In the JournalsPerspective

Zika-exposed infants without congenital Zika syndrome at risk for abnormal neurodevelopment

Sarah B. Mulkey, MD, PhD
Sarah B. Mulkey

Infants without congenital Zika syndrome who were exposed to Zika in utero are at risk for abnormal neurodevelopmental outcomes during their first 18 months of life, according to a longitudinal study published in JAMA Pediatrics.

“Women should take care during pregnancy to avoid mosquito bites and other known Zika transmission routes if they live in a location at risk for Zika or if they are traveling to a location with circulating Zika virus,” Sarah B. Mulkey, MD, PhD, a fetal and neonatal neurologist at Children’s National Hospital, told Healio.

There are no ongoing Zika outbreaks anywhere in the world, but the CDC recommends that pregnant women or women planning on becoming pregnant talk to their health care provider before traveling to areas where current or past transmission of the virus has been documented.

“Women also may consider alternative travel plans during pregnancy to avoid risk of Zika exposure. Women can consult the CDC travel website to learn about risk in different areas,” Mulkey added.

Mulkey and colleagues examined the neurodevelopment of 77 Zika-exposed Colombian infants born between Aug. 1, 2016, and Nov. 30, 2017. They included infants who were live born, were normocephalic at birth, had normal fetal brain findings on MRI and ultrasonography and had normal examination results without any clinical evidence of Zika.

They assessed neurodevelopment using the Warner Initial Developmental Evaluation of Adaptive and functional Skills and the Alberta Infant Motor Scale at one or two time points from 4 and 18 months of age.

Of the 77 Zika-exposed infants, 70 were uninfected with the virus. Of the 70 uninfected infants, multidomain neurodevelopmental assessment scores deviated from the norm as the children aged. Domain scores for communication (–0.036; P = .001), social cognition (–0.1; P < .001) and mobility (–0.14; P = .001) showed linear declines with increasing age, the researchers reported.

Mulkey noted the study’s largest limitation was a lack of a non-Zika-exposed control group and emphasized that the norms for the assessments were not from Colombian children.

“For future studies, the inclusion of a comparable control cohort would help with this limitation or the use of a neurodevelopmental assessment tool with prior validation in Colombian children pre-Zika virus,” she said.

Mulkey also suggested health care providers consider the longitudinal effects of Zika exposure among their patients.

“Clinicians should continue to think about Zika virus and the potential for long-term effects in their patients,” Mulkey said. “When a clinician sees a child with a developmental delay, the clinician should think about the possibility of Zika exposure. The mother may be unaware that she had Zika infection during pregnancy because up to 80% of infections are asymptomatic.” – by Eamon Dreisbach

Disclosures: Mulkey reports receiving grants from the Thrasher Research Fund during the conduct of the study and providing technical expertise to the Zika studies by the CDC outside the submitted work. Please see the study for all other authors’ relevant financial disclosures.

Sarah B. Mulkey, MD, PhD
Sarah B. Mulkey

Infants without congenital Zika syndrome who were exposed to Zika in utero are at risk for abnormal neurodevelopmental outcomes during their first 18 months of life, according to a longitudinal study published in JAMA Pediatrics.

“Women should take care during pregnancy to avoid mosquito bites and other known Zika transmission routes if they live in a location at risk for Zika or if they are traveling to a location with circulating Zika virus,” Sarah B. Mulkey, MD, PhD, a fetal and neonatal neurologist at Children’s National Hospital, told Healio.

There are no ongoing Zika outbreaks anywhere in the world, but the CDC recommends that pregnant women or women planning on becoming pregnant talk to their health care provider before traveling to areas where current or past transmission of the virus has been documented.

“Women also may consider alternative travel plans during pregnancy to avoid risk of Zika exposure. Women can consult the CDC travel website to learn about risk in different areas,” Mulkey added.

Mulkey and colleagues examined the neurodevelopment of 77 Zika-exposed Colombian infants born between Aug. 1, 2016, and Nov. 30, 2017. They included infants who were live born, were normocephalic at birth, had normal fetal brain findings on MRI and ultrasonography and had normal examination results without any clinical evidence of Zika.

They assessed neurodevelopment using the Warner Initial Developmental Evaluation of Adaptive and functional Skills and the Alberta Infant Motor Scale at one or two time points from 4 and 18 months of age.

Of the 77 Zika-exposed infants, 70 were uninfected with the virus. Of the 70 uninfected infants, multidomain neurodevelopmental assessment scores deviated from the norm as the children aged. Domain scores for communication (–0.036; P = .001), social cognition (–0.1; P < .001) and mobility (–0.14; P = .001) showed linear declines with increasing age, the researchers reported.

Mulkey noted the study’s largest limitation was a lack of a non-Zika-exposed control group and emphasized that the norms for the assessments were not from Colombian children.

“For future studies, the inclusion of a comparable control cohort would help with this limitation or the use of a neurodevelopmental assessment tool with prior validation in Colombian children pre-Zika virus,” she said.

Mulkey also suggested health care providers consider the longitudinal effects of Zika exposure among their patients.

“Clinicians should continue to think about Zika virus and the potential for long-term effects in their patients,” Mulkey said. “When a clinician sees a child with a developmental delay, the clinician should think about the possibility of Zika exposure. The mother may be unaware that she had Zika infection during pregnancy because up to 80% of infections are asymptomatic.” – by Eamon Dreisbach

Disclosures: Mulkey reports receiving grants from the Thrasher Research Fund during the conduct of the study and providing technical expertise to the Zika studies by the CDC outside the submitted work. Please see the study for all other authors’ relevant financial disclosures.

    Perspective
    Kristina M. Adams Waldorf

    Kristina M. Adams Waldorf

    The Zika virus epidemic that swept across much of the Americas from 2015 to 2016 took the medical and scientific community off guard. Four years later, Zika virus continues to surprise us. At no point has the data indicated that we can reassure worried mothers that a Zika virus exposure will not affect the long-term brain health of their child.

    Several case series and animal studies have shown that head size at birth cannot be used as an indicator of whether or not the fetal brain was injured by Zika. What has not been clear is the time course over which neurodevelopmental deficits might appear in children exposed to Zika virus during fetal life but were born with a normal head size and had normal neuroimaging.

    This study investigates the neurodevelopment of 77 Colombian children exposed to Zika virus during fetal life who were followed closely up to 18 months of age. Typical of most Zika virus cohort studies, 91% of the children were born with a normal head size.

    There were several key findings. Neurodevelopmental scores across two validated assessment tools, Warner Initial Developmental Evaluation of Adaptive and Functional Skills and Alberta Infant Motor Scale (AIMS), deteriorated over time despite normal head size and cranial imaging. Nonspecific findings on postnatal neuroimaging studies were risk factors for a worse neurodevelopmental outcome. Mildly abnormal findings, such as lenticulostriate vasculopathy and subependymal cysts, which occurred in one-third of the children, were associated with worse neurodevelopmental scores. Clear strengths of the study included the close follow-up, sequential neuroimaging and video scoring of the AIMS examinations. 

    Because Zika has disappeared from the news cycle, many think that it is no longer a threat to pregnancies. Zika virus is now endemic in most countries of South and Central America and the Caribbean and continues to pose a risk to pregnant women who have not previously been infected. Although the number of new infections in the Americas is much lower now, there remains a risk to pregnant women who lack immunity to Zika. Our imperative now is to accelerate the development of Zika vaccines and therapeutics so that we can avoid another epidemic.

    • Kristina M. Adams Waldorf, MD
    • Adjunct professor, global health
      Professor, obstetrics and gynecology
      University of Washington

    Disclosures: Waldorf reports no relevant financial disclosures.