SUMMARY:

On October 20th, the CDC released interim guidance for the diagnosis and management of infants with possible congenital Zika infection.  According to the guidance document,

All infants born to mothers with possible Zika virus exposure during pregnancy should receive a standard evaluation at birth and at each subsequent well-child visit including a comprehensive physical examination, age-appropriate vision screening and developmental monitoring and screening using validated tools and newborn hearing screen at birth, preferably using auditory brainstem response (ABR) methodology.

Jump to:

• Zika testing in pregnancy
• Prenatal diagnosis & Zika
• Congenital Zika – clinical findings
• Infant findings present
  • Possible maternal exposure
• No infant findings
  • Positive maternal labs
  • No maternal labs, possible maternal exposure

Definitions

• Possible Zika virus exposure
  • Includes travel to, or residence in an area with mosquito borne Zika virus transmission OR
  • Sex without the use of condoms with a partner who has traveled to or resides in an area with mosquito borne Zika virus transmission 

• Laboratory evidence of possible Zika virus infection during pregnancy: Defined as  
  • NAT: Zika virus infection detected by a Zika virus NAT on any maternal, placental, or fetal specimen (referred to as NAT-confirmed OR 
  • Serology: Positive/equivocal Zika virus IgM and Zika virus plaque reduction neutralization test (PRNT) titer ≥10, regardless of dengue virus PRNT value or negative Zika virus IgM, and positive or equivocal dengue virus IgM, and Zika virus PRNT titer ≥10, regardless of dengue virus PRNT titer 

• • Note: The use of PRNT for confirmation of Zika virus infection, including in pregnant women, is not routinely recommended in Puerto Rico

• Assessment of visual acuity: Responses to teller or grating tests (if possible), pupillary response, external examination, anterior segment examination, intraocular pressure measurement if indicated, and dilated fundus examination 
  • After 3–4 months of age, also assess ocular motility, cycloplegia refraction and accommodation by dynamic retinoscopy 
  • If physical abnormalities are present, recommend photo documentation if resources are available

Updated Guidance for Testing of Pregnant Women with Possible Zika Virus Exposure  

• Zika virus NAT testing should be offered as part of routine obstetric care to asymptomatic pregnant women with ongoing possible Zika virus exposure (residing in or frequently traveling to an area with risk for Zika virus transmission) 
• Serologic testing is no longer routinely recommended because of the limitations of IgM tests  
• Zika virus testing is not routinely recommended for asymptomatic pregnant women who have possible recent, but not ongoing, Zika virus exposure (however, guidance might vary among jurisdictions)  
• Communication regarding possible maternal exposures between pediatric health care providers and obstetric care providers is critical 
• For families of infants with possible congenital Zika virus infection health care providers should  
  • Ensure that psychosocial support is in place and that families have access to care 
  • Communicate that the long-term prognosis for infants with congenital Zika virus infection is not yet known 
  • Address families’ concerns, facilitate early identification of abnormal findings, and refer infants for neurodevelopmental follow-up and therapy when indicated

Special Considerations for the Prenatal Diagnosis of Congenital Zika Virus Infection

Ultrasound

• Routine screening for fetal abnormalities is a component of prenatal care in the United States 
  • Comprehensive ultrasound examination to evaluate fetal anatomy is recommended for all women at 18–22 weeks’ gestation
  • If maternal testing does not suggest infection, patients should receive the same ultrasound screening as any other pregnant woman as part of standard routine prenatal care 
• Prenatal ultrasound findings associated with congenital Zika virus infection include  
  • Intracranial calcifications at the gray-white matter junction 
  • Ventriculomegaly 
  • Abnormalities of the corpus callosum 
  • Microcephaly 
  • Limb anomalies  
• Sensitivity, specificity, NPV and PPV of ultrasound findings for Zika virus unknown at this time  
• Abnormalities have been detected anywhere from 2 to 29 weeks after symptom onset  
• Brain abnormalities associated with congenital Zika syndrome have been identified by ultrasound in the second and third trimesters in published case reports  
• Serial Ultrasound Monitoring  
  • CDC previously recommended serial ultrasounds every 3–4 weeks for women exposed during pregnancy with laboratory evidence of Zika virus infection 
  • No data specific to congenital Zika virus infection to guide these timing recommendations  
    • Clinicians may consider extending the time interval between ultrasounds in accordance with patient preferences and clinical judgment  
  • Women with possible exposure but without laboratory evidence of Zika virus infection during pregnancy should receive ultrasound screening as recommended for routine prenatal care 

Amniocentesis

• The role of amniocentesis for the detection of congenital Zika virus infection is unknown 
• PPV, NPV and optimal timing are unknown  
• Positive Zika test results in amniotic fluid  
  • Zika virus RNA has been detected in amniotic fluid specimens 
  • Serial amniocenteses have demonstrated that Zika virus RNA might only be present transiently 
  • A negative test result on amniotic fluid cannot rule out congenital Zika virus infection 
  • If amniocentesis is indicated as part of the evaluation for abnormal prenatal findings, NAT testing for Zika virus should be considered to assist with the diagnosis of fetal infection 

Summary of prenatal diagnosis of congenital Zika virus infection

• A shared decision-making model is essential to ensure that pregnant women and their families understand the risks and benefits of screening in the context of the patient’s preferences and values 
• Decisions should be individualized 

Congenital Zika Virus Infection

• Microcephaly  
• Brain anomalies 
  • Thin cerebral cortices with enlarged ventricles and increased extra-axial fluid collections 
  • Intracranial calcifications  
  • Absent or hypoplastic corpus callosum 
  • Hypoplasia of the cerebellum or cerebellar vermis 
  • Hypoplasia of the ventral cord  
• Eye anomalies (both anterior and posterior) 
  • Microphthalmia 
  • Coloboma 
  • Intraocular calcifications 
  • Optic nerve hypoplasia and atrophy 
  • Macular scarring with focal pigmentary retinal mottling
  • Even in absence of structural eye lesions, cortical visual impairment may be present due to anomalies in visual system of the brain  
• Other neurologic sequelae  
  • Congenital limb contractures, dysphagia, sensorineural hearing loss, epilepsy, and abnormalities of tone or movement, including marked hypertonia and signs of extrapyramidal involvement  
• Additional findings since last update 
  • Eye findings in infants without microcephaly or other brain anomalies  
  • Postnatal-onset microcephaly in infants born with normal head circumferences 
  • Postnatal-onset hydrocephalus in infants born with microcephaly
  • Abnormalities on sleep electroencephalogram (EEG) in some infants with microcephaly who did not have recognized seizures
  • Diaphragmatic paralysis in infants born with microcephaly and arthrogryposis 

Infants with Clinical Findings Consistent with Congenital Zika Syndrome and Mothers with Possible Zika Virus Exposure in Pregnancy

• Laboratory Testing 
  • Zika virus testing is recommended, regardless of maternal testing results 
  • Testing CSF for Zika virus RNA and Zika virus IgM antibodies should be considered, especially if serum and urine testing are negative and another etiology has not been identified 
• Clinical Evaluation and Management in addition to standard evaluation 
  • 1 month 
    • Head ultrasound 
    • Comprehensive ophthalmologic exam 
    • Automated ABR if the newborn hearing screen was passed using only otoacoustic emissions methodology  
  • Referral to a developmental specialist and early intervention service programs are recommended 
  • Consider the following referrals  
    • Infectious disease  
    • Clinical genetics for confirmation of the clinical phenotype and evaluation for other causes of microcephaly or congenital anomalies 
    • Neurology by age 1 month  
    • Other consultations based on clinical findings 
  • Note change from previous guidance: Diagnostic ABR is no longer recommended at age 4–6 months for infants who passed the initial hearing screen with automated ABR because of the absence of data suggesting delayed-onset hearing loss in infants with congenital Zika virus infection 

Infants without Clinical Findings Consistent with Congenital Zika Syndrome and Mothers with Laboratory Evidence of Possible Zika Virus Infection During Pregnancy

• Laboratory Testing 
  • Zika virus testing is recommended
• Clinical Evaluation and Management in addition to standard evaluation 
  • 1 month 
    • Head ultrasound 
    • Comprehensive ophthalmologic exam 
    • Automated ABR if the newborn hearing screen was passed using only otoacoustic emissions methodology  
  • Health care providers should perform  
    • Standard evaluation along with routine preventive pediatric care and immunizations at each subsequent well-child visit 
    • Remain vigilant for signs that might be associated with congenital Zika virus infection 
    • Refer if suspicious findings identified at any time 
• Infants with Laboratory Evidence of Congenital Zika Virus Infection 
  • Laboratory evidence of congenital Zika virus infection includes  
    • Positive Zika virus NAT or  
    • A nonnegative Zika virus IgM with confirmatory neutralizing antibody testing, if PRNT confirmation is performed 
  • Follow recommendations for infants with clinical findings even in the absence of clinically apparent abnormalities 
• Infants without laboratory evidence of congenital Zika virus infection 
  • If laboratory and clinical findings are both negative, infection is unlikely  
  • Infants should continue to receive routine pediatric care, and health care providers should remain alert for any new findings 

Infants without Clinical Findings Consistent with Congenital Zika Syndrome and Mothers with Possible Zika Virus Exposure in Pregnancy but No Laboratory Evidence

• This category refers to mothers who were never tested or results could be negative related to timing or test related issues  
• Laboratory Testing 
  • Not routinely recommended for infants born to mothers in this category  
  • If abnormal findings are identified, these infants should receive further evaluation, including evaluation and testing for congenital Zika virus infection 
• Clinical Evaluation and Management 
  • Infants should have a standard evaluation performed at birth and at each subsequent well-child visit along with routine preventive pediatric care and immunizations 
  • Further clinical evaluation for congenital Zika virus infection beyond a standard evaluation and routine pediatric care is not routinely indicated 
  • Health care providers can consider additional evaluation in consultation with families, including
    • possible risks of screening (e.g., identification of incidental findings)
    • Maternal factors, such as the presence and timing of symptoms
    • Type, location, and length of possible Zika virus exposure 
  • Older infants in whom maternal Zika virus exposure was not assessed at birth and who are evaluated later might also have more clinical data  
  • If findings consistent with congenital Zika syndrome are identified at any time, referral as needed consistent with recommendations above for children with suspected Zika virus 

Learn More – Primary Sources:

Update: Interim Guidance for the Diagnosis, Evaluation, and Management of Infants with Possible Congenital Zika Virus Infection — United States, October 2017

ACOG/SMFM October 2017 Update: Practice Advisory Interim Guidance for Care of Obstetric Patients During a Zika Virus Outbreak

Related ObG Topics:

CDC Guidance on Zika and Pregnancy

Microcephaly – Beyond the Zika Virus

Zika virus: transmission, symptoms and management

Zika Virus Disease: How to Counsel Your Patient About Prevention

CDC Guidance for Non-Pregnant Patients and Available Diagnostic Tests for Zika Virus