Study investigates how Zika affects brain function in children born to infected mothers in Mexico


Following the Zika virus epidemic that started in Brazil between 2014 and 2015, some pregnant women who had the Zika virus infection had infants born with congenital Zika virus syndrome. Among other signs, this syndrome is characterized by microcephaly, a condition where a baby's head is much smaller than expected, and other central nervous system malformations. Sometimes, birth defects related to Zika exposure in utero are apparent at birth. Other times, babies who are exposed are born asymptomatic.

The Zika virus is highly neurotropic, which means it has an affinity for neurologic tissue, according to Itziar Familiar, an assistant professor in the department of psychiatry in the MSU College of Osteopathic Medicine. This led experts in the field to suspect that the virus could have more subtle effects on the developing brain in exposed, asymptomatic children. That’s why Familiar and her colleagues set out to investigate how and if neurodevelopment was affected in infants and toddlers who were exposed to the virus during pregnancy.

In the pilot study, which was recently published in Child: Care, Health and Development, Familiar worked with Department of Psychiatry colleagues Michael Boivin, Jed Magen and Horacio Ruisenor-Escudero to assess the motor, language, cognitive skills and attention spans of a group of 60 Zika-exposed infants in Mérida, Yucatán, Mexico. Several College of Osteopathic Medicine students also contributed to the study.

“We try to incorporate students into our research and have them contribute, learn and build their resumes by participating in these types of publications,” Familiar said.

Their findings suggest that children born to women with Zika virus in Mexico may be at a neurodevelopmental disadvantage and do warrant evaluation and follow up even if they have normal head volume at birth.

Familiar and her colleagues chose to do the research in Mexico for two main reasons. First, there’s a long-standing relationship between the College of Osteopathic Medicine and hospitals in Méridan. Second, researchers have observed differences in the neurodevelopmental effects of Zika virus exposure across different countries. Microcephaly in infants exposed to Zika virus seems to be more common in some regions than others. Mexico has a lower incidence compared to countries like Brazil and Colombia, making it an ideal setting to discover whether infants born without obvious symptoms might still be at neurodevelopmental risk.

While there’s never a silver lining to an epidemic, Familiar said this research situation did result in major advances in child development assessment tools.

“Standard evaluations of neurodevelopment in Western countries like the U.S. and Europe are typically done at the specialist level, meaning they’re performed by pediatricians, psychologists and neuropsychologists,” Familiar said. But these health staff often aren’t as readily available in less-developed settings and finding ways to administer these assessments with minimally trained staff was a huge priority in the Americas.

Luckily, the Global Neuropsychiatry Research Group at MSU specializes in the neurodevelopmental assessment of children, including in Africa.

“We had experience adapting a lot of these tools and training staff in their administration in low- and middle-income settings,” Familiar said. “We transferred this know-how and the protocols we have for quality assurance of the administration of these tests to the team in the field in Mexico.”

In the study, the researchers used two different multifaceted tests to assess neurodevelopment. The first was the Mullen Scales of early Learning, looking at motor, language and overall cognitive skill development. The second was the Fagan Test of Infant Intelligence, which has been around since the 70s.

“These are specialized to a range of areas that start to develop in the brain of infants and then toddlers,” Familiar said. “It's important to make sure that these neurodevelopmental milestones are being met.”

Significantly, Familiar and her colleagues innovated in how these tests were administered, using technology to combat test administrator bias. For instance, the Fagan test involves measuring how long it takes infants to change their gaze from a face they recognize to a new one. Normally, the length of the gaze would be measured by a human, but in this study, the researchers used a camera with eye-tracking capacity that follows movements and gaze, which was then analyzed using specialized software.

One of the biggest strengths of the study was that the researchers compared all of the assessments in all areas to account for the variation between individual children in reaching developmental milestones.

“We see this with our own children or other children we see in preschool; they tend to develop differently. So, there's a range,” Familiar explained.

Another major strength was that the study used a comparison group of infants whose mothers had not had Zika virus during pregnancy.

Now that the pilot study is complete, proposals are underway to secure funding to follow up with the original cohort. The participants are 5 or 6 years old now.

“As children get older, the range of developmental and cognitive domains you're able to measure is greater and richer, so it's important to repeat some of these evaluations at a later time,” Familiar said.

In the next round of research, she sees reason to be hopeful about how the participants will fare, along with an opportunity to ensure their needs are met if neurodevelopmental delays are confirmed.

“Because there's such good neuroplasticity at early ages, there tends to be some ability to catch up. It will be important to see if that underlying biological process was enough for these children to sort of ‘make up,’ or if interventions are needed so these children can effectively catch up to their peers.”