, San Diego. M Abzug, MD, The Children's Hospital and Univ of Colorado School of Medicine, Denver; J Paisley, MD, Poudre Valley Hospital, Fort Collins; J Pape, Colorado Dept of Public Health and Environment; W Tyson, MD, Presbyterian/St. Luke's Hospital, Denver; M Wheeler, MD, Univ of Colorado Health Sciences Center, Denver. M Mets, MD, Children's Memorial Hospital, Chicago, Illinois. W Allan, MD, Foundation for Blood Research, Scarborough, Maine. C Meissner, MD, Tufts New England Medical Center, Boston, Massachusetts. J Bale, MD, Univ of Utah and Primary Children's Medical Center, Salt Lake City, Utah. J Rutledge, MD, Children's Hospital and Regional Medical Center, Seattle, Washington. J Brown, DVM, G Campbell, MD, S Kuhn, R Lanciotti, PhD, A Marfin, MD, L Petersen, MD, Div of Vector-Borne Infectious Diseases, National Center for Infectious Diseases; J Cordero, MD, J Mulinare, MD, National Center for Birth Defects and Developmental Disabilities, CDC.

References
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2. Kerdpanich A, Watanaveeradej V, Samakoses R, et al. Perinatal dengue infection. Southeast Asian J Trop Med Public Health 2001;32:488-93.
3. Robert E, Vial T, Schaefer C, Arnon J, Reuvers M. Exposure to yellow fever vaccine in early pregnancy. Vaccine 1999;17:283-5.
4. Thaithumyanon P, Thisyakorn U, Deerojnawong J, Innis BL. Dengue infection complicated by severe hemorrhage and vertical transmission in a parturient woman. Clin Infect Dis 1994;18:248-9.
5. Alpert SG, Fergerson J, Noel LP: Intrauterine West Nile virus: ocular and systemic findings. Am J Ophthalmol 2003;136: 733-5.
6. CDC. Intrauterine West Nile virus infection-New York, 2002. MMWR 2002;51:1135-6.


*Data as of February 18, 2004.

†Guidance on diagnosis of WNV can be obtained by contacting local or state health departments or is available from CDC, telephone 970-221-6400 or at http://www.cdc.gov/ncidod/dvbid/westnile/resources/fact_sheet_clinician.htm.