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

Abstract

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 realtime 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 domainspecific 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

Serum Proteomics Reveals Alterations in Protease Activity, Axon Guidance, and Visual Phototransduction Pathways in Infants With In Utero Exposure to Zika Virus Without Congenital Zika Syndrome

“…In addition, exposed children had lower weight, length, and fat-free masses in the first three months of life compared to unexposed children (Soares et al, 2019). Zika virus-exposed infants without CZS also showed lower receptive language scores in the first year of life (Valdes et al, 2019), besides multiple cerebral and visual abnormalities, which would not have been identified without prolonged medical monitoring (Rice et al, 2018).…”

“…Reports of other congenital infections, such as cytomegalovirus and toxoplasmosis, indicate that hearing loss and eye damage can occur from 33 to 44 months after birth for symptomatic and asymptomatic infants, respectively (Dahle et al, 2000). Thus, stressing the importance of evaluating and monitoring not only symptomatic infants, but all exposed ones as the development of late complications has been increasingly supported by reports of clinical evidence (Pomar et al, 2018;Rice et al, 2018;Soares et al, 2019;Valdes et al, 2019).…”

African-lineage Zika virus replication dynamics and maternal-fetal interface infection in pregnant rhesus macaques

“…This suggests that the vRNA burden in the maternal-fetal interface is not a robust predictor of clinical outcome for the fetus, but it does not preclude the possibility that infants may develop clinical sequelae later in life due to viral exposure, or placental insufficiency during gestation. Many normal-appearing infants exposed to ZIKV in utero develop neurodevelopmental delays in the years after birth (29)(30)(31)(32). This cohort of macaques infected with an African-lineage virus was compared to a cohort of macaques infected with an Asian-lineage virus and a mock-infected control group.…”

Zika Virus Congenital Microcephaly Severity Classification and the Association of Severity with Neuropsychomotor Development

“…Head circumference establishes the diagnosis of microcephaly but, of course, does not provide information to establish a prognosis for brain development, which include learning and intellectual disabilities and lifelong neurological impairments (19). The central nervous system (CNS) lesions include destructive, calcification, hypoplasia and migration disturbances of the CNS (20); moreover, studies of developmental outcomes show that severity of microcephaly was associated with severity of cognitive (21) and motor (22) impairments. In an endemic area of Brazil, cerebral calcifications were identified as a predominant outcome in ZikV-related microcephaly.…”