Exploring neurodevelopment among Zika virus-exposed children without Zika syndrome

In a recent study published in Pediatric Research, researchers assessed neurodevelopment in Zika-exposed preschool children without congenital Zika syndrome.

Study: Preschool neurodevelopment in Zika virus-exposed children without congenital Zika syndrome. Image credit: Kateryna Kon/Shutterstock

Children exposed to Zika virus (ZIKV) during gestation at the time of the ZIKV pandemic have aged into early childhood. Congenital Zika syndrome (CZS) refers to the phenotype of infants with multiple neurological defects and extensive medical needs. Early research on neurodevelopmental outcomes shows a risk of neurodevelopmental deficits in the first two years of life among children exposed to ZIKV during pregnancy. The neurological and neurodevelopmental effects of children with the full spectrum of congenital ZIKV exposure need to be understood.

About the study

In the present study, the researchers aimed to examine whether children exposed to ZIKV in utero who did not have CZS had aberrant effects on preschool neurodevelopment.

In the Atlantic department of Colombia, the team performed a prospective cohort analysis of ZIKV-exposed and non-ZIKV-exposed control children. A total of 70 three- to four-year-old children with prenatal exposure to ZIKV without a diagnosis of CZS from the longitudinal pregnancy cohort were eligible. As part of the early outcomes investigation, children were normocephalic at birth, had normal sequential prenatal ultrasound as well as magnetic resonance imaging (MRI), scans, no clinical evidence of CZS at birth, and a minimum of one assessment of neurological development by the time they were 18 months old. Their mothers experienced symptomatic ZIKV infection during pregnancy and lived in a place with endemic ZIKV transmission with a laboratory-confirmed diagnosis of ZIKV.

The eligible date of birth was chosen to enroll controls of a similar age to exposed cases, but who were born before the arrival of ZIKV circulation in Colombia. Children exposed to ZIKV were recruited through face-to-face or telephone contact in their homes and resided in or near Sabanalarga, Atlántico, Colombia.

Using the ZIKV Outcome Toolbox, neurodevelopment was assessed. The Toolbox contains parent surveys and standardized child assessments. The team used The Pediatric Evaluation of Disability Inventory (PEDI-CAT), a computerized questionnaire that quantifies the physiological functions of daily routines, mobility, responsibility and social-cognitive skills. The Behavior Rating Inventory of Executive Function-P (BRIEF-P) is also a questionnaire designed to assess executive function. Parents also answered the Parental Stress Index (PSI-4) along with questionnaires on the home and family environment and their children’s medical history.

The team assessed the children using the Movement Assessment Battery for Children, Second Edition (MABC) and the Bracken School Readiness Assessment (BSRA). The BSRA assesses a child’s understanding of five subject areas: letters, colors, counting or numbers, comparisons, or sizes and shapes. In addition, the MABC assessed balance, hand dexterity, and the ability to aim and catch.

results

At a mean age of 3.6 years, 55 of 70 children with in utero exposure to ZIKV were evaluated. Their mothers were infected with ZIKV during the first two trimesters of pregnancy. Fetal exposure was reported to occur at an average of 7.9 weeks of gestation. At age 5.2 years, 70 controls who were not exposed to ZIKV were evaluated. Most mothers who contracted ZIKV during pregnancy reported that their anxiety did not affect their interactions with their offspring. Because of their ZIKV diagnosis, 13 mothers reported feeling different compared to other pregnant women during their pregnancies.

About 12 parents of children exposed to ZIKV expressed concern about their baby’s health, compared with five parents of children in the control group. Six infections and one control included parents who reported mood problems in their children. There were more reports of childhood vision difficulties among the infected than among the controls, but there was no difference in the proportion of children who received rehabilitation therapy. The study also reported that 33 children exposed to ZIKV attended daycare, while the rest were cared for by family or friends. In addition, 59 participants in the control group had started primary school during the assessment.

PEDI-CAT t-scores associated with infections were lower for responsibility and mobility, indicating lower child function. However, this score was higher among social or cognitive tasks and daily activities compared to controls. The team also noted that BRIEF-P flexibility and change scores were higher among cases than controls.

Overall, the study results showed that children exposed to ZIKV in utero who did not develop CZS indicated improvements in neurodevelopment. However, as they prepare to start school, these children may need additional help with early executive function skills and school readiness concepts.

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