Literature Review

CDC Updates Guidance on Infants With Possible Zika Infection

Testing and management may vary according to the infant’s clinical findings and the mother’s exposure to the virus.


Infants with possible prenatal exposure to Zika who test positive for the virus should receive an in-depth ophthalmologic exam, intensified hearing testing, and a thorough neurologic evaluation with brain imaging within one month of birth, according to new interim guidance from the Centers for Disease Control and Prevention (CDC).

The new clinical management guidelines, published in the October 20 issue of Morbidity and Mortality Weekly Report, supersede the CDC guidance issued in August 2016. The update was the product of a forum on the diagnosis, evaluation, and management of Zika in infants that the centers convened with the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists. Practicing clinicians and federal agency representatives reviewed the evolving body of knowledge on how best to care for these infants. Since Zika emerged as a public health concern, clinicians have reported postnatal onset of some symptoms, including eye abnormalities, incident microcephaly in infants with a normal head circumference at birth, EEG abnormalities, and diaphragmatic paralysis.

Tolulope Adebanjo, MD

“This updated interim guidance is based on current, limited data about Zika virus infection, the interpretation of individual expert opinion collected during the forum, and knowledge about other congenital infections, and reflects the information available as of September 2017,” according to Tolulope Adebanjo, MD, of the National Center for Immunization and Respiratory Diseases, at the CDC in Atlanta, and coauthors. “As more information becomes available, this guidance will be updated.”

Infants With Clinical Findings Consistent With Zika Syndrome

Infants with clinical findings consistent with congenital Zika syndrome who are born to mothers with possible Zika virus exposure in pregnancy should be tested for Zika virus with serum and urine tests. If those tests are negative, and there is no other apparent cause of the symptoms, they should have a CSF sample tested for Zika RNA and IgM Zika antibodies.

By one month, these infants should undergo a head ultrasound and a detailed ophthalmologic exam. The eye exam should pick up any anomalies of the anterior and posterior eye, including microphthalmia, coloboma, intraocular calcifications, optic nerve hypoplasia and atrophy, and macular scarring with focal pigmentary retinal mottling.

By one month, these infants also should undergo auditory brainstem response (ABR) audiometry, especially if the initial newborn hearing screen was done by otoacoustic emissions alone. Zika syndrome can include sensorineural hearing loss, although late-onset hearing loss has not been seen. Therefore, the follow-up ABR previously recommended at four to six months is no longer deemed necessary.

A comprehensive neurologic exam also is recommended. Seizures are sometimes part of Zika syndrome, but infants can also have subclinical EEG abnormalities. Advanced neuroimaging can identify obvious and subtle brain abnormalities, such as cortical thinning, corpus callosum abnormalities, calcifications at the junction of white and gray matter, and ventricular enlargement.

As infants grow, clinicians should be alert for signs of increased intracranial pressure that could signal postnatal hydrocephalus. Diaphragmatic paralysis also has been seen; it manifests as respiratory distress. Dysphagia that interferes with feeding can develop as well.

“The follow-up care of [these infants] requires a multidisciplinary team and an established medical home to facilitate the coordination of care and ensure that abnormal findings are addressed,” said Dr. Adebanjo and colleagues.

Asymptomatic Infants of Mothers With Possible Infection

Infants without clinical findings born to mothers with laboratory evidence of possible Zika virus infection during pregnancy should have the same early head ultrasound, hearing, and eye exams as those with clinical findings. All of these infants also should be tested for Zika virus just as those with clinical findings should be.

If tests are positive, these infants should have all the investigations and follow-up recommended for babies with clinical findings. If laboratory testing is negative, and clinical findings are normal, Zika infection is highly unlikely, and the infants can receive routine care. Clinicians and parents should be on the lookout, however, for new symptoms that might suggest postnatal Zika syndrome.

Asymptomatic Infants Whose Mothers Had Unconfirmed Zika Exposure

Infants without clinical findings consistent with congenital Zika syndrome born to mothers with possible Zika virus exposure in pregnancy, but without laboratory evidence of possible Zika virus infection during pregnancy, constitute a large group. Some women, for example, are never tested during pregnancy, and others have false negative test results. “Because the latter issues are not easily discerned, all mothers with possible exposure to Zika virus during pregnancy who do not have laboratory evidence of possible Zika virus infection, including those who tested negative with currently available technology, should be considered in this group,” said Dr. Adebanjo and colleagues.

The CDC do not recommend further Zika evaluation for these infants unless additional testing confirms maternal infection. For older infants, parents and clinicians should decide together whether further evaluations would be helpful. “If findings consistent with congenital Zika syndrome are identified at any time, referrals to the appropriate specialists should be made, and subsequent evaluation should follow recommendations for infants with clinical findings consistent with congenital Zika syndrome,” said the authors.

The CDC also reiterated their special recommendations for infants who had a prenatal diagnosis of Zika infection. For now, these recommendations remain unchanged, although “as more data become available, understanding of the diagnostic role of prenatal ultrasound and amniocentesis … will improve, and guidance will be updated.”

The optimal timing for a Zika diagnostic ultrasound is uncertain. The CDC recommend that serial ultrasounds be performed every three to four weeks for women with laboratory-confirmed prenatal Zika exposure. Women with possible exposure need only routine ultrasound screenings.

While Zika RNA has been identified in amniotic fluid, there is no consensus on the value of amniocentesis as a prenatal diagnostic tool. Investigations of serial amniocentesis suggest that viral shedding into the amniotic fluid might be transient. If amniocentesis is performed for other reasons, Zika nucleic acid testing can be incorporated.

A shared decision-making process about screening is key, said Dr. Adebanjo and colleagues. “For example, serial ultrasound examinations might be inconvenient, unpleasant, and expensive, and might prompt unnecessary interventions; amniocentesis carries additional known risks such as fetal loss. These potential harms of prenatal screening for congenital Zika syndrome might outweigh the clinical benefits for some patients; therefore, these decisions should be individualized.”

—Michele G. Sullivan

Suggested Reading

Adebanjo T, Godfred-Cato S, Viens L, et al. Update: Interim guidance for the diagnosis, evaluation, and management of infants with possible congenital Zika virus infection - United States, October 2017. MMWR Morb Mortal Wkly Rep. 2017;66(41):1089-1099.

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