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Zika Virus Evaluation and Potential Outcomes

Congenital Zika Virus Infection

What should healthcare providers do to evaluate infants born to mothers with laboratory evidence of confirmed or possible Zika virus infection during pregnancy?

Initial evaluation of all infants born to mothers with laboratory evidence of Zika virus infection during pregnancy should include a comprehensive physical exam, including a neurologic assessment, postnatal head ultrasound, standard newborn hearing screen, and Zika virus testing of the infant. Infants with confirmed or probable congenital Zika virus infection should have a comprehensive ophthalmologic exam and hearing assessment by auditory brainstem response (ABR) testing before 1 month of age.  

What additional follow up is recommended for infants with abnormalities consistent with congenital Zika syndrome (e.g., microcephaly, intracranial calcifications or other brain or eye abnormalities)?

Consultations are recommended with a neurologist, infectious disease specialist, ophthalmologist, endocrinologist and geneticist. A complete blood count including platelet count, metabolic panel, and tests for liver enzymes and function should also be conducted. Primary care providers should assess for feeding difficulties, and refer to lactation, occupational therapy, speech therapy, nutrition, and/or gastroenterology as needed for poor suck, swallowing dysfunction, gastroesophageal reflux, or aspiration concerns. Swallowing dysfunction might not be evident initially and feeding should be monitored closely. Testing for other congenital infections is also recommended. Consideration should be given to performing advanced neuroimaging in consultation with a neurologist. If any additional anomalies are identified through history, clinical examination, or imaging studies, genetic and other teratogenic causes should be considered.

What long-term follow up is recommended for infants with confirmed or probable congenital Zika infection, based on Zika virus test results?

Recommendations for follow up for infants with confirmed or probable congenital Zika infection based on laboratory test results depend on whether these infants have abnormalities consistent with congenital Zika syndrome.

Infants with abnormalities consistent with congenital Zika syndrome (e.g., microcephaly, intracranial calcifications or other brain or eye abnormalities) require a multidisciplinary team and established medical home to facilitate the coordination of care. Before the infant’s discharge from the birth hospital, continued follow up with subspecialists and recommended services should be established. If not already initiated, neurology referral should occur for any abnormalities, including sleep problems and excessive irritability. If the newborn ophthalmology exam was normal, another exam (including retinal assessment) is recommended at age 3 months. If the newborn hearing screen was normal, an ABR should be performed at age 4–6 months. Infants with abnormal brain development can be at risk for hypothalamic dysfunction leading to pituitary insufficiency, and early manifestations of endocrine dysfunction might not be detected by routine newborn screening. Thyroid testing (TSH, free T3 and T4) should be performed at age 2 weeks and again at age 3 months. If either of these results is abnormal, further evaluation of pituitary function should be performed. Referral to a developmental specialist and early intervention services should occur as soon as possible.

Infants with laboratory evidence of Zika virus infection but without abnormalities consistent with congenital Zika syndrome should receive routine care including monitoring of head (occipitofrontal) circumference, length, and weight. Additionally, developmental monitoring should occur at every visit, and age-appropriate standardized validated developmental screening should occur at 9 months. A vision screening, including visual regard, should be performed at each well-child visit, and referral to an ophthalmologist should be made for any caregiver or provider concerns. Infants who passed an initial ABR should be referred for behavioral audiological diagnostic testing at age 9 months, or sooner for any hearing concerns.

Overall, families and caregivers of infants with congenital Zika virus infection will require ongoing psychosocial assessment and support.  As a critical component of patient care and to facilitate early identification of developmental delays, families should be empowered to be active participants in their child’s monitoring and care.   

If a mother had Zika virus infection during pregnancy but her newborn tests negative for Zika virus, what is recommended for additional follow-up?

In the absence of abnormal findings on examination, the infant should receive routine pediatric care including measurement of growth and development, and appropriate evaluation and follow-up for any clinical findings that arise. If the newborn has abnormal findings on history or examination, diagnostic testing for other causes of the newborn’s conditions should be performed, including testing for other congenital viral infections if indicated.

A newborn born to a mother who had Zika virus infection during pregnancy meets criteria for reporting to the US Zika Pregnancy Registry and the Puerto Rico Zika Active Pregnancy Surveillance System. CDC requests that healthcare providers collect and report pertinent clinical information about these infants to their designated health department.

Is there any information on outcomes in newborns if they are exposed to Zika virus during labor and delivery (perinatal transmission)?

Perinatal transmission of Zika virus infection has been reported. However, information is limited to rare cases. An asymptomatic case and a symptomatic case (with thrombocytopenia and a diffuse rash) have been reported. Evidence from other flaviviruses, such as West Nile virus and dengue virus, indicate that transmission has resulted in findings in the neonate ranging from no symptoms to severe illness (including fever, thrombocytopenia, hemorrhage, encephalopathy, and adverse neurologic outcomes). The spectrum of clinical features that might be observed in infants who acquire Zika virus during the perinatal period is currently unknown.

What is the prognosis for infants with congenital Zika virus infection?

The prognosis for infants with congenital Zika virus infection is currently unknown. The updated guidance includes recommendations for testing infants for congenital Zika infection and clinical management recommendations for infants with evidence of Zika virus infection, both with and without apparent birth defects, to ensure careful screening and monitoring of infant development.

CDC established the US Zika Pregnancy Registry and with colleagues from the Puerto Rico Department of Health, the Zika Active Pregnancy Surveillance System, to monitor pregnancies and to provide information about pregnancy and infant outcomes including the chances that a woman infected with Zika virus during pregnancy will deliver a baby with a birth defect. The registry will also help determine the range of problems associated with Zika infection in pregnancy.

Is there specific treatment for congenital Zika virus infection?

For infants with congenital Zika virus infection, care is focused on diagnosing and managing conditions that are present, monitoring the child’s development over time, and addressing problems as they arise.

Postnatal Zika Virus Infection

Are there concerns for long-term complications in older infants and children who are infected with Zika virus?

Information on long-term outcomes among infants and children with postnatal Zika virus disease is limited. Until more evidence is available to inform recommendations, routine pediatric care is advised for these infants and children. Most children infected with Zika virus are asymptomatic or have mild illness, similar to the findings seen in adults with Zika virus infection. 

Can Zika virus infection cause Guillain-Barré syndrome (GBS) or death in infants or children?

In general, the risk for GBS from any cause appears to increase with increasing age. GBS has been reported following Zika virus infection, although a causal link has not been established. It is unclear how often GBS following Zika virus infection has occurred in children; one report from Brazil refers to 6 patients, aged 2–57 years, with neurologic syndromes (4 with GBS and 2 with acute disseminated encephalomyelitis) after laboratory-confirmed Zika virus infection. Deaths due to Zika virus infection appear to be rare at all ages.

Is there specific treatment for infants and children with postnatal Zika virus infection?

Evidence indicates that Zika virus disease in children is usually mild, and treatment is supportive; this includes rest and fluids to prevent dehydration. Non-steroidal anti-inflammatory drugs (NSAIDS) should not be used until dengue is ruled out as a cause of illness and should be avoided in children aged <6 months. Aspirin is not recommended for use with postnatal viral illnesses due to the risk of Reye’s syndrome.