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

Updated Recommendations for the Initial Laboratory Testing and Evaluation of Infants with Possible Congenital Zika Virus Infection

Infant diagnostic testing. Laboratory testing for congenital Zika virus infection is recommended for infants born to mothers with laboratory evidence of Zika virus infection, and for infants with findings suggestive of congenital Zika syndrome and a maternal epidemiologic link suggesting possible transmission, regardless of maternal testing results (Figure). Laboratory evidence of maternal Zika virus infection includes Zika virus RNA detected in any maternal clinical specimen by rRT-PCR and positive Zika virus IgM with confirmatory neutralizing antibody titer for Zika virus or flavivirus, not otherwise specified. Zika virus rRT-PCR testing should be performed on both infant serum and urine, and Zika virus IgM enzyme-linked immunosorbent assay (ELISA) should concurrently be performed on infant serum. If cerebrospinal fluid (CSF) is obtained for other studies, rRT-PCR testing for Zika virus RNA and Zika virus IgM should be performed on CSF. Laboratory testing should be performed on infant specimens; cord blood is not recommended because it can yield false positive results through contamination with maternal blood and might also yield false negative results (21). Infant laboratory testing for Zika virus should be performed within the first 2 days after birth; if testing is performed later, distinguishing between congenital, perinatal, and postnatal infection will be difficult. If the timing of infection cannot be determined, infants should be managed as if they have congenital Zika virus infection.

A Zika rRT-PCR positive result in an infant sample confirms the diagnosis of congenital Zika virus infection (Table 1). Zika virus IgM detected in an infant, without detectable Zika virus RNA, should be interpreted as probable congenital Zika virus infection. The plaque reduction neutralization test (PRNT) measures virus-specific neutralizing antibodies and is used to confirm the specificity of the IgM antibodies against Zika virus and rule out a false positive IgM result (20). If the infant’s initial sample is IgM-positive, but PRNT was not performed on the mother’s sample, PRNT should be performed on the infant’s initial sample. However, PRNT cannot distinguish between maternal and infant antibodies. Because of this, it might be necessary to wait until the child is at least age 18 months, when maternal antibodies are expected to wane, to confirm congenital infection. PRNT should be performed on a sample collected from a child aged ≥18 months whose initial sample was IgM positive if Zika-specific neutralizing antibodies were detected by PRNT on either the infant’s or mother’s sample. If the infant’s initial sample is negative by both IgM ELISA and rRT-PCR but clinical concerns remain (e.g., microcephaly with negative evaluation for other known causes), PRNT at age 18 months can be considered. If PRNT results at 18 months are negative, the child is considered to not have congenital Zika virus infection. If PRNT results are positive, congenital Zika infection is presumed, but postnatal infection cannot be excluded, especially for children living in an area with active Zika virus transmission.

In many cases, infant laboratory testing results will not be available before hospital discharge. In these cases, infants should be presumed to have congenital Zika virus infection until test results are available. For the purposes of this guidance, infants with confirmed or probable Zika virus infection should be managed in the same manner.

Detection of Zika virus RNA in the placenta can confirm the presence of maternal infection, but cannot distinguish between maternal and congenital infection. For circumstances in which maternal testing was not previously performed, performed more than 12 weeks after exposure (22), or was not definitive (e.g., flavivirus not otherwise specified) (20), a positive placental rRT-PCR result can confirm maternal Zika virus infection. Based on unpublished CDC data, placentas from mothers with Zika virus infection during pregnancy can have detectable Zika virus RNA at the time of delivery, regardless of the timing of maternal infection. Clinical implications for an infant with Zika virus RNA detected in the placenta, in the absence of laboratory evidence of Zika virus in the infant, are unknown.

Limited data are currently available regarding perinatal Zika virus transmission (23). Guidelines for evaluation and management of infants and children with postnatally acquired Zika virus disease (1) will be updated as more information is available.

Clinical evaluation of infants. Infants born to mothers with laboratory evidence of Zika virus infection should receive a comprehensive physical examination, including precise measurement of head (occipitofrontal) circumference,* length and weight, assessment of gestational age, and examination for neurologic abnormalities and dysmorphic features (Table 2). A postnatal head ultrasound should be performed on all infants born to mothers with laboratory evidence of Zika virus infection before discharge from the hospital, including those infants with normal prenatal ultrasound findings, because some abnormal findings associated with congenital Zika syndrome might not be readily apparent on prenatal ultrasounds. All infants should receive a hearing screen per universal screening recommendations before hospital discharge. Infants with laboratory evidence of congenital Zika virus infection should be referred for a comprehensive ophthalmologic exam and evaluation of hearing by ABR testing before 1 month of age. Other evaluations should be performed as clinically indicated.

Infants with negative IgM and negative rRT-PCR testing born to a mother with laboratory evidence of Zika virus infection should receive routine care, including monitoring of head circumference at every well child visit and age-appropriate developmental screening (24). Health care providers should report information on pregnant women in the United States and the U.S. territories with laboratory evidence of Zika virus infection and their infants (regardless of infant test results) to state, tribal, local, or territorial health departments for inclusion in the U.S. Zika Pregnancy Registry (http://www.cdc.gov/zika/hc-providers/registry.html), or the Puerto Rico Zika Active Pregnancy Surveillance System (ZAPSS) (http://www.cdc.gov/zika/public-health-partners/zapss.html).

For all infants with abnormal findings consistent with congenital Zika syndrome, an extensive evaluation is recommended (Box 2). Transfer to a facility with access to pediatric subspecialty care might facilitate this evaluation. However, the decision should not be based solely on the presence of maternal Zika virus infection during pregnancy. Health care providers should consider both the immediate needs of the infant and the potential negative impact of possible separation from his or her family. The recommended evaluation includes a complete blood count and metabolic panel, including liver function tests, a comprehensive examination by an ophthalmologist, ABR testing, and consideration of advanced neuroimaging in consultation with a neurologist. In addition, infants should be evaluated for other causes of microcephaly or intracranial calcifications, including genetic conditions and other congenital infections.

Infants born to mothers with risk factors for maternal Zika virus infection (travel to or residence in an area of Zika virus transmission or sex with a partner who traveled to or resided in such an area) and for whom maternal testing was not performed before delivery, should have a comprehensive physical examination, including standardized measurement of head circumference. Maternal diagnostic testing should be performed (20,22), and testing of the placenta for Zika virus PCR should be considered (http://www.cdc.gov/zika/hc-providers/test-specimens-at-time-of-birth.html); infant testing should be performed if maternal testing is consistent with laboratory evidence of Zika virus infection. If an infant appears clinically well, further evaluation, including head ultrasound, ophthalmologic assessment, and infant laboratory Zika virus testing, can be deferred until maternal test results are available. However, if there is concern about infant follow-up, head ultrasound, ophthalmologic assessment and infant Zika virus testing should be performed before hospital discharge. CDC recommends standard precautions in all health care settings to protect both health care personnel and patients from infection with blood-borne pathogens, including Zika virus (25).

Although Zika virus has been detected in breast milk (26), no cases of Zika virus infection associated with breastfeeding have been reported, and current evidence suggests that the benefits of breastfeeding outweigh the theoretical risks of Zika virus transmission. All women with Zika virus infection during pregnancy should be encouraged and supported to breastfeed their infants, regardless of infant Zika virus testing results.

Quelle: CDC (Center for Disease Control and Prevention)

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