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Zika-Exposed ‘Normal’ Infants May Do Worse as Time Goes On

A small cohort of Colombian infants with exposure to Zika virus in utero, but who were not diagnosed with congenital Zika syndrome at birth, showed declines in adaptive and functional skills as they aged into toddlers, researchers found.

Because most newborns with prenatal Zika exposure do not have clinical manifestations of congenital Zika syndrome (such as microcephaly or abnormal brain imaging) at birth, “the spectrum of neurodevelopmental impairment” for these infants is of “major importance,” Sarah Mulkey, MD, PhD, of Children’s National Hospital in Washington, and colleagues reported in JAMA Pediatrics.

Infants without congenital Zika syndrome underwent developmental evaluation at one or two time points: age 4 months to 8 months and age 9 months to 18 months. Inclusion criteria were infants born from August 2016 to November 2017 who were normocephalic at birth, had normal fetal brain imaging, and had normal examination results without clinical evidence of congenital Zika syndrome. The majority also had postnatal brain imaging.

Assessments were performed using the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA) and the Alberta Infant Motor Scale (AIMS).

Of the 77 infants from Colombia who met the criteria, 70 had no evidence of congenital Zika syndrome and were able to undergo these assessments. There were 40 infants evaluated from ages 4 to 8 months (median of almost 6 months) and 60 infants evaluated from ages 9 to 18 months (median age of 13 months). There was no change in head circumference z scores, they said, when controlling for age of gestational exposure to Zika virus.

The authors found that WIDEA scores had “a curvilinear pattern of decline” over time, although the self-care domain declined up to age 12 months, and “increased to normative levels by 20 months.” Mobility and social cognition scores had consistent, modest declines. They noted that while AIMS scores tended to decrease over time, these declines were not statistically significant.

There were 19 of 57 infants who had previously undergone postnatal imaging with “mild, nonspecific findings.” Compared to infants without these findings, there was a decline in social cognition scores.

In an accompanying editorial, Margaret Honein, PhD, of the CDC in Atlanta, and colleagues, wrote that while “the clinical significance of these non-specific findings is not yet clear, the importance of postnatal neuroimaging for all children with Zika virus exposure in utero was made extremely clear.”

“The [study] findings add to the growing evidence of the need for long-term follow-up for all children with Zika virus exposure in utero to ensure they receive the recommended clinical evaluations even when no structural defects are identified at birth,” Honein and colleagues wrote.

“Evaluation of infants solely at the time of birth is clearly inadequate, as growing evidence exists of infants with clinically normal assessments who subsequently developed neurodevelopmental issues and infants with documented microcephaly at birth whose microcephaly was resolved and whose neurodevelopmental assessment results were normal on follow-up,” they added.

Study limitations included its small size and “a lack of a normative Colombian population for the WIDEA and AIMS assessments.”

The study was supported by the NIH National Center for Advancing Translational Sciences and the Leadership Education in Neurodevelopmental and Related Disorders Training Program.

Mulkey disclosed support from the Thrasher Research Fund, and providing technical expertise to the Zika studies by the CDC.

A co-author disclosed providing support from the Children’s National Hospital.

Honein disclosed no relevant relationships with industry.