Infants with possible prenatal Zika exposure who test positive for the virus should receive an in-depth ophthalmologic exam, intensified hearing testing, and a thorough neurological evaluation with brain imaging within 1 month of birth, according to new interim guidance set forth by the Centers for Disease Control and Prevention.

The new clinical management guidelines, published in the Oct. 20 issue of the Morbidity and Mortality Weekly Report, supersede the most recent CDC guidance, issued in August 2016. The agency deemed the update necessary after a recent convocation sponsored by the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists. The meeting drew dozens of practicing clinicians and federal agency representatives, who reviewed the ever-evolving body of knowledge on how to best manage the care of these infants. Since Zika emerged as a public health threat, clinicians have reported postnatal onset of some symptoms, including eye abnormalities, a developing microcephaly in infants with a normal head circumference at birth, EEG abnormalities, and diaphragmatic paralysis.

“The updated interim guidance is based on current, limited data about Zika virus infection, the interpretation of individual expert opinion 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. “As more information becomes available, this guidance will be updated.”

The guidance focuses on three groups: infants with clinical findings of Zika syndrome born to mothers with possible Zika exposure during pregnancy; infants without clinical findings of Zika syndrome whose mothers had lab-confirmed Zika exposure; and infants without symptoms whose mothers might have been exposed, but who did not have laboratory-confirmed infection ( MMWR. 2017 Oct 20;66[41]:1089-120 ).

Infants with clinical findings consistent with Zika syndrome and mothers with possible prenatal Zika exposure

These infants should be tested for Zika virus with serum and urine tests. If those are negative and there is no other apparent cause of the symptoms, they should have a cerebrospinal fluid sample tested for Zika RNA and IgM Zika antibodies.

By 1 month, these infants need 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.

Also by that time, they should undergo auditory brainstem response (ABR) audiometry – especially if the initial newborn hearing screen was done by otoacoustic emissions. Sensorineural hearing loss can be part of Zika syndrome, although late-onset hearing loss has not been seen. Therefore, the 4- to 6-month-old follow-up ABR previously recommended is no longer deemed necessary.

A comprehensive neurological exam also is part of the recommendation. Seizures are sometimes part of Zika syndrome, but infants can also have subclinical EEG abnormalities. Advanced neuroimaging can identify both obvious and subtle brain abnormalities: cortical thinning, corpus callosum abnormalities, calcifications at the white/gray matter junction, and ventricular enlargement are possible findings.

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

The complicated clinical picture calls for a team approach, Dr. Adebanjo said. “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.”

Infants without clinical findings, whose mothers have lab-confirmed Zika exposure

Initially, these infants should have the same early head ultrasound, hearing, and eye exams as those who display clinical findings. All of these infants also should be tested for Zika virus in the same way as those with clinical findings.

If tests return a positive result, they should have all the investigations and follow-ups recommended for babies with clinical findings. If lab testing is negative, and clinical findings are normal, Zika infection is highly unlikely and they can receive routine care, although clinicians and parents should be on the lookout for any new symptoms that might suggest postnatal Zika syndrome.

Infants without clinical findings, whose mothers had possible, but unconfirmed, Zika exposure

This is a varied and large group, which includes women who were never tested during pregnancy, as well as those who could have had a false negative test. “Because the latter issue is not easily discerned, all mothers with possible exposure to Zika virus infection, including those who tested negative with currently available technology, should be considered in this group,” Dr. Adebanjo said.

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

CDC also reiterated its special recommendations for infants who had a prenatal diagnosis of Zika infection. For now, these remain unchanged from 2016, although “as more data become available, understanding of the diagnostic role of prenatal ultrasound and amniocentesis will improve and guidance will be updated.”

No one has yet identified the optimal timing for a Zika diagnostic ultrasound. CDC recommends serial ultrasounds be done every 3-4 weeks for women with lab-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 suggests that viral shedding into the amniotic fluid might be transient. If the procedure is done for other reasons, Zika nucleic acid testing can be incorporated.

A shared decision-making process is key when making screening decisions that should be individually weighed, Dr. Adebanjo said. “For example, serial ultrasounds 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.”

Neither Dr. Adebanjo nor any of the coauthors had any financial disclosures.


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