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Update: Interim Guidance for the Evaluation and Management of Infants with Possible Congenital Zika Virus Infection — United States, August 2016

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    • Journal Article:
      MMWR. Morbidity and Mortality Weekly Report
    • Description:
      On August 19, 2016, this report was posted online as an MMWR Early Release.

      CDC has updated its interim guidance for U.S. health care providers caring for infants born to mothers with possible Zika Virus infection during pregnancy (1). Laboratory tTesting is recommended for 1) infants born to mothers with laboratory evidence of Zika Virus infection during pregnancy and 2) infants who have abnormal clinical or neuroimaging findings suggestive of Congenital Zika syndrome and a maternal epidemiologic link suggTesting possible Transmission, regardless of maternal Zika Virus test results. Congenital Zika syndrome is a recently recognized pattern of Congenital anomalies associated with Zika Virus infection during pregnancy that includes microcephaly, intracranial calcifications or other brain anomalies, or eye anomalies, among others (2). Recommended infant laboratory evaluation includes both molecular (real-time reverse transcription–polymerase chain reaction [rRT-PCR]) and serologic (immunoglobulin M [IgM]) tTesting. Initial samples should be collected directly from the infant in the first 2 days of life, if possible; tTesting of cord blood is not recommended. A positive infant serum or urine rRT-PCR test result confirms Congenital Zika Virus infection. Positive Zika Virus IgM tTesting, with a negative rRT-PCR result, indicates probable Congenital Zika Virus infection. In addition to infant Zika Virus tTesting, initial evaluation of all infants born to mothers with laboratory evidence of Zika Virus infection during pregnancy should include a comprehensive physical examination, including a neurologic examination, postnatal head ultrasound, and standard newborn hearing screen. Infants with laboratory evidence of Congenital Zika Virus infection should have a comprehensive ophthalmologic exam and hearing assessment by auditory brainstem response (ABR) tTesting before 1 month of age. Recommendations for follow-up of infants with laboratory evidence of Congenital Zika Virus infection depend on whether abnormalities consistent with Congenital Zika syndrome are present. Infants with abnormalities consistent with Congenital Zika syndrome should have a coordinated evaluation by multiple specialists within the first month of life; additional evaluations will be needed within the first year of life, including assessments of vision, hearing, feeding, growth, and neurodevelopmental and endocrine function. Families and caregivers will also need ongoing psychosocial support and assistance with coordination of care. Infants with laboratory evidence of Congenital Zika Virus infection without apparent abnormalities should have ongoing developmental monitoring and screening by the primary care provider; repeat hearing tTesting is recommended. This guidance will be updated when additional information becomes available.

      Zika Virus infection during pregnancy is a cause of microcephaly and other serious brain anomalies (3); however, the clinical spectrum of the effects of Zika Virus infection during pregnancy is not yet known. A wide range of neurologic abnormalities, in addition to microcephaly, has been observed among infants with presumed or confirmed Congenital Zika Virus infection (2,4). Reported neuroimaging findings include intracranial calcifications; ventriculomegaly and extra-axial fluid; abnormal gyral patterns (e.g., polymicrogyria); decreased brain parenchymal volume; cortical atrophy and malformation; hypoplasia of the cerebellum, cerebellar vermis or brainstem; delayed myelination; and thinning or hypoplasia of the corpus callosum (5,6). Neurologic abnormalities apparent on examination of these infants have included hypertonia, hypotonia, spasticity, hyperreflexia, severe irritability, and seizures (2,4). Zika Virus appears to primarily target neural progenitor cells resulting in cell death and disruption of neuronal proliferation, migration and differentiation, which slows brain growth and affects neural cell viability (7–9). Ocular findings reported in infants with presumed or confirmed Congenital Zika Virus infection have included chorioretinal atrophy or scarring, pigmentary changes, optic nerve hypoplasia, optic disc pallor, increased optic disc cupping, hemorrhagic retinopathy and abnormal retinal vasculature (10–12). Some infants with presumed or confirmed Congenital Zika Virus infection have had a phenotype consistent with fetal brain disruption sequence, characterized by severe microcephaly, collapse of the skull, overlapping cranial sutures, prominent occipital bone, redundant scalp skin, and severe neurologic impairment (13,14). Other findings seen in infants with Congenital Zika Virus infection have included clubfoot and contractures of single or multiple joints (arthrogryposis), presumably secondary to central nervous system damage (4).

      Experience with other Congenital infections can provide insight to guide clinical management until more data emerge regarding outcomes associated with Congenital Zika Virus infection. Infants with Congenital infections, such as cytomegaloVirus (CMV) and rubella, can develop a range of clinical manifestations, including hearing loss, seizures, neurodevelopmental delays and diabetes mellitus later in life (15,16), even without apparent clinical manifestations of Congenital infection at birth (17).

      Diagnostic tTesting for Congenital Zika Virus infection can be challenging. Whereas a positive molecular (rRT-PCR) tTesting result in an infant can confirm Zika Virus infection, a negative result does not exclude infection. Viral shedding can be prolonged in Congenital CMV and rubella infections (18,19); however, little is known about the duration of viral shedding in infants with Congenital Zika Virus infection. IgM results might assist in making the Diagnosis, but can be difficult to interpret because of false-positive results occurring from cross-reacting IgM antibodies or nonspecific reactivity (20). Because maternal IgG crosses the placenta, the presence of IgG in an infant specimen cannot be used as evidence of Congenital infection.

      Currently, there are >1,000 pregnant women with laboratory evidence of possible Zika Virus infection in the United States and U.S. territories (http://www.cdc.gov/zika/geo/pregwomen-uscases.html). Pediatric health care providers need information to guide appropriate laboratory tTesting and clinical evaluation and management of infants born to these mothers. On July 21–22, 2016, CDC, in collaboration with the American Academy of Pediatrics (AAP), convened a meeting to obtain individual input from experts and partners to inform the development of guidance for the evaluation and management of infants with Congenital Zika Virus infection. In attendance were experts in pediatrics, infectious Diseases, neurology, developmental and behavioral pediatrics, ophthalmology, audiology, physical medicine and rehabilitation, neonatology, lactation and nutrition, maternal-fetal medicine, clinical Genetics, hospitalist medicine, neonatology, and endocrinology, and representatives from principal partner groups (Box 1). Discussion focused on three areas: 1) initial evaluation and laboratory tTesting of infants born to mothers with laboratory evidence of Zika Virus infection during pregnancy, 2) outpatient management and follow-up of infants with microcephaly or other findings consistent with Congenital Zika syndrome, and 3) outpatient management and follow-up of infants with laboratory evidence of Congenital Zika Virus infection but without findings consistent with Congenital Zika syndrome.

      Suggested citation for this article: Russell K, Oliver SE, Lewis L, et al. Update: Interim Guidance for the Evaluation and Management of Infants with Possible Congenital Zika Virus Infection — United States, August 2016. MMWR Morb Mortal Wkly Rep 2016;65:870–878. DOI: http://dx.doi.org/10.15585/mmwr.mm6533e2.

    • Pubmed ID:
      27559830
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