From the Journals

Zika virus syndrome may adversely affect children normocephalic at birth



Microcephaly may be the hallmark of congenital Zika virus syndrome, but neurologic abnormalities also are common in normocephalic children exposed to the virus in utero, according to data from a large pediatric referral center in Rio de Janeiro.

a purple and white microscopic cells with red dots scatted around it CDC/ Cynthia Goldsmith

The retrospective analysis demonstrated that there is a “spectrum of clinical manifestations” in children with congenital Zika virus syndrome, including those who “had initially been perceived as developing normally based on [head circumference],” Jessica S. Cranston, a medical student at the University of California, Los Angeles, and associates wrote in JAMA Network Open.

Previous studies have described the poor clinical outcomes in Zika virus–exposed infants with microcephaly, but the current analysis evaluated head circumference (HC) as a continuous variable and stratified outcomes according to the presence or absence of microcephaly, they explained.

In the cohort of 215 children referred to Instituto Fernandes Figueira who had laboratory-confirmed antenatal Zika virus exposure, 53 had microcephaly (cephalic perimeter z score of less than –2 standard deviations) and 162 were normocephalic, the investigators said.

The children were evaluated monthly for the first 6 months of life and then every 3 months. Neurodevelopmental evaluation with the Bayley Scales of Infant and Toddler Development, Third Edition, between 6 months and 3 years of age showed that all of those with microcephaly had abnormal neuromotor findings. All but two of the children with microcephaly had abnormal neuroimaging results, and 38 (72%) had failure to thrive, they reported.

Among the children with normocephaly at birth, 68% had abnormal neurologic findings, including hyperreflexia (27%), abnormal tone (39%), and other congenital neuromotor signs (42%). Results of neuroimaging results, primarily in the form of transfontanelle ultrasonography, were abnormal in 29% of children with normocephaly.

“Infants with a larger birth HC, within the normocephalic range (±2 SDs), had higher overall neurodevelopmental scores on the Bayley-III assessment,” Sarah B. Mulkey, MD, PhD, said in an invited commentary, “whereas infants with a smaller birth HC within the normocephalic range had lower scores in the domains of cognitive and language functions.”

If HC measurements could be combined with early neurologic data such as the results of neuroimaging or a neurological exam, she suggested, it might provide “a practical tool to help determine risk for adverse clinical outcomes in a [Zika virus–]exposed infant at birth that can be widely used in a variety of follow-up settings.”

In nutritional assessments performed for 143 children with normocephaly, 51% had failure to thrive “because of neurologic repercussions leading to poor feeding,” Ms. Cranston and associates wrote, adding that 15 of the 73 (21%) infants with normocephaly and failure to thrive developed secondary microcephaly.

Altogether, 17 of the 162 (10.5%) children with normocephaly developed microcephaly during the follow-up, with the reverse – microcephaly resolving in infants who were microcephalic at birth – occurring in 4 of the 53 (7.5%) affected infants, indicating that “head circumference was not static,” they said.

“The trajectory of head growth is critical,” said Dr. Mulkey of the Prenatal Pediatrics Institute at Children’s National Hospital in Washington. “The neurologic outcome of a child who develops postnatal microcephaly would be very concerning compared with an infant who is born with normocephaly and maintains a steady HC percentile over time.”

HC is just one piece of the puzzle, however, since children with Zika virus syndrome may exhibit “a variety of manifestations and outcomes.” This lack of certainty suggests that “careful monitoring and evaluation of children with suspected exposure is essential for ensuring early detection of possible disabilities and referral to interventional services,” the investigators wrote.

The findings of this study “are both highly statistically significant and clinically significant,”said Kevin T. Powell, MD, PhD, a pediatric hospitalist and clinical ethics consultant living in St. Louis who was not associated with the study.

“While outcomes at birth are dichotomized into those with and without microcephaly, the developmental outcomes measured at 3 years of age are on a spectrum. ... Those with microcephaly tend to be more severely affected, but many infants with small but normal-sized heads are also mild to moderately impacted. The flip side is that 64% of infected babies ended up with average or better development” based on Bayley-III evaluations, said Dr. Powell, who is a member of the Pediatric News editorial advisory board.

The study was funded by grants from the National Institute of Allergy and Infectious Diseases, the National Eye Institute, and the Thrasher Foundation and by awards from Brazil’s National Council of Scientific and Technological Development; Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro. Individual investigators received fees and grants from these and other organizations.

Dr. Mulkey received a contract from the Centers for Disease Control and Prevention for technical expertise for Zika virus studies and received support for Zika studies from the Thrasher Research Fund. Dr. Powell had no relevant financial disclosures.

SOURCE: Cranston JS et al. JAMA Netw Open. 2020 July 7;3(7):e209303.

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