Background Few studies have assessed neurodevelopmental outcomes in normocephalic infants born to women with Zika virus (ZIKV) infection during pregnancy in Mexico. We sought to evaluate ZIKV exposed infants in Yucatan, Mexico, with performance-based and eye-gaze measures of neurodevelopment, removing observer bias. Methods We enrolled 60 infants about 6-month old born to women with PCR + test for ZIKV during pregnancy. Infants were normocephalic and asymptomatic. Sixty infants born to women without a history of ZIKV infection were included as comparison. Children were assessed with the Mullen scales of early learning (MSEL), a test with scales in motor, language, and overall cognitive skills development, and the Fagan test of infant intelligence (FTII) using automated eye-tracking instrumentation to evaluate infant visual preference of human faces, where longer gaze lengths to unfamiliar (i.e., new) faces are expected. Results All MSEL subscale scores, except expressive language, were significantly lower among ZIKV exposed children compared to controls, including the overall standard composite (80 +/- 10 vs. 87 +/- 7.4, respectively; p < 0.001). FTII eye-tracking measures of fixation and gaze length were in the expected direction, with longer times recorded among infants in the control group (i.e., higher attention), but none reached statistical significance. In adjusted linear regressions, the FTII high novelty score (expected preference for a novel face) predicted fine motor (beta = 3.61, p = 0.04) and receptive language (beta = 2.55, p = 0.03) scores. Conclusions Nonmicrocephalic children born to women with ZIKV during pregnancy in Mexico merit early neurodevelopmental evaluation to allow for appropriate interventions and clinical follow-up. It is possible that long-term monitoring of cognitive deficits may need to be established for a proportion of affected cases.
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