Zika exposure in womb may impact development into preschool age, study finds
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Children who were exposed to Zika virus in utero may demonstrate developmental differences into preschool age, even if they did not have congenital Zika syndrome, according to a study published in Pediatric Research.
Early in the Zika virus epidemic, Sarah B. Mulkey, MD, PhD, a prenatal-neonatal neurologist at Children’s National Hospital in Washington, D.C., and colleagues enrolled a group of pregnant women in Colombia with symptomatic Zika virus into a study to follow their pregnancies.
Children who were exposed to Zika virus in utero may demonstrate developmental differences into preschool age, even if they did not have congenital Zika syndrome, according to a study published in Pediatric Research. Source: Adobe Stock
“From that group of mothers, we had a number of babies who were born who were exposed to Zika but did not have the birth defects of Zika virus infection,” Mulkey said. “We know from looking at multiple cohorts that only about 5% to 12% of babies born to mothers with Zika virus infection during pregnancy have birth defects. The vast majority of babies are otherwise normal appearing but were born following their mother's infection.”
Mulkey and colleagues reported in an earlier study that infants who were exposed to Zika in utero but did not develop congenital Zika syndrome were at risk for abnormal neurodevelopmental outcomes during their first 18 months of life. The infants had lower neurological development scores compared with unexposed infants.
“Based on those findings, it was very important for us to continue to follow these children as they got older and near school age,” Mulkey said. “In this study, we are reporting the outcome of these children now at age 3 to 5 years old, right before they're entering school, to report on their developments.”
The 55 study participants included children aged 3 to 5 years who had no birth defects and had previously undergone neuroimaging “to confirm that they did not have brain malformations,” Mulkey said. The researchers also enrolled a control group of 70 children from the same region, aged 4 to 5 years, who had been born before Zika’s emergence in Colombia and had not been exposed to the virus.
The authors then performed neurodevelopmental assessments, including the Pediatric Evaluation of Disability Inventory (PEDI-CAT), Behavior Rating Inventory of Executive Function (BRIEF-P), Bracken School Readiness Assessment, and Movement Assessment Battery for Children.
“We had questionnaires that the mothers completed about different aspects of their development, including their adaptive and functional skills at home, their behavior and mood ... then we did in-person evaluations with the children to assess their motor skills and their school readiness and knowledge,” Mulkey said.
Ultimately, the resultant BRIEF-P t-scores were higher for children in the study group than those in the control group in shift and flexibility domains, but the study group had lower PEDI-CAT mobility t-scores compared with their controlled peers.
“One thing that we did find kind of interesting between these kids and in those children who were Zika exposed [was that] the parents reported a higher level of mood problems” in their children, Mulkey said.
Mulkey also acknowledged that “there may be some difference in more adaptive skills between the cases and controls that we'll have to examine in the future.”
“Child development happens over many years, and so if we only focus on those children early at birth after having an exposure in utero, then we really may miss the outcome that these children may manifest over time,” Mulkey said. “On the flip side of that, when pediatricians are evaluating children who have a learning disability — or developmental delay, or mood behavior disorder — it's important to go back and see if there was any exposure early on in their life. A mother having an infection in pregnancy might be an important factor with what we're seeing going on in the child.”
No U.S. state has reported a locally acquired Zika virus case since 2017, although infections continue to occur in U.S. territories and some states still report travel-associated cases.
In early 2022, researchers estimated that around 5% of infants born to mothers with Zika virus infection in the U.S. and its territories had a Zika-associated brain or eye defect. The estimate was based on data from nearly 6,800 births reported to the U.S. Zika Pregnancy and Infant Registry.
References:
.Mulkey S, et al. Pediatr Res. 2022;doi: 10.1038/s41390-022-02373-5.
Zika-exposed children may display neurodevelopmental differences. https://childrensnational.org/news-and-events/childrens-newsroom/2022/zika-exposed-children-may-display-neurodevelopmental-differences. Published Nov. 29, 2022. Accessed Nov. 30, 2022.
Perspective
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Congenital Zika syndrome, which defines severe clinical manifestations in children exposed to maternal Zika virus in pregnancy, has been the topic of many studies. Nevertheless, there is a spectrum of clinical manifestations following fetal exposure to maternal Zika virus. The majority of children born to women with Zika during pregnancy do not have congenital Zika syndrome.
The manuscript by Dr. Mulkey and colleagues is highly relevant to the body of literature evaluating longer term outcomes in this population. In this study, professional assessment could not identify higher rates of motor or cognitive deficits in Zika-exposed children as compared with controls, but parents of these children reported a higher frequency of mobility, mood and responsibility-related issues in their offspring, causing higher levels of parental distress. Although the findings are reassuring, neurodevelopmental assessments evaluate children for relatively brief periods of time and do not capture the extensive interactions experienced by parents caring for children on a daily basis. Although parents may be overvigilant because of concerns about Zika exposure in pregnancy, their assessment of their children should not be dismissed. More subtle manifestations triggered by viral exposure in utero leading to mood disorders or poor school preparedness may be present in these children, highlighting the continued need for long-term follow-up.
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