A 'Healthy' Baby With Developmental Delay: Could It Be Zika?

Cynthia A. Moore, MD


January 06, 2020


The Centers for Disease Control and Prevention (CDC), in collaboration with partner organizations, has published Guidance for the Diagnosis, Evaluation, and Management of Infants with Possible Congenital Zika Virus Infection.

Congenital Zika virus infection can cause serious fetal brain anomalies and microcephaly. In some cases, a unique pattern of birth defects and disabilities, called "congenital Zika syndrome (CZS)," is found among fetuses and infants infected with Zika virus during pregnancy. Of 1450 babies at least 1 year of age born to mothers in US territories with laboratory evidence of confirmed or possible Zika infection during pregnancy who had some follow-up reported, 6% had Zika-associated birth defects.

Guidance for laboratory testing and clinical evaluation exists for three clinical scenarios in the setting of possible maternal Zika virus exposure (Figure):

  1. Infants with clinical findings consistent with CZS regardless of maternal Zika testing results,

  2. Infants without clinical findings consistent with CZS who were born to mothers with laboratory evidence of possible Zika virus infection during pregnancy, and

  3. Infants without clinical findings consistent with CZS who were born to mothers without laboratory evidence of possible Zika virus infection.

Figure. Evaluation and management of infants with possible congenital Zika infection.

According to CDC's guidance, 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 screening at birth, preferably using AABR methodology.

Infants with maternal laboratory evidence of Zika virus exposure during pregnancy but no obvious findings consistent with congenital Zika virus on standard evaluation should have a head ultrasound performed by 1 month of age and a comprehensive ophthalmologic examination performed by 1 month of age by an ophthalmologist experienced in assessment of and intervention in infants. Infants should be referred for AABR testing by 1 month of age if the newborn hearing screen was passed using only OAE methodology.

Because levels of Zika virus RNA and IgM antibodies decline over time, laboratory testing of infants should be performed as early as possible, preferably within the first few days after birth, although testing specimens for Zika virus RNA or IgM within the first few weeks to months after birth might possibly be useful. If the initial evaluation is normal and testing performed at birth is negative, there are no recommendations for additional Zika virus testing of the infant.

The infant in this case, however, did not receive the complete recommended initial evaluation after birth. The sensitivity and specificity of testing for Zika virus in infants are unknown, and negative laboratory results without a complete evaluation are not sufficient to conclude that consequences of congenital Zika virus infection (eg, structural defects, hearing loss) are not present in an infant whose mother had laboratory evidence of infection during pregnancy.

Generally, PRNTs can be used to resolve false-positive IgM results in mothers and infants by measuring virus-specific neutralizing antibody titers for Zika, dengue, and other flaviviruses (primarily immunoglobulin G [IgG]). However, availability of PRNT may be limited, and there are several caveats to using this test, including the likelihood that maternal IgG antibodies will persist in infant serum for a year or more after delivery.

Consultation with an infectious disease specialist for evaluation of other congenital infections (TORCH infections: toxoplasmosis, other [eg, syphilis, hepatitis B], rubella, cytomegalovirus, herpes simplex virus) is not indicated at this time but may be considered if clinical findings suggest congenital infection.

The long-term prognosis for infants with congenital Zika virus infection is not yet known; therefore, healthcare providers should strive to address families' concerns, facilitate early identification of abnormal findings, and refer infants for neurodevelopmental follow-up and therapy when indicated.

Case 2: Possible Exposure In Utero, Infant With Visual Abnormalities

A mother brings her 3-month-old daughter into the clinic for a first visit. She reports concerns that her infant is not able to see well. The infant is not making good eye contact with the mother and is not following the toys that the mother waves in front of her. The infant is cooing and pushes up on her elbows when lying on her stomach. The mother also informs the healthcare provider that during her pregnancy she traveled to an area experiencing a Zika outbreak at that time. She does not recall being bitten by mosquitoes during travel and did not report the travel to her obstetric provider during pregnancy or at delivery. No Zika virus testing was performed on either mother or infant.

On physical examination, the infant has normal tone and primitive reflexes, but doesn't regard face or fix and follow. Her head circumference is normal for her age, with appropriate growth since birth. There were no complications at birth, and she passed the newborn hearing screen using the AABR methodology.

The pediatrician orders a head ultrasound and comprehensive ophthalmologic examination. The ophthalmologic examination reveals chorioretinal atrophy and scarring over the macula with pigmentary mottling. The head ultrasound shows no abnormalities.