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    Original Investigation
    October 25, 2019

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

    Author Affiliations
    • 1Laboratories of Cognitive Neuroscience, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts
    • 2Obstetrics and Gynecology, Maternal-Infant Studies Center, University of Puerto Rico School of Medicine, Medical Sciences Campus, San Juan, Puerto Rico
    • 3Harvard Graduate School of Education, Cambridge, Massachusetts
    JAMA Netw Open. 2019;2(10):e1914061. doi:10.1001/jamanetworkopen.2019.14061
    Key Points español 中文 (chinese)

    Question  Is prenatal maternal exposure to Zika virus (ZIKV) associated with cognitive scores among infants after adjusting for confounders, including demographic characteristics, socioeconomic status, maternal mental health, and exposure to Hurricane Maria?

    Findings  In this cross-sectional study of 65 Puerto Rican infants aged 3 to 12 months, those with prenatal ZIKV exposure had lower receptive language scores. Exposure to ZIKV and Hurricane Maria both were significantly and inversely associated with receptive language scores.

    Meaning  Even among infants without microcephaly or congenital Zika syndrome, prenatal maternal ZIKV infection is associated with lower receptive language scores during the first year of life; however, exposure to ZIKV does not appear to be associated with other domains of cognitive development.


    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.