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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during pregnancy (CDC, unpublished data, 2003).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
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
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
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).
1. Recommended clinical evaluation of infants born
to mothers infected with
West Nile virus (WNV) during pregnancy
thorough physical examination of the newborn should
be conducted, including careful measurement of the
infant's head circumference, length, weight, and assessment
of gestational age.
newborn should be evaluated carefully for neurologic
abnormalities, dysmorphic features, splenomegaly, hepatomegaly,
and rash or other skin lesions. Any rash, skin lesions,
or dysmorphic features should be photographed. If an
abnormality is noted, consultation with an appropriate
specialist is recommended.
serum should be obtained within 2 days of birth and
at about age 8 weeks to test for IgM and IgG antibody
to WNV. Free testing of samples by CDC can be arranged
by contacting state public health laboratories.
newborn hearing screen should be completed by evoked
otoacoustic emissions testing or auditory brainstem
response testing, either before discharge from the
hospital or within 1 month after birth. Infants who
fail the initial hearing screen should be referred
to an audiologist for further evaluation.
examination of the placenta by a pathologist is encouraged.
Regardless of whether this is done, the entire placenta,
a sample of umbilical cord tissue, and a sample of
serum from the umbilical cord should be retained for
further evaluation if congenital WNV infection is identified
or strongly suspected. A section of the placenta and
umbilical cord should be frozen, and the remainder
of the placenta should be preserved in formalin; a
sample of umbilical cord blood should be centrifuged,
and the serum should be refrigerated or frozen.
2. Recommended clinical evaluation of infants with
clinical or laboratory evidence of possible congenital
West Nile virus (WNV) infection
tomography (CT) scan of the head and brain. If abnormal,
a pediatric neurologist should be consulted.
ophthalmologic evaluation, including examination of
blood count, platelet count, and liver function tests,
including alanine aminotransferase (ALT) and aspartate
aminotransferase (AST). Examination of the CSF should
be considered, and if done, should include testing
of the CSF for IgM to WNV.
by a dysmorphologist or clinical geneticist.
evaluation of any congenital abnormalities to determine
alternative causes, including genetic, infectious,
or other teratogenic causes.
hearing screen at age 6 months.
evaluation of head circumference, physical characteristics,
and developmental milestones throughout the first year
examination of infant serum for IgG and IgM antibody
to WNV at age 6 months.
examination of the placenta and umbilical cord, testing
of frozen placental tissue and cord tissue for WNV
nucleic acid, and testing of cord serum for IgM and
IgG antibody to WNV.
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
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.
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.
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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.
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.