Cognitive Development of Infants Exposed to the Zika Virus in Puerto Rico

IMPORTANCE: Existing research has established a causal link between Zika virus (ZIKV) infection and severe birth defects or consequent health impairments; however, more subtle cognitive impairments have not been explored. OBJECTIVE: To determine whether infants of mothers with at least 1 positive ZIKV test show differences in cognitive scores at ages 3 to 6 months and ages 9 to 12 months. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study recruited infants enrolled in existing ZIKV study cohorts associated with the Maternal-Infant Studies Center and the Puerto Rico Clinical and Translational Research Consortium at the University of Puerto Rico and from the broader San Juan metropolitan area. The study took place at the Puerto Rico Clinical and Translational Research Consortium at the University of Puerto Rico. Participants were recruited through convenience sampling if their mothers underwent ZIKV testing prenatally and were at the target ages during the study period. Infants who were born preterm (<36 weeks’ gestational age), with low birth weight (<2500 g), or with a known genetic disorder were excluded. Infants were tested from ages 3 to 6 months or ages 9 to 12 months from May 2018 to April 2019. Data analysis was performed from March to April 2019. EXPOSURES: Zika virus status was measured prenatally and in the early postnatal period using real-time polymerase chain reaction or a ZIKV IgM antibody capture enzyme-linked immunosorbent assay. MAIN OUTCOMES AND MEASURES: The infants’ development was assessed using the Mullen Scales of Early Learning (translated to Spanish and adapted for Puerto Rico), and assessors were blinded to each infant’s ZIKV status. RESULTS: A total of 65 study participants were included. The mean (SD) age of the infants at the time of cognitive testing was 8.98 (3.19) months. Most of the infants were white (55 [84.6%]) and Puerto Rican (64 [98.5%]); 38 of the infants were male (58.5%). General cognitive and domain-specific scores did not differ significantly between prenatally ZIKV-positive and ZIKV-negative infants except for receptive language score (mean difference = 5.52; t = 2.10; P = .04). Exposure to ZIKV (B = −5.69; β = −0.26 [95% CI −11.01 to −0.36]; P = .04) and a measure of Hurricane Maria exposure (time without water, B = −0.05; β = −0.27 [95% CI, −0.10 to −0.01]; P = .03) were both independently and significantly associated with receptive language scores after adjusting for key confounders. CONCLUSIONS AND RELEVANCE: Although infants exposed to ZIKV prenatally showed unaffected motor and visually mediated cognitive development, they did show deficits in receptive language scores. Receptive language skills were also associated with the degree of exposure to Hurricane Maria, with those who spent more time without water after the hurricane having lower receptive language scores.