Visual Acuity Deficits in Otherwise Normally Developing Zika Virus Exposed Children

Background: The Zika virus (ZIKV) targets neural stem cells in the developing brain. It remains unclear whether ZIKV-Exposed Children (ZEC) with no apparent neurological manifestations at birth were protected from ZIKV neurotropism during gestation or harbor subtle pathology that might disrupt neurodevelopment. In this prospective study, we tracked a cohort of normocephalic ZIKV-exposed children (NZEC) in parallel with normocephalic unexposed controls (UC) from birth to 30 months of age to determine whether NZEC show higher rates of neurodevelopmental delays relative to UC. Methods: A total of 384 pregnant women were recruited from public health centers in Grenada, West Indies and enrolled between April 2016 and March 2017, which was a period of active ZIKV transmission. Serum samples were collected from mothers during the prenatal and postnatal period and assessed for ZIKV antibodies using a plasmonic-gold platform. Infants were classified as NZEC if their mothers tested positive for ZIKV infection during pregnancy and they were normocephalic, as defined by World Health Organization Child Growth Standards. Children were classified as UC if their mothers tested negative for ZIKV infection during and following pregnancy. Outcome measures included the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) package and Cardiff Vision Tests, which were administered and scored by research staff blinded to participants’ exposure status. Findings: A total of 68 NZEC and 63 UC completed outcome measures between 22 to 30 months of age. There were no group differences in socio-demographics. Visual acuity deficits were apparent in NZEC in the absence of any other cognitive, motor, language, or behavioral delays. Interpretation: The presence of visual acuity deficits in NZEC suggests that the visual system may be selectively vulnerable in otherwise normally developing children. Continued neurocognitive surveillance of this cohort will address whether early vision problems place NZEC at risk for future deficits in visuo-spatial functions and learning disorders. Funding Statement: TWINDREF GSP-SRGI-18009 (KB); USAID AID-OAA-A-14-00028 (ADL), NIH R21HD093551-01 (RW, BL, MF), Stanford Maternal Child Health Research Institute (ADL). MF is supported by an Academic Clinical Fellowship in Paediatrics from the National Institute for Health Research, UK, to the University of Southampton. Declaration of Interests: None of the authors have any conflicts of interest to disclose. Ethics Approval Statement: Institutional Review Board approval was obtained at St George’s University (IRB#16061) and Stanford University (IRB#45242). Informed consent was obtained from all mothers who participated in this study. There was no financial compensation.