Congenital Zika Virus Disease
2024 Case Definition

Clinical Criteria

^†To meet the clinical criteria for congenital Zika virus disease, the liveborn infant must not have an identified genetic or other cause for the findings, including a positive test for another likely etiology^††, and should have one or more of the following brain or eye anomalies or neurological sequelae specific for congenital Zika virus disease and typically identifiable in the neonatal period:

• Microcephaly (occipital frontal circumference >2 standard deviations below the mean for age and sex) at birth or postnatal onset,
• cortical hypoplasia or abnormal gyral patterns (polymicrogyria, lissencephaly, heterotopia),
• increased volume of cerebrospinal fluid (CSF) (hydrocephalus ex vacuo, unspecified hydrocephalus, ventriculomegaly) due to loss of brain parenchyma,
• intracranial calcifications (most commonly between the cortex and subcortex),
• congenital contractures of major joints (arthrogryposis) associated with structural brain anomalies,
• congenital paralysis of the diaphragm associated with structural brain anomalies,
• corpus callosum agenesis/hypoplasia,
• cerebellar hypoplasia,
• scarring of the macula with coarse deposits of pigment in the retina (focal retinal pigmentary mottling), OR
• other structural eye anomalies (microphthalmia, cataracts, chorioretinal atrophy, optic nerve hypoplasia).

^†Clinical findings can be observed during prenatal or postnatal evaluations. Consult with CDC as needed for assistance with congenital Zika virus disease clinical determinations.
^††Other clinical considerations for congenital Zika virus disease: Among congenital infections, cytomegalovirus infection has clinical findings most consistent with Zika virus infection and should be ruled out by diagnostic testing. While other infectious etiologies (e.g., rubella virus, varicella zoster virus, herpes simplex virus, lymphocytic choriomeningitis virus, Toxoplasma gondii, or Treponema pallidum) have clinical findings less consistent with congenital Zika virus disease, testing for these infections should be considered as part of the complete evaluation for congenital disease.

Laboratory Criteria

Confirmatory laboratory evidence:

 Detection of Zika virus, viral antigen, or viral RNA in infant CSF, blood, urine, or postmortem tissue^‡; OR

• Detection of anti-Zika virus IgM antibodies in infant CSF or blood^‡, with positive anti-Zika virus-specific neutralizing antibody titers.

Presumptive laboratory evidence:

• Detection of Zika virus, viral antigen, or viral RNA in amniotic fluid, placenta, umbilical cord, or cord blood^‡; OR
• Detection of anti-Zika virus IgM antibodies in infant CSF or blood^‡ with no neutralizing antibody testing performed.

Note: The categorical labels used here to stratify laboratory evidence are intended to support the standardization of case classifications for public health surveillance. The categorical labels should not be used to interpret the utility or validity of any laboratory test methodology.
^‡To prevent misclassifying postnatal Zika virus infections as congenital cases, in Zika virus endemic areas specimens should be collected within 4 weeks after birth.

Probable

• Meets the clinical criteria for congenital Zika virus disease, AND
• Meets presumptive laboratory criteria for congenital Zika virus disease, AND
• Whose gestational parent meets:
  • epidemiologic linkage criteria, OR
  • confirmatory laboratory criteria for non-congenital Zika virus disease during this pregnancy.

Confirmed

• Meets the clinical criteria for congenital Zika virus disease, AND
• Meets confirmatory laboratory criteria for congenital Zika virus disease, AND
• Whose gestational parent meets:
  • epidemiologic linkage criteria, OR
  • confirmatory laboratory criteria for non-congenital Zika virus disease during this pregnancy.

• Zika Virus Disease | 2024 Case Definition
• Zika Virus Disease and Zika Virus Infection | 2016 Case Definition, Approved June 2016
• Zika Virus Disease, Non-congenital Infection and Zika Virus, Congenital Infection | 2016 Interim Case Definition, Approved February 26, 2016