Neurodevelopmental Outcomes of Children Born to Women Who Traveled to a Zika Virus-Endemic Region During Pregnancy
Authors: Cayton Christelle , Razo Elaina , Spanton Rachel , Kabakov Sabrina , Ausderau Karla , Mohr Emma 
Published: November 2023

Abstract

Background
Zika virus (ZIKV) exposure during pregnancy causes a wide range of congenital malformations and developmental deficits, but we do not know whether potential ZIKV exposure during pregnancy without a formal ZIKV diagnosis results in worse developmental outcomes. Pregnant women without symptoms are not recommended to be tested for ZIKV infection per CDC guidelines. However, ZIKV infections can be asymptomatic, which means that pregnant women may have unknowingly been infected with ZIKV during travel to an endemic region. Our study aims to determine whether neurodevelopmental outcomes of children born to women with a travel history to a ZIKV-endemic region at the height of the pandemic are worse than children without a maternal travel history.

Methods
We identified women who presented to a maternal-fetal medicine clinic within the University of Wisconsin Hospitals and Clinics system in Madison, WI, between 2015-2018 and recently traveled to a ZIKV-endemic region (n=175) and conducted a retrospective chart review. Children with no maternal travel history to a ZIKV-endemic region were identified by state registry data and matched based on month of birth and gestational age (n=189). Developmental outcomes were defined from regular screening tools obtained during well child visits, the Ages and Stages Questionnaire (ASQ-3), and the Modified Checklist for Autism in Toddlers (MCHAT). We compared the number of “No Concern”, “Borderline” and “Concern” ASQ scores between groups using a generalized linear mixed effects model with a logit link function. The number of Low, Medium or High MCHAT risk scores at 18 and 24 months were compared between groups using Fisher’s exact test. Birth weight, maternal age and maternal race were included as covariates. All reported p-values are two-sided and P&lt;0.05 was used to define statistical significance.

Results
Cases had a significantly higher rate (13.9%) of borderline/concern scores in the ASQ screening tool compared to controls (7.7%) at 16-22 months (p=0.0288), which appeared to be driven by differences in the personal-social domain where more cases (16.1%) had borderline/concern scores than the controls (5.5%, p=0.0348). There were no differences seen at 9-15 months or at 23-36 months. We also found that cases had higher rates of moderate-high risk scores (10.3%) on the MCHAT compared to controls (2.2%) at 18 months (p=0.0240), but this difference wasn’t statistically significant at 24 months. There were no differences in birth weight, maternal age and gestational age between groups. Very few of the mothers (18.3%) reported 1 or more signs or symptoms consistent with a ZIKV infection, and of the 105 women with ZIKV testing, 103 were negative.

Conclusions
Our findings indicate that children born to mothers who traveled to a ZIKV-endemic region during pregnancy, regardless of the maternal ZIKV testing result, had worse developmental screening scores around 18 months of age. This suggests that children with maternal travel history to a ZIKA-endemic region should be regularly monitored and receive early formal developmental testing as needed.