Table 2.

What We Know and What We Do Not Know About the Consequences of Congenital ZIKV

	What We Know	What We Do Not Know
Overall	CZS is a severe manifestation of congenital ZIKV infection. Most frequencies reported are in children with the severe CZS phenotype.	How many children had congenital ZIKV infection and may have sequelae but have not presented with CZS?
Head growth	Some cases have been reported of infants with normal head circumference at birth whose heads do not grow appropriately and subsequently develop postnatal microcephaly. These cases also have associated brain anomalies.	How frequently does postnatal microcephaly occur in infants with congenital ZIKV infection? How do the developmental trajectories of infants with postnatal microcephaly compare with those with microcephaly at birth?
Vision	Ophthalmologic abnormalities occur in approximately 20% of infants with prenatal Zika infection, most commonly affecting the retina and optic nerve, regardless of head circumference at birth. Visual function is abnormal in nearly all infants with CZS (strabismus, nystagmus, visual acuity, visual fields, and visual milestones). Glasses are beneficial but do not fully restore vision.	How does visual function evolve over time? What are effective interventions to improve vision outcomes in this population?
Hearing	Reports of hearing impairment vary between 10% and 68%. No evidence thus far of delayed-onset hearing impairment.	What is the impact of hearing aids or cochlear implants in this population?
Feeding/nutrition	Intrauterine growth restriction and small for gestational age are common findings prenatally and at birth associated with CZS. Dysphagia occurs in 14%–77% of infants with CZS.	Does supplemental feeding impact growth trajectories or developmental trajectories? What is the risk of malnutrition? What is the risk for aspiration?
Motor development	Hypertonia is frequently noted in the first month of life. Motor impairment consistent with mixed pyramidal/extrapyramidal cerebral palsy occurs in 37%–100% of infants with CZS. Some infants may have unilateral or bilateral hemiparesis.	What percentage of children become ambulatory? What percentage can self-feed? What percentage are able to support their heads?
Language/cognitive development	Severe brain anomalies are likely to be associated with intellectual disability. May be impacted by co-occurring hearing or motor impairment. Limited data in series of infants up to age 24 mo suggest severe global developmental delay.	Do interventions for hearing and motor improve language or cognitive outcomes? What are these infants’ ultimate developmental potential?
Epilepsy	Seizures occur in approximately half of CZS patients and may be intractable. EEGs are abnormal, with a variety of epileptiform and nonepileptiform patterns.	Which therapies may be most effective in this disorder?
Hydrocephalus	Ex vacuo hydrocephalus is most common, but hypertensive hydrocephalus may also occur.	How frequently are neurosurgical interventions needed for hydrocephalus? What is the best way to monitor for those infants who may require neurosurgical intervention?
Orthopedic	Congenital contractures are common: clubfoot in 15% and arthrogryposis in 10%. Likely at risk of orthopedic problems later in life secondary to motor impairment/CP.	What are the outcomes of splinting or surgical orthopedic interventions?
Behavior	Irritability during first months is common and seems to improve over time. Sleep problems are common. At risk of other behavioral problems, given cognitive and communication limitations.	What are the behavioral profiles during childhood and adolescence? Do less affected children develop behavioral problems?
Other co-occurring conditions	Congenital heart disease (ASD and VSD) in 10%–14% of patients. Neurogenic bladder may occur.	What other medical comorbidities exist and does their management differ from other populations?
Family and social concerns	Low-income families at increased risk associated with health care disparities. Mothers have high anxiety and low quality of life. In affected countries, there is an increased demand for social services for people with disabilities.	What are effective interventions to aid families prenatally and after birth?

ASD, atrial septal defect; CP, cerebral palsy; CZS, congenital Zika syndrome; EEG, electroencephalogram; VSD, ventricular septal defect; ZIKV, Zika virus.