Zika virus infection evaluation of infants

Sexually transmitted diseases Main Page
Zika virus infection Microchapters
Home
Patient Information
Overview
Historical Perspective
Pathophysiology
Causes
Classification
Differentiating Zika Virus Infection from other Diseases
Epidemiology and Demographics
Risk Factors
Natural History, Complications, and Prognosis
Diagnosis
History and Symptoms
Physical Examination
Laboratory Findings
Evaluation of Pregnant Women
Evaluation of Infants
Collection and Submission of Fetal Tissues
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Guidelines for Pregnant Women
Travel Notice
Blood Donation
Sexual transmission
Secondary Prevention
CDC Response Planning Tips
Risk-based Preparedness for States
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Zika virus infection evaluation of infants On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Zika virus infection evaluation of infants All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Zika virus infection evaluation of infants
CDC on Zika virus infection evaluation of infants
Zika virus infection evaluation of infants in the news
Blogs on Zika virus infection evaluation of infants
Directions to Hospitals Treating Zika virus infection
Risk calculators and risk factors for Zika virus infection evaluation of infants

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

According to the CDC, zika virus testing is recommended among 1) infants with microcephaly or intracranial calcifications born to women who traveled to or resided in an area with Zika virus transmission while pregnant, or 2) infants born to mothers with positive or inconclusive test results for Zika virus infection. When an infant is born with microcephaly or intracranial calcifications to a mother who was potentially infected with Zika virus during pregnancy, the infant should be tested for Zika virus infection and ophthalmologic examination. For an infant without microcephaly or intracranial calcifications born to a mother who was potentially infected with Zika virus during pregnancy, subsequent evaluation is dependent on results from maternal Zika virus testing. Developmental monitoring and screening during the first year of life is recommended for all children with congenital Zika virus infection.

Evaluation of Infants

• Pediatric health care providers should work closely with obstetric providers to identify infants whose mothers were potentially infected with Zika virus during pregnancy (see Travel Notice), and review fetal ultrasounds and maternal testing for Zika virus infection (see Zika virus infection evaluation of pregnant women|Evaluation of Pregnant Women]].
• Zika virus testing is recommended for the following infant groups:

• Infants with microcephaly or intracranial calcifications born to women who traveled to or resided in an area with Zika virus transmission while pregnant
• Infants born to mothers with positive or inconclusive test results for Zika virus infection.

• For infants with laboratory evidence of a possible congenital Zika virus infection, additional clinical evaluation and follow-up is recommended
• Health care providers should contact their state or territorial health department to facilitate testing. As an arboviral disease, Zika virus disease is a nationally notifiable condition.

Recommendations for Infants with Microcephaly or Intracranial Calcifications Detected Prenatally or at Birth Whose Mothers Were Potentially Infected with Zika Virus During Pregnancy

Recommended Zika virus laboratory testing for infants when indicated* Test infant serum for Zika virus RNA, Zika virus immunoglobulin (Ig) M and neutralizing antibodies, and dengue virus IgM and neutralizing antibodies. The initial sample should be collected either from the umbilical cord or directly from the infant within 2 days of birth, if possible. If cerebrospinal fluid is obtained for other studies, test for Zika virus RNA, Zika virus IgM and neutralizing antibodies, and dengue virus IgM and neutralizing antibodies. Consider histopathologic evaluation of the placenta and umbilical cord with Zika virus immunohistochemical staining on fixed tissue and Zika virus RT-PCR on fixed and frozen tissue. If not already performed during pregnancy, test mother’s serum for Zika virus IgM and neutralizing antibodies, and dengue virus IgM and neutralizing antibodies. *Indications for testing include 1) infants with microcephaly or intracranial calcifications born to women who traveled to or resided in an area with Zika virus transmission while pregnant, or 2) infants born to mothers with positive or inconclusive test results for Zika virus infection.

• For the purpose of evaluating an infant for possible congenital Zika virus infection, microcephaly is defined as occipitofrontal circumference less than the third percentile, based on standard growth charts (e.g., Fenton, Olsen, CDC, or WHO growth curves) for sex, age, and gestational age at birth. For a diagnosis of microcephaly to be made, the occipitofrontal circumference should be disproportionately small in comparison with the length of the infant and not explained by other etiologies (e.g., other congenital disorders). If an infant’s occipitofrontal circumference is equal to or greater than the third percentile but is notably disproportionate to the length of the infant, or if the infant has deficits that are related to the central nervous system, additional evaluation for Zika virus infection might be considered.
• When an infant is born with microcephaly or intracranial calcifications to a mother who was potentially infected with Zika virus during pregnancy, the infant should be tested for Zika virus infection. In addition, further clinical evaluation and laboratory testing is recommended for the infant.
• The mother should also be tested for a Zika virus infection, if this testing has not already been performed during pregnancy. An ophthalmologic evaluation, including retinal examination, should occur during the first month of life, given reports of abnormal eye findings in infants with possible congenital Zika virus infection.
• For infants with any positive or inconclusive test findings for Zika virus infection, health care providers should report the case to the state, territorial, or local health department and assess the infant for possible long-term sequelae. This includes a repeat hearing screen at age 6 months, even if the initial hearing screening test was normal, because of the potential for delayed hearing loss as has been described with other infections such as cytomegalovirus.
• For infants with microcephaly or intracranial calcifications who have negative results on all Zika virus tests performed, health care providers should evaluate for other possible etiologies and treat as indicated.

• The following algorithm shows the interim guidelines for the evaluation and testing of infants with microcephaly* or intracranial calcifications whose mothers traveled to or resided in an area with Zika virus transmission during pregnancy^§.

Microcephaly or intracranial calcifications detected prenatally or at birth

Perform Zika virus testing and other clinical evaluation in infant

Positive or inconclusive test for Zika virus infection in infant

Negative tests for Zika virus infection in infant

Report ccase and assess infant for possible long-term seqelae

Evaluate and treat for other possible etiologies

Microcephaly defined as occipitofrontal circumference less than the third percentile for gestational age and sex not explained by other etiologies
*Laboratory evidence of Zika virus infection includes 1) detectable Zika virus, Zika virus RNA, or Zika virus antigen in any clinical sample, or 2) positive Zika virus immunoglobulin M with confirmatory neutralizing antibody titers that are ≥4-fold.
^§higher than dengue virus neutralizing antibody titers in serum or cerebrospinal fluid. Testing would be considered inconclusive if Zika virus neutralizing antibody titers are <4-fold higher than dengue virus neutralizing antibody titers.
Algorithm adapted from the Centers for Disease Control and Prevention [2], Retrieved on February 1st, 2016.

Recommended clinical evaluation and laboratory testing for infants with possible congenital Zika virus infection

For all infants with possible congenital Zika virus infection, perform the following:

• Comprehensive physical examination, including careful measurement of the occipitofrontal circumference, length, weight, and assessment of gestational age.
• Evaluation for neurologic abnormalities, dysmorphic features, splenomegaly, hepatomegaly, and rash or other skin lesions. Full body photographs and any rash, skin lesions, or dysmorphic features should be documented. If an abnormality is noted, consultation with an appropriate specialist is recommended.
• Cranial ultrasound, unless prenatal ultrasound results from third trimester demonstrated no abnormalities of the brain.
• Evaluation of hearing by evoked otoacoustic emissions testing or auditory brainstem response testing, either before discharge from the hospital or within 1 month after birth. Infants with abnormal initial hearing screens should be referred to an audiologist for further evaluation.
• Ophthalmologic evaluation, including examination of the retina, either before discharge from the hospital or within 1 month after birth. Infants with abnormal initial eye evaluation should be referred to a pediatric ophthalmologist for further evaluation.
• Other evaluations specific to the infant’s clinical presentation.

For infants with microcephaly or intracranial calcifications, additional evaluation includes the following:

• Consultation with a clinical geneticist or dysmorphologist.
• Consultation with a pediatric neurologist to determine appropriate brain imaging and additional evaluation (e.g., ultrasound, computerized tomography scan, magnetic resonance imaging, and electroencephalogram).
• Testing for other congenital infections such as syphilis, toxoplasmosis, rubella, cytomegalovirus infection, lymphocytic choriomeningitis virus infection, and herpes simplex virus infections. Consider consulting a pediatric infectious disease specialist.
• Complete blood count, platelet count, and liver function and enzyme tests, including alanine aminotransferase, aspartate aminotransferase, and bilirubin.
• Consideration of genetic and other teratogenic causes based on additional congenital anomalies that are identified through clinical examination and imaging studies.

Recommended long-term follow-up for infants with possible congenital Zika virus infection

• Report case to state, territorial, or local health department and monitor for additional guidance as it is released.
• Conduct additional hearing screen at age 6 months, plus any appropriate follow-up of hearing abnormalities detected through newborn hearing screening.
• Carefully evaluate occipitofrontal circumference and developmental characteristics and milestones throughout the first year of life, with use of appropriate consultations with medical specialists (e.g., pediatric neurology, developmental and behavioral pediatrics, physical and speech therapy).

Recommendations for Infants without Microcephaly or Intracranial Calcifications Whose Mothers Were Potentially Infected with Zika Virus During Pregnancy

• For an infant without microcephaly or intracranial calcifications born to a mother who was potentially infected with Zika virus during pregnancy, subsequent evaluation is dependent on results from maternal Zika virus testing.

• If the test results for the mother were negative for Zika virus infection, the infant should receive routine care (e.g., newborn metabolic and hearing screens).
• If the mother received positive or inconclusive results of tests for Zika virus infection, the infant should be tested for a possible congenital Zika virus infection.
• If the results of all of the infant’s tests are negative for evidence of Zika virus infection, then no further Zika virus testing and evaluation is recommended.
• If any of the infant’s samples test positive or inconclusive, then the infant should undergo further clinical evaluation.

• The infant should also be followed to assess for possible long-term sequelae, and the infant’s case should be reported to the state, territorial, or local health department.
• Infant follow-up should include a cranial ultrasound to assess for subclinical findings, unless prenatal ultrasound results from the third trimester demonstrated no abnormalities of the brain. Ophthalmologic examination and a repeat hearing screen are also recommended, as previously described for infants with microcephaly or intracranial calcifications.
• Developmental monitoring and screening during the first year of life is recommended for all children with congenital Zika virus infection.

• If the mother has not undergone any previous testing for Zika virus infection during pregnancy, CDC recommends that she receive testing only if she reported symptoms consistent with Zika virus disease during or within 2 weeks of any time spent in an area with ongoing Zika virus transmission while she was pregnant.
• If the mother has any positive or inconclusive findings from tests for Zika virus infection, then the infant should undergo testing for evidence of a congenital Zika virus infection.
• If the mother has not received any previous testing for Zika virus, and did not report clinical illness consistent with Zika virus disease during pregnancy, no further testing of the mother or infant is recommended.