In Utero Zika Exposure May Cause Unexpected Neurodevelopmental Abnormalities

During the headline-grabbing 2015-16 Zika virus epidemic, many infants were exposed to the virus in utero without showing immediate signs of disability. While these infants were not diagnosed with congenital Zika syndrome, some clinicians have been concerned about the possibility of future neurodevelopmental abnormalities.

Results from a new study in JAMA Pediatrics have validated these concerns, finding infants with in utero Zika exposure who were not diagnosed with congenital Zika syndrome appear to be at risk for abnormal neurodevelopmental outcomes in the first 18 months of life.

In 2016, investigators prospectively enrolled 82 pregnant women with symptomatic Zika virus infection in Atlántico Department, Colombia, and Washington DC, into the study. Investigators monitored the pregnancies with serial fetal magnetic resonance imaging (MRI) and ultrasonography.

Infants born from August 1, 2016 through November 30, 2017 were included in the study if they were live born, were normocephalic at birth, had normal fetal brain findings on MRI and ultrasonography, and did not show clinical evidence of congenital Zika syndrome.

Head circumference, birth weight, and length were collected for all infants.

In total, 77 infants with clinically normal presentation at birth formed the study cohort. All infants who ultimately met inclusion criteria were born in Colombia.

In the study cohort, infant development was assessed with the Alberta Infant Motor Scale (AIMS) as well as the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA).

AIMS is a motor examination of an infant’s movements in prone, sitting, supine, and standing positions. WIDEA is a 50-item questionnaire available in English or Spanish depending on the parent’s primary language. It is usable for children up to 30 months of age, compromising parental assessment of mobility, self-care, communication, and social cognition.

Out of the 77 Colombian infants included in the study, 70 underwent 1 to 2 neurodevelopmental assessments. Forty infants were evaluated at 4 to 8 months of age and 60 underwent assessment between 9 and 18 months of age.

The median WIDEA total score was 60.5 at time point 1 and 102.5 at time point 2. The WIDEA total z score demonstrated a curvilinear pattern of decline over time (coefficients: age = 0.227 vs age² = 0.006; P < .003).

WIDEA self-care scores had a similar curvilinear decline to 12 months of age, though scores increased to normative levels by 20 months of age (coefficients: age = —0.238 vs age² = 0.01; P < .008).

WIDEA z scores of mobility with age coefficients (-0.14 P < .001), social cognition (-0.10; P < .001), and communication (-0.036; P = .001) decreased over the study period.

On the AIMS assessment, the median score was 25 at time point 1 and 49 at time point 2. Although AIMS score decreased over time, the decrease did not approach statistical significance.

Examined individually, many of the infants displayed normal neurodevelopmental scores through 18 months of age. Yet for some infants, scores in multiple areas of development decreased from normative mean scores over time.

“These infants were expected to have low risk for subsequent neurodevelopmental deficits, yet these deficits emerged in the first year of life and without a reduction in head circumference,” study authors wrote in their report.

Investigators also noted another finding that stood out.

“We also found that nonspecific postnatal neuroimaging findings of lenticulostriate vasculopathy, germinolytic or subependymal cysts, and choroid plexus cysts, which were present in up to 37% of newborns exposed to ZIKV in utero, may be potential risk factors for worse early neurodevelopmental outcomes.”